title: Postnatal Fish Oil Supplementation in High-Risk Infants to Prevent Allergy: Randomized Controlled Trial Transforming growth factor beta in human milk does not change in response to modest intakes of docosahexaenoic acid A New Liquid Human Milk Fortifier and Linear Growth in Preterm Infants Effect of dietary intervention to reduce the n-6/n-3 fatty acid ratio on maternal and fetal fatty acid profile and its relation to offspring growth and body composition at 1 year of age Effect of two doses of docosahexaenoic acid (DHA) in the diet of preterm infants on infant fatty acid status: results from the DINO trial. PUFA and LC-PUFA intake during the first year of life: can dietary practice achieve a guideline diet? Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments children's IQ at 4 years of age. Optimal Growth and Lower Fat Mass in Preterm Infants Fed a Protein-enriched Postdischarge Formula Erythrocyte fatty acids of term infants fed either breast milk, standard formula, or formula supplemented with long-chain polyunsaturates Fatty acid composition of plasma and erythrocytes in term infants fed human milk and formulae with and without docosahexaenoic and arachidonic acids from egg yolk lecithin. Randomized controlled trial of early enteral fat supplement and fish oil to promote intestinal adaptation in premature infants with an enterostomy. Fatty acid composition in maternal milk and plasma during supplementation with cod liver oil Impact of early dietary gamma-linolenic acid supplementation on atopic eczema in infancy. The Groningen LCPUFA Study: No Effect of Short-Term Postnatal Long-Chain Polyunsaturated Fatty Acids in Healthy Term Infants on Cardiovascular and Anthropometric Development at 9 Years Visual, cognitive, and language assessments at 39 months: a follow-up study of children fed formulas containing long-chain polyunsaturated fatty acids to 1 year of age. Long-chain PUFA supplementation in rural African infants: a randomized controlled trial of effects on gut integrity, growth, and cognitive development123 Lower Proportion of CD45R0+ Cells and Deficient Interleukin-10 Production by Formula-Fed Infants, Compared With Human-Fed, Is Corrected With Supplementation of Long-Chain Polyunsaturated Fatty Acids Fish consumption during the first year of life and development of allergic diseases during childhood Feeding a Formula Supplemented With Long Chain Polyunsaturated Fatty Acids Modifies the “Ex Vivo” Cytokine Responses to Food Proteins in Infants at Low Risk for Allergy The influence of a formula supplemented with dairy lipids and plant oils on the erythrocyte membrane omega-3 fatty acid profile in healthy full-term infants: a double-blind randomized controlled trial Allergic disease in infants up to 2 years of age in relation to plasma omega-3 fatty acids and maternal fish oil supplementation in pregnancy and lactation. Synthesis of long-chain polyunsaturated fatty acids in preterm newborns fed formula with long-chain polyunsaturated fatty acids. Effect of providing a formula supplemented with long-chain polyunsaturated fatty acids on immunity in full-term neonates. Effects of maternal docosahexaenoic acid intake on visual function and neurodevelopment in breastfed term infants. Molecular Fingerprints of the Human Fecal Microbiota From 9 to 18 Months Old and the Effect of Fish Oil Supplementation Dietary Long-Chain Polyunsaturated Fatty Acids Do Not Influence Growth of Term Infants: A Randomized Clinical Trial Lower Incidence of Necrotizing Enterocolitis in Infants Fed a Preterm Formula with Egg Phospholipids Long-Chain Polyunsaturated Fatty Acid Supplementation in Infancy Reduces Heart Rate and Positively Affects Distribution of Attention Maternal fish oil supplementation in lactation: Effect on visual acuity and n−3 fatty acid content of infant erythrocytes Influence of long-chain polyunsaturated fatty acids on infant cognitive function Long-chain PUFA supplementation improves PUFA profile in infants with cholestasis Fish oil supplementation of lactating mothers affects cytokine production in 2 1/2-year-old children A randomized trial of visual attention of preterm infants fed docosahexaenoic acid until two months Influence of formulas with borage oil or borage oil plus fish oil on the arachidonic acid status in premature infants Fish Oil Supplementation During Lactation: Effects on Cognition and Behavior at 7 Years of Age Soy-Based Infant Formula Supplemented with DHA and ARA Supports Growth and Increases Circulating Levels of these Fatty Acids in Infants Higher dose of docosahexaenoic acid in the neonatal period improves visual acuity of preterm infants: results of a randomized controlled trial. A randomized trial of supplementation with docosahexaenoic acid-rich tuna oil and its effects on the human milk cytokines interleukin 1 beta, interleukin 6, and tumor necrosis factor alpha. Fish oil supplementation modulates immune function in healthy infants. Blood lipid concentrations of docosahexaenoic and arachidonic acids at birth determine their relative postnatal changes in term infants fed breast milk or formula. Visual-acuity development in healthy preterm infants: effect of marine-oil supplementation. Infant nutrition and stereoacuity at age 4-6 y. Effect of long-chain n-3 fatty acid supplementation on visual acuity and growth of preterm infants with and without bronchopulmonary dysplasia. A randomized controlled trial of long-chain polyunsaturated fatty acid supplementation of formula in term infants after weaning at 6 wk of age. Nutritional effect of including egg yolk in the weaning diet of breast-fed and formula-fed infants: a randomized controlled trial. Long-chain polyunsaturated fatty acids have a positive effect on the quality of general movements of healthy term infants. Maternal fish oil supplementation during lactation does not affect blood pressure, pulse wave velocity, or heart rate variability in 2.5-y-old children. Fish oil affects blood pressure and the plasma lipid profile in healthy Danish infants. Visual maturation of term infants fed long-chain polyunsaturated fatty acid-supplemented or control formula for 12 mo. Maturation of visual acuity is accelerated in breast-fed term infants fed baby food containing DHA-enriched egg yolk. Gamma-linolenic acid supplementation for prophylaxis of atopic dermatitis--a randomized controlled trial in infants at high familial risk. A randomized trial of different ratios of linoleic to alpha-linolenic acid in the diet of term infants: effects on visual function and growth. Similar effects on infants of n-3 and n-6 fatty acids supplementation to pregnant and lactating women. Maternal Fish Oil Supplementation in Lactation and Growth during the First 2.5 Years of Life Evaluation of a long-chain polyunsaturated fatty acid supplemented formula on growth, tolerance, and plasma lipids in preterm infants up to 48 weeks postconceptional age. Fish oil supplementation in early infancy modulates developing infant immune responses The effect of supplementation of docosahexaenoic acid and arachidonic acid on visual acuity and neurodevelopment in larger preterm infants. [Effect of long-chain polyunsaturated fatty acids on arachidonate and docosahexaeonic acid in healthy infants in the first four months of life]. The impact of early nutrition on incidence of allergic manifestations and common respiratory illnesses in children. Maternal fish oil supplementation in lactation: effect on developmental outcome in breast-fed infants. Effect of Dietary Omega-3 Fatty Acids on Retinal Function of Very-Low-Birth-Weight Neonates A randomised controlled study of the effect of long chain polyunsaturated fatty acid supplementation on stool hardness during formula feeding Diet and the essential fatty acid status of term infants Safety and efficacy of omega-3 fatty acids in the nutrition of very low birth weight infants: soy oil and marine oil supplementation of formula. Pre- and post-term growth in pre-term infants supplemented with higher-dose DHA: a randomised controlled trial. Effect of DHA‐containing formula on growth of preterm infants to 59 weeks postmenstrual age Body Composition in Preterm Infants Who Are Fed Long-Chain Polyunsaturated Fatty Acids: A Prospective, Randomized, Controlled Trial DHA Supplementation during Pregnancy and Lactation Affects Infants' Cellular but Not Humoral Immune Response Dietary supplementation of long‐chain polyunsaturated fatty acids in preterm infants: effects on cerebral maturation Effect of Supplementation of Preterm Formula With Long Chain Polyunsaturated Fatty Acids on Mineral Balance in Preterm Infants Growth and Development of Premature Infants Fed Predominantly Human Milk, Predominantly Premature Infant Formula, or a Combination of Human Milk and Premature Formula Early neurological and neurophysiological development of the preterm infant and polyunsaturated fatty acids supply Effect of reducing the n-6:n-3 long-chain PUFA ratio during pregnancy and lactation on infant adipose tissue growth within the first year of life: an open-label randomized controlled trial. Effects of long-chain PUFA supplementation in infant formula on cognitive function in later childhood. The introduction of allergenic foods and the development of reported wheezing and eczema in childhood: the Generation R study. Relationship between omega3 long-chain polyunsaturated fatty acid status during early infancy and neurodevelopmental status at 1 year of age. Growth and development in term infants fed long-chain polyunsaturated fatty acids: a double-masked, randomized, parallel, prospective, multivariate study. A novel infant formula milk with added long-chain polyunsaturated fatty acids from single-cell sources: a study of growth, satisfaction and health High-Dose Docosahexaenoic Acid Supplementation of Preterm Infants: Respiratory and Allergy Outcomes A Critical Appraisal of the Role of Dietary Long-Chain Polyunsaturated Fatty Acids on Neural Indices of Term Infants: A Randomized, Controlled Trial Effect of omega 3 and omega 6 fatty acid intakes from diet and supplements on plasma fatty acid levels in the first 3 years of life. Effect of Fish Oil Supplementation on the n-3 Fatty Acid Content of Red Blood Cell Membranes in Preterm Infants Vitamin E status of low birthweight infants fed formula enriched with long-chain polyunsaturated fatty acids. Safety of supplementing infant formula with long-chain polyunsaturated fatty acids and Bifidobacterium lactis in term infants: a randomised controlled trial. Docosahexaenoic Acid in Red Blood Cells of Term Infants Receiving Two Levels of Long-Chain Polyunsaturated Fatty Acids Fatty acid balance studies in preterm infants fed formula milk containing long‐chain polyunsaturated fatty acids (LCP) II Maternal fish oil supplementation during lactation may adversely affect long-term blood pressure, energy intake, and physical activity of 7-year-old boys. Plasma lipid and apolipoprotein concentrations in full term infants fed formula supplemented with long-chain polyunsaturated fatty acids and cholesterol Enhanced Feeding and Diminished Postnatal Growth Failure in Very-Low-Birth-Weight Infants Formula Supplementation With Long-chain Polyunsaturated Fatty Acids: Are There Developmental Benefits? Supplementation of DHA but not DHA with arachidonic acid during pregnancy and lactation influences general movement quality in 12-week-old term infants. Growth and development in preterm infants fed long-chain polyunsaturated fatty acids: a prospective, randomized controlled trial. The DIAMOND (DHA Intake And Measurement Of Neural Development) Study: a double-masked, randomized controlled clinical trial of the maturation of infant visual acuity as a function of the dietary level of docosahexaenoic acid. Long chain polyunsaturated fatty acid supplementation in infant formula and blood pressure in later childhood: follow up of a randomised controlled trial Docosahexaenoic acid transfer into human milk after dietary supplementation: a randomized clinical trial. Three-year outcomes of dietary fatty acid modification and house dust mite reduction in the Childhood Asthma Prevention Study. Plasma fatty-acid composition and antioxidant capacity in low birth-weight infants fed formula enriched with n-6 and n-3 long-chain polyunsaturated fatty acids from purified phospholipids. Early introduction of oats associated with decreased risk of persistent asthma and early introduction of fish with decreased risk of allergic rhinitis. Visual function in breast-fed term infants weaned to formula with or without long-chain polyunsaturates at 4 to 6 months: a randomized clinical trial. Docosahexaenoic Acid Status of Term Infants Fed Breast Milk or Infant Formula Containing Soy Oil or Corn Oil Visual Acuity, Erythrocyte Fatty Acid Composition, and Growth in Term Infants Fed Formulas with Long Chain Polyunsaturated Fatty Acids for One Year Effects of long-chain polyunsaturated fatty acid supplementation of infant formula on cognition and behaviour at 9 years of age. Are long-chain polyunsaturated fatty acids essential nutrients in infancy? Breast milk fatty acid profile in relation to infant growth and body composition: results from the INFAT study Oxidative stress in preterm infants fed a formula containing long-chain polyunsaturated fatty acids (LCPUFA). Erythrocyte fatty acid composition in term infants fed human milk or a formula enriched with a low eicosapentanoic acid fish oil for 4 months Th1 and Th2 Chemokines, Vaccine-Induced Immunity, and Allergic Disease in Infants After Maternal ω-3 Fatty Acid Supplementation During Pregnancy and Lactation A randomized controlled study on the effectiveness of a multifaceted intervention program in the primary prevention of asthma in high-risk infants. Fish oil supplementation improves docosahexaenoic acid status of malnourished infants Effect of formula supplemented with docosahexaenoic acid and gamma-linolenic acid on fatty acid status and visual acuity in term infants. Growth and development of preterm infants fed infant formulas containing docosahexaenoic acid and arachidonic acid. Developmental quotient at 24 months and fatty acid composition of diet in early infancy: a follow up study Effects of high-dose fish oil supplementation during early infancy on neurodevelopment and language: a randomised controlled trial. The Effect of Fish Oil Supplementation on Heart rate in Healthy Danish Infants Maternal diet rich in saturated fat during breastfeeding is associated with atopic sensitization of the infant Effect of Feeding a Formula Supplemented With Long-chain Polyunsaturated Fatty Acids for 14 Weeks Improves the Ex Vivo Response to a Mitogen and Reduces the Response to a Soy Protein in Infants at Low Risk for Allergy A Multicenter Long-Term Safety and Efficacy Trial of Preterm Formula Supplemented with Long-Chain Polyunsaturated Fatty Acids Visual Acuity and the Essentiality of Docosahexaenoic Acid and Arachidonic Acid in the Diet of Term Infants Effect of reducing the n-6/n-3 fatty acid ratio on the maternal and fetal leptin axis in relation to infant body composition. Neurodevelopmental Quotient of Healthy Term Infants at 4 Months and Feeding Practice: The Role of Long-Chain Polyunsaturated Fatty Acids Nutritional effects on auditory brainstem maturation in healthy term infants Double-blind, randomized trial of long-chain polyunsaturated fatty acid supplementation in formula fed to preterm infants. Influence of long-chain polyunsaturated fatty acid formula feeds on vitamin E status in preterm infants. The Use of Low-EPA Fish Oil for Long-Chain Polyunsaturated Fatty Acid Supplementation of Preterm Infants Allergy prevention by maternal elimination diet during late pregnancy--a 5-year follow-up of a randomized study. Alpha linolenic acid in cholesterol esters: a marker of alphalinolenic acid intake in newborns Effect of Different Levels of Docosahexaenoic Acid Supply on Fatty Acid Status and Linoleic and &agr;-Linolenic Acid Conversion in Preterm Infants Neurodevelopmental outcomes at 7 years’ corrected age in preterm infants who were fed high-dose docosahexaenoic acid to term equivalent: a follow-up of a randomised controlled trial Effects of a low birthweight infant formula containing human milk levels of docosahexaenoic and arachidonic acids. Long-Term Feeding of Formulas High in Linolenic Acid and Marine Oil to Very Low Birth Weight Infants: Phospholipid Fatty Acids 10-year Cognition in Preterms After Random Assignment to Fatty Acid Supplementation in Infancy Effect of maternal docosahexaenoic acid supplementation on postpartum depression and information processing. Reduced ex vivo stimulated IL-6 response in infants randomized to fish oil from 9 to 18 months, especially among PPARG2 and COX2 wild types. Effects of diet on the lipid and fatty acid status of full-term infants at 4 months. Diet and prevalence of atopic eczema in 6 to 7-year-old schoolchildren in Spain: ISAAC phase III. A Randomized Controlled Intervention With Fish Oil Versus Sunflower Oil From 9 to 18 Months of Age: Exploring Changes in Growth and Skinfold Thicknesses Effects of maternal diet during late pregnancy and lactation on the development of atopic diseases in infants up to 18 months of age—in‐vivo results Prevention of asthma during the first 5 years of life: a randomized controlled trial. The effect of genetic and environmental factors on the prevalence of allergic disorders at the age of two years Enhanced Nutrient Supply to Very Low Birth Weight Infants is Associated with Improved White Matter Maturation and Head Growth Visual evoked potentials and dietary long chain polyunsaturated fatty acids in preterm infants. Influence of feeding artificial-formula milks containing docosahexaenoic and arachidonic acids on the postnatal long-chain polyunsaturated fatty acid status of healthy preterm infants. Assessment of the Efficacious Dose of Arachidonic and Docosahexaenoic Acids in Preterm Infant Formulas: Fatty Acid Composition of Erythrocyte Membrane Lipids Dietary essential fatty acid supply and visual acuity development. Early enteral fat supplement and fish oil increases fat absorption in the premature infant with an enterostomy. Effect of long-chain polyunsaturated fatty acids in infant formula on problem solving at 10 months of age Cognitive function in 18-month-old term infants of the DIAMOND study: a randomized, controlled clinical trial with multiple dietary levels of docosahexaenoic acid. Long-term effects of LCPUFA supplementation on childhood cognitive outcomes. Effect of docosahexaenoic acid supplementation of lactating women on the fatty acid composition of breast milk lipids and maternal and infant plasma phospholipids. Modulation of infant formula fat profile alters the low-density lipoprotein/high-density lipoprotein ratio and plasma fatty acid distribution relative to those with breast-feeding. Growth and development of term infants fed with milk with long-chain polyunsaturated fatty acid supplementation. Supplementation with 200 mg/Day Docosahexaenoic Acid from Mid-Pregnancy through Lactation Improves the Docosahexaenoic Acid Status of Mothers with a Habitually Low Fish Intake and of Their Infants Fatty acid absorption in preterms on formulas with and without long-chain polyunsaturated fatty acids and in terms on formulas without these added Infant formula composition affects energetic efficiency for growth: the BeMIM study, a randomized controlled trial. Three randomized controlled trials of early long-chain polyunsaturated Fatty Acid supplementation on means-end problem solving in 9-month-olds. Oral administration of docosahexaenoic acid attenuates interleukin-1β response and clinical course of septic neonates. Fatty acid profiles, antioxidant
  status, and growth of preterm infants fed diets without or with
  long-chain polyunsaturated fatty acids Effect of increasing breast milk docosahexaenoic acid on plasma and erythrocyte phospholipid fatty acids and neural indices of exclusively breast fed infants The 10-year follow-up of a randomised trial of long-chain polyunsaturated fatty acid supplementation in preterm infants: effects on growth and blood pressure Omega-3 and omega-6 fatty acid exposure from early life does not affect atopy and asthma at age 5 years. Circulating Adiponectin in Preterm Infants Fed Long-Chain Polyunsaturated Fatty Acids (LCPUFA)-Supplemented Formula—A Randomized Controlled Study Effect of dietary linoleic/alpha-linolenic acid ratio on growth and visual function of term infants. A randomized controlled trial of early dietary supply of long-chain polyunsaturated fatty acids and mental development in term infants. Circulating visfatin levels in healthy preterm infants are independently associated with high-density lipoprotein cholesterol levels and dietary long-chain polyunsaturated fatty acids. Randomized, double-blind trial of long-chain polyunsaturated fatty acid supplementation with fish oil and borage oil in preterm infants. The Infant Fish Oil Supplementation Study (IFOS): design and research protocol of a double-blind, randomised controlled n--3 LCPUFA intervention trial in term infants. Feeding preterm infants milk with a higher dose of docosahexaenoic acid than that used in current practice does not influence language or behavior in early childhood: a follow-up study of a randomized controlled trial. [Evaluation of a local infant formula enriched with polyunsaturated fatty acids produced in Israel]. Docosahexaenoic acid supplementation and time at achievement of gross motor milestones in healthy infants: a randomized, prospective, double-blind, placebo-controlled trial. Dietary supplementation with n-3 polyunsaturated fatty acids in early childhood: effects on blood pressure and arterial structure and function at age 8 y. Effect of omega-3 fatty acid concentrations in plasma on symptoms of asthma at 18 months of age. A randomized trial of DHA intake during infancy: school readiness and receptive vocabulary at 2-3.5 years of age. Effect of supplementation of arachidonic acid (AA) or a combination of AA plus docosahexaenoic acid on breastmilk fatty acid composition. Efficacy and safety of long-chain polyunsaturated fatty acid supplementation of infant-formula milk: a randomised trial Assessment of feeding different amounts of arachidonic and docosahexaenoic acids in preterm infant formulas on the fatty acid content of lipoprotein lipids Serum cholesterol, cholesteryl ester, and high-density lipoprotein development in newborn infants: response to formulas supplemented with cholesterol and gamma-linolenic acid. Effect of Supplementing Pregnant and Lactating Mothers With n-3 Very-Long-Chain Fatty Acids on Children's IQ and Body Mass Index at 7 Years of Age Impact of Diet on the Intestinal Microbiota in 10-month-old Infants Retinal development in very-low-birth-weight infants fed diets differing in omega-3 fatty acids. Modification of dietary polyunsaturated fatty acids via complementary food enhances n-3 long-chain polyunsaturated fatty acid synthesis in healthy infants: a double blinded randomised controlled trial Enhanced feeding in very-low-birth-weight infants may cause electrolyte disturbances and septicemia--a randomized, controlled trial. Lipoprotein-cholesterol responses in healthy infants fed defined diets from ages 1 to 12 months: comparison of diets predominant in oleic acid versus linoleic acid, with parallel observations in infants fed a human milk-based diet. Impaired Fetal Growth and Arterial Wall Thickening: A Randomized Trial of Omega-3 Supplementation Respiratory hospitalisation of infants supplemented with docosahexaenoic acid as preterm neonates. Visual Acuity and Fatty Acid Status of Term Infants Fed Human Milk and Formulas with and without Docosahexaenoate and Arachidonate from Egg Yolk Lecithin1 Docosahexaenoic acid and arachidonic acid enhance growth with no adverse effects in preterm infants fed formula. Does maternal docosahexaenoic acid supplementation during pregnancy and lactation lower BMI in late infancy? Visual acuity and cognitive outcomes at 4 years of age in a double-blind, randomized trial of long-chain polyunsaturated fatty acid-supplemented infant formula. Docosahexaenoic acid administered in the acute phase protects the nutritional status of septic neonates. Impact of Early Dietary Intake and Blood Lipid Composition of Long-Chain Polyunsaturated Fatty Acids on Later Visual Development Neurodevelopmental outcomes of preterm infants fed high-dose docosahexaenoic acid: a randomized controlled trial. The Groningen LCPUFA study: no effect of postnatal long-chain polyunsaturated fatty acids in healthy term infants on neurological condition at 9 years. Prostanoid Formation during Feeding of a Preterm Formula with Long-Chain Polyunsaturated Fatty Acids in Healthy Preterm Infants during the First Weeks of Life Improved Cognitive Development Among Preterm Infants Attributable to Early Supplementation of Human Milk With Docosahexaenoic Acid and Arachidonic Acid Fish oil-supplementation from 9 to 12 months of age affects infant attention in a free-play test and is related to change in blood pressure.
abstract: BACKGROUND AND OBJECTIVE : Relative deficiency of dietary omega 3 polyunsaturated fatty acids ( n-3 PUFA ) has been implicated in the rising allergy prevalence in Westernized countries . Fish oil supplementation may provide an intervention strategy for primary allergy prevention . The objective of this study was to assess the effect of fish oil n-3 PUFA supplementation from birth to 6 months of age on infant allergic disease . METHODS : In a double-blind r and omized controlled trial , 420 infants at high atopic risk received a daily supplement of fish oil containing 280 mg docosahexaenoic acid and 110 mg eicosapentaenoic acid or a control ( olive oil ) , from birth to age 6 months . PUFA levels were measured in 6-month-old infants ’ erythrocytes and plasma and their mothers ’ breast milk . Eczema , food allergy , asthma and sensitization were assessed in 323 infants for whom clinical follow-up was completed at 12 months of age . RESULTS : At 6 months of age , infant docosahexaenoic acid and eicosapentaenoic acid levels were significantly higher ( both P < .05 ) and erythrocyte arachidonic acid levels were lower ( P = .003 ) in the fish oil group . Although n-3 PUFA levels at 6 months were associated with lower risk of eczema ( P = .033 ) and recurrent wheeze ( P = .027 ) , the association with eczema was not significant after multiple comparisons and there was no effect of the intervention per se on the primary study outcomes . Specifically , between-group comparisons revealed no differences in the occurrence of allergic outcomes including sensitization , eczema , asthma , or food allergy . CONCLUSIONS : Postnatal fish oil supplementation improved infant n-3 status but did not prevent childhood allergic disease Long-chain polyunsaturated fatty acids have been associated with aspects of immune regulation including cytokine production . The purpose of this study was to investigate the effect of maternal dietary supplementation with tuna oil , rich in docosahexaenoic acid ( DHA ) , on the concentration of transforming growth factor beta 1 ( TGFβ1 ) and TGFβ2 in breast milk . In this r and omized , dietary intervention trial , mothers of term infants consumed a daily supplement of 2000 mg oil containing either placebo ( n=40 ) , 300 mg DHA ( n=40 ) , or 600 mg DHA ( n=40 ) . The DHA increase in milk and plasma was proportional to dietary DHA . There was no relationship between milk DHA status and TGFβ1 and TGFβ2 levels OBJECTIVES : To evaluate the growth , tolerance , and safety of a new ultraconcentrated liquid human milk fortifier ( LHMF ) design ed to provide optimal nutrients for preterm infants receiving human breast milk in a safe , nonpowder formulation . METHODS : Preterm infants with a body weight ≤1250 g fed expressed and /or donor breast milk were r and omized to receive a control powder human milk fortifier ( HMF ) or a new LHMF for 28 days . When added to breast milk , the LHMF provided ∼20 % more protein than the control HMF  . Weight , length , head circumference , and serum prealbumin , albumin , blood urea nitrogen , electrolytes , and blood gases were measured . The occurrence of sepsis , necrotizing enterocolitis , and serious adverse events were monitored . RESULTS : This multicenter , third party – blinded , r and omized controlled , prospect i ve study enrolled 150 infants . Achieved weight and linear growth rate were significantly higher in the LHMF versus control groups ( P = .04 and 0.03 , respectively ) . Among infants who adhered closely to the protocol , the LHMF had a significantly higher achieved weight , length , head circumference , and linear growth rate than the control HMF ( P = .004 , P = .003 , P = .04 , and P = .01 , respectively ) . There were no differences in measures of feeding tolerance or days to achieve full feeding volumes . Prealbumin , albumin , and blood urea nitrogen were higher in the LHMF group versus the control group ( all P < .05 ) . There was no difference in the incidence of confirmed sepsis or necrotizing enterocolitis . CONCLUSIONS : Use of a new LHMF in preterm infants instead of powder HMF is safe . Benefits of LHMF include improvements in growth and avoidance of the use of powder products in the NICU Background / Objective : Evidence is accumulating that the long-chain PUFA ( LCPUFA ) are associated with offspring growth and body composition . We investigated the relationship between LCPUFAs in red blood cells ( RBCs ) of pregnant women/breastfeeding mothers and umbilical cord RBCs of their neonates with infant growth and body composition ⩽1 year of age . Subjects/ Methods : In an open-label r and omized , controlled trial , 208 healthy pregnant women received a dietary intervention ( daily supplementation with 1200 mg n-3 LCPUFAs and dietary counseling to reduce arachidonic acid ( AA ) intake ) from the 15th week of gestation until 4 months of lactation or followed their habitual diet . Fatty acids of plasma phospholipids ( PLs ) and RBCs from maternal and cord blood were determined and associated with infant body weight , body mass index ( BMI ) , lean body mass and fat mass assessed by skinfold thickness measurements and ultrasonography . Results : Dietary intervention significantly reduced the n-6/n-3 LCPUFA ratio in maternal and cord-blood plasma PLs and RBCs . Maternal RBCs docosahexaenoic acid ( DHA ) , n-3 LCPUFAs and n-6 LCPUFAs at the 32nd week of gestation were positively related to birth weight . Maternal n-3 LCPUFAs , n-6 LCPUFAs and AA were positively associated with birth length . Maternal RBCs AA and n-6 LCPUFAs were significantly negatively related to BMI and Ponderal Index at 1 year postpartum , but not to fat mass . Conclusion : Maternal DHA , AA , total n-3 LCPUFAs and n-6 LCPUFAs might serve as prenatal growth factors , while n-6 LCPUFAs also seems to regulate postnatal growth . The maternal n-6/n-3 LCPUFA ratio does not appear to have a role in adipose tissue development during early postnatal life Formula supplemented with docosahexaenoic acid ( DHA ) improves retinal function of preterm infants but the optimal dose is unknown . In a r and omized controlled trial we examined the effect of increasing the DHA concentration of human milk and formula on circulating fatty acids of preterm infants . Infants born <33 weeks gestation were fed high-DHA milk ( 1 % total fat as DHA ) or st and ard-DHA milk ( 0.2 - 0.3 % DHA ) until reaching their estimated due date ( EDD ) . Milk arachidonic acid ( AA ) concentration was approximately 0.5 % for both groups . At EDD , erythrocyte membrane phospholipid DHA was elevated in the high-DHA group compared with st and ard-DHA ( mean+/-SD , high-DHA 6.8+/-1.2 , st and ard-DHA 5.2+/-0.7 , p<0.0005 ) but AA was lower ( high-DHA 14.9+/-1.3 , st and ard-DHA 16.0+/-1.2 , p<0.0005 ) . Feeding preterm infants human milk and formula with 1 % DHA raises but does not saturate erythrocyte phospholipids with DHA . Milk exceeding 1 % DHA may be required to increase DHA status to levels seen in term infants Background : An appropriate supply of n-3 long-chain polyunsaturated fatty acids ( LC-PUFAs ) during early childhood may enhance cognitive development . Little attention is paid to the fatty acid ( FA ) supply during the complementary feeding period . We examined the polyunsaturated fatty acids ( PUFAs ) and LC-PUFAs pattern in dietary practice of two study groups and evaluated the results against the present Dietary Guidelines in Germany . Methods : The food consumption and FA pattern of dietary practice in subjects from two prospect i ve studies ( n=102 and n=184 , respectively ) at the age of 3 , 6 and 9 months was assessed by weighed diet records , and changes during the first year of life were compared with the food-based dietary guidelines for the first year of life . Results : Dietary practice in the complementary feeding period was clearly dominated by commercial food products . The FA composition in dietary practice was different from the Guideline Diet and the ratio of n-6/n-3 PUFAs was less favorable . Consumption of breast milk or formula was still of major importance for the intake of LC-PUFAs in the complementary feeding period . Conclusion : LC-PUFAs are predominantly provided by breast milk and formula during the first year of life and consequently decrease when milk consumption decreases . For compensation , commercial complementary food might come closer to the Guideline Diet by lowering the n-6/n-3 PUFA ratio through appropriate vegetable oil along with an increase in total fat content up to the legal limit OBJECTIVES Docosahexaenoic acid ( DHA ; 22:6 n-3 ) and arachidonic acid ( AA ; 20:4 n-6 ) are important for development of the central nervous system in mammals . There is a growth spurt in the human brain during the last trimester of pregnancy and the first postnatal months , with a large increase in the cerebral content of AA and DHA .  The fetus and the newborn infant depend on maternal supply of DHA and AA . Our hypothesis was that maternal intake of DHA during pregnancy and lactation is marginal and that high intake of this fatty acid would benefit the child . We examined the effect of supplementing pregnant and lactating women with very-long-chain n-3 polyunsaturated fatty acids ( PUFAs ; cod liver oil ) on mental development of the children , compared with maternal supplementation with long-chain n-6 PUFAs ( corn oil ) . METHODS The study was r and omized and double-blinded . Pregnant women were recruited in week 18 of pregnancy to take 10 mL of cod liver oil or corn oil until 3 months after delivery . The cod liver oil contained 1183 mg/10 mL DHA , 803 mg/10 mL eicosapentaenoic acid ( 20:5 n-3 ) , and a total of 2494 mg/10 mL summation operator n-3 PUFAs . The corn oil contained 4747 mg/10 mL linoleic acid ( 18:2 n-6 ) and 92 mg/10 mL alpha-linolenic acid ( 18:3 n-3 ) . The amount of fat-soluble vitamins was identical in the 2 oils ( 117 micro g/mL vitamin A , 1 micro g/mL vitamin D , and 1.4 mg/mL dl-alpha-tocopherol ) . A total of 590 pregnant women were recruited to the study , and 341 mothers took part in the study until giving birth . All infants of these women were scheduled for assessment of cognitive function at 6 and 9 months of age , and 262 complied with the request . As part of the protocol , 135 subjects from this population were invited for intelligence testing  with the Kaufman Assessment Battery for Children ( K-ABC ) at 4 years of age . Of the 135 invited children , 90 came for assessment . Six children did not complete the examination . The K-ABC is a measure of intelligence and achievement design ed for children aged 2.5 years through 12.5 years . This multisubtest battery comprises 4 scales : Sequential Processing , Simultaneous Processing , Achievement ( not used in the present study ) , and Nonverbal Abilities . The Sequential Processing and Simultaneous Processing scales are hypothesized to reflect the child 's style of problem solving and information processing . Scores from these 2 scales are combined to form a Mental Processing Composite , which serves as the measure of intelligence in the K-ABC . RESULTS We received dietary information from 76 infants ( 41 in the cod liver oil group and 35 in the corn oil group ) , documenting that all of them were breastfed at 3 months of age . Children who were born to mothers who had taken cod liver oil ( n = 48 ) during pregnancy and lactation scored higher on the Mental Processing Composite of the K-ABC at 4 years of age as compared with children whose mothers had taken  corn oil  ( n = 36 ; 106.4 [ 7.4 ] vs 102.3 [ 11.3 ] ) . The Mental Processing Composite score correlated significantly with head circumference at birth ( r = 0.23 ) , but no relation was found with birth weight or gestational length . The children 's mental processing scores at 4 years of age correlated significantly with maternal intake of DHA and eicosapentaenoic acid during pregnancy . In a multiple regression model , maternal intake of DHA during pregnancy was the only variable of statistical significance for the children 's mental processing scores at 4 years of age . CONCLUSION Maternal intake of very-long-chain n-3 PUFAs during pregnancy and lactation may be favorable for later mental development of children Background and Objectives : Postdischarge formulas with extra energy and protein improve short-term growth but may also influence long-term body composition in an unwanted manner . Energy- and protein-enriched formulas with an increased protein-to-energy ratio improves gain of lean mass . The objective of the study was to investigate whether feeding a nutrient-enriched formula without extra energy after term , usually 3 to 4 weeks after discharge , would influence growth and body composition in infancy . Methods : In this r and omized controlled trial preterm infants were fed fortified human milk or preterm formula until term . At term , 102 infants were r and omized to a nutrient-enriched formula without extra energy or st and ard formula until 6 months corrected age . Twenty-six infants received unfortified human milk after term . At term and 6 months corrected age , anthropometry and a dual-energy x-ray absorptiometry ( DEXA ) scan were performed . Lean and fat mass ( FM ) were corrected for height . Results : There were no differences in growth or body size between the feeding groups . Infants fed the enriched formula gained less FM and had lower FM corrected for body size at 6 months corrected age than infants fed st and ard formula . Infants fed human milk had lower lean mass and higher FM corrected for body size at 6 months corrected age than formula-fed infants . Conclusions : Feeding nutrient-enriched formula without extra energy after term does not change quantity of growth but does influence type of weight gain and body composition of preterm infants . Infants fed the nutrient-enriched formula had lower FM corrected for body size at 6 months corrected age than infants fed st and ard formula or human milk The purpose of our study was to assess whether a supplement of fish oil ( FO ) and evening primrose oil ( EPO ) for formula-fed infants was capable of avoiding reductions in erythrocyte docosahexaenoic acid ( DHA , 22∶6n−3 ) and arachidonic acid ( AA , 20∶4n−6 ) associated with st and ard formula feeding . Healthy , term infants , whose mothers chose to formula feed , were r and omized to either a  placebo or supplemented formula for their first 30 wk of life . A reference group of beast-fed infants also was enrolled . Erythrocyte fatty acids were measured by capillary gas chromatography on day 5 and in weeks 6 , 16 , and 30 . Supplementation of formula with 0.36 % of total fatty acids as DHA result ed in erythrocyte DHA being maintained at or above breast-fed levels for the entire 30-wk study period , and breast feeding ( 0.21 % DHA ) result ed in a modest fall in erythrocyte DHA relative to baseline ( day 5 ) values . The level of erythrocyte DHA in placebo formula-fed infants was halved by week 16 . AA levels decreased in all infants in the first six weeks , but the levels in breast- and placebo formula-fed infants increased with age and returned to approximate baseline ( day 5 ) values by 16 and 30 wk of age , respectively . Erythrocyte AA in FO+EPO-supplemented infants remained low and below breast- and placebo formula-fed levels . Our data suggest that dietary supplementation with DHA at 0.36 % total fatty acids results in erythrocyte DHA levels above those found in breast-fed infants . EPO supplementation was not effective at maintaining erythrocyte AA when given with FO Human milk contains small but nutritionally significant amounts of long-chain polyunsaturated fatty acids ( LCP ) , such as arachidonic ( AA , 20:4n-6 ) and docosahexaenoic ( DHA , 22:6n-3 ) acids , which are not present in most infant formulae . In the present study , the fatty acid composition of plasma and erythrocytes was determined at birth and again at 7 days , 1 and 3 months in 49 healthy full-term infants ( 37 - 42 week 's gestation ) . One group of infants was fed exclusively with human milk ( n=16 ) and the others were r and omly assigned to a st and ard term formula ( F ) ( n=15 ) or the same formula with egg yolk lecithin providing DHA ( 0.15 % ) and AA ( 0.30 % ) ( LCP-F ) ( n=18 ) . Plasma and erythrocyte LCP values of the three dietary groups did not differ at 7 days of age , but the contents of DHA and AA in plasma and erythrocytes at 1 and 3 months were significantly lower ( P<0.05 ) in infants fed non supplemented formula than in infants fed breast milk and supplemented formula . There were no differences in plasma or erythrocyte AA or DHA concentrations between the group fed breast milk and the group fed supplemented formula during the period studied OBJECTIVE To test the hypothesis that early enteral supplementing fat and fish oil decreases the duration of parenteral nutrition ( PN ) and increases enteral nutrition ( EN ) before bowel reanastomosis in premature infants with an enterostomy . STUDY DESIGN Premature infants ( < 2 months old ) who had an enterostomy and tolerated enteral feeding at 20 mL/kg/day were r and omized to usual care ( control=18 ) or early supplementing enteral fat supplement and fish oil ( treatment=18 ) .  Intravenous lipid was decreased as enteral fat intake was increased . Daily weight , clinical and nutrition data , and weekly length and head circumference were recorded . The primary outcomes were the duration of PN and volume of EN intake , and the secondary outcomes were weight gain ( g/day ) , ostomy output ( mL/kg/d ) , and serum conjugated bilirubin level ( mg/dL ) from initiating feeding to reanastomosis . Data were analyzed by Student t test or Wilcoxon rank sum test . RESULTS There were no differences in the duration of PN , ostomy output , and weight gain between the 2 groups before reanastomosis . However , supplemented infants received less intravenous lipid , had greater EN intake , and lower conjugated bilirubin before reanastomosis , and they also received greater total calorie , had fewer sepsis evaluations and less exposure to antibiotics and central venous catheters before reanastomosis , and had greater weight and length gain after reanastomosis ( all P<.05 ) . CONCLUSION Early enteral feeding of a fat supplement and fish oil was associated with decreased exposure to intravenous lipid , increased EN intake , and reduced conjugated bilirubin before reanastomosis and improved weight and length gain after reanastomosis in premature infants with an enterostomy Objective : We investigated how cod liver oil influences the amount of essential fatty acids in mothers ’ breast milk . Design and Intervention : Lactating mothers ( n=22 ) were r and omized into four groups 3–8 weeks after parturition . They were supplemented for 14 days with 0 , 2.5 , 5 and 10 ml cod liver oil ( 7.7 g eicosapentaenoic acid ( EPA , 20:5n-3 ) , 10.2 g docosahexaenoic acid ( DHA , 22:6n-3 ) and 22.9 g n-3 fatty acids in total per 100 ml ) . Results : In maternal plasma phospholipids there was an increase in the content of EPA and DHA in the group supplemented with 10 ml cod liver oil daily ( P≤0.05 ) . DHA concentrations in breast milk pre-supplementation ranged from 0.15 to 1.56 wt% and increased in all supplemented groups ( P≤0.05 ) . The concentration of EPA in breast milk increased in the groups supplemented with 5 or 10 ml cod liver oil ( P≤0.05 ) , whereas the concentration of arachidonic acid ( AA , 20:4n-6 ) did not change in any of the supplemented groups . Total intake of DHA adjusted to body mass index ( BMI ) , correlated to DHA concentrations in plasma ( r=0.49 , P=0.02 ) and breast milk ( r=0.45 , P=0.04 ) . The concentration of tocopherol did not change during the supplementation period , neither in plasma nor in breast milk . Conclusion : Dietary intake of DHA is reflected in the concentration of DHA in breast milk , without affecting the concentration of AA or tocopherol . Sponsorship : Supported by Peter Möller avd . av Orkla Polyunsaturated fatty acids ( PUFAs ) are components of cell membranes and may play an immunomodulating role in the pathogenesis of atopic dermatitis ( AD ) . The goal was to determine the impact of PUFAs on AD by dietary supplementation of infants . Based on the parents ' decision on their babies ' primary feeding , mothers and newborns were r and omized to the supplementation with gamma-linolenic acid ( GLA ) or placebo for up to 6 months . Breastfed infants received GLA by supplementing their mothers . Formula diet was commercial whey hydrolysate unsupplemented with PUFAs .  Of 131 eligible infants , 24 developed AD within the first year of life . Of these , nine belonged to the exclusively breastfed group ( n = 58 ) , 14 to the combined-fed group ( n = 53 ) , and one to the never breastfed group ( n = 20 ) . We could not find an influence of GLA on the development of AD . In subjects with AD , at 1 yr of age the serum-immunoglobulin E ( IgE ) was the lowest in the GLA-supplemented group A-subjects . In the GLA-supplemented group , GLA-levels in breast milk were similar in atopic and non-atopic infants . In the non-supplemented group the GLA-content of breast milk was 0.07 % of total fatty acids in atopic infants vs. 0.17 % in non-atopic infants ( p < 0.01 ) . Dietary GLA-supplementation could not prevent AD . Interestingly , the number of infants developing AD was the lowest in never breastfed children . In infants suffering from AD , GLA-supplementation seemed to reduce total IgE in the first year of life Conflicting evidence exists on the effect of long-chain polyunsaturated fatty acid ( LCPUFA ) formula supplementation on cardiovascular health in term infants . It is known that LCPUFA supplementation does not affect infant growth , but long term outcome data are not available . The current study investigates whether 2 mo LCPUFA formula supplementation affects cardiovascular and anthropometric development at 9 y. A prospect i ve , double-blind , r and omized trial was performed in healthy term infants : a st and ard formula control group ( CF , n = 169 ) and a LCPUFA-supplemented group [ LF , n = 145 ; 0.45 % ( by wt ) AA  and 0.30 % ( by wt ) docosahexaenoic acid ( DHA ) ] . A breastfed group ( BF ; n = 159 ) served as reference . At the age of 9 y , systolic and diastolic blood pressure , heart rate , head circumference , weight , and height were measured . Univariate and multivariate analyses were performed ; 63 to 79 % of children were assessed . None of the cardiovascular or anthropometric measurements differed between the formula groups . Breastfed children had a marginally lower heart rate than formula-fed children , in particular compared with children fed control formula . Blood pressure and parameters of growth including BMI of breast and formula-fed children did not differ . In conclusion , the study suggests that short-term LCPUFA supplementation does not influence cardiovascular and anthropometric development at 9 OBJECTIVE Docosahexaenoic acid ( DHA ) and arachidonic acid ( ARA ) are long-chain polyunsaturated fatty acids found in breast milk and recently added to infant formulas . Their importance in infant nutrition was recognized by the rapid accretion of these fatty acids in the brain during the first postnatal year , reports of enhanced intellectual development in breastfed children , and recognition of the physiologic importance of DHA in visual and neural systems from studies in animal models . These considerations led to clinical trials to evaluate whether infant formulas that are supplemented with DHA or both DHA and ARA would enhance visual and cognitive development or whether conversion of linoleic acid and alpha-linolenic acid , the essential fatty acid precursors of ARA and DHA , respectively , at the levels found in infant formulas is sufficient to support adequately visual and cognitive development . Visual and cognitive development were not different with supplementation in some studies , whereas other studies reported benefits of adding DHA or both DHA and ARA to formula . One of the first trials with term infants that were fed formula supplemented with DHA or both DHA and ARA evaluated growth , visual acuity ( Visual Evoked Potential ; Acuity Card Procedure ) , mental and motor development ( Bayley Scales of Infant Development ) , and early language development ( MacArthur Communicative Developmental Inventories ) . Growth , visual acuity , and mental and motor development were not different among the 3 formula groups or between the breastfed and formula-fed infants in the first year of life . At 14 months of age , infants who were fed the formula with DHA but no ARA had lower vocabulary production and comprehension scores than infants who were fed the unsupplemented control formula or who were breastfed , respectively . The present follow-up study evaluated IQ , receptive and expressive vocabulary , visual-motor function , and visual acuity of children from the original trial when they reached 39 months of age . METHODS Infants were r and omized within 1 week after birth and fed a control formula ( n = 65 ) , one containing DHA ( n = 65 ) , or one containing both ARA and DHA ( n = 66 ) to 1 year of age . A comparison group ( n = 80 ) was exclusively breastfed for at least 3 months after which the infants continued to be exclusively breastfed or were supplemented with and /or weaned to infant formula . At 39 months , st and ard tests of IQ ( Stanford Binet IQ ) , receptive vocabulary ( Peabody Picture Vocabulary Test-Revised ) , expressive vocabulary ( mean length of utterance ) , visual-motor function ( Beery Visual-Motor Index ) , and visual acuity ( Acuity Card Procedure ) were administered . Growth , red blood cell fatty acid levels , and morbidity also were evaluated . RESULTS Results were analyzed using analysis of variance or linear regression models . The regression model for IQ , receptive and expressive language , and the visual-motor index controlled for site , birth weight , sex , maternal education , maternal age , and the child 's age at testing . The regression model for  visual acuity  controlled for site only . A variable selection model also identified which of 22 potentially prognostic variables among different categories ( feeding groups , the child and family demographics , indicators of illness since birth , and environment ) were most influential for IQ and expressive vocabulary . A total of 157 ( 80 % ) of the 197 infants studied at 12 months participated in this follow-up study . Characteristics of the families were representative of US families with children up to 5 years of age , and there were no differences in the demographic or family characteristics among the r and omized formula groups . As expected , the formula and breastfed groups differed in ethnicity , marital status , parental education , and the prevalence of smoking . Sex , ethnicity , gestational age at birth , and birth weight for those who participated at 39 months did not differ from those who did not . The 12-month Bayley mental and motor scores and 14-month vocabulary scores of the children who participated also were were not different from those who did not . At 39 months , IQ , receptive and expressive language , visual-motor function , and visual acuity were not different among the 3 r and omized formula groups or between the breastfed and formula groups . The adjusted means for the control , ARA+DHA , DHA , and breastfed groups were as follows : IQ scores , 104 , 101 , 100 , 106 ; Peabody Picture Vocabulary Test , 99.2 , 97.2 , 95.1 , 97.4 ; mean length of utterance , 3.64 , 3.75 , 3.93 , 4.08 ; the visual-motor index , 2.26 , 2.24 , 2.05 , 2.40 ; and visual acuity ( cycles/degree ) , 30.4 , 27.9 , 27.5 , 28.6 , respectively . IQ was positively associated with female sex and maternal education and negatively associated with the number of siblings and exposure to cigarette smoking in utero and /or postnatally . Expressive language also was positively associated with maternal education and negatively associated with the average hours in child care per week and hospitalizations since birth but only when the breastfed group was included in the analysis . The associations between maternal education and child IQ scores are consistent with previous reports as are the associations between prenatal exposure to cigarette smoke and IQ and early language development . Approximately one third of the variance for IQ was explained by sex , maternal education , the number of siblings , and exposure to cigarette smoke . Growth achievement , red blood cell fatty acid levels , and morbidity did not differ among groups . CONCLUSIONS We reported previously that infants who were fed an unsupplemented formula or one with DHA or with both DHA and ARA through 12 months or were breastfed showed no differences in mental and motor development , but those who were fed DHA without ARA had lower vocabulary scores on a st and ardized , parent-report instrument at 14 months of age when compared with infants who were fed the unsupplemented formula or who were breastfed . When the infants were reassessed at 39 months using age-appropriate tests of receptive and expressive language as well as IQ , visual-motor function and visual acuity , no differences among the formula groups or between the formula and breastfed groups were found . The 14-month observation thus may have been a transient effect of DHA ( without ARA ) supplementation on early vocabulary development or may have occurred by chance . The absence of differences in growth achievement adds to the evidence that DHA with or without ARA supports normal growth in full-term infants . In conclusion , adding both DHA and ARA when supplementing infant formulas with long-chain polyunsaturated fatty acids supports visual and cognitive development through 39 months Background : Intestinal damage and malabsorption caused by chronic environmental enteropathy are associated with growth faltering seen in infants in less-developed countries . Evidence has suggested that supplementary omega-3 ( n−3 ) long-chain PUFAs ( LC-PUFAs ) might ameliorate this damage by reducing gastrointestinal inflammation . LC-PUFA supplementation may also benefit cognitive development . Objective : We tested whether early n−3 LC-PUFA supplementation improves  infant intestinal integrity , growth , and cognitive function . Design : A r and omized , double-blind , controlled trial [ 200 mg DHA and 300 mg EPA or 2 mL olive oil/d for 6 mo ] was conducted in a population of 172 rural Gambian infants aged 3–9 mo . The primary endpoints were anthropometric measures and gut integrity [ assessed by using urinary lactulose : mannitol ratios ( LMRs ) ] . Plasma fatty acid status , intestinal mucosal inflammation ( fecal calprotectin ) , daily morbidity , and cognitive development ( 2-step means-end test and an attention assessment ) were secondary endpoints . Results : PUFA supplementation result ed in a significant increase in plasma n−3 LC-PUFA concentrations ( P < 0.001 for both DHA and EPA ) and midupper arm circumference ( MUAC ) ( effect size : 0.31 z scores ; 95 % CI : 0.06 , 0.56 ; P = 0.017 ) at 9 mo of age . At 12 mo , MUAC remained greater in the intervention group , and we observed significant increases in skinfold thicknesses ( P ≤ 0.022 for all ) . No other significant differences between treatment groups were detected for growth or LMRs at 9 mo or for secondary outcomes . Conclusions : Fish-oil supplementation successfully increased plasma n−3 fatty acid status . However , in young , breastfed Gambian infants , the intervention failed to improve linear growth , intestinal integrity , morbidity , or selected measures of cognitive development . The trial was registered at www.is rct n.org as IS RCT N66645725 Background The immune consequences of adding 20:4n-6 and 22:6n-3 fatty acids to preterm infant formula are not known . Methods The effect of feeding preterm infants ( 14–42 days of age ) human milk ( Human Milk group ) , infant formula ( Formula group )  , or formula with added long-chain polyunsaturated fatty acids 20:4n-6 and 22:6n-3 ( Formula + LCP group ) on isolated peripheral blood lymphocytes ( by flow cytometry ) and lipid composition ( by gas – liquid chromatography ) was determined . Lymphocytes were stimulated in vitro with phytohemagglutinin to measure soluble interleukin (sIL)-2R and IL-10 production ( by enzyme-linked immunosorbent assay ) . Results With age , the percentage of CD3+CD4 + T cells and the percentage of CD20 + cells increased in the Human Milk and Formula + LCP groups ( P < 0.05 ) , but not in the unsupplemented Formula group . Compared with the Formula group , CD4 + cells from the Formula + LCP and Human Milk groups expressed more CD45R0 ( antigen mature ) and less CD45RA ( antigen naive ) at 42 days of age ( P < 0.05 ) . At 42 days , IL-10 production was lower ( P < 0.05 ) in cells of the Formula group than in cells of the Human Milk group . Production of IL-10 by the cells of the Formula + LCP group was not different from that produced by the Human Milk group cells . An age-related decrease ( P < 0.05 ) in sIL-2R production by Formula + LCP lymphocytes was observed , but sIL-2R production at 42 days in the Formula + LCP group did not differ significantly from that in the Human Milk group . Compared with Formula alone , adding LCP to formula result ed in a lower C18:2n-6 and higher C20:4n-6 content in lymphocyte phospholipids ( P < 0.05 ) . Conclusions Adding LCP to a preterm infant formula result ed in lymphocyte population s , phospholipid composition , cytokine production , and antigen maturity that are more consistent with that in human milk – fed infants . This may affect the ability of the infant to respond to immune challenges Background : Fish consumption during infancy has been regarded as a risk factor for allergic disease but later evidence suggests a protective role . However , method ological limitations in the studies make conclusions uncertain . The aim of this study was to assess the association between fish consumption during the first year of life and development of allergic diseases by age 4 Long chain polyunsaturates ( LCP ) status during the early neonatal period is associated with a reduced risk of atopic symptoms and later allergies . In this study , we characterized the immune response of low-risk , term , formula-fed infants r and omized at ≤14 d of age to st and ard term formula ( Formula ) or formula containing LCP ( Formula+LCP ) for 4 wks . Infants exclusively fed human milk  were included for comparison . Peripheral blood was collected at 14 and 42 d of age , and lymphocyte phenotype , proliferation , and cytokine production ( IL-2 , IL-4 , IL-6 , IL-10 , IL-12 , IFN-γ , TNF-α , TGFβ ) were assessed after incubation with β-lactoglobulin ( BLG ) and soy protein ( SOY ) . Lymphocyte proliferation did not differ between groups . Compared with human milk-fed infants at 2 wks , formula-fed infants produced more TNF-α and IFN-γ and had more cells expressing ICAM-1 ( CD54 ) after incubation with BLG and SOY ( p < 0.05 ) . At 6 wks of age , infants fed Formula+LCP  produced more TNF-α with SOY ( 3.2-fold ) and IFN-γ ( 3.3-fold ) with BLG compared with infants fed Formula ( p < 0.05 ) . In conclusion , low-risk term infants fed formula before 14 d of age  produced more TNF-α and IFN-γ in response to food proteins . Feeding Formula+LCP for 4 wks maintained the higher TNF-α and IFN-γ response to these food proteins Background Human milk is the optimal nutrition for infants . When breastfeeding is not possible , supplementation of infant formula with long chain polyunsaturated fatty acids appears to promote neurodevelopmental outcome and visual function .  Plant oils , that are the only source of fat in most of infant formulas , do not contain specific fatty acids that are present in human and cow milk and do not encounter milk fat triglyceride structure . Experimental data suggest that a mix of dairy lipids and plant oils can potentiate endogenous synthesis of n-3 long chain polyunsaturated fatty acids . This trial aims to determine the effect of an infant formula supplemented with a mixture of dairy lipids and plant oils on the erythrocyte membrane omega-3 fatty acid profile in full-term infants ( primary outcome ) . Erythrocyte membrane long chain polyunsaturated fatty acids and fatty acids content , the plasma lipid profile and the insulin-growth factor 1 level , the gastrointestinal tolerance , the changes throughout the study in blood fatty acids content , in growth and body composition are evaluated as secondary outcomes . Methods / Design In a double-blind controlled r and omized trial , 75 healthy full-term infants are r and omly allocated to receive for four months a formula supplemented with a mixture of dairy lipids and plant oils or a formula containing only plant oils or a formula containing plant oils supplemented with arachidonic acid and docosahexaenoic acid .  Twenty-five breast-fed infants constitute the reference group .  Erythrocyte membrane omega-3 fatty acid profile , long chain polyunsaturated fatty acids and the other fatty acids content , the plasma lipid profile and the insulin-growth factor 1 level are measured after four months of intervention . Gastrointestinal tolerance , the changes in blood fatty acids content , in growth and body composition , assessed by means of an air displacement plethysmography system , are also evaluated throughout the study . Discussion The achievement of an appropriate long chain polyunsaturated fatty acids status represents an important goal in neonatal nutrition . Gaining further insight in the effects of the supplementation of a formula with dairy lipids and plant oils in healthy full-term infants could help to produce a formula whose fat content , composition and structure is more similar to human milk . Trial registration Clinical Trials.gov Identifier We have previously reported a protective effect of maternal omega-3 long-chain polyunsaturated fatty acids ( ω-3 LCPUFA ) supplementation in pregnancy and lactation on IgE-associated eczema and food allergy in the infant during the first year of life . Here we investigate whether the effects of the LCPUFA supplementation on IgE-associated diseases last up to 2 yr of age and assess the relationship between plasma proportions of ω-3 PUFAs and the frequency and severity of infant allergic disease . 145 pregnant women , at risk of having an allergic infant , were r and omized to daily supplementation with 1.6 g eicosapentaenoic acid ( EPA ) and 1.1 g docosahexaenoic acid ( DHA ) or placebo starting in the 25th gestational week and continuing through 3.5 months of breastfeeding . Clinical examinations , skin prick tests and analysis of maternal and infant plasma phospholipid fatty acids and infant specific IgE were performed . No difference in the prevalence of allergic symptoms was found between the intervention groups . The cumulative incidence of IgE-associated disease was lower in the ω-3-supplemented group ( 6/54 , 13 % ) compared with the placebo group ( 19/62 , 30 % , p=0.01 ) . Higher maternal and infant proportions of DHA and EPA were associated with lower prevalence of IgE associated disease ( p=0.01 - 0.05 ) in a dose-dependent manner . Higher maternal and infant proportions of DHA and EPA were found if the infants presented none , when compared with multiple allergic symptoms , ( p<0.05 ) regardless of sensitization . In summary , the ω-3 supplementation offered no obvious preventive effect on the prevalence of clinical symptoms of allergic disease , but the decrease in cumulative incidence of IgE-associated disease seen during the first year still remained until 2 yr of age . Furthermore , high proportions of DHA and EPA in maternal and infant plasma phospholipids were associated with less IgE-associated disease and a reduced severity of the allergic phenotype BACKGROUND Docosahexaenoic acid ( DHA ) and arachidonic acid ( AA ) are long-chain polyunsaturated fatty acids ( LCPs ) that play pivotal roles in growth and neurodevelopment . OBJECTIVE We aim ed to quantify the synthesis of LCPs in preterm infants fed infant formula containing LCPs . DESIGN Twenty-two preterm infants were r and omly assigned to either the no-LCP group ( fed formula without LCPs ; n = 11 ) or the LCP group ( fed formula with LCPs ; n = 11 ) . Dietary LCPs had higher (13)C content than did the endogenously synthesized LCPs , which were derived from linoleic and alpha-linolenic acids . The (13)C content of major selected plasma fatty acids was measured by using gas chromatography-isotope ratio mass spectrometry at birth and at age 1 , 3 , and 7 mo . Absolute LCP synthesis and the percentage of LCP synthesis relative to dietary intake were calculated . RESULTS Percentage AA synthesis was 67.2 + /- 7.8 % , 35.9 + /- 9.8 % , and 29.0 + /- 10.3 % , and that of DHA was 41.7 + /- 14.9 % , 10.5 + /- 8.1 % , and 7.4 + /- 6.2 % at 1 , 3 , and 7 mo old , respectively . Absolute AA synthesis was 26.7 + /- 4.2 , 14.4 + /- 3.9 , and 11.6 + /- 4.1 mg x kg(-1 ) x d(-1 ) and that of DHA was 12.6 + /- 4.5 , 3.2 + /- 2.5 , and 2.3 + /- 1.9 mg x kg(-1 ) . d(-1 ) at 1 , 3 , and 7 mo old , respectively . AA and DHA synthesis decreased significantly ( P < 0.01 ) with time , and AA synthesis was significantly ( P < 0.01 ) greater than DHA synthesis . CONCLUSIONS By this novel approach , we measured endogenous LCP synthesis in infants receiving dietary LCPs over long periods . By age 7 mo , LCP synthesis was dramatically lower in preterm infants fed LCPs To determine the effect of feeding formula containing long-chain PUFA ( LCP ) on immune function , healthy term infants were r and omised at age 2 weeks to either a st and ard term formula ( Formula ; n 14 ) or the same formula supplemented with the LCP 20 : 4n-6 and 22 : 6n-3 ( Formula+LCP ; n 16 ) . Peripheral blood was collected at 2 and 6 weeks to measure immune cell response ( the rate of [3H]thymidine uptake and cytokine production after stimulation with phytohaemagglutinin ( PHA ) ) . Compared with cells from infants receiving only human milk ( HM ) , the rate of [3H]thymidine uptake in response to PHA , but not IL-2 production , was lower for Formula+LCP infants ( P < 0.05 ) . Compared with HM-fed infants , Formula-fed infants ( but not Formula+LCP infants ) produced more TNF-alpha ( unstimulated ) and had a fewer CD3+CD44 + cells before stimulation and fewer CD11c+ cells post-stimulation ( P < 0.05 ) . However , compared with Formula-fed infants , the Formula+LCP infants had an immune cell distribution ( higher percentage CD3+CD44 + and CD4+CD28 + cells ) and cytokine profile ( lower production of TNF-alpha post-stimulation ) that did not differ from HM infants . Additionally , it was found that feeding infants formula during the first 10 d of life influenced immune function . These infants had a higher percentage of CD3 + , CD4+CD28 + , and lower percentage of CD14 + cells and produced more TNF-alpha and interferon-gamma after PHA stimulation than HM-fed infants ( P < 0.05 ) . These results demonstrate that early diet influences both the presence of specific cell types and function of infant blood immune cells . Since many diseases have a strong immunological component , these immune changes may be of physiological importance to the developing infant BACKGROUND Normal brain and visual development is thought to require exogenous docosahexaenoic acid ( DHA ; 22:6n-3 ) intake , but the amount needed is debatable . Because the supplementation of breastfeeding mothers with DHA increases the DHA content of their infants ' plasma lipids , we hypothesized that it might also improve brain or visual function in the infants . OBJECTIVE The objective was to determine the effect of DHA supplementation of breastfeeding mothers on neurodevelopmental status and visual function in the recipient infant . DESIGN Breastfeeding women received capsules containing either a high-DHA algal oil ( approximately 200 mg DHA/d ) or a vegetable oil ( no DHA ) for 4 mo after delivery . Outcome variables included the fatty acid pattern of maternal plasma phospholipid and milk lipids 4 mo postpartum , the fatty acid pattern of plasma phospholipids and visual function in infants at 4 and 8 mo of age , and neurodevelopmental indexes of the infants at 12 and 30 mo of age . RESULTS Milk lipid and infant plasma phospholipid DHA contents of the supplemented and control groups were approximately 75 % and approximately 35 % higher , respectively , at 4 mo postpartum . However , neither the neurodevelopmental indexes of the infants at 12 mo of age nor the visual function at 4 or 8 mo of age differed significantly between groups . In contrast , the Bayley Psychomotor Development Index , but not the Mental Development Index , of the supplemented group was higher ( P < 0.01 ) at 30 mo of age . CONCLUSION DHA supplementation  of breastfeeding mothers results in higher infant plasma phospholipid DHA contents during supplementation and a higher Bayley Psychomotor Development Index at 30 mo of age but results in no other advantages either at or before this age Objectives : The aim of this study was to monitor changes in the fecal microbiota from 9 to 18 months and to investigate the effect of increasing dietary n-3 polyunsaturated fatty acids on the fecal microbiota . Patients and Methods : In a double-blind controlled trial with r and om allocation to daily supplementation with 5 mL of fish oil ( FO ) or sunflower oil ( SO ) from 9 to 18 months of age , stool sample s were collected from 132 healthy Danish infants .  Molecular fingerprints of the bacterial DNA were obtained by terminal restriction fragment length polymorphism ( T-RFLP ) . Results : The T-RFLP profiles indicated that a few T-RFs became dominant with age ( bp100 and 102 , both presumed to be Bacteroidetes ) concomitantly with an overall increase in the microbial diversity ( P = 0.04 ) . Breast-feeding influenced both the T-RFLP profiles at 9 months and the changes from 9 to 18 months , and breast-feeding cessation during the trial modified the response to the dietary oils . In the FO group , the increase in bp102 was significantly reduced among children weaned before compared with those weaned during the trial ( P = 0.027 ) , whereas the increase in bp100 was reduced in the preweaned children of the SO group relative to those weaned during the trial ( P = 0.004 ) . This was supported by intervention group differences in the changes in bp102 and bp100 among the earlier weaned children ( P = 0.06 and P = 0.09 , respectively ) . Conclusions : Cessation of breast-feeding played a dominant role relative to developmental changes in the fecal microbiota from 9 to 18 months . FO compared with SO supplementation affected changes in large bacterial groups , but only among children who had stopped breast-feeding before 9 months of age Objective . To determine if dietary long-chain polyunsaturated fatty acids ( LCPUFA ) affect the growth of formula-fed infants relative to breastfed infants . Methods . A r and omized , double-blind trial of three formula-fed groups and a parallel reference group of breastfed infants was conducted . The three treatments were a placebo ( no LCPUFA ) , docosahexaenoic acid ( DHA ) supplemented , and DHA plus arachidonic acid supplemented formulas fed for 12 months . Infant weight , length , head circumference , and fatty acid status were assessed at 6 , 16 , 34 weeks , and 1 year of age . Anthropometrics were repeated at 2 years of age . Results . There were no differences between the r and omized formula groups for weight , length , or head circumference even after adjustment for gender , gestational age , and the actual age at assessment . Post hoc regressions demonstrated a small negative association between DHA status at 16 weeks of age and weight at 1 and 2 years . Conclusions . Dietary LCPUFA do not influence growth of healthy term infants to a clinical ly significant degree Necrotizing enterocolitis ( NEC ) causes approximately 4000 deaths/y and significant morbidity among U.S.-born preterm infants alone . Various combinations of inadequate tissue oxygenation , bacterial overgrowth , and enteral feeding with immaturity may cause the initial damage to intestinal mucosa that culminates in necrosis . Presently , there is not a way to predict the onset of the disease or to prevent its occurrence . As part of risk-benefit assessment , we compared disease in hospitalized preterm infants fed a commercial ( control ) preterm formula or an experimental formula with egg phospholipids  for a r and omized , double-masked , clinical study of diet and infant neurodevelopment . Infants fed the experimental formula developed significantly less stage II and III NEC compared with infants fed the control formula ( 2.9 versus 17.6 % , p < 0.05 ) , but had similar rates of bronchopulmonary dysplasia ( 23.4 versus 23.5 % ) , septicemia ( 26 versus 31 % ) , and retinopathy of prematurity ( 38 versus 40 % ) . Compared with the control formula , the experimental formula provided 7-fold more esterified choline , arachidonic acid ( AA , 0.4 % of total fatty acids ) , and docosahexaenoic acid ( 0.13 % ) . Phospholipids are constituents of mucosal membranes and intestinal surfactant , and their components , AA and choline , are substrates for intestinal vasodilatory and cytoprotective eicosanoids ( AA ) and the vasodilatory neurotransmitter , acetylcholine ( choline ) , respectively . One or more of these components of egg phospholipids may have enhanced one or more immature intestinal functions to lower the incidence of NEC in this study . Regardless of the potential mechanism , a larger r and omized trial design ed to test the effect of this egg phospholipid-containing formula on NEC seems warranted A double-blind , r and omized , controlled , parallel-group prospect i ve trial was conducted to determine whether a dose-response existed for four different levels of docosahexaenoic acid ( DHA ) supplementation on the cognitive performance of infants . A total of 122 term infants were fed one of four different formulas varying in their DHA composition ( 0.00 , 0.32 , 0.64 , and 0.96 % of total fatty acids as DHA ) from birth to 12 mo . The three DHA-supplemented formulas also contained 0.64 % of total fatty acids as arachidonic acid ( ARA , 20:4n-6 ) . Infants were tested at 4 , 6 , and 9 mo of age on a visual habituation protocol that yielded both behavioral and psychophysiological indices of attention . Infants in all DHA+ARA-supplemented conditions had lower heart rates than those in the unsupplemented condition ; there was no dose-response for this effect . The distribution of time that infants spent in different phases of attention ( a cognitive index derived from the convergence of behavioral and cardiac responses ) varied as a function of dosage . Infants supplemented at the two lower DHA doses spent proportionately more time engaged in active stimulus processing than infants fed the unsupplemented formula , whereas infants fed the highest dose were intermediate and did not differ from any other group Studies on formula-fed infants indicate a beneficial effect of dietary DHA on visual acuity . Cross-sectional studies have shown an association between breast-milk DHA levels and visual acuity in breast-fed infants . The objective in this study was to evaluate the biochemical and functional effects of fish oil ( FO ) supplements in lactating mothers . In this double-blinded r and omized trial , Danish mothers with habitual fish intake below the 50th percentile of the Danish National Birth Cohort were r and omized to microencapsulated FO [ 1.3 g/d long-chain n−3 FA ( n−3 LCPUFA ) ] or olive oil ( OO ) . The intervention started within a week after delivery and lasted 4 mon . Mothers with habitual high fish intake and their infants were included as a reference group . Ninety-seven infants completed the trial ( 44 OO-group , 53 FO-group ) and 47 reference infants were followed up . The primary outcome measures were : DHA content of milk sample s ( 0 , 2 , and 4 mon postnatal ) and of infant red blood cell ( RBC ) membranes ( 4 mon postnatal ) , and infant visual acuity ( measured by swept visual evoked potential at 2 and 4 mon of age ) . FO supplementation gave rise to a threefold increase in the DHA content of the 4-mon milk sample s ( P<0.001 ) . DHA in infant RBC reflected milk contents ( r=0.564 , P<0.001 ) and was increased by almost 50 % ( P<0.001 ) . Infant visual acuity was not significantly different in the r and omized groups but was positively associated at 4 mon with infant RBC-DHA ( P=0.004 , multiple regression ) . We concluded that maternal FO supplementation during lactation did not enhance visual acuity of the infants who completed the intervention . However , the results showed that infants with higher RBC levels of n−3 LCPUFA had a better visual acuity at 4 mon of age , suggesting that n−3 LCPUFA may influence visual maturation Long-chain polyunsaturated fatty acids ( LCPUFA ) are important for normal visual and cortical development . In a previous study of the effects of LCPUFA on cognitive function of term infants at the age of 3 mon , we indicated that infants with evidence of reduced growth parameters at birth and impaired attention control as manifested by a late peak fixation during infant habituation assessment may benefit from LCPUFA supplementation . The aim of this prospect i ve study was to determine whether LCPUFA supplementation and late peak fixation are related to means-end problem-solving ability in these same infants at the age of 9 mon . Term infants ( 58 ) were r and omized to one of two formulas containing either LCPUFA or no LCPUFA and completed 4 mon of feeding with their formula .  Cognitive function was assessed at 3 mon of age by measures of infant habituation . Infants ( 20 LCPUFA and 20 no-LCPUFA )  completed the problem-solving assessment at 9 mon . The no-LCPUFA group had lower scores on both measures of intention and number of solutions , but neither of these differences was significant . Analysis of covariance for the effects of group and peak fixation , covaried with gestation and birth weight , showed that the number of solutions was significantly reduced in the late peak-fixation infants receiving no LCPUFA ( P<0.02 ) . Intention scores tended to be reduced in this group ( P<0.06 ) . The late peak-fixation infants who received LCPUFA had solution and intention scores similar to early peak-fixation infants receiving LCPUFA or no LCPUFA . These findings suggest that in term infants who have reduced growth parameters at birth and who show evidence of impaired attention control , information processing and problem-solving ability in infancy may be enhanced by LCPUFA supplementation Long-chain PUFA ( LCP ) deficiency is a frequent complication in cholestatic infants . We investigated the effects of LCP-supplemented formula on EFA status in infants with cholestasis . Twenty-three infants with cholestasis ( biliary atresia after surgery , 8 ; intrahepatic cholestasis , 15 ) aged 1.9 to 4.9 mon ( median 3.1 mon ) were r and omized to receive commercial infant formulas either without LCP or with LCP from egg phospholipids for 1 mon . Liver tests , nutrient intakes , and plasma phospholipid  FA ( % w/w ) were determined at baseline and after intervention . At baseline , patients had high serum direct bilirubin levels ( 5.9 ± 3.0 mg/dL ; mean ± SD ) , they were malnourished ( body fat mass : 40 ± 13 % of normal ) and presented with PUFA deficiency [ plasma phospholipid PUFA : 28.43%w/w ( 26.56–30.53 ) in patients vs. 37.02%w/w ( 34.53–39.58 ) in controls ; median ( 1st–3rd quartile ) ] with elevated Mead acid and palmitoleic acid . LCP-supplemented ( n=11 and -nonsupplemented groups ( n=12 ) did not differ in age , indicators of liver function , and EFA status at baseline . After the intervention , LCP-supplemented infants had higher levels of arachidonic acid [ 7.2 ( 5.9–8.8 ) vs. 4.2 ( 3.0–5.3 ) % w/w ; P<0.001 ] and DHA [ 2.8 ( 2.2–3.2 ) vs. 1.6 ( 1.0–2.1 ) % w/w ; P<0.05 ] , accompanied by increased [ BARS concentration : 1.9 ( 1.4–2.2 ) vs. 1.3 ( 1.1–1.6 ) nmol/mL ; P<0.05 ] . We concluded that LCP-supplemented formulae  improve LCP status of infants with severe cholestasis but may enhance lipid peroxidation Abstract n−3 PUFA influence immune functioning and may affect the cytokine phenotype during development . To examine whether maternal fish oil supplementation during lactation could modify later  immune responses in children , 122 lactating Danish mothers with a fish intake below the population median were r and omized to groups supplemented for the first 4 mon of lactation with 4.5 g/d of fish oil ( equivalent to 1.5 g/d of n−3 long-chain PUFA ) or olive oil .  Fifty-three mothers with a fish intake in the highest quartile of the population were also included . The FA composition of erythrocyte membranes was measured at 4 mon and at 2 1/2 yr . Plasma immunoglobulin E ( IgE ) levels and cytokine production in lipopolysaccharide-stimulated whole-blood cultures were determined at 2 1/2 yr . Erythrocyte n−3 PUFA at 4 mon were higher in infants from the fish oil group compared with the olive oil group ( P<0.001 ) but were no longer different at 2 1/2 yr . The median production of lipopolysaccharide-induced interferon γ(IFN-γ ) in the fish oil group was fourfold higher than that in the olive oil group ( P=0.034 ) , whereas interleukin-10 ( IL-10 ) production was similar . The IFN-γ/IL-10 ratio was twofold higher in the fish oil group ( P=0.019 ) and was positively correlated with 20∶5n−3/20∶4n−6 in erythrocytes at 4 mon ( P=0.050 ) . The percentages of atopic children and plasma IgE were not different in the two groups , but the study was not design ed to look at atopy . Cytokine responses and erythrocyte FA composition in children of mothers with a high fish intake were intermediate in comparison with those in the r and omized groups . Fish oil supplementation during lactation result ed in increased in vitro IFN-γ production in the children 2 yr after the supplementation was given , which may reflect a faster maturation of the immune system This was a r and omized , double-blind trial to determine if a nutrient-enriched ( preterm ) formula supplemented with 0.2 % docosahexaenoic acid ( DHA , 22∶6n−3 ) from a low eicosapentaenoic acid ( 0.06 % ) source of marine oil would enhance visual novelty preference and attention of preterm infants . Both the st and ard and experimental formulas contained 3 % of total fatty acids as linolenic acid ( 18∶3n−3 ) and were fed from approximately three days of age to two months past term . After two months , both diet groups were fed a commercially-available term formula with linolenic acid as the only source of n−3 fatty acid . At 12 mo visual recognition memory ( novelty preference ) and visual attention ( number and duration of discrete looks ) were determined with the Fagan Test of Infant Intelligence . The DHA-supplemented group compared with the control group had more and shorter duration looks in comparisons of familiar and novel stimuli , confirming earlier evidence that DHA can increase information processing speed of preterm infants who otherwise are receiving good intakes of linolenic acid . Because supplementation was stopped at two months and the effects seen at 12 mon , this study demonstrates for the first time that a relatively short period of DHA supplementation can produce significant effects on later visual attention Several studies have reported that feeding γ-linolenic acid ( GLA ) has result ed in no increase in arachidonic acid ( AA ) in newborns . This result was ascribed to the eicosapentaenoic acid (EPA)-rich fish oil used in these formulas . Docosahexaenoic acid ( DHA ) sources with only minor amounts of EPA are now available , thus the addition of GLA to infant formulas might be considered an alternative to AA supplementation . Sixty-six premature infants were r and omized to feeding one of four formulas [ ST : no GLA , no long-chain polyunsaturated fatty acids ; BO : 0.6 % GLA ( borage oil ) ; BO + FOLOW : 0.6 % GLA , 0.3 % DHA , 0.06 % EPA ; BO + FOHIGH : 0.6 % GLA , 0.3 % DHA , 0.2 % EPA ] or human milk ( HM , nonr and omized ) for 4 wk . Anthropometric measures and blood sample s were obtained at study entry and after 14 and 28 d. There were no significant differences between groups in anthropometric measures , tocopherol , and retinol status at any of the studied time points . The AA content of plasma phospholipids was similar between groups at study start and decreased significantly until day 28 in all formulafed groups , but not in the breast-fed infants [ ST : 6.6±0.2 % , BO : 6.9±0.3 % , BO + FOLOW : 6.9±0.4 % , BO + FOHIGH : 6.7±0.2 % , HM : 8.6±0.5 % , where values are reported as mean ±st and ard error ; all formulas significantly different ( P≤0.05 ) from HM ] . There was no significant influence  of GLA or fish oil addition to the diet . GLA had only a very limited effect on AA status which was too small to obtain satisfactory concentrations ( concentrations similar to breast-fed babies ) under the circumstances tested . The effect of GLA on AA is independent of the EPA and DHA content in the diet within the dose ranges studied Early accumulation of n-3 long-chain PUFA ( LCPUFA ) in the brain may contribute to differences in later cognitive abilities . In this study , our objective was to examine whether fish oil ( FO ) supplementation during lactation affects processing speed , working memory , inhibitory control , and socioemotional development at 7 years . Danish mothers ( n = 122 ) were r and omized to FO [ 1.5 g/d n-3 LCPUFA ] or olive oil ( OO ) supplementation during the first 4 months of lactation . The trial also included a high-fish intake ( HFI ) reference group ( n = 53 ) . Ninety-eight children were followed-up with an assessment of processing speed , an age-appropriate Stroop task , and the Strength and Difficulties Question naire  at 7 year . A group effect of the intervention ( FO vs. OO ) was found in prosocial behavior scores ; this negative effect was carried by the boys . Exploratory analyses including all participants revealed the speed of processing scores were predicted by maternal n-3 LCPUFA intake during the intervention period ( negative relation ) and maternal education ( positive relation ) . Stroop scores indicative of working memory and inhibitory control were predicted by infant erythrocyte DHA status at 4 months of age ( negative relation ) . Early fish oil supplementation may have a negative effect on later cognitive abilities . Speed of processing and inhibitory control/working memory are differentially affected , with speed of processing showing effects of fish oil intake as a whole , whereas inhibitory control/working memory was related more specifically to DHA status Healthy term infants ( n = 244 ) were r and omized to receive : ( 1 ) control , soy-based formula without supplementation or ( 2 ) docosahexaenoic acid−arachidonic acid ( DHA + ARA ) , soy-based formula supplemented with at least 17 mg DHA/100 kcal ( from algal oil ) and 34 mg ARA/100 kcal ( from fungal oil ) in a double-blind , parallel group trial to evaluate safety , benefits , and growth from 14 to 120 days of age  . Anthropometric measurements were taken at 14 , 30 , 60 , 90 , and 120 days of age and 24-h dietary and tolerance recall were recorded at 30 , 60 , 90 , and 120 days of age . Adverse events were recorded throughout the study . Blood sample s were drawn from subsets of 25 infants in each group . Capillary column gas chromatography was used to analyze the percentages of fatty acids in red blood cell ( RBC ) lipids and plasma phospholipids . Compared with the control group , percentages of fatty acids such as DHA and ARA in total RBC and plasma phospholipids were significantly higher in infants in the DHA + ARA group at 120 days of age ( P < 0.001 ) . Growth rates did not differ significantly between feeding groups at any assessed time point . Supplementation did not affect the tolerance of formula or the incidence of adverse events . Feeding healthy term infants soy-based formula supplemented with DHA and ARA from single cell oil sources at concentrations similar to human milk significantly increased circulating levels of DHA and ARA when compared with the control group . Both formulas supported normal growth and were well tolerated BACKGROUND Preterm infants have improved visual outcomes when fed a formula containing 0.2 - 0.4 % docosahexaenoic acid ( DHA ) compared with infants fed no DHA , but the optimal DHA dose is unknown . OBJECTIVE We assessed visual responses of preterm infants fed human milk ( HM ) and formula with a DHA concentration estimated to match the intrauterine accretion rate ( high-DHA group ) compared with infants fed HM and formula containing DHA at current concentrations . DESIGN A double-blind r and omized controlled trial studied preterm infants born at <33 wk gestation and fed HM or formula containing 1 % DHA ( high-DHA group ) or approximately 0.3 % DHA ( current practice ; control group ) until reaching their estimated due date ( EDD ) . Both groups received the same concentration of arachidonic acid . Sweep visual evoked potential ( VEP ) acuity and latency were assessed at 2 and 4 mo corrected age ( CA ) . Weight , length , and head circumference were assessed at EDD and at 2 and 4 mo CA . RESULTS At 2 mo CA , acuity of the high-DHA group did not differ from the control group [ high-DHA group ( x + /- SD ) : 5.6 + /- 2.4 cycles per degree ( cpd ) , n = 54 ; control group : 5.6 + /- 2.4 cpd , n = 61 ; P = 0.96 ] . By 4 mo CA , the high-DHA group exhibited an acuity that was 1.4 cpd higher than the control group ( high-DHA : 9.6 + /- 3.7 cpd , n = 44 ; control : 8.2 + /- 1.8 cpd ; n = 51 ; P = 0.025 ) . VEP latencies and anthropometric measurements were not different between the high-DHA and control groups . CONCLUSION The DHA requirement of preterm infants may be higher than currently provided by preterm formula or HM of Australian women BACKGROUND Increased consumption of n-3 long-chain polyunsaturated fatty acids ( PUFAs ) has been recommended during pregnancy and lactation . The production of proinflammatory cytokines by human peripheral blood mononuclear cells ( P BMC s ) can be modified by dietary n-3 PUFAs . OBJECTIVE We sought to determine whether dietary supplementation of lactating women with docosahexaenoic acid ( DHA ) can modulate the concentration of cytokines in the aqueous phase of human milk and the production of cytokines by human milk cells ( HMCs ) and P BMC s. DESIGN In this double-blind , prospect i ve , r and omized trial , mothers of healthy full-term infants were asked to consume daily a nutritional supplement of 2000 mg oil containing either placebo ( n = 40 ) , 300 mg DHA + 70 mg eicosapentaenoic acid ( EPA ; n = 40 ) , or 600 mg DHA + 140 mg EPA ( n = 40 ) . The fatty acid composition of plasma , P BMC s , milk , and HMCs from lactating mothers at 4 wk postpartum was measured by gas chromatography . The concentration of interleukin 6 and tumor necrosis factor alpha in milk and the production of interleukin 1beta , tumor necrosis factor alpha , and interleukin 6 by P BMC s and HMCs after stimulation with lipopolysaccharide was measured by enzyme-linked immunosorbent assay . RESULTS At 4 wk postpartum , 82 mothers were still breast-feeding their infants .  DHA increases in maternal plasma , P BMC s , milk , and HMCs were proportional to dietary DHA . There was no relation between tissue DHA status and cytokine concentrations . CONCLUSIONS Consumption of < or = 600 mg DHA and 140 mg EPA/d for 4 wk increased n-3 PUFA concentrations in relevant tissues but did not cause perturbations in cytokine concentrations in human milk ( n-3 ) PUFA influence immune function  in adults and may also affect immune maturation during development . This r and omized trial is , to our knowledge , the first to investigate whether fish oil supplementation in late infancy modifies immune responses . The study was a 2 x 2 intervention in 64 healthy Danish infants , who received cow 's milk or infant formula alone or with fish oil ( FO ) ( 3.4 + /- 1.1 mL/d ) from 9 to 12 mo of age . Before and after the intervention , fatty acid composition of erythrocyte membranes , plasma IgE , C-reactive protein , and soluble IL-2 receptor concentrations were measured . TNF-alpha , INF-gamma , and IL-10 concentrations in whole-blood cultures , stimulated for 22 h with LPS+phytohemaglutinin ( PHA ) or Lactobacillus paracasei , were also determined . IgA was measured in feces when infants were 10 mo of age . FO supplementation effectively raised erythrocyte ( n-3 ) PUFA ( P < 0.001 ) , increased L. paracasei-induced INF-gamma ( P = 0.05 ) and tended to reduce LPS+PHA-induced IL-10 ( P = 0.08 ) . The FO intervention did not affect any of the other analyzed immune variables . The erythrocyte content of eicosapentanoic acid was negatively associated with LPS+PHA-induced IL-10 ( r = -0.38 , P = 0.02 ) . Feeding milk rather than formula did not affect cytokine production , but plasma soluble IL-2 receptor concentration was greater in the formula group than in the cow 's milk group ( P = 0.03 ) . Since the capacity to produce INF-gamma has been proposed as a maturation marker for the immune system in early life , this study suggests a faster immune maturation with FO supplementation with no apparent reduction in immune activation . The implication s for later health need further investigation BACKGROUND Factors other than dietary fatty acids could be involved in the variability observed in blood docosahexaenoate ( 22:6n-3 ) and arachidonate ( 20:4n-6 ) status in formula-fed infants . OBJECTIVE We considered the 22:6n-3 and 20:4n-6 status at birth to be one of these factors and studied its influence on postnatal changes in term infants fed 4 different diets . DESIGN The blood phospholipid composition was determined at birth and on day 42 of feeding in 83 term infants fed breast milk , nonsupplemented formula , or 2 different 22:6n-3-supplemented formulas .  Relations between 22:6n-3 and 20:4n-6 status at birth and their relative postnatal changes , calculated by the difference between status at the end of the feeding period ( 6 wk of age ) and at birth , were assessed . RESULTS Postnatal changes in the plasma and erythrocyte phospholipids 22:6n-3 and 20:4n-6 were negatively related to their respective concentrations at birth ( P < 0.01 ) and the slopes of the regression lines were not significantly affected by the type of milk ingested . Adjusted mean values for phospholipid 22:6n-3 in nonsupplemented-formula-fed infants and for 20:4n-6 in formula-fed infants decreased significantly more than they did in the other infant groups ( P < 0.02 ) . The status at birth and the type of milk ingested explained 33 - 64 % and 7 - 47 % , respectively , of the variability in postnatal changes . CONCLUSIONS The status of 22:6n-3 and 20:4n-6 at birth in term infants is one of the major determinants of postnatal changes in these fatty acids . This finding indicates that research is required to characterize environmental , genetic , or both factors , which , in addition to maternal diet , could influence fatty acid status at birth Docosahexaenoic acid ( DHA ; 22:6n-3 ) is important for normal visual development . We hypothesized that preterm infants fed formulas with marine oil as a source of DHA  would have better visual acuity than infants fed formulas without marine oil  , as measured by the Teller Acuity Card procedure . Marine oil ( P < 0.001 ) and age ( P < 0.0001 ) influenced visual acuity , by repeated- measures analysis of variance ( ANOVA ) corrected for the effect of subject . Marine-oil-supplemented infants had better visual acuity than those fed st and ard formulas at 2 and 4 mo of age , by Fishers ' least-squares difference ( LSD ) . Acuity of both dietary groups improved through 6.5 mo of age , then plateaued . Through 4 mo of age , acuity was inversely related to oxygen supplementation ( log10 h ) and positively related to DHA status , by general-linear-models ( GLM ) analysis . After 4 mo of age , birth weight and gestational age were the only variables consistently related to visual acuity by GLM . We conclude that marine-oil-supplemented formula improved visual acuity of preterm infants through 4 mo of age by improving DHA status BACKGROUND Breastfeeding has been reported to benefit  visual development in children . A higher concentration of docosahexaneoic acid ( DHA ) in breast milk than in formula has been proposed as one explanation for this association and as a rationale for adding DHA to infant formula , but few long-term data support this possibility . OBJECTIVE The objectives of the study were , first , to test the hypothesis that breastfeeding benefits stereoscopic visual maturation and , second , if that benefit is shown , to ascertain whether it is mediated by the dietary intake of DHA . DESIGN Stereoacuity was measured by using the r and om dot E test ( primary outcome ) , and visual acuity was measured by using the Sonksen-Silver acuity system ( secondary outcome ) in previously breastfed ( n = 78 ) or formula-fed ( n = 184 ) children aged 4 - 6 y who had been followed prospect ively from birth . In the formula-fed group , children were r and omly assigned to receive formula with either DHA or arachidonic acid ( n = 94 ) or a control formula ( n = 90 ) for the first 6 mo . RESULTS Breastfed children had a significantly ( P = 0.001 ) greater likelihood of foveal stereoacuity ( high- grade or < 100 s/arc ) than did formula-fed children ( odds ratio : 2.5 ; 95 % CI : 1.4 , 4.5 ) independent of potential confounding ( P = 0.005 ) . Stereoacuity did not differ significantly between children r and omly assigned to DHA-supplemented or control formula . None of the groups differed in Sonksen-Silver visual acuity . CONCLUSIONS These findings support the hypothesis that breastfeeding benefits long-term stereoscopic development . An effect of DHA can not be excluded , but the lack of difference in stereoacuity between infants r and omly assigned to DHA-containing and those assigned to control formula raises the hypothesis that factors in breast milk other than DHA account for the observed benefits Healthy preterm infants fed formula with long-chain n-3 fatty acids ( n-3 LCFAs ) from marine oil have better early visual acuity but lower plasma phosphatidylcholine ( PC ) arachidonic acid ( AA ) and growth than infants fed formula containing  linolenic acid ( LLA ) as the sole n-3 fatty acid . This r and omized , double-blind trial was design ed to study the effects of a different source of n-3 LCFAs and a shorter feeding interval on visual acuity ( by Teller Acuity Card ) and growth of preterm infants ( n = 59 ; 747 - 1275 g birth wt ) , some of whom required long periods of supplemental oxygen and developed bronchopulmonary dysplasia ( BPD ) . Infants were studied at 0 , 2 , 4 , 6 , 9 , and 12 mo past term . Plasma PC AA , and normalized weight , length , and head circumference were not influenced by BPD or n-3 LCFAs except that n-3 LCFA-supplemented infants weighed less at 6 ( P<0.05 ) and 9 ( P<0.01 ) mo and had smaller head circumferences at 9 mo ( P<0.05 ) . Compared with control infants , however , those fed n-3 LCFAs had lower weight-for-length at 2 , 6 , 9 , and 12 mo ( P<0.0003 , P<0.0114 , P<0.0008 , and P<0.006 , respectively ) . n-3 LCFAs  improved early ( 2-mo ) but not later acuity among infants without BPD ( P<0.02 ) . Regardless of diet , infants with BPD had poorer grating acuity at 2 ( P<0.0002 ) and 4 ( P<0.04 ) mo but not thereafter BACKGROUND The critical period during which the dietary supply of long-chain polyunsaturated fatty acids ( LCPs ) may influence the maturation of cortical function in term infants is unknown . OBJECTIVE The aim of the present study was to determine the relative importance for maturation of the visual cortex of the dietary supply of LCPs during the first 6 wk of life compared with that during weeks 7 - 52 . DESIGN A r and omized controlled clinical trial of LCP supplementation in 65 healthy term infants who were weaned from breast-feeding at 6 wk of age was conducted to determine whether the dietary supply of LCPs after weaning influenced the maturation of visual acuity and stereoacuity . RESULTS Despite a dietary supply of LCPs from breast milk during the first 6 wk of life , infants who were weaned to formula that did not provide LCPs had significantly poorer visual acuity at 17 , 26 , and 52 wk of age and significantly poorer stereoacuity at 17 wk of age than did infants who were weaned to LCP-supplemented formula .  Better acuity and stereoacuity at 17 wk was correlated with higher concentrations of docosahexaenoic acid in plasma . Better acuity at 52 wk was correlated with higher concentrations of docosahexaenoic acid in plasma and red blood cells . No significant effects of diet on growth were found . CONCLUSION The results suggest that the critical period during which the dietary supply of LCPs can influence the maturation of cortical function extends beyond 6 wk of age BACKGROUND Egg yolks can be a source of docosahexaenoic acid ( DHA ) and iron but are often associated with adverse consequences on plasma cholesterol . OBJECTIVE Our goal was to investigate the effect of consumption of 4 egg yolks/wk on infant DHA status and hemoglobin , ferritin , and plasma cholesterol concentrations . Secondary outcomes included plasma iron , transferrin , and transferrin saturation . DESIGN This was a r and omized controlled trial comparing no dietary intervention , consumption of 4 regular egg yolks/wk , and consumption of 4 n-3 fatty acid-enriched egg yolks/wk in breast-fed and formula-fed infants from 6 to 12 mo of age .  Erythrocyte DHA concentrations , cholesterol , and iron status were assessed at 6 and 12 mo of age . RESULTS Of the 82 breast-fed infants recruited , 23 of 28 ( no intervention ) , 23 of 27 ( regular eggs ) , and 24 of 27 ( n-3 eggs ) completed the trial . Of the 79 formula-fed infants enrolled , 23 of 27 ( no intervention ) , 24 of 26 ( regular eggs ) , and 20 of 26 ( n-3 eggs ) completed the trial .  Erythrocyte DHA concentrations were 30 - 40 % higher after the n-3 egg intervention than after treatment with regular eggs or no eggs in both breast-fed and formula-fed infants . Egg treatment had no significant effect on plasma cholesterol , hemoglobin , ferritin , and transferrin but did result in improvements in plasma iron and transferrin saturation compared with no egg treatment . CONCLUSIONS n-3 Fatty acid-enriched eggs may provide a means of increasing dietary DHA during the second 6 mo of life . Egg yolks may also be a useful source of iron during the weaning period and can be safely included in the weaning diet with no perturbations in plasma cholesterol BACKGROUND Whether long-chain polyunsaturated fatty acids ( LCPs ) play a role in the development of the young nervous system in term infants is debated . OBJECTIVE We investigated whether supplementation of formula with LCPs for 2 mo improves the quality of general movements ( GMs ) in healthy term infants at 3 mo of age . DESIGN A prospect i ve , double-blind , r and omized controlled study was conducted with 2 groups of healthy term infants : a control-formula ( CF ) group ( n = 131 ) and an LCP-supplemented-formula ( LF ) group ( n = 119 ) . A breastfed ( BF ) group ( n = 147 ) served as a reference . Information on potential confounders was collected at enrollment . Videotapes were made of the infants ' spontaneous motor behavior at 3 mo of age to assess the quality of their GMs . On the basis of quality , normal GMs were classified as normal-optimal or normal-suboptimal , and abnormal GMs were classified as mildly or definitely abnormal . Attrition at 3 mo of age was 15 % and nonselective . Multivariate regression analyses with adjustment for confounders were carried out to evaluate the effect of the type of feeding . RESULTS None of the infants had definitely abnormal GMs . Infants in the CF group had mildly abnormal GMs significantly more often than did infants in the LF and BF groups ( 31 % compared with 19 % and 20 % , respectively ) . Infants in the BF group had normal-optimal GMs more frequently than did infants in the LF and CF groups ( 34 % compared with 18 % and 21 % , respectively ) . Logistic regression analyses confirmed these findings . CONCLUSION Supplementation of healthy term infants with LCPs during the first 2 mo of life reduces the occurrence of mildly abnormal GMs Maternal ( n-3 ) PUFA deficiency is associated with higher  blood pressure ( BP ) later in life in rat offspring , and early intake of ( n-3 ) PUFA in formula-fed infants was shown to modify later BP . BP , heart rate ( HR ) , and heart rate variability ( HRV ) are affected by dietary ( n-3 ) PUFA in adults . In this study , we investigated whether fish oil ( FO ) supplementation of lactating mothers could modify BP , pulse wave velocity ( PWV ) , and HRV in their children after 2 y. Mothers with low fish intake were r and omly assigned to FO or olive oil ( OO ) supplementation for the first 4 mo after delivery . A reference group of mothers with a high habitual fish intake ( HFI ) was also followed . At the follow-up study at 2.5 y of age , BP and PWV were measured , and electrocardiograms were recorded for 0.5 h. FO supplementation significantly increased RBC levels of long-chain ( n-3 ) PUFA of the 4 mo-old children , but at 2.5 y , the FO and OO groups did not differ . BP , PWV , HR , and HRV also did not differ among the groups . However , for all 3 groups , the children 's intake of ( n-3 ) PUFA at 2.5 y was negatively correlated with mean arterial pressure after adjustment for outdoor temperature ( r = -0.245 , P = 0.04 ) . In conclusion , maternal FO supplementation had no overall effect on BP , PWV , or HRV of the children , indicating that ( n-3 ) PUFA intake of Danish mothers may be sufficient in this sense . However , children 's dietary intake of ( n-3 ) PUFA might have a beneficial effect on BP in childhood Animal and epidemiologic studies indicate that early nutrition has lasting effects on metabolism and cardiovascular disease risk . In adults , ( n-3 ) long-chain PUFA ( LCPUFA ) from fish oils improve blood pressure , the lipid profile , and possibly cardiovascular disease mortality . This r and omized trial is the first to investigate the effects of fish oil on blood pressure and the lipid profile in infancy . Healthy term 9-mo old infants ( n = 83 ) were r and omly assigned to 5 mL fish oil daily or no fish oil for 3 mo and to 2 different milk types . Before and after the intervention , blood pressure was measured with an oscillometric device , and blood was sample d for analysis of erythrocyte fatty acid composition and the plasma lipid profile . This paper examines the effects of the fish oil supplement , with adjustment for the effects of the milk intervention when relevant . The fish oil intervention increased erythrocyte ( n-3 ) LCPUFA content ( P < 0.001 ) . At 12 mo , infants administered fish oil had a lower systolic blood pressure [ adjusted mean difference ( 95 % CI ) ] 6.3 mm Hg ( 0.9 , 11.7 ) ( P = 0.02 ) , a 0.51 mmol/L ( 0.07 , 0.95 ) higher plasma total cholesterol ( P = 0.02 ) , and a 0.52 mmol/L ( 0.02,1.01 ) higher LDL cholesterol ( P = 0.04 ) than infants not administered fish oil . Plasma triacylglycerol was inversely associated with the erythrocyte content of eicosapentaenoic acid ( r = 0.34 , P < 0.01 ) , a biomarker of fish oil dose . The observed effects of fish oil are in accordance with findings in adults . The long-term health implication s warrant further investigation BACKGROUND Several studies found a benefit of long-chain polyunsaturated fatty acid ( LCP ) supplementation for visual or mental development , but others found no benefit . Likely contributors to differences among studies are the amount of LCP supplementation , functional outcomes , and sample size . OBJECTIVE We evaluated LCP supplementation in amounts typical for human milk ( based on local and worldwide surveys ) in a large cohort of infants by using sweep visual evoked potential ( VEP ) acuity as the functional outcome . DESIGN The study was a double-masked , r and omized , controlled clinical trial in 103 term infants . By age 5 d , infants were r and omly assigned to receive either formula with no docosahexaenoic acid ( DHA ) or arachidonic acid ( ARA ) or formula supplemented with DHA and ARA as 0.36 % and 0.72 % , respectively , of total fatty acids .  Sweep VEP acuity was the primary outcome . R and om dot stereoacuity , blood lipid profile , growth , and tolerance were secondary outcomes . RESULTS VEP acuity in the LCP-supplemented group was significantly better than that in the control group at ages 6 , 17 , 26 , and 52 wk . Stereoacuity in the LCP-supplemented group was significantly better than that in the control group at age 17 wk but not at ages 39 and 52 wk . By ages 17 and 39 wk , the red blood cell DHA concentration in the LCP-supplemented group was more than double and more than triple , respectively , that in the control group . Growth of infants fed LCP-supplemented and control formulas did not differ significantly , and both diets were well tolerated . CONCLUSION LCP supplementation of term infant formula during the first year of life yields clear differences in visual function and in total red blood cell lipid composition Between 6 and 12 mo of age , blood levels of the ( n-3 ) long-chain PUFA , docosahexaenoic acid ( DHA ) , in breast-fed infants typically decrease due to diminished maternal DHA stores and the introduction of DHA-poor solid foods displacing human milk as the primary source of nutrition . Thus , we utilized a r and omized , clinical trial format to evaluate the effect of supplemental DHA in solid foods on visual development of breast-fed infants with the primary outcome , sweep visual-evoked potential ( VEP ) acuity , as an index for maturation of the retina and visual cortex . At 6 mo of age , breast-fed infants were r and omly assigned to receive 1 jar ( 113 g)/d of baby food containing egg yolk enriched with DHA ( 115 mg DHA/100 g food ; n = 25 ) or control baby food ( 0 mg DHA ; n = 26 ) . Gravimetric measures were used to estimate the supplemental DHA intake which was 83 mg DHA/d in the supplemented group and 0 mg/d in controls . Although many infants in both groups continued to breast-feed for a mean of 9 mo , RBC DHA levels decreased significantly between 6 and 12 mo ( from 3.8 to 3.0 g/100 g total fatty acids ) in control infants , whereas RBC DHA levels increased by 34 % from 4.1 to 5.5 g/100 g by 12 mo in supplemented infants . VEP acuity at 6 mo was 0.49 logMAR ( minimum angle of resolution ) and improved to 0.29 logMAR by 12 mo in controls . In DHA-supplemented infants , VEP acuity was 0.48 logMAR at 6 mo and matured to 0.14 logMAR at 12 mo ( 1.5 lines on the eye chart better than controls ) . At 12 mo , the difference corresponded to 1.5 lines on the eye chart . RBC DHA levels and VEP acuity at 12 mo were correlated ( r = -0.50 ; P = 0.0002 ) , supporting the need of an adequate dietary supply of DHA throughout 1 y of life for neural development BACKGROUND Studies suggest that low concentrations of n-6 long-chain polyenes in early life are correlated to atopic disease in later life . OBJECTIVE The purpose of the study was to investigate the possible preventive effect of gamma-linolenic acid ( GLA ) supplementation on the development of  atopic dermatitis in infants at risk . DESIGN In a double-blind , r and omized , placebo-controlled trial , formula-fed infants ( n = 118 ) with a maternal history of atopic disease received borage oil supplement ( containing 100 mg GLA ) or sunflower oil supplement as a placebo daily for the first 6 mo of life . Main outcome measures were the incidence of atopic dermatitis in the first year of life ( by UK Working Party criteria ) , the severity of atopic dermatitis ( SCORing Atopic Dermatitis ; SCORAD ) , and the total serum immunoglobulin E ( IgE ) concentration at the age of 1 y. RESULTS The intention-to-treat analysis showed a favorable trend for severity of atopic dermatitis associated with GLA supplementation ( x+/- SD SCORAD : 6.32 + /- 5.32 ) in the GLA-supplemented group as compared with 8.28 + /- 6.54 in the placebo group ( P = 0.09 ; P = 0.06 after adjustment for total serum IgE at baseline , age 1 wk ) , but no significant effects on the other atopic outcomes . The increase in GLA concentrations in plasma phospholipids between baseline and 3 mo was negatively associated with the severity of atopic dermatitis at 1 y ( Spearman 's correlation coefficient = -0.233 , P = 0.013 ) . There was no significant effect on total serum IgE concentration . CONCLUSION Early supplementation with GLA in children at high familial risk does not prevent the expression of atopy as reflected by total serum IgE , but it tends to alleviate the severity of atopic dermatitis in later infancy in these children BACKGROUND There are nutritional recommendations that the ratio of linoleic to alpha-linolenic acid ( LA : ALA ) in formula for term infants be between 5:1 and 15:1 . These recommendations were made in the absence of data on functional or clinical outcomes . OBJECTIVE We compared the fatty acid status , visual evoked potential ( VEP ) acuity , and growth of term infants fed formula containing an LA : ALA of 10:1 or 5:1 with those of a breast-fed reference cohort . DESIGN Formula-fed infants were allocated r and omly in a double-blind fashion to receive formula with an LA : ALA of either 10:1 ( 16.9:1.7 ; n = 36 ) or 5:1 ( 16.3:3.3 ; n = 37 ) from near birth to 34 wk of age . Increased ALA was attained by replacing soy oil with low-erucic acid cannola oil . A parallel group of breast-fed infants was also recruited . Infant growth and fatty acid status were assessed at 6 , 16 , and 34 wk of age . VEP acuity was assessed at 16 and 34 wk . RESULTS Infants fed the 5:1 formula had greater docosahexaenoic acid ( DHA ) concentrations in plasma and erythrocyte phospholipids than did infants fed the 10:1 formula , but DHA concentrations of infants fed the 5:1 formula remained less than those in breast-fed infants . The VEP acuity of all formula-fed and breast-fed infants was not significantly different at 16 and 34 wk of age . At birth , infants fed the 5:1 formula were heavier , were longer , and had a greater head circumference than infants assigned to the 10:1 formula group ; this differential was maintained throughout the trial . The rate of gain in weight , length , and head circumference was not significantly different between the 2 formula-fed groups , although breast-fed infants had lower weight and length gains than did formula-fed infants between 16 and 34 wk of age . CONCLUSION Lowering the LA : ALA in formula from 10:1 to 5:1 by using low-erucic acid canola oil result ed in a modest increase in plasma DHA but had no effect on VEP acuity or growth rate OBJECTIVE There have been indications that high intake of n-3 long-chain polyunsaturated fatty acids ( PUFAs ) during pregnancy may increase birth weight and gestational length . In addition , n-3 long-chain PUFAs may be important for the neurobiological development of the infants . High levels of docosahexaenoic acid ( DHA , 22:6 n-3 ) are found in the gray matter of the cerebral cortex and in the retina , and it seems as if the availability of long-chain PUFAs may be limiting cerebral development . The fetus and the newborn are dependent on a high supply from their mothers , either via the placenta or via breast milk . We supplemented pregnant and lactating women with n-3 or n-6 long-chain PUFAs to evaluate the effect on birth weight , gestational length , and infant development . DESIGN We performed a double-blind , r and omized study recruiting 590 pregnant , healthy , nulli- or primiparous women ( 19 - 35 years old ) in weeks 17 to 19 of pregnancy . The women were provided 10 mL of either cod liver oil or corn oil daily until 3 months after delivery . MAIN OUTCOME MEASURES Primary outcomes were gestational length and birth weight . Electroencephalography ( EEG ) was done on the second day of life and at 3 months of age . Novelty preference ( Fagan test ) was used as an indicator of cognitive function at 6 and 9 months of age . The fatty acid pattern in umbilical plasma phospholipids and in breast milk was measured , and dietary assessment s were performed , both on the mothers during pregnancy and on the infants at 3 months of age . The growth of the infants was followed up to 1 year of age . RESULTS Three hundred forty-one mothers took part in the study until delivery . There were no significant differences in maternal body mass index before pregnancy and at birth , or parity between the 2 groups . Smoking habits and parental education were also similar in the 2 groups . The mean age of the mothers receiving cod liver oil was , by chance , 1 year higher than the age of the mothers receiving corn oil ( 28.6 [ 3.4 ] vs 27.6 [ 3.2 ] years ) . The maternal dietary intake in the 2 groups receiving cod liver oil or corn oil was similar , except for the supplementation . There were no differences in gestational length or birth weight between the cod liver oil group and the corn oil group ( 279.6 [ 9.2 ] vs 279.2 [ 9.3 ] days ; 3609 [ 493 ] vs 3618 [ 527 ] g , respectively ) . Birth length , head circumference , and placental weight were also similar in the 2 groups . The concentrations of the n-3 fatty acids eicosapentaenoic acid ( 20:5 n-3 ) , docosapentaenoic acid ( 22:5 n-3 ) , and DHA in umbilical plasma phospholipids were higher in the cod liver oil group compared with the corn oil group ( 10.8 [ 7.6 ] vs 2.5 [ 1.8 ] microg/mL , 5.0 [ 2.6 ] vs 2.9 [ 1.3 ] microg/mL , 55.8 [ 20.6 ] vs 45.3 [ 12.8 ] microg/mL , respectively ) . Neonates with high concentration of DHA in umbilical plasma phospholipids ( upper quartile ) had longer gestational length than neonates with low concentration ( lower quartile ; 282.5 [ 8.5 ] vs 275.4 [ 9.3 ] days ) . No differences in EEG scores or Fagan scores were found , but neonates with mature EEG ( N = 70 ) had a higher concentration of DHA in umbilical plasma phospholipids than neonates with immature EEG ( N = 51 ) on the second day of life . Dietary information from 251 infants at 3 months of age was collected and 85 % of these infants were exclusively breastfed , in addition to 12 % who were partly breastfed . The breast milk of mothers supplemented with cod liver oil contained more n-3 long-chain PUFAs and less n-6 long-chain PUFAs than breast milk of mothers supplemented with corn oil . There were no significant differences in infant growth during the first year of life between the 2 groups . CONCLUSIONS This study shows neither harmful nor beneficial effects of maternal supplementation of long-chain n-3 PUFAs regarding pregnancy outcome , cognitive development , or growth , as compared with supplementation with n-6 fatty acids . However , it confirms that DHA concentration may be related to gestational length and cerebral maturation of the newborn Fish oil addition to infant formulas has raised concern on whether increased intake of n-3 long-chain polyunsaturated fatty acid ( n-3LCPUFA ) affects infant growth .  The objective of this study was to determine whether maternal fish oil supplementation during 0–4 mo of lactation influences growth in infancy and early childhood . In a r and omized , blinded intervention trial , lactating Danish mothers with a fish intake below the population median were r and omized to 4.5 g/d fish oil or olive oil . A reference group of 53 mothers with a fish intake in the highest quartile of the population and their infants were included in the study .  Head circumference , weight , length , skinfold thickness , and waist circumference of children were measured at 2 , 4 , and 9 mo and at 2.5 y. One hundred children completed the intervention trial , and 72 were followed up at 2.5 y together with 29 from the reference group .  Growth in weight , length , and head circumference did not differ between the r and omized groups up to 9 mo , but at 2.5 y , body composition differed significantly . Children in the fish oil group had larger waist circumference body mass index ( BMI ; 0.6 kg/m2 ; p = 0.022 ) , and head circumference compared with those in the olive oil group . Adjusted for sex , ponderal index at birth and current energy intake , BMI at 2.5 y was associated with docosahexaenoic acid in maternal erythrocytes after the intervention . In conclusion , the n-3LCPUFA intake of lactating mothers may be important for growth of young children . The long-term effect on weight and BMI remains to be investigated BACKGROUND The last trimester of pregnancy is a period of rapid accretion of long-chain polyunsaturated fatty acids , both in the central nervous system and the body as a whole . Human milk contains these fatty acids , whereas some preterm infant formulas do not . Infants fed formulas without these fatty acids have lower plasma and erythrocyte concentrations than infants fed human milk . Pre clinical and clinical studies have demonstrated that single-cell sources ( algal and fungal ) of long-chain polyunsaturated fatty acids are bioavailable . A balanced addition of fatty acids from these oils to preterm formula results in blood fatty acid concentrations in low birth weight infants comparable to those of infants fed human milk . METHODS In the present study the growth , acceptance ( overall incidence of discontinuation , reasons for discontinuation , overall incidence and type of individual adverse events ) , and plasma fatty acid concentrations were compared in three groups of infants fed a long-chain polyunsaturated fatty acid-supplemented preterm infant formula , an unsupplemented control formula , or human milk .  The study was prospect i ve , double-blind ( formula groups only ) , and r and omized ( formula groups only ) . Two hundred eighty-eight infants were enrolled ( supplemented formula group , n = 77 ; control formula group , n = 78 ; human milk group , n = 133 ) . RESULTS Anthropometric measurements at enrollment , at first day of full oral feeding , and at both 40 and 48 weeks postconceptional age did not differ between the formula groups , whereas the human milk-fed group initially grew at a lower rate . The incidence of severe adverse events was rare and not significantly different between formula groups . The groups fed either human milk or supplemented formula had long-chain polyunsaturated fatty acid concentrations higher than those in the control formula group . CONCLUSIONS The results of this study demonstrate the safety and efficacy of a preterm formula supplemented with long-chain polyunsaturated fatty acids from single-cell oils Maternal fish oil supplementation during pregnancy has been associated with altered infant  immune responses and a reduced risk of infant sensitization and eczema BACKGROUND Preterm infants may be born with deficits of both docosahexaenoic acid ( DHA ) and arachidonic acid ( AA ) , but studies on supplementation of DHA and AA for preterm infants are limited . METHODS Preterm infants with a gestational age between 30 and 37 weeks who met all the inclusion criteria were enrolled in this double blind , r and omized , comparative study . Infants over 2000 g body weight , over 32 weeks of gestation and in full feeding status would enter into the active intervention period of 6 months . Sixteen infants received Neoangelac Plus with AA and DHA supplementation .  Eleven infants received Neoangelac without AA and DHA supplementation . The babies had scheduled physical examinations and their cognitive development , visual acuity , and vital signs to be checked . Adverse events were also recorded . RESULTS The mean Mental Development Index ( MDI ) scores for the supplementation and non-supplementation groups were 96.1 + /- 8.6 and 91.7 + /- 10.4 respectively at 6 months and 98.7 + /- 8.0 and 90.5 + /- 6.9 respectively at 1 year . The mean Physical Development Index ( PDI ) scores of these two groups were 102.2 + /- 10.5 and 95.4 + /- 13.2 respectively at 6 months and 98.0 + /- 5.8 and 86.7 + /- 11.1 respectively at 1 year . By repeated measures ANOVA , significant differences existed between groups for MDI and PDI ( p = 0.020 and 0.008 ) . However , there were no differences in visual acuity , physical examination variables or vital signs between these two groups . No obvious adverse effects were observed during the study period . CONCLUSION These results showed possible benefits in the neurodevelopment of larger preterm infants given formula supplemented with DHA and AA Fatty acid compositions of plasma phospholipids ( PL ) , triglycerides ( TG ) and sterol esters ( STE ) were measured by high resolution capillary gas-liquid chromatography in formula fed healthy infants at the ages of 5 days and 1 , 2 , 3 and 4 months . The infants were r and omly assigned to receive either conventional infant formula ( F , n = 10 ) without long-chain polyunsaturates ( LCP ) or the same formula supplemented with LCP ( LCP-F , n = 12 ) in amounts and ratios similar to those characteristic to human milk . From the age of 1 month onwards , percentage contributions of the principal omega-6 LCP , arachidonic acid were significantly higher in plasma lipids of infants fed LCP-F than in those receiving conventional formula without dietary LCP . Values of the principal omega-3 LCP , docosahexaenoic acid were also significantly lower in the infants fed conventional formula than in those receiving LCP-F throughout the study . The data obtained indicate that from the formula supplemented with LCP both arachidonic and docosahexaenoic acids were effectively absorbed and incorporated into infantile plasma lipids . Recent data of the literature suggest that supplementation of infant formula with LCP may beneficially influence visual and psychomotor development also in healthy , term infants OBJECTIVE To investigate the incidence of  allergic and respiratory diseases  through age 3 years in children fed docosahexaenoic acid (DHA)- and arachidonic acid (ARA)-supplemented formula during infancy . STUDY DESIGN Children who completed r and omized , double-blind studies of DHA/ARA-supplemented  ( 0.32%-0.36%/0.64%-0.72 % of total fatty acids , respectively ) versus nonsupplemented ( control ) formulas , fed during the first year of life , were eligible . Blinded study nurses review ed medical charts for upper respiratory infection ( URI ) , wheezing , asthma , bronchiolitis , bronchitis , allergic rhinitis , allergic conjunctivitis , otitis media , sinusitis , atopic dermatitis ( AD ) , and urticaria . RESULTS From the 2 original cohorts , 89/179 children participated ; 38/89 were fed DHA/ARA formula . The DHA/ARA group had significantly lower odds for developing URI ( odds ratio [ OR ] , 0.22 ; 95 % confidence interval [ CI ] , 0.08 - 0.58 ) , wheezing/asthma ( OR , 0.32 ; 95 % CI , 0.11 - 0.97 ) , wheezing/asthma/AD ( OR , 0.25 ; 95 % CI , 0.09 - 0.67 ) , or any allergy ( OR , 0.28 ; 95 % CI , 0.10 - 0.72 ) . The control group had significantly shorter time to first diagnosis of URI ( P = .006 ) , wheezing/asthma ( P = .03 ) , or any allergy ( P = .006 ) . CONCLUSIONS DHA/ARA supplementation was associated with delayed onset and reduced incidence of URIs and common allergic diseases up to 3 years of age Docosahexaenoic acid ( DHA ) accumulates in the brain during the 1st and 2nd years of life . The objective of this study was to see if an increased content of DHA in breast-milk via maternal fish oil (FO)-supplementation affects mental development in term infants . one hundred twenty-two Danish mothers with a habitual fish intake below the population median were r and omized to  4.5 g.d(-1 ) of FO or olive oil ( OO ) for the first four months of lactation .  Fifty-three mothers with habitual fish intake in the highest quartile were included as reference group . The effect of the result ing increase in infant DHA-intake and RBC-DHA level was assessed on problem solving ability at nine months and language at one and two years of age . Infants in the three groups performed equally well on the problem test and no association was observed between problem solving and erythrocyte-DHA at four months . Passive vocabulary at one year was lower in the children of the FO- compared with the OO-group ( P < 0.05 ) , but no differences were found at two years of age . Word comprehension at one year was inversely associated with erythrocyte-DHA at four months . The trial indicate a small effect of DHA levels in breast-milk on early language development of breast-fed infants ABSTRACT : Retinal function was assessed by electroretinogram in 32 neonates r and omly assigned to formulas of different ω-3 fatty acid content and in 10 infants fed human milk . All neonates had a birth weight of 1000 - 1500 g and were fed study diets from d 10 to 45 or discharge . Group A received formula containing predominantly 18:2 ω-6 . Group B received a balanced mix of 18:2 ω-6 and 18:3 ω- 3 . Group C was given a formula containing both essential fatty acids and supplemented with marine oil to provide 22:6 ω-3 content similar to that of human milk . The fatty acid composition of plasma and red blood cell ( RBC ) lipids were similar for all groups on entry but marked dietinduced differences were found after feeding the study diets . Group C was comparable to the human milk-fed group , but group A had lower 22:6 ω-3 and ω-3 long-chain polyunsaturated fatty acids ( LCPUFA ) in plasma and RBC membranes . Cone function was not affected by dietary essential fatty acids . Rod electroretinogram thresholds were significantly higher for group A relative to the human milk-fed group and group C and significantly correlated with RBC ω-3 LCPUFA ( r = -0.63 , p < 0.0001 ) ; 44 % of the variance could be explained by RBC and plasma ω-3 LCPUFA content . Rod electroretinogram amplitude was significantly lower for group A relative to the human milkfed group and group C and related to plasma 22:6 ω-3 ( r = 0.55 ) and total ω-3 LCPUFA ( r = 0.58 ) ( both p < 0.0001 ) ; 42 % of the variance was explained by plasma ω-3 LCPUFA , the ratio of ω-6/ω-3 LCPUFA in RBC , and gestational age at birth . Our results support an essential role for ω-3 fatty acids in retinal development BACKGROUND The passage of hard stools is significantly more common in formula fed infants than breast fed infants and this might be the result of differences in fat absorption between breast and formula fed infants . Experimental studies indicate that long chain polyunsaturated fatty acids ( LCPUFAs ) might influence fat hydrolysis and absorption . AIM To investigate the relation of LCPUFA supplementation to stool frequency and consistency during the first 4 months of life . DESIGN Double blind , r and omised , controlled study of 88 healthy infants . RESULTS 1905 stools ( 858 from LCPUFA supplemented infants , 1047 non-supplemented infants ) were examined . The mean ( SEM ) number of stools passed for each three day study period was significantly less in the LCPUFA group ( 5.5 (0.3)v 6.2 ( 0.2 ) ; p < 0.05 ) . In both groups , there was a significant reduction in the number of stools passed with age ( p < 0.001 ) . During the first 3 months , the mean ( SEM ) percentage of hard stools passed by infants in the LCPUFA supplemented group was 7.7 ( 2.1 ) compared with 19.2 ( 2.8 ) for unsupplemented infants ( p = 0.001 ) . CONCLUSION The prevalence of hard stools is significantly reduced in infants fed a formula that is supplemented with LCPUFAs Long‐chain polyunsaturated fatty acids with 20 and 22 carbon atoms ( LCPs ) seem to play an important role during the rapid development of the infant brain in the late fetal and early postnatal period . These LCPs are integral constituents of biological membranes and they are involved in the regulation of functional properties like fluidity , permeability and activity of membrane‐bound enzymes . Human milk contains LCPs in an amount of 0.5–3 wt% of total fatty acids , whereas commercially available infant formulae are almost free of them . Recently , several clinical trials , primarily with preterm infants , have reported that the content of LCPs in the blood and a functional parameter like visual acuity correlate with the content of LCPs in the diet . In this clinical trial we studied the effect of different diets on the fatty acid pattern of plasma and erythrocyte lipids of healthy term infants during the first 3 months of life . Breast‐fed infants were compared with formula‐fed babies who received a commercially available formula without LCPs or a new experimental formula enriched with LCPs that was similar to human milk . The results indicate that the introduction of milk feeding leads to marked differences in the blood lipid composition during the first months of life , independent of the feeding regimen . Secondly , the supplementation of a formula with LCPs seems to result in a blood lipid composition similar to infants fed with human milk . This supports the hypothesis that the newborn term infant has a limited desaturating capacity and depends on an exogenous supply of LCPs during the first months of life Because formula-fed preterm infants may be at risk of omega 3 essential fatty acid deficiency , we tested experimental formulas supplemented with soy oil to provide alpha-linolenic acid or marine oil to provide preformed omega 3 long-chain polyunsaturated fatty acids at a level comparable to that of human milk . This report addresses the effect of feeding formula supplemented with soy oil or with soy and marine oils on growth , clinical tolerance , coagulation test results , changes in erythrocyte membrane fluidity , and plasma concentrations of vitamins A and E in very low birth weight infants from 30 to 57 weeks of postconceptional age . " Healthy " preterm infants were maternally selected to receive human milk or selected at r and om to receive commercial ready-to-feed  liquid formula  , which provided limited omega 3 fatty acid , or experimental formulas supplemented with soy oil or soy and marine oils . Results of this study indicate that formula enriched with soy oil or soy and marine oils containing preformed omega 3 long-chain polyunsaturated fatty acids does not induce abnormalities in growth , clotting function , erythrocyte membrane fluidity , or vitamin A or E levels in healthy very low birth weight preterm infants . Additional studies to evaluate safety in a representative preterm population are required The effect of the dietary n-3 long-chain PUFA , DHA ( 22 : 6n-3 ) , on the growth of pre-term infants is controversial . We tested the effect of higher-dose DHA ( approximately 1 % dietary fatty acids ) on the growth of pre-term infants to 18 months corrected age compared with st and ard feeding practice ( 0·2 - 0·3 % DHA ) in a r and omised controlled trial . Infants born < 33 weeks gestation ( n 657 ) were r and omly allocated to receive breast milk and /or formula with higher DHA or st and ard DHA according to a concealed schedule stratified for sex and birth-weight ( < 1250 and ≥ 1250 g ) . The dietary arachidonic acid content of both diets was constant at approximately 0·4 % total fatty acids . The intervention was from day 2 to 5 of life until the infant 's expected date of delivery ( EDD ) . Growth was assessed at EDD , and at 4 , 12 and 18 months corrected age . There was no effect of higher DHA on weight or head circumference at any age , but infants fed higher DHA were 0·7 cm ( 95 % CI 0·1 , 1·4 cm ; P = 0·02 ) longer at 18 months corrected age . There was an interaction effect between treatment and birth weight strata for weight ( P = 0·01 ) and length ( P = 0·04 ) . Higher DHA result ed in increased length in infants born weighing ≥ 1250 g at 4 months corrected age and in both weight and length at 12 and 18 months corrected age . Our data show that DHA up to 1 % total dietary fatty acids does not adversely affect growth Between May 1993 , and September 1994 , a r and omized , blinded clinical trial was conducted to evaluate measures of growth and body composition in 63 ( 32 males ; 31 females ) healthy , low‐birth‐weight infants ( 940–2250 g ) who were r and omly assigned to an infant formula with docosahexaenoic acid ( 22:6n3 , DHA , 0.2 wt% ) from fish oil or to a control formula . A preterm formula with or without DHA was fed beginning at 7–10 days prior to hospital discharge through 43 weeks postmenstrual age ( PMA ) . Then , from 43‐59 weeks PMA , infants were fed a term infant formula with or without a corresponding amount of DHA . Growth ( weight , length , head circumference ) , regional body fatness ( triceps , subscapular , suprailiac skinfold thicknesses ) , circumferences ( arm , abdominal , chest ) , and estimates of body composition determined by total body electrical conductivity ( TOBEC ) ( fat‐free mass [ FFM ] ) were evaluated . Growth was slower in males fed the DHA formula . They had significantly ( P < 0.05 ) smaller gains in weight , length , and head circumference between study enrollment to 59 weeks PMA than those fed the control formula . At 51 weeks PMA , males in the DHA group had significantly smaller head circumferences ( P < 0.05 ) and lower FFM ( P < 0.05 ) . At 59 weeks PMA , males in the DHA group weighed less ( P < 0.05 ) , had shorter recumbent lengths ( P < 0.01 ) , smaller head circumferences ( P < 0.05 ) , and lower FFM ( P < 0.01 ) than those fed the control formula . Energy intakes from formula ( kcal/d ) , however , were lower at 51 weeks ( P < 0.05 ) and 59 weeks ( P < 0.05 ) PMA in males fed the DHA formula . Adjusted for body weight ( kcal/kg/d ) , mean energy intakes from formula at 51 and 59 weeks PMA were not significantly different between feeding groups . The differences in recumbent length , head circumference , and FFM remained statistically significant after controlling for energy and protein intakes ( P < 0.01 ) . For all males , neither FFM nor total body fat ( TBF ) , when expressed as a percentage of total body weight , differed significantly between feeding groups . Among females , there were no significant differences between the feeding groups in measures of growth , body composition , or energy intake . The results indicated that infant formula with fish oil containing DHA and EPA in a 5:1 ratio had a significant , negative effect on growth and body composition in males during the first 6 months of life . It is not clear why the growth deficits were limited to males and not females . The eicosanoids , bioactive metabolites of omega‐3 and omega‐6 fatty acids , may mediate several important growth hormones . The present results do not support the addition of DHA alone in infant formulas . Am . J. Hum . Biol . 11:457–467 , 1999 . © 1999 Wiley‐Liss , The objective of this study was to evaluate growth and body composition of premature infants who were fed formulas with arachidonic acid ( ARA ; 20:4n6 ) and docosahexaenoic acid ( DHA ; 22:6n3 ) to 1 y of gestation-corrected age ( CA ) . Preterm infants ( 750–1800 g birth weight and <33 wk gestational age ) were assigned within 72 h of first enteral feeding to one of three formulas : control ( n = 22 ) , DHA+ARA from fish/fungal oil [ DHA+ARA(FF ) ; n = 20 ] , or DHA+ARA from egg/fish oil [ DHA+ARA(EF ) ; n = 18 ] . Human milk feeding was allowed on the basis of the mother 's choice . Infants were fed breast milk and /or preterm formulas with or without 0.26 % DHA and 0.42 % ARA to term CA followed by breast milk or postdischarge preterm formulas with or without 0.16 % DHA and 0.42 % ARA to 12 mo CA . Body composition was measured by dual-energy x-ray absorptiometry . There were no significant differences among the three study groups at any time point in weight , length , or head circumference . Bone mineral content and bone mineral density did not differ among groups . At 12 mo CA , infants who were fed DHA+ARA-supplemented formulas had significantly greater lean body mass ( p < 0.05 ) and significantly less fat mass ( p < 0.05 ) than infants who were fed the unsupplemented control formula . The DHA+ARA-supplemented formulas supported normal growth and bone mineralization in premature infants who were born at <33 wk gestation . Preterm formulas that had DHA+ARA at the levels and ratios in this study and were fed to 1 y CA led to increased lean body mass and reduced fat mass by 1 y of age Background . It is currently recommended that diet of pregnant mothers contain 200–300 mg DHA/day . Aim . To determine whether DHA supplementation during pregnancy and lactation affects infants ' immune response . Methods . 60 women in ≥3rd pregnancy studied ; 30 r and omly assigned to receive DHA 400 mg/day from 12th week gestation until 4 months postpartum . From breast-fed infants , blood obtained for anti-HBs antibodies , immunoglobulins , lymphocyte subset phenotyping , and intracellular cytokine production . Results . CD4 + lymphocytes did not differ between groups , but CD4CD45RA/CD4 ( naïve cells ) significantly higher in infants in DHA+ group . Proportion of CD4 and CD8 cells producing IFNγ significantly lower in DHA+ group , with no differences in proportion of IL4-producing cells . Immunoglobulins and anti-HBs levels did not differ between groups . Conclusions . In infants of mothers  receiving DHA supplementation , a higher percentage of CD4 naïve cells and decreased CD4 and CD8 IFNγ production is compatible with attenuation of a proinflammatory response Aim : To study the influence of dietary‐supplied long‐chain polyunsaturated fatty acids on structural brain maturation in preterm infants and to investigate parameters of functional brain development , relating them to structural maturation . Other studies have suggested that dietary supplementation of long‐chain polyunsaturated fatty acids in preterm infants may enhance their visual development . The influence on structural brain development has never been evaluated . Methods : In a prospect i ve , double‐blind study , 42 formula‐fed premature infants were r and omized to be fed either a st and ard preterm formula without long‐chain polyunsaturated fatty acids or an identical formula supplemented with docosahexaenoic acid ( 0.015 g/100 ml ) and arachidonic acid ( 0.031 g/100ml ) . Infants with significant cerebral damage , retinopathy , chronic disease or feeding problems were excluded . Follow‐up was focused on assessment of cerebral myelination by MRI . Psychomotor , mental and visual development was analysed and flash‐visual evoked potentials were recorded . Results : It was found that progress of myelination , mental and motor development and latencies of visual evoked potentials were not positively influenced by supplementation of long‐chain polyunsaturated fatty acids . At each test age , visual acuity was slightly better in the supplemented infants than in the non‐supplemented infants , but the difference never reached significance Background Incorporation of long chain polyunsaturated fatty acids ( LCP ) into formulas may interfere with mineral metabolism . We investigate mineral balance in preterm infants who were fed a formula with LCP .  Methods Infants were r and omized in a double-blind manner , 20 infants in each group , to receive a formula with LCP ( F+LCP ) or without LCP ( F ) for 30 days . Plasma levels ( at the beginning and after 30 days ) and nutritional balance ( after 1 week ) for Ca , P , Mg , Zn , and Cu were obtained for all infants . Results Groups were similar regarding birth weight , gestational age , weight , and corrected age at study start . During the 30-day study period , the groups had comparable milk intake and reached similar and satisfactory weight gains and longitudinal growth . Within each group , there was no change in plasma mineral concentrations over the course of the study , and there were no differences at each time point between groups . All values were within the normal range for age . No differences in mineral balance were detected between the F and F+LCP groups , with both groups demonstrating comparable intake , net retention , and fecal losses of each mineral . Conclusions Adding a content of LCP blend similar to that of human milk to a preterm formula caused no disturbance in Ca , P , Mg , Zn , or Cu nutritional balance Background In a recent meta- analysis , human milk feeding of low birth-weight ( LBW ) infants was associated with a 5.2 point improvement in IQ tests . However , in the studies in this meta- analysis , feeding regimens were used ( unfortified human milk , term formula ) that no longer represent recommended practice . Objective To compare the growth , in-hospital feeding tolerance , morbidity , and development ( cognitive , motor , visual , and language ) of LBW infants fed different amounts of human milk until term chronologic age ( CA ) with those of LBW infants fed nutrient-enriched formulas from first enteral feeding . Methods The data in this study were collected in a previous r and omized controlled trial assessing the benefit of supplementing nutrient-enriched formulas for LBW infants with arachidonic acid and docosahexaenoic acid .  Infants ( n = 463 , birth weight , 750–1,800 g ) were enrolled from nurseries located in Chile , the United Kingdom , and the United States . If human milk was fed before hospital discharge , it was fortified ( 3,050–3,300 kJ/L , 22–24 kcal/oz ) . As infants were weaned from human milk , they were fed nutrient-enriched formula with or without arachidonic and docosahexaenoic acids ( 3,300 kJ/L before term , 3,050 kJ/L thereafter ) until 12 months CA . Formula fed infants were given nutrient-enriched formula with or without added arachidonic and docosahexaenoic acids ( 3,300 kJ/L to term , 3,050 kJ/L thereafter ) until 12 months CA . For the purpose s of this evaluation , infants were categorized into four mutually exclusive feeding groups : 1 ) predominantly human milk fed until term CA ( PHM-T , n = 43 ) ; 2 ) ≥ 50 % energy from human milk before hospital discharge ( ≥ 50 % HM , n = 98 ) ; 3 ) < 50 % of energy from human milk before hospital discharge ( < 50 % HM , n = 203 ) ; or 4 ) predominantly formula fed until term CA ( PFF-T , n = 119 ) . Results PFF-T infants weighed approximately 500 g more at term CA than did PHM-T infants . This absolute difference persisted until 6 months CA . PFF-T infants were also longer ( 1.0–1.5 cm ) and had larger head circumferences ( 0.3–1.1 cm ) than both PHM-T and ≥ 50 % HM infants at term CA . There was a positive association between duration of human milk feeding and the Bayley Mental Index at 12 months CA ( P = 0.032 full and P = 0.073 reduced , statistical models ) after controlling for the confounding variables of home environment and maternal intelligence . Infants with chronic lung disease fed ≥ 50 % HM until term CA ( n = 22 ) had a mean Bayley Motor Index about 11 points higher at 12 months CA compared with infants PFF-T ( n = 24 , P = 0.033 full model ) . Conclusion Our data suggest that , despite a slower early growth rate , human milk fed LBW infants have development at least comparable to that of infants fed nutrient-enriched formula . Exploratory analysis suggests that some subgroups of  human milk fed LBW infants may have enhanced development , although this needs to be confirmed in future studies OBJECTIVES To compare the early neurological maturation of premature newborns ( PT ) fed breast milk ( BM ) or a formula containing only 18-carbon polyunsaturated fatty acids ( PUFA ) (  A ) or enriched with long chain ( LC ) PUFA ( B ) . METHODS PT enrolled the 2nd day of enteral feeding ( D0 ) were fed BM  ( n = 15 ; 4 dropped out ) or r and omly assigned to A ( n = 11 ; 2 ) or B ( n = 14 ; 1 ) for at least 30 days ( D30 ) . Auditory and visual evoked potentials ( EPs ) and nerve conduction velocity ( NCV ) and plasma and red blood cell ( RBC ) phospholipid composition were determined at D0 and D30 . No difference was found between groups for the D0-D30 changes in EP parameters . The maturation of motor NCV was slower in the B group than in the two other groups . In plasma , the changes were higher in B than in the BM and A groups for linoleic acid ( P < 0.05 ) , in BM versus B group for arachidonic acid ( P < 0.02 ) . In RBC , formula groups displayed higher linoleic acid level than the BM group ( P < 0.05 ) . No difference was found between groups for the changes in arachidonic and docosahexaenoic acids . CONCLUSIONS A balanced supply of n-6 and n-3 PUFA without addition of LC-PUFA allowed an adequate early maturation of the central nerve system . The effects of LC-PUFA on the maturation of NCV remain to be confirmed BACKGROUND The composition of long-chain PUFAs ( LCPUFAs ) in the maternal diet may affect obesity risk in the mother 's offspring . OBJECTIVE We hypothesized that a reduction in the n-6 (omega-6):n-3 ( omega-3 ) LCPUFA ratio in the diet of pregnant women and breastfeeding mothers may prevent expansive adipose tissue growth in their infants during the first year of life . DESIGN In a r and omized controlled trial , 208 healthy pregnant women were r and omly assigned to an intervention ( 1200 mg n-3 LCPUFAs as a supplement per day and a concomitant reduction in arachidonic acid intake ) or a control diet from the 15th wk of pregnancy to 4 mo of lactation . The primary outcome was infant fat mass estimated by skinfold thickness ( SFT ) measurements at 4 body sites at 3 - 5 d , 6 wk , and 4 and 12 mo postpartum . Secondary endpoints included sonographic assessment of abdominal subcutaneous and preperitoneal fat , fat distribution , and child growth . RESULTS Infants did not differ in the sum of their 4 SFTs at ≤1 y of life [ intervention : 24.1 ± 4.4 mm ( n = 85 ) ; control : 24.1 ± 4.1 mm ( n = 80 ) ; mean difference : -0.0 mm ( 95 % CI : -1.3 , 1.3 mm ) ] or in growth . Likewise , longitudinal ultrasonography showed no significant differences in abdominal fat mass or fat distribution . CONCLUSIONS We showed no evidence that supplementation with n-3 fatty acids and instructions to reduce arachidonic acid intake during pregnancy and lactation relevantly affects fat mass in offspring during the first year of life . Prospect i ve long-term studies are needed to explore the efficacy of this dietary approach for primary prevention . This trial was registered at clinical trials.gov as NCT00362089 BACKGROUND Evidence is accumulating that a dietary supply of long-chain polyunsaturated fatty acids ( LC-PUFAs ) enhances the development of attention and efficient information processing in infants . However , it is uncertain whether LC-PUFAs in infancy influence cognitive development in later childhood . OBJECTIVE The objective was to determine the effects of dietary LC-PUFAs in infancy on measures of cognitive function at age 6 y. DESIGN Infants were r and omly assigned to receive formula containing either docosahexaenoic acid and arachidonic acid or no LCPUFAs for a period of 4 mo . A reference breastfed group was also included . In a follow-up conducted at age 6 y , children received assessment s of intelligence quotient ( IQ ) , attention control ( Day-Night Test ) , and speed of processing on the Matching Familiar Figures Test ( MFFT ) . RESULTS At follow-up there were 71 children in the LC-PUFA group , 76 in the control group , and 88 in the breastfed group . The formula groups did not differ on measures of Full-Scale IQ ( LCPUFA mean = 98.0 ; control mean = 100.9 ) or attention control ( LCPUFA mean = 12.7 ; control mean = 12.8 ) . MFFT error scores were the same for both formula groups , but when making correct responses , the LC-PUFA group was significantly faster ( mean = 6.2 s ) than the control group [ mean = 7.8 s ; F(1 , 131 ) = 6.09 , P = 0.015 ] . CONCLUSIONS IQ scores of children who were fed a formula containing either LC-PUFAs or no LC-PUFAs did not differ at age 6 y. However , children who received LC-PUFAs were faster at processing information compared with children who received unsupplemented formula . Variation in the dietary supply of LC-PUFAs in the first months of life may have long-term consequences for the development of some cognitive functions in later childhood OBJECTIVE To examine whether the timing of introduction of the allergenic foods cow 's milk , hen 's egg , peanuts , tree nuts , soy , and gluten is associated with  eczema and wheezing in children 4 years of age or younger . DESIGN Population -based prospect i ve cohort study from fetal life until young adulthood . SETTING Rotterdam , the Netherl and s , from April 2002 through January 2006 . PARTICIPANTS A total of 6905 preschool children participating in the Generation R study . MAIN EXPOSURE Timing of introduction of cow 's milk , hen 's egg , peanuts , tree nuts , soy , and gluten collected by question naires at 6 and 12 months of age . MAIN OUTCOME MEASURES Information on the outcomes eczema and wheezing were obtained by questions from the age-adapted version of the " International Study of Asthma and Allergies in Childhood " core question naire and question naire data on parentally reported physician diagnosis for eczema . RESULTS Of 6905 children ,  wheezing was reported in 31 % at age 2 years and in 14 % at ages 3 and 4 years . Eczema was reported in 38 % , 20 % , and 18 % of children at the ages of 2 , 3 , and 4 years , respectively . The introduction of cow 's milk , hen 's egg , peanuts , tree nuts , soy , and gluten before the age of 6 months was not significantly associated with eczema or wheezing at any age after adjustment for potential confounders ( P > .10 for all comparisons ) . The results did not alter after stratification according to the child 's history of cow 's milk allergy and parental history of atopy . CONCLUSION This study does not support the recommendation for delayed introduction of allergenic foods after age 6 months for the prevention of eczema and wheezing OBJECTIVE To determine the influence of alpha-linolenic acid ( ALA ; 18 : 3omega3 ) intake and , hence , the influence of plasma and /or erythrocyte phospholipid content of docosahexaenoic acid ( DHA ; 22 : 6omega3 ) during early infancy on neurodevelopmental outcome of term infants . METHODS The Bayley Scales of Infant Development ( second edition ) , the Clinical Adaptive Test/ Clinical Linguistic and Auditory Milestone Scale ( CAT/CLAMS ) and the Gross Motor Scale of the Revised Gesell Developmental Inventory were administered at a mean age of 12.26 + /- 0.94 months to 44 normal term infants enrolled in a study evaluating the effects of infant formulas differing only in ALA content ( 0.4 , 1.0 , 1.7 and 3.2 % of total fatty acids ) . RESULTS As reported previously [ Jensen et al. , Lipids 13 ( 1996 ) 107 ; J. Pediatr . 131 ( 1997 ) 200 ] , the group fed the formula with the lowest ALA content had the lowest mean plasma and erythrocyte phospholipid DHA contents at 4 months of age . This group also had the lowest mean score on every neurodevelopmental measure . The difference in mean gross motor developmental quotient of this group versus the group fed the formula with 1.0 % ALA but not of the other groups was statistically significant ( P < 0.05 ) . Across the groups , motor indices correlated positively with each other and with the plasma phospholipid DHA content at 4 months of age ( P=0.02 - 0.03 ) . The CLAMS developmental quotient correlated with the erythrocyte phospholipid content of 20 : 5omega3 ( P < 0.01 ) but not with DHA . CONCLUSIONS These statistically significant correlations suggest that the omega3 fatty acid status during early infancy may be important with respect to neurodevelopmental status at 1 year of age and highlight the need for further studies of this possibility OBJECTIVE To evaluate the effects of dietary intake of the long-chain polyunsaturated fatty acids , arachidonic acid ( AA ) , and docosahexaenoic acid ( DHA ) on multiple indices of infant growth and development . DESIGN A double-masked , r and omized , parallel trial was conducted with term infants fed formulas with or without AA+DHA for 1 year ( N = 239 ) . Reference groups of breastfed infants ( N = 165 ) weaned to formulas with and without AA+DHA  were also studied . Infants in the formula groups were r and omized at < /=9 days of age to a control formula with no AA or DHA ( n = 77 ) or 1 of 2 otherwise identical formulas containing AA+DHA ( AA , 0.46 % and DHA , 0.14 % of total fatty acids ) from either egg-derived triglyceride ( egg-DTG [ n=80 ] ) or fish oil and fungal oil ( fish/fungal [ n = 82 ] ) at levels similar to the average in breast milk sample s as measured in the reference group . All formulas contained 50 % of energy from fat with the essential dietary fatty acids , linoleic acid ( 20 % fatty acids ) and alpha-linolenic acid ( 2 % fatty acids ) . The main study outcomes were AA and DHA levels in plasma and red blood cells , and multiple measures of infant development at multiple ages from birth to 14 months : growth , visual acuity , information processing , general development , language , and temperament . RESULTS  AA and DHA levels in plasma and red cells were higher in AA+DHA-supplemented groups than in the control formula group and comparable to those in reference groups . No developmental test results distinguished these groups . Expected differences in family demographics associated with breastfeeding were found , but no advantages to breastfeeding on any of the developmental outcome demonstrated . CONCLUSIONS These findings do not support adding AA+DHA to formulas containing 10 % energy as linoleic acid and 1 % energy as alpha-linolenic acid to enhance growth , visual acuity , information processing , general development , language , or temperament in healthy , term infants during the first 14 months after birth.infant development , breast feeding , infant formula , long-chain polyunsaturated fatty acids , docosahexaenoic acid Objective : To evaluate the growth , feeding and health of babies fed a novel infant formula milk  with added long chain polyunsaturated fatty acids ( LCPs ) produced from single-cell sources , at concentrations similar to those found in mature breast milk . Design : R and omized double-blind control trial . Subjects : One-hundred and forty healthy , full-term infants of birth weight 2.5–4.5 kg born at the Maternity Department , East Glamorgan General Hospital , Wales , whose mothers had already decided to bottle feed . Interventions : Subjects were r and omized to two groups ; one ( control group ) to receive a st and ard formula milk and the other to receive the trial milk with added LCPs . Milks were supplied in a double-blind fashion and given for the first 12 weeks of life . Anthropometric measurements were made at recruitment , 3 months , 6 months and 1 y. Feeding diaries were completed at 6 weeks and 3 months , and a parental record was kept of any ill health suffered by the subjects during the first year of life . Results : Of 140 infants recruited , 31 did not complete the protocol . Small but statistically significant differences were found only in the subscapular skinfold thickness at 6 weeks and 3 months , that in the trial group being slightly higher , but unlikely to be of any clinical importance . No differences were found in the feeding patterns of the infants in the two groups . Stool patterns were similar , as were the frequencies of illness and allergy . Conclusions : This study supports the view that LCPs from single-cell sources do not have detrimental effects on the growth , feeding and general health of infants . Sponsorship : The research nurse and equipment used in this study were funded by Cow & Gate Nutricia ( UK ) Ltd . European Journal of Clinical Nutrition ( 2000 ) 54 , BACKGROUND : Docosahexaenoic acid ( DHA ) has been associated with downregulation of inflammatory responses . OBJECTIVE : To report the effect of DHA supplementation on  long-term atopic and respiratory outcomes in preterm infants . METHODS : This study is a multicenter , r and omized controlled trial comparing the outcomes for preterm infants <33 weeks ' gestation who consumed expressed breast milk from mothers taking either tuna oil ( high-DHA diet ) or soy oil ( st and ard-DHA ) capsules .  Data collected included incidence of bronchopulmonary dysplasia ( BPD ) and parental reporting of atopic conditions over the first 18 months of life . RESULTS : Six hundred fifty-seven infants were enrolled ( 322 to high-DHA diet , 335 to st and ard ) , and 93.5 % completed the 18-month follow-up . There was a reduction in BPD in boys ( relative risk [ RR ] : 0.67 [ 95 % confidence interval ( CI ) : 0.47–0.96 ] ; P = .03 ) and in all infants with a birth weight of < 1250 g ( RR : 0.75 [ 95 % CI : 0.57–0.98 ] ; P = .04 ) . There was no effect on duration of respiratory support , admission length , or home oxygen requirement . There was a reduction in reported hay fever in all infants in the high-DHA group at either 12 or 18 months ( RR : 0.41 [ 95 % CI : 0.18–0.91 ] ; P = .03 ) and at either 12 or 18 months in boys ( RR : 0.15 [ 0.03–0.64 ] ; P = .01 ) . There was no effect on asthma , eczema , or food allergy . CONCLUSIONS : DHA supplementation for infants of <33 weeks ' gestation reduced the incidence of BPD in boys and in all infants with a birth weight of < 1250 g and reduced the incidence of reported hay fever in boys at either 12 or 18 months Objective . To determine whether dietary long-chain polyunsaturated fatty acids ( LCPUFA ) , such as docosahexaenoic acid ( DHA ) and arachidonic acid , affect visual evoked potential ( VEP ) acuity of formula-fed infants , relative to breastfed infants . A secondary objective was to assess the effect of LCPUFA on Bayley 's mental developmental index ( MDI ) and psychomotor developmental index ( PDI ) . Methods . Formula-fed infants were r and omly allocated , in a double-blind manner , to either a placebo ( no LCPUFA;n = 21 ) , DHA supplemented ( n = 23 ) , or DHA+arachidonic acid supplemented formula ( n = 24 ) . Infants were fed their assigned formula from the first week of life until 1 year of age . A parallel reference group of breastfed infants was recruited and followed ( n = 46 ) . Infant VEP acuity was assessed at 16 and 34 weeks , and Bayley 's MDI and PDI were assessed at 1 and 2 years of age . Results . There were no differences among the r and omized formula groups for VEP acuity at either 16 or 34 weeks of age . Breastfed infants had better VEP acuity at 34 weeks of age , but not at 16 weeks , compared with all formula-fed infants . Bayley 's MDI and PDI were similar in the 3 formula-fed groups at 1 and 2 years . Breastfed infants had higher MDI scores than formula-fed infants at 2 years of age even after adjusting for environmental variables . Conclusions . LCPUFA supplementation did not influence VEP acuity development in these well-nourished , formula-fed infants BACKGROUND The optimal method for conducting omega (n-)3 polyunsaturated fatty acid ( PUFA ) supplementation trials in children is unknown . AIM To assess the impact of n-3 and n-6 PUFA intake from the background diet on plasma levels of n-3 and n-6 PUFA in children aged 0 - 3 years , with and without n-3 supplementation . METHODS Subjects were r and omised antenatally to receive either n-3 PUFA supplements and low n-6 PUFA cooking oils and spreads or a control intervention , design ed to maintain usual fatty acid intake . Dietary intake was assessed at 18 months by 3-day weighed food record and at 3 years by food frequency question naire . Plasma phospholipids were measured at both time points . Associations were tested by regression . RESULTS N-3 PUFA intake from background diet did not significantly affect plasma n-3 levels . In contrast , n-6 PUFA intake in background diet was positively related to plasma n-6 levels in both study groups . In addition , n-6 PUFA intake from diet was negatively associated with plasma n-3 levels at 18 months and 3 years ( -0.16%/g n-6 intake , 95%CI -0.29 to -0.03 and -0.05%/g n-6 intake , 95%CI -0.09 to -0.01 , respectively ) in the active group , but not in the control group . CONCLUSION Interventions intending to increase plasma n-3 PUFA in children by n-3 supplementation should also minimise n-6 PUFA intake in the background diet ABSTRACT . : Very low birth weight infants demonstrate significant reductions in red blood cell membrane docosahexaenoic acid ( DHA , 22:6n-3 ) following delivery unless fed human milk . The purpose of the present study was to determine if a dietary source of DHA ( MaxEPA , R. P. Scherer Corporation , Troy , MI ) could prevent the decline in red blood cell phospholipid DHA in very low birth weight infants whose enteral feeding consisted of a preterm formula without DHA . Longitudinal data were obtained on membrane phospholipid DHA in both un supplemented and MaxEPA-supplemented infants by a combination of thin layer and gas chromatography . These infants ( n = 39 ) ranged in age from 10 to 53 days at enrollment ( 0 time ) . At enrollment , phospholipid DHA and arachidonic acid ( 20:4n-6 ) were inversely correlated with age in days . During the study , mean red blood cell phospholipid DHA declined without supplementary DHA as determined by biweekly measurement , but infants supplemented with MaxEPA maintained the same weight percent of phospholipid ( phosphatidylethanolanine , phosphatidylcholine , and phospharidylserine ) DHA as at enrollment . The pattern of red blood cell phospholipid fatty acids in supplemented infants was similar to that reported for preterm infants fed human milk It is recommended in Europe that low birthweight infants ( LBWI ) who do not receive human milk ( HM )  should be fed formula enriched with long-chain polyunsaturated fatty acids ( LCP ) . The question has been raised whether LCP supplementation to LBWI formula may have adverse effects on antioxidant status in the recipient infant , particularly on the major lipid-soluble antioxidant vitamin E ( alpha-tocopherol , alpha-toc . ) . We studied alpha-toc . status in LBWI fed HM ( n = 15 ) or formula either without ( f , n = 8) or with LCP derived from egg lipids and fish oil ( LCP-F , n = 9 ) on days 4 and 21 of life . Plasma alpha-toc . concentrations increased significantly in infants fed HM [ d. 4 : 4.53 ( 1.31 ) , d. 21 : 6.35 ( 2.18 ) , mg/l , mean ( SD ) , p < 0.01 ] , whereas there were no changes in infants fed F of LCP-F. Plasma alpha-toc./total lipid ratios and erythrocyte membrane alpha-toc . concentrations did not change significantly between days 4 and 21 in either group . In contrast , erythrocyte membrane alpha-toc./total lipid ratios decreased significantly in infants fed LCP-F [ 0.42 ( 0.13 ) vs. 0.31 ( 0.06 ) , p < 0.05 ] , whereas no change occurred in the other two groups . We conclude that an LCP supplementation based on egg lipids and fish oil to formula may induce an early postnatal decrease of alpha-toc./total lipid ratios in erythrocyte membranes of LBWI . Therefore , the effects of different forms of LCP supplementation to infant formula on infantile vitamin E status should be carefully evaluated Probiotics and long-chain PUFA ( LC-PUFA ) may be beneficial supplements for infants who are not breast-fed . The aim of the present study is to evaluate the safety of an infant formula containing the LC-PUFA DHA and arachidonic acid ( AA ) and the probiotic Bifidobacterium lactis by comparing the growth rate of infants fed the supplemented and unsupplemented formulas . One hundred and forty-two healthy , term infants were enrolled in a single-centre , r and omised , double-blind , controlled , parallel-group trial , and allocated to receive either st and ard or probiotic and LC-PUFA-containing experimental formulas . The infants were fed with their assigned formulas for 7 months . The primary outcome ( weight gain ) and the secondary outcomes ( length , head circumference and formula tolerance ) were measured throughout the study . LC-PUFA status was assessed at 4 months of age and immune response to childhood vaccines was measured at 7 months of age . There was no significant difference in growth between the two groups . The 90 % CI for the difference in mean weight gain was - 0.08 , 3.1 g in the intention-to-treat population and 0.1 - 3.8 g in the per protocol population , which lay within the predefined boundaries of equivalence , - 3.9 - 3.9 . There were no significant differences in mean length and head circumference . DHA and AA concentrations were higher in infants in the experimental formula group compared with the control formula group . No influence of the supplements on the response to vaccines was observed . Growth characteristics of term infants fed the starter formula containing a probiotic and LC-PUFA were similar to st and ard formula-fed infants Objectives : A r and omized , double-blind , prospect i ve trial assessed effects of different formula levels of polyunsaturated fatty acids on blood phospholipid docosahexaenoic ( DHA ; 22:6&ohgr;3 ) and arachidonic acids ( ARA ; 20:4&ohgr;6 ) in term infants at 120 days of age . Methods : Healthy , formula-fed term infants ( n = 78 ) were r and omized to 1 ) routine milk-based formula with 8 mg DHA , 21 mg ARA , 110 mg & agr;-linolenic ( ALA ; 18:3&ohgr;3 ) , and 1,000 mg linoleic acids ( LA ; 18:2&ohgr;6 ) per 100 kcal ( Lower-long-chain polyunsaturated fatty acids [ LCPUFA ] ; n = 39 ) or 2 ) routine milk-based formula  with 17 mg DHA , 34 mg ARA , 85 mg ALA , and 860 mg LA per 100 kcal ( Higher-LCPUFA ; n = 39 ) . Fatty acid methyl esters from red blood cell ( RBC ) and plasma phospholipid fractions were assessed using capillary column gas chromatography . Results : Compared with infants fed Lower-LCPUFA formula , the Higher-LCPUFA group had significantly greater percentages of fatty acids as DHA in RBC phosphatidylethanolamine ( PE ) , RBC phosphatidylcholine ( PC ) , total RBC , and plasma phospholipids ( P < 0.001 ) . Infants fed Lower-LCPUFA formula had higher percentages of precursor & ohgr;6 fatty acids in the desaturation/elongation pathway but lower percentages of ARA ( RBC PE , RBC PC , and plasma phospholipid , P < 0.001 ; total RBC , P = 0.017 ) compared with the Higher-LCPUFA group . Conclusions : Greater amounts of dietary ALA do not produce as great an increase in DHA in blood lipids as preformed dietary DHA . Infants fed DHA at levels similar to human milk had significantly greater percentage of DHAat 120 days of age compared with the Lower-LCPUFA group despite higher precursor levels of ALA A milk formula ( Prematil‐LCP ) containing long‐chain polyunsaturated fatty acids ( LCP ) and with a fatty acid profile closely resembling breast milk has recently been introduced for preterm infants . A double‐blind r and omized controlled trial was performed comparing fatty acid absorption from Prematil‐LCP ( n= 10 ) and st and ard Prematil ( n= 10 ) . Formula‐fed preterm infants underwent 3 d fat balances ( once full enteral feeds were established ) along with a parallel human milk fed group ( n= 11 ) . Plasma sample s were taken on the last day . Median total fat excretion ( absorption , % ) was 2.34 g kg ( 82.0 ) , 2.64 g kg ( 82.9 ) and 1.65 g kg ( 87.8 ) with Prematil , Prematil‐LCP and human milk feeding , respectively . This reflected differences in the excretion and absorption of long‐chain saturated fatty acids . All groups excreted detectable LCP . LCP disappearance was higher in infants fed human milk than in those fed Prematil‐LCP , particularly for n‐6 LCP ( p < 0:01 ) . Nevertheless , excreted LCP equated to < 30 % dietary intake , with Prematil‐LCP feeding . Plasma lipid fatty acid composition reflected differences in dietary LCP intake Early nutrition may program obesity and cardiovascular risk later in life , and one of the potential agents is ( n-3 ) long-chain PUFA ( LCPUFA ) . In this study , our objective was to examine whether fish oil ( FO ) supplementation during lactation affects  blood pressure and body composition of children . Danish mothers ( n = 122 ) were r and omized to FO [ 1.5 g/d ( n-3 ) LCPUFA ] or olive oil ( OO ) supplementations during the first 4 mo of lactation . The trial also included a high-fish intake reference group ( n = 53 ) . Ninety-eight children were followed-up with blood pressure and anthropometry measurements at 7 y. Diet and physical activity level ( PAL ) were assessed by 4-d weighed dietary records and ActiReg . The PAL value was 4 % lower ( P = 0.048 ) and energy intake ( EI ) of the boys was 1.1 + /- 0.4 MJ/d higher ( P = 0.014 ) in the FO group than in the OO group . Starch intake was 15 + /- 6 g/d higher ( P = 0.012 ) in the FO group , but there were no other differences in diet . Body composition did not differ between the r and omized groups with or without adjustment for starch intake , EI , and PAL . FO boys had 6 mm Hg higher diastolic and mean arterial blood pressure than OO boys ( P < 0.01 ) , but girls did not differ . Within the r and omized groups , blood pressure was not correlated with maternal RBC ( n-3 ) LCPUFA after the intervention , but PAL values were ( r = -0.277 ; P = 0.038 ) . We previously found higher BMI at 2.5 y in the FO group , but the difference did not persist . The differences in blood pressure , EI , and PAL , particularly among boys , suggest that early ( n-3 ) LCPUFA intake may have adverse effects , which should be investigated in future studies Abstract Recent data indicate that supplementation of infant formula with ω-3 and ω-6 long-chain polyunsaturated fatty acids might offer developmental benefits for full term infants . We investigated biochemical consequences of feeding formula supplemented with egg lipids to provide long-chain polyunsaturated fatty acids and compared triglyceride , cholesterol , lipoprotein cholesterol ( HDL2-cholesterol , HDL3-cholesterol , non-HDL-cholesterol ) and apolipoprotein A-I , A-II and B concentrations in full term infants fed either conventional formula ( n = 10 ) or a formula supplemented with ω-3 and ω-6 long-chain polyunsaturated fatty acids and cholesterol  in amounts similar to those found in mature human milk ( n = 12 ) . At the age of 5 days , cholesterol , non-HDL-cholesterol and triglyceride concentrations were significantly higher in infants fed supplemented than in those receiving conventional formula . At the age of 30 days , triglyceride concentrations were significantly higher with supplemented than with conventional formula . Thereafter throughout the study , no significant differences were seen between the two groups . Conclusion Full term infants  fed formula supplemented with ω-3 and ω-6 long-chain polyunsaturated fatty acids and cholesterol showed significantly higher plasma cholesterol and triglyceride concentrations than infants receiving conventional formula on day 5 and on days 5 and 30 , respectively . Thereafter no appreciable effect of diet on plasma phospholipid , triglyceride , cholesterol , lipoprotein cholesterol and apolipoprotein concentrations were seen Objective : The aim of the present study was to determine whether an increased supply of energy , protein , essential fatty acids , and vitamin A reduces postnatal growth failure in very-low-birth-weight infants . Methods : Fifty infants with birth weight < 1500 g were r and omized to an intervention ( n = 24 ) or a control ( n = 26 ) feeding protocol within 24 hours after birth . Forty-four infants were included in the final analysis . This study was discontinued because of an increased occurrence of septicemia in the intervention group . Results : The intervention group had a lower mean birth weight ( P = 0.03 ) and a higher proportion of infants small-for-gestational age  ( P = 0.04 ) than the control group . Other baseline characteristics were similar . The median ( interquartile range ) energy and protein supplies during the first 4 weeks of life were higher in the intervention group : 139 ( 128–145 ) versus 126 ( 121–128 ) kcal · kg−1 · day−1 ( P < 0.001 ) and 4.0 ( 3.9–4.2 ) versus 3.2 ( 3.1–3.3 ) g · kg−1 · day−1 ( P < 0.001 ) . The infants in the intervention group regained birth weight faster ( P = 0.001 ) and maintained their z scores for weight and head circumference from birth to 36 weeks ’ postmenstrual age ( both P < 0.001 ) . The median ( interquartile range ) growth velocity was 17.4 ( 16.3–18.6 ) g · kg−1 · day−1 in the intervention group and 13.8 ( 13.2–15.5 ) g · kg−1 · day−1 in the control group ( P < 0.001 ) . In line with the improved growth in the intervention group , the proportion of growth-restricted infants was 11 of 23 both at birth and at 36 weeks ’ postmenstrual age , whereas this proportion increased among the controls from 4 of 21 to 13 of 21 ( P = 0.04 ) . Conclusions : Enhanced supply of energy , protein , essential fatty acids , and vitamin A caused postnatal growth along the birth percentiles for both weight and head circumference Objective . To evaluate the developmental outcomes of children who participated in an augmented r and omized clinical trial of supplementing a st and ard infant formula with long-chain polyunsaturated fatty acids . Design . R and omized clinical trial , augmented with a nonr and omized human milk comparison group . There were three r and omized formula groups : st and ard formula , st and ard formula containing docosahexaenoic acid ( DHA ) , and st and ard formula containing DHA and arachidonic acid . Setting . Three clinical sites serving diverse population s : Kansas City , MO ; Portl and , OR ; and Seattle , WA . Participants . A total of 274 healthy full-term infants were enrolled in the infant-feeding protocol ; of these , 197 ( 72 % ) participated in assessment s of developmental outcome . Formula Supplements . In the r and omized trial , one group received a st and ard formula , another group received a formula that had been supplemented with DHA from fish oil , and a third group received a formula supplemented with both DHA and arachidonic acid from an egg phospholipid . Outcome Measures . Mental and Motor Scales of the Bayley Scales of Infant Development at 12 months of age ; vocabulary and gesture communication scores from the MacArthur Communicative Development Inventories at 14 months of age . Results . There were no statistically significant differences for either the Bayley Mental Scale or the Bayley Motor Scale , neither when the analysis was restricted to the three r and omized formula groups nor when the analysis included all four groups . However , the DHA formula group had significantly lower scores on two of the MacArthur scales : the DHA group scored lower than the nonr and omized human milk comparison group on the Vocabulary Comprehension Scale , and the DHA group scored lower than the r and omized control formula group on the Vocabulary Production Scale . Moreover , additional analyses both in the formula groups and in the human milk comparison group found significant negative correlations between DHA levels and vocabulary outcomes . Conclusion . We believe that additional research should be undertaken before the introduction of these supplements into st and ard infant formulas DHA and arachidonic acid ( AA ) are important for neurodevelopment . A traditional neonatal neurological examination and the evaluation of general movement quality are sensitive techniques for assessing neurodevelopment in young infants . Mildly abnormal general movements at 3 months have been associated with a non-optimal current brain condition . We investigated whether supplementation of DHA during pregnancy and lactation influences the infant 's brain development and whether additional AA modulates this effect . Healthy women were r and omly assigned to DHA ( 220 mg/d , n 42 ) , DHA+AA ( 220 mg each/d , n 41 ) or control ( n 36 ) , from about week 17 ( range 14 - 20 weeks ) of pregnancy until 12 weeks postpartum . The control and the DHA+AA groups had approximately comparable dietary DHA/AA ratios . The st and ardised neonatal neurological examination was carried out at 2 weeks . General movement quality was assessed at 2 and 12 weeks . Neither DHA alone nor DHA+AA influenced outcomes in the traditional examination . General movement quality of infants in the DHA group was lower than that of infants in the other two groups , especially at 12 weeks : 61 % of the infants in the DHA group showed mildly abnormal general movements compared with 31 % in the control group ( P = 0.008 ) and 34 % in the DHA+AA group ( P = 0.015 ) . We conclude that general movement quality at 12 weeks is sensitive to the maternal dietary DHA/AA balance OBJECTIVES A r and omized , masked , controlled trial was conducted to assess effects of supplementing premature infant formulas with oils containing the long-chain polyunsaturated fatty acids , arachidonic acid ( AA ; 20:4 n6 ) , and docosahexaenoic acid ( DHA ; 22:6 n3 ) on growth , visual acuity , and multiple indices of development . METHODS Infants ( N = 470 ) with birth weights 750 to 1800 g were assigned within 72 hours of the first enteral feeding to 1 of 3 formula groups with or without long-chain polyunsaturated fatty acids : 1 ) control ( N = 144 ) , 2 ) AA+DHA from fish/fungal oil ( N = 140 ) , and 3 ) AA+DHA from egg-derived triglyceride (egg-TG)/fish oil ( N = 143 ) .  Infants were fed human milk and /or Similac Special Care with or without 0.42 % AA and 0.26 % DHA to term corrected age ( CA ) , then fed human milk or NeoSure with or without 0.42 % AA and 0.16 % DHA to 12 months ' CA . Infants fed exclusively human milk to term CA ( EHM-T ; N = 43 ) served as a reference . RESULTS Visual acuity measured by acuity cards at 2 , 4 , and 6 months ' CA was not different among groups . Visual acuity measured by swept-parameter visual-evoked potentials in a subgroup from 3 sites ( 45 control , 50 AA+DHA [ fish/fungal ] ; 39 AA+DHA [ egg-TG/fish ] ; and 23 EHM-T ) was better in both the AA+DHA ( fish/fungal ; least square [ LS ] means [ cycle/degree ] + /- st and ard error [ SE ; octaves ] 11.4 + /- 0.1 ) and AA+DHA ( egg-TG/fish ; 12.5 + /- 0.1 ) than control ( 8.4 + /- 0.1 ) and closer to that of the EHM-T group ( 16.0 + /- 0.2 ) at 6 months ' CA . Visual acuity improved from 4 to 6 months ' CA in all but the control group . Scores on the Fagan test of novelty preference were greater in AA+DHA ( egg-TG/fish ; LS means + /- SE , 59.4 + /- 7.7 ) than AA+DHA ( fish/fungal ; 57.0 + /- 7.5 ) and control ( 57.5 + /- 7.4 ) at 6 months ' CA , but not at 9 months ' CA . There were no differences in the Bayley Mental Development Index at 12 months ' CA . However , the Bayley motor development index was higher for AA+DHA ( fish/fungal ; LS means + /- SE , 90.6 + /- 4.4 ) than control ( 81.8 + /- 4.3 ) for infants < /=1250 g. When Spanish-speaking infants and twins were excluded from the analyses , the MacArthur Communicative Development Inventory revealed that control infants ( LS means + /- SE , 94.1 + /- 2.9 ) had lower vocabulary comprehension at 14 months ' CA than AA+DHA ( fish/fungal ) infants ( 100.6 + /- 2.9 ) or AA+DHA ( egg-TG/fish ) infants ( 102.2 + /- 2.8 ) . There were no consistent differences in weight , length , head circumference , or anthropometric gains . CONCLUSION These results showed a benefit of supplementing formulas for premature infants with AA and DHA from either a fish/fungal or an egg-TG/fish source from the time of first enteral feeding to 12 months ' CA BACKGROUND The range of human milk docosahexaenoic acid ( DHA ) concentrations worldwide is much broader than the range explored in r and omized clinical trials to date . OBJECTIVE The primary objective was to determine the effect of 4 amounts of DHA supplementation on the visual acuity of formula-fed infants at 12 mo of age . Secondary objectives were to evaluate visual acuity maturation , red blood cell fatty acids , tolerance , anthropometric measures , and adverse events . DESIGN This double-masked , r and omized trial was conducted at 2 sites ( Dallas and Kansas City ) . Three hundred forty-three healthy , term , formula-fed infants were enrolled at 1 - 9 d of age and were r and omly assigned to be fed 1 of the following 4 infant formulas containing equivalent nutrient amounts , except for long-chain polyunsaturated fatty acids : control ( 0 % DHA ) , 0.32 % DHA , 0.64 % DHA , or 0.96 % DHA ; DHA-supplemented formulas also provided 0.64 % arachidonic acid .  Visual acuity was measured by visual evoked potentials in 244 infants who completed the 12-mo primary outcome examination . RESULTS Infants fed control formula had significantly poorer visual evoked potential visual acuity at 12 mo of age than did infants who received any of the DHA-supplemented formulas ( P < 0.001 ) . There were no significant differences in visual evoked potential visual acuity between the 3 amounts of DHA supplementation for either site at any age tested . CONCLUSIONS DHA supplementation of infant formula at 0.32 % of total fatty acids improves visual acuity . Higher amounts of DHA supplementation were not associated with additional improvement of visual acuity . This trial was registered at clinical trials.gov as NCT00753818 Abstract Objective : To determine whether supplementation of infant formula milk with long chain polyunsaturated fatty acids ( LCPUFAs ) influences blood pressure  in later childhood . Design : Follow up of a multicentre , r and omised controlled trial . Setting : Four study centres in Europe . Participants : 147 formula fed children , with a reference group of 88 breastfed children . Intervention : In the original trial newborn infants were r and omised to be fed with a formula supplemented with LCPUFAs ( n=111 ) or a formula without LCPUFAs but otherwise nutritionally similar ( n=126 ) . In the present follow up study the blood pressure of the children at age 6 years was measured . Main outcome measures : Systolic , diastolic , and mean blood pressure . Results : 71 children in the  LCPUFA supplementation group ( 64 % of the original group ) and 76 children in the non-supplementation group ( 60 % ) were enrolled into the follow up study . The LCPUFA group had significantly lower mean blood pressure ( mean difference −3.0 mm Hg ( 95 % confidence interval −5.4 mm Hg to −0.5 mm Hg ) ) and diastolic blood pressure ( mean difference −3.6 mm Hg ( −6.5 mm Hg to −0.6 mm Hg ) ) than the non-supplementation group . The diastolic pressure of the breastfed children ( n=88 ( 63 % ) ) was significantly lower than that of the non-supplemented formula group but did not differ from the LCPUFA formula group . Conclusions : Dietary supplementation with LCPUFAs during infancy is associated with lower blood pressure in later childhood . Blood pressure tends to track from childhood into adult life , so early exposure to dietary LCPUFAs may reduce cardiovascular risk in adulthood . What is already known on this topic Breast milk contains long chain polyunsaturated fatty acids , and breastfed children have lower blood pressure than children fed with formula milk Blood pressure differences in childhood are known to carry through into adulthood Dietary omega 3 fatty acid supplementation can lower blood pressure in adults with hypertension What this paper adds Supplementation with long chain polyunsaturated fatty acids in infancy results in lower blood pressure later in Docosahexaenoic acid ( DHA ) is important for infant development . The DHA transfer from maternal diet into human milk has not been investigated in detail . We studied the effects of DHA supplementation on the fatty acid composition of human milk and the secretion of dietary (13)C-labeled fatty acids , including DHA , into human milk . Ten lactating women were r and omized to consume , from 4 to 6 weeks postpartum , an oil rich in DHA ( DHASCO , 200 mg of DHA/day ) ( n = 5 ) or a placebo oil ( n = 5 ) . Dietary intakes were followed by 7-day protocol s. On study day 14 a single dose of [U-(13)C]DHASCO was given orally , milk sample s were collected over 48 h , and milk production was recorded . Milk fatty acid composition was determined by gas-liquid chromatography and isotopic enrichment was determined by gas chromatography- combustion-isotope ratio mass spectrometry ( GC-C-IRMS ) . Milk DHA content did not differ between the supplemented and placebo group at study entry ( 0.29 vs. 0.28 wt% , median ) . After 2 weeks of supplementation the milk DHA content was almost 2-fold higher in the supplemented versus placebo group ( 0.37 vs. 0.21 wt% , P = 0.003 ) . Cumulative recovery of [(13)C]palmitic , [(13)C]oleic , and [(13)C]docosahexaenoic acids in human milk at 48 h was similar between supplemented and placebo groups ( palmitic acid 7.40 vs. 8 . 14 % , oleic acid 9.14 vs. 9.97 % , and docosahexaenoic acid 9.09 vs. 8 . 03 % of dose , respectively ) . Notable lower recovery was observed for [(13)C]myristic acid in both the supplemented and placebo groups , 0 . 62 versus 0.77 % of dose . Dietary DHA supplementation increases the DHA content in human milk . DHA transfer from the diet into human milk is comparable to palmitic and oleic acid transfer BACKGROUND Two factors thought to influence the risk of asthma are the promoting effect of sensitization to house dust mites and the preventive effect of increased omega-3 fatty acids . Although house dust mite allergen avoidance has been used as a preventive strategy in several trials , the effect of omega-3 fatty acid supplementation in the primary prevention of asthma and allergic disease is not known . OBJECTIVE To measure the effects of dietary supplementation with omega-3 fatty acids and house dust mite allergen avoidance in children with a family history of asthma . METHODS A total of 616 children at high risk of asthma were enrolled antenatally in a r and omized controlled trial , and 526 children remained in the trial at age 3 years . The outcomes were symptoms of allergic disease and allergen sensitization . RESULTS There was a significant 10.0 % ( 95 % CI , 3.7 - 16.4 ) reduction in the prevalence of cough in atopic children in the active diet group ( P=.003 ; number needed to treat , 10 ) but a negligible 1.1 % ( 95 % CI , -7.1 to 9.5 ) reduction cough among nonatopic children . There was a 7.2 % ( 95 % CI , 10.11 - 14.3 ) reduction in sensitization to house dust mite in the active allergen avoidance group ( P=.05 ; number needed to treat , 14 ) . No significant differences in wheeze were found with either intervention . CONCLUSION These results suggest that our interventions , design ed to be used in simple public health campaigns , may have a role in preventing the development of allergic sensitization and airways disease in early childhood . This offers the prospect of reducing allergic disease in later life OBJECTIVE To determine whether a formula containing n-6 and n-3 long-chain polyunsaturated fatty acids ( LCP ) from purified phospholipids increases the content of 20:4n-6 and 22:6n-3 of plasma lipids and modifies the plasma antioxidant capacity in low-birth-weight infants . STUDY DESIGN Seventeen infants were fed a conventional formula for low birth-weight infants ( F ) , and 17 a formula containing n-6 and n-3 LCP from purified pig-brain phospholipids ( LCP-F ) .  Fourteen infants receiving human milk from a human milk bank were used as a reference ( HM ) . Growth index were measured and blood sample s were taken at entry and after 15 days and 30 days of feeding . RESULTS In infants fed LCP-F the levels of 22:6n-3 in total plasma lipids and in plasma phospholipids and triglycerides were higher than in infants fed F and closer to the levels of HM group throughout the study . Docosahexaenoic acid concentration in total plasma lipids was 3.46+/-0.19 mg/dl in infants fed LCP-F and 2.08+/-0.20 in infants fed F after 15 days of feeding ( P<0.001 ) , and 3.83+/-0.30 and 2.15+/-0.20 in infants fed LCP-F and F respectively , after 30 days of feeding ( P<0.001 ) . The concentration of 20:4n-6 in the LCP-F was significantly higher than in the F group at 15 and 30 days of feeding . Plasma antioxidant capacity did not differ significantly between the study groups . CONCLUSION Feeding low birth-weight infants a formula containing LCP phospholipids results in an increase of n-3 and n-6 LCP in plasma towards that of infants fed human milk The evidence of the effect of the age at introduction of new foods during infancy on the development of  asthma and allergic rhinitis  is inconsistent and scarce . We set out to study these associations . A prospect i ve birth cohort of infants with increased HLA-DQB1-conferred risk for type 1 diabetes was recruited in 1996 - 2000 . The families completed at home a record on the age at introduction of new foods .  Persistent asthma and allergic rhinitis were assessed at the age of 5 years with an International Study of Asthma and Allergies in Childhood-type question naire . The Cox proportional hazards regression analyses were adjusted for parental asthma and allergic diseases , and several perinatal and sociodemographical factors . Out of the 1293 children , 77 ( 6.0 % ) developed  persistent asthma ; and out of the 1288 children , 185 ( 14.4 % ) developed allergic rhinitis by the age of 5 years . Early age at introduction of oats was associated with a reduced risk of persistent asthma ( hazard ratio ( HR ; 95 % CI ) for the first and mid-tertiles compared with the latest tertile was 0.36 ( 0.15 , 0.85 ) and 0.37 ( 0.22 , 0.62 ) , respectively , P < 0.001 ) . Early age at introduction of fish was dose dependently associated with a decreased risk of allergic rhinitis ( HR ( 95 % CI ) for the first and mid-tertiles compared with the latest tertile was 0.34 ( 0.22 , 0.54 ) and 0.45 ( 0.28 , 0.70 ) , respectively , P < 0.001 ) . The present finding that age at introduction of oats is inversely and independently associated with development of persistent asthma is novel . We confirmed the earlier observation that the age at introduction of fish is inversely related to the risk of allergic rhinitis . Clinical implication s remain to be determined OBJECTIVE Breast-fed infants receive docosahexaenoic acid ( DHA ) and arachidonic acid ( ARA ) in their diet . Upon weaning , infants lose this dietary source of long-chain polyunsaturates because many commercial formulas do not contain these important constituents for neural membrane biogenesis . We evaluated the benefits of postweaning dietary supplementation of DHA + ARA on visual maturation . STUDY DESIGN Healthy term infants ( n = 61 ) were breast-fed to 4 to 6 months , then were r and omly assigned to commercial formula or formula supplemented with DHA ( 0.36 % ) + ARA ( 0.72 % ) . Measurements of red blood cell ( RBC ) fatty acids , visually evoked potential ( VEP ) acuity , and stereoacuity were done before and after weaning . RESULTS At 1 year of age , RBC-DHA in the commercial formula-fed group was reduced by 50 % from the weaning level , whereas there was a 24 % increase in the DHA + ARA-supplemented group . The primary outcome measure , VEP acuity , was significantly more mature in supplemented infants at 1 year of age . Elevated RBC-DHA levels were associated with more mature VEP acuity . There were no significant diet-related differences in stereoacuity . CONCLUSIONS These data extend through the first year of life the critical period in which a dietary supply of DHA and ARA can contribute in optimizing visual development in term infants ABSTRACT : The objective of this study was to compare circulating lipid docosahexaenoic acid [ 22:6(n-3 ) , DHA ] levels in term infants fed a powdered ( CORN oil ) or liquid ( SOY oil ) infant formula or human milk ( HM ) . Infants whose mothers chose not to breast feed were r and omly assigned to the CORN or SOY formula group . The formula fat differed in linolenic acid [ 18:3(n-3 ) ] content : it was 0.8 % for the CORN and 4.8 % for the SOY . Linoleic acid ( 18:2(n-6 ) ] was 31.5 and 34.2 % fatty acids in the CORN and SOY formula , respectively . The formulas or HM were fed from birth through 8 wk of age , and growth and the plasma and red blood cell ( RBC ) phospholipid fatty acid composition was determined at 3 d , 4 wk , and 8 wk of age . Growth did not differ among groups . The plasma phospholipid and RBC phosphatidylethanolamine DHA was similar in the CORN and SOY formula groups at all ages . Plasma and RBC phosphatidylethanolamine levels of DHA were significantly lower in infants fed the CORN or SOY formula than in infants fed HM during wk 4 and 8 . Plasma and RBC 22:5(n-6 ) was not increased in the formula groups at any age . The formula content of linolenic acid had no effect on the RBC or plasma DHA levels of the infants . The biologic or functional significance of the lower plasma and RBC DHA in infants fed formula rather than HM is unknown . The need for a dietary source of DHA and specificity of plasma or RBC phospholipid DHA as a measure of desaturation and elongation of linolenic acid in developing organs remains uncertain The CNS and the retina are enriched in long chain polyunsaturated ( LCP ) fatty acids , specifically docosahexaenoic acid ( DHA , 22:6n-3 ) and arachidonic acid ( AA , 20:4n-6 ) , which are present in human milk but not in most infant formulas . In the present study of 134 formula-fed and 63 breast-fed infants , we prospect ively evaluated whether providing a source of DHA and AA or DHA alone in formula would increase red blood cell ( RBC ) phospholipid levels of these fatty acids , enhance visual function , or affect growth during the first year .  Healthy term infants < 7 d old were r and omized to be fed formulas containing linoleic acid ( ≈10 % kcal ) and α-linolenic acid ( ≈1 % kcal ) plus ( 1 ) no added LCP fatty acids ( control formula ) , ( 2 ) DHA ( 0.12 wt% fatty acids ) and AA ( 0.43 wt% ) from egg yolk phospholipid ( AA + DHA formula ) , or ( 3 ) DHA ( 0.2 wt% ) from fish oil ( DHA formula ) . A breast-fed group was studied concurrently and permitted formula supplementation after 3 mo . Visual acuity was measured using both the acuity card procedure and a visual evoked potential method at 2 , 4 , 6 , 9 , and 12 mo . Infants fed the control formula had 10 - 40 % lower RBC levels of DHA and AA than infants in the breast-fed group . Infants fed the AA+ DHA formula had levels of both LCP within ≈10 % of the values for infants in the breast-fed group , and infants fed the DHA formula had 25 - 55 % higher DHA levels and 15 - 40 % lower AA levels . There were no differences in growth or in visual function during this 12-mo feeding study AIM Long-chain polyunsaturated fatty acid ( LCPUFA ) supplementation of infant formula may have a beneficial effect on cognitive development . This study aim ed to investigate the effect of LCPUFA formula supplementation primarily on cognition and secondarily on behaviour at age 9 years . Special attention was paid to the potentially modifying effect of maternal smoking during pregnancy . METHOD A double-blind , r and omized control study was performed in two groups of healthy infants born at term : one group , constituting the control group , received st and ard formula ( n=169 ) and another group received st and ard formula supplemented with LCPUFAs ( n=146 ) . A breastfed group ( n=159 ) served as an additional reference . At 9 years of age , 72 % of the children ( control group : n=123 ; 71 males , 52 females ; LCPUFA group : n=91 ; 42 males , 49 females ; breastfed group : n=127 , 64 males , 63 females ) underwent extensive cognitive and behavioural testing . RESULTS An interaction between infant nutrition and smoking during pregnancy was found . Among children exposed to smoking during pregnancy , LCPUFA supplementation was associated with higher mean verbal IQ scores ( p=0.007 ) and learning and memory ( p=0.006 ) . Among children not exposed to smoking during pregnancy , LCPUFA supplementation was associated with lower mean verbal memory scores ( p=0.003 ) . Executive function scores were significantly lower in the LCPUFA-supplemented group than in the control group ( p=0.001 ) . Breastfeeding was associated with better performance on IQ ( p=0.005 ) . INTERPRETATION No consistent beneficial effect of LCPUFA formula supplementation on cognitive development in term-born infants was found . The study confirmed that breastfeeding is associated with better cognition We investigated whether the disparity in neural maturation between breastfed and formula-fed term infants could be corrected by the addition of fish oil , a source of docosahexaenoic acid ( DHA , 22:6 omega 3 ) , to infant formula . Healthy , term infants were r and omised at birth to receive either a supplemented or placebo formula if their mothers had chosen to bottle feed . Breastfed term infants were enrolled as a reference group . Infant erythrocyte fatty acids and anthropometry were assessed on day 5 and at 6 , 16 , and 30 weeks of age . Visual evoked potential ( VEP ) acuity was determined at 16 and 30 weeks . VEP acuities of breastfed and supplemented-formula-fed infants were better than those of placebo-formula-fed infants at both 16 and 30 weeks of age ( p < 0.001 and p < 0.01 ) . Erythrocyte DHA in breastfed and supplemented-formula-fed infants was maintained near birth levels throughout the 30-week study period but fell in placebo-formula-fed infants ( p < 0.001 ) . Erythrocyte DHA was the only fatty acid that consistently correlated with VEP acuity in all infants at both ages tested . A continuous supply of DHA may be required to achieve optimum VEP acuity since infants breastfed for short periods ( < 16 weeks ) had slower development of VEP than infants receiving a continuous supply of DHA from either breastmilk or supplemented formula . Erythrocyte arachidonic acid ( 20:4 omega 6 ) in supplemented-formula-fed infants was reduced below that of infants fed breastmilk or placebo formula at 16 and 30 weeks ( p < 0.001 ) , although no adverse effects were noted , with growth of all infants being similar . DHA seems to be an essential nutrient for the optimum neural maturation of term infants as assessed by VEP acuity . Whether supplementation of formula-fed infants with DHA has long-term benefits remains to be eluci date Background : There is some evidence that the n-6/n-3 long-chain polyunsaturated fatty acids ( LCPUFAs ) ratio in early nutrition , and thus in breast milk , could influence infant body composition . Methods : In an open-label r and omized controlled trial ( RCT ) , 208 healthy pregnant women were allocated to a dietary intervention ( supplementation with 1,200 mg n-3 LCPUFAs per day and instructions to reduce arachidonic acid ( AA ) intake ) from the 15th wk of gestation until 4 mo of lactation or to follow their habitual diet . Breast milk LCPUFAs at 6 wk and 4 mo postpartum were related to infant body composition assessed by skinfold thickness ( SFT ) measurements and ultrasonography during the first year of life . Results : Dietary intervention significantly reduced breast milk n-6/n-3 LCPUFAs ratio . In the whole sample , early breast milk docosahexaenoic acid ( DHA ) , eicosapentaenoic acid ( EPA ) , and n-3 LCPUFAs at 6 wk postpartum were positively related to the sum of four SFT measurements at age 1 . Breast milk AA and n-6 LCPUFAs at 6 wk postpartum were negatively associated with weight , BMI , and lean body mass ( LBM ) up to 4 mo postpartum . Conclusion : Breast milk n-3 LCPUFAs appear to stimulate fat mass growth over the first year of life , whereas AA seems to be involved in the regulation of overall growth , especially in the early postpartum period Our study examined if dietary long-chain polyunsaturated fatty acids ( LCPUFA ) have an impact on oxidative stress in preterm infants .  Serum malonyldialdehyde ( MDA ) , total peroxide concentrations , and total antioxidant capacity were determined at mean ( st and ard deviation [ SD ] ) 34.7 ( 10.9 ) days of life in 104 healthy preterm infants ( gestational age , 32.6 [ 2.9 ] weeks ; birthweight ; 1605 [ 285 ] g ) who were r and omly assigned to be fed since birth either a formula containing LCPUFA ( arachidonic and docosahexaenoic ) ( group A , n = 50 ) or a LCPUFA-free formula with identical compositions for other nutrients ( group B , n = 54 ) . Clinical and anthropometric characteristics did not differ significantly between the two groups . Mean ( SD ) serum MDA levels did not differ significantly between groups A ( 0.23 [ 0.04 ] micromol/L ) and B ( 0.22 [ 0.05 ] micromol/L ) . The concentrations of total peroxides were below the detection limits of the assay in 41 of 50 ( 82 % ) infants of group A and 43 of 54 ( 79 % ) infants of group B and not significantly different between the two infant groups . No difference was observed in serum total antioxidant capacity between groups A ( 340.0 [ 46.2 ] micromol/L ) and B ( 354.7 [ 46.5 ] micromol/L ) . We concluded that supplementation of infant formulas with LCPUFA does not affect lipid peroxidation in healthy preterm infants Abstract When term infants are fed st and ard formula that does not contain long-chain polyunsaturated fatty acids ( LC-PUFA ) , they still show lower levels of docosahexaenoic acid ( DHA ) in red blood cell ( RBC ) phospholipids by several weeks or months postnatally . This study was design ed in order to evaluate a potential alternative for supplementing term infant formulas with DHA by adding a high-DHA/low-eicosapentanoic acid fish oil to levels similar to that in human milk ( 0.3 % ) . A total of 37 term infants were included in the study at 3 days of life .  DHA concentrations remained stable between inclusion and 4 months of life at around 8 % of the RBC phospholipids in the LC-PUFA enriched formula-fed group whereas it decreased significantly in the st and ard formula-fed group . In the human milk-fed group , RBC DHA concentrations at 4 months of age were significantly lower than that at birth and were significantly correlated with the duration of breast feeding ( r = 0.85 ; P = 0.0002 ) . A significant decrease of arachidonic acid between inclusion and 4 months of age was observed in the enriched formula-fed group and reached a mean value at 4 months , which was significantly lower than that observed in the human milk or st and ard formula-fed groups ( P < 0.0001 ) . Conclusion Supplementing term formulas with a high-docosahexaenoic acid/low-eicosapentanoic acid fish oil up to 4 months of age is efficient in improving docosahexaenoic acid status , however it increases the risk of impaired n-6 fatty acid status We investigated whether the previously reported preventive effect of maternal ω-3 fatty acid supplementation on  IgE-associated allergic disease in infancy may be mediated by facilitating a balanced circulating Th2/Th1 chemokine profile in the infant . Vaccine-induced immune responses at 2 y of age were also evaluated . Pregnant women , at risk of having an allergic infant , were r and omized to daily supplementation with 1.6 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid or placebo from the 25th gestational week through 3.5 mo of breastfeeding . Infant plasma was analyzed for chemokines ( cord blood , 3 , 12 , 24 mo ) and anti-tetanus and anti-diphtheria IgG ( 24 mo ) . High Th2-associated CC-chemokine lig and 17 ( CCL17 ) levels were associated with infant allergic disease ( p < 0.05 ) . In infants without , but not with , maternal history of allergy , the ω-3 supplementation was related to lower CCL17/CXC-chemokine lig and 11 ( CXCL11 ) ( Th2/Th1 ) ratios ( p < 0.05 ) . Furthermore , in nonallergic , but not in allergic infants , ω-3 supplementation was linked with higher Th1-associated CXCL11 levels ( p < 0.05 ) , as well as increased IgG titers to diphtheria ( p = 0.01 ) and tetanus ( p = 0.05 ) toxins . Thus , the prospect of balancing the infant immune system toward a less Th2-dominated response , by maternal ω-3 fatty acid supplementation , seems to be influenced by allergic status BACKGROUND The prevalence of asthma has increased in developed countries in the past 2 decades . The effectiveness of intervention measures on the primary prevention of asthma has not been well studied . OBJECTIVE To assess the effectiveness of a multifaceted intervention program in the primary prevention of asthma in high-risk infants ( in this study , infants are defined as persons from birth to the age of 1 year ) . DESIGN Prospect i ve , prenatally r and omized , controlled study with follow-up through the age of 1 year . SETTING University hospital-based setting s at 2 Canadian centers : Vancouver , British Columbia , and Winnipeg , Manitoba . PARTICIPANTS A total of 545 high-risk infants ( at least 1 first-degree relative with asthma or 2 first-degree relatives with other IgE-mediated allergic diseases ) identified before birth . INTERVENTIONS Avoidance of house dust mite and pet allergens and environmental tobacco smoke , encouragement of breastfeeding , and supplementation with a partially hydrolyzed formula . MAIN OUTCOME MEASURES Probable or possible asthma , rhinitis without apparent colds , and a prick skin test result positive for common inhalant allergens . RESULTS Thirty-eight ( 15.1 % ) of the 251 infants available for assessment in the intervention group and 49 ( 20.2 % ) of the 242 infants available for assessment in the control group fulfilled the criteria for possible or probable asthma ( adjusted relative risk , 0.66 ; 90 % confidence interval , 0.44 - 0.98 ) . Also , 16.7 % of the infants in the intervention group and 27.3 % of the infants in the control group developed rhinitis without colds ( adjusted relative risk , 0.51 ; 90 % confidence interval , 0.35 - 0.74 ) . The incidence of positive skin test results to 1 or more inhalant allergens was similar in both groups ( 4.4 % in the intervention group and 4.6 % in the control group ) . CONCLUSIONS Our multifaceted intervention program result ed in a modest but significant ( P= .04 ) reduction in the risk of possible or probable asthma and rhinitis without apparent colds at the age of 12 months in high-risk infants . In the absence of a vali date d definition of asthma at the age of 12 months , follow-up studies are needed to determine the effectiveness of the intervention program in the primary prevention of asthma in high-risk infants AIM To investigate whether the low docosahexaenoic acid ( DHA ) status of malnourished , mostly breast fed , Pakistani children can be improved by fish oil ( FO ) supplementation . METHODS Ten malnourished children ( aged 8–30 months ) received 500 mg FO daily for nine weeks . The supplement contained 62.8 mol% ( 314 mg ) long chain polyunsaturated fatty acids of the ω3 series ( LCPUFAω3 ) and 22.5 mol% ( 112 mg ) DHA . Seven FO unsupplemented children served as controls . Red blood cell ( RBC ) fatty acids were analysed at baseline and at the study end . RESULTS FO supplementation  augmented mean ( SD ) RBC DHA from 2.27 ( 0.81 ) to 3.35 ( 0.76 ) mol% , without significantly affecting the concentrations of LCPUFAω6 . Unsupplemented children showed no RBC fatty acid changes . One FO supplemented child with very low initial RBC arachidonic acid showed a remarkable increase from 4.04 to 13.84 mol% , whereas another with high RBC arachidonic acid showed a decrease from 15.64 to 10.46 mol% . CONCLUSION FO supplementation improves the DHA status of malnourished children . The supplement is apparently well absorbed and not exclusively used as a source of energy BACKGROUND Docosahexaenoic acid is present in high concentration in retina and does not influence visual development in preterm infants . It is still under discussion whether docosahexaenoic acid is important for visual development in term infants . METHODS Thirty-seven infants fed formula for a median of 14 days were r and omized at median age of 25 days to three formulas : a ) DHAGF : 0.3 wt% docosahexaenoic acid and 0.5 wt% gamma-linolenic acid ; b ) DHAF 0.3 wt% docosahexaenoic acid ; or c ) STF : st and ard formula without long-chain polyunsaturated fatty acids and  17 breast-fed infants were observed , using blood sample s and anthropometric measurements from 1 to 4 months of age . At 4 months , visual acuity was measured by swept steady-state visual evoked potential . A cross-sectional study on 25 breast-fed infants was carried out as a reference group for the analyses . RESULTS Infants fed the two docosahexaenoic acid-supplemented formula had relative docosahexaenoic acid concentrations in red blood cell phospholipids almost as high as those in breast-fed infants , whereas infants in the st and ard formula group had significantly lower levels . The addition of gamma-linolenic acid to the formula had a positive effect on red blood cell arachidonic acid levels , compared with levels obtained using fish oil only . Visual acuity was significantly different among all feeding groups ( analysis of variance ; p = 0.05 , means + /- st and ard deviation : breast-fed , 0.37+/-0.06 logMAR ; DHAF and DHAGF combined , 0.40+/-0.07 logMAR ; and st and ard formula 0.44+/-0.07 logMAR . However , there was no statistical difference among the formula groups . In a multiple regression analysis including all formula-fed infants , weight at delivery ( p = 0.002 ) , but not type of formula , was significantly associated with visual acuity at 4 months of age . CONCLUSIONS The addition of docosahexaenoic acid result ed in concentrations in red blood cells at similar levels as those in breast-fed infants , whereas the increase in visual acuity did not reach significance . The addition of gamma-linolenic acid result ed in higher arachidonic acid concentrations in red blood cells OBJECTIVES To evaluate safety and benefits of feeding preterm infants formulas containing docosahexaenoic acid ( DHA ) and arachidonic acid ( ARA )  until 92 weeks postmenstrual age ( PMA ) , with follow-up to 118 weeks PMA . STUDY DESIGN This double-blinded study of 361 preterm infants r and omized across three formula groups : ( 1 ) control , no supplementation ; ( 2 ) algal-DHA ( DHA from algal oil , ARA from fungal oil ) ; and ( 3 ) fish-DHA ( DHA from fish oil , ARA from fungal oil ) . Term infants breast-fed > or = 4 months ( n = 105 ) were a reference group . Outcomes included growth , tolerance , adverse events , and Bayley development scores . RESULTS Weight of the algal-DHA group was significantly greater than the control group from 66 to 118 weeks PMA and the fish-DHA group at 118 weeks PMA but did not differ from term infants at 118 weeks PMA . The algal-DHA group was significantly longer than the control group at 48 , 79 , and 92 weeks PMA and the fish-DHA group at 57 , 79 , and 92 weeks PMA but did not differ from term infants from 79 to 118 weeks PMA . Supplemented groups had higher Bayley mental and psychomotor development scores at 118 weeks PMA than did the control group . Supplementation did not increase morbidity or adverse events . CONCLUSIONS Feeding formulas with DHA and ARA from algal and fungal oils result ed in enhanced growth . Both supplemented formulas provided better developmental outcomes than unsupplemented formulas AIM A follow up study of developmental quotient ( DQ ) at 24 months of toddlers whose diets in early infancy differed in fatty acid composition , and in whom an association between diet and DQ was observed at 4 months . METHODS 81 toddlers were distributed among three groups according to early type of diet : st and ard infant formula ( SFo , n = 30 ) ; long chain polyunsaturated fatty acid ( LC-PUFA ) enriched formula ( LCPFo , n = 26 ) ; human milk ( HM , n = 25 ) . DQ at 24 months was assessed by Brunet-Lézine ’s psychomotor developmental test . A subgroup ( n = 20 ; SFo 8 ; LCPFo 6 ; HM 6 ) was tested for erythrocyte phosphatidylcholine and phosphatidylethanolamine . RESULTS No DQ differences were found by analysis of variance . Neither DQ nor erythrocyte docosahexaenoic acid at 4 months were predictors of DQ scores at 24 months . Phosphatidylcholine arachidonic and docosahexaenoic acid correlated positively , and phosphatidylcholine linoleic acid and phosphatidylethanolamine eicosapentaenoic acid negatively , with DQ . Multiple regression analysis including these variables explained 52 % of interindividual DQ variance . A strong association was found between the erythrocyte phosphatidylcholine arachidonic/linoleic acid ratio and DQ ( r= 0.75 ; p = 0.0001 ) . CONCLUSIONS The diet/DQ association found at 4 months was not predictive of DQ scores at 24 months . Irrespective of dietary or genetic factors , there appears to be a strong correlation between the LC-PUFA composition of the red cell membrane and higher neurodevelopmental performance n-3 Long-chain PUFA ( LC-PUFA ) intake during infancy is important for neurodevelopment ; however , previous studies of n-3 LC-PUFA supplementation have been inconclusive possibly due to an insufficient dose and limited methods of assessment . The present study aim ed to evaluate the effects of direct supplementation with high-dose fish oil ( FO ) on infant neurodevelopmental outcomes and language . In the present r and omised , double-blind , placebo-controlled trial , 420 healthy term infants were assigned to receive a DHA-enriched FO supplement ( containing at least 250 mg DHA/d and 60 mg EPA/d ) or a placebo ( olive oil ) from birth to 6 months . Assessment occurred at 18 months via the Bayley Scales of Infant and Toddler Development ( 3rd edition ; BSID-III ) and the Child Behavior Checklist . Language assessment occurred at 12 and 18 months via the Macarthur-Bates Communicative Development Inventory .  The FO group had significantly higher erythrocyte DHA ( P = 0·03 ) and plasma phospholipid DHA ( P = 0·01 ) levels at 6 months of age relative to placebo . In a small subset analysis ( about 40 % of the total population ) , children in the FO group had significantly higher percentile ranks of both later developing gestures at 12 and 18 months ( P = 0·007 ; P = 0·002 , respectively ) and the total number of gestures ( P = 0·023 ; P = 0·006 , respectively ) . There was no significant difference between the groups in the st and ard or composite scores of the BSID-III . The results suggest that improved postnatal n-3 LC-PUFA intake in the first 6 months of life using high-dose infant FO supplementation was not beneficial to global infant neurodevelopment . However , some indication of benefits to early communicative development was observed Polyunsaturated n-3 fatty acids ( n-3PUFA ) may improve brain development and prevent cardiovascular disease . Heart rhythm is autonomically controlled and among the affected cardiovascular risk markers in adults . The aim of the study was to examine whether fish oil supplementation in late infancy could modify heart rate ( HR ) and heart rate variability ( HRV ) . In a 2 × 2-intervention , 83 healthy Danish infants were r and omized to ± fish oil ( 3.4 ± 1.1 mL/d ) and cow 's milk or infant formula from 9 to 12 mo of age . In 57 infants , 0.5-h ECG recordings were successfully obtained before and after the intervention and erythrocyte fatty acid composition was determined in 30 of these . Fish oil supplementation raised erythrocyte n-3PUFA content ( p < 0.001 ) . No significant group differences were seen in HR or HRV . However , a fish-oil × gender interaction was observed on mean RR interval ( p = 0.001 ) with a 6 % longer mean RR interval in fish-oil-supplemented boys ( p = 0.007 ) . Irrespective of gender , there was a positive association between the 9- and 12-mo changes in RR interval and erythrocyte n-3PUFA ( p < 0.001 ) . In infants with confirmed changes in erythrocyte n-3PUFA , mean RR interval was found to be longer ( p = 0.011 ) in the fish-oil-supplemented groups . The study suggests that fish oil may affect heart rhythm in infants similar to that observed in adults . This may imply low n-3PUFA-status in late infancy and n-3PUFA influence on CNS function Objective : To investigate the impact of maternal diet during breastfeeding on  atopic sensitization of infants at risk . Design : Prospect i ve cohort study . Setting : Turku University Central Hospital , Finl and .Subjects and methods : Altogether 114 infants with a family history of atopic disease were followed during their first year of life . The mothers completed a 4 day food record during breastfeeding just before the infants were 3 months old . Atopic sensitization of the infants was determined by a positive skin prick test result at 12 months . Results : Positive skin prick test reactivity to at least one antigen was detected in 27/114 ( 24 % ) infants at 12 months . The energy intake of the mothers was low , mean 8.0 MJ/day ( 95 % CI 7.7–8.3 ) , and the proportion of energy derived from fat was high , mean 36.6 E% ( 95 % CI 35.6–37.6 ) . Atopic mothers had a higher intake of total fat and saturated fat and a lower intake of carbohydrate as a percentage of total energy intake than non-atopic mothers ; P=0.017 , P=0.050 , P=0.004 respectively . Maternal intake of saturated fat during breastfeeding was associated with atopic sensitization of the infant , OR=1.16 ( 95 % CI 1.001–1.36 ) ; P=0.048 irrespective of the maternal atopic status . Conclusions : Our results show that an unbalanced maternal diet during breastfeeding may be a risk factor underlying the later development of atopic sensitization of the infant regardless of maternal atopic disease . The observation thus extends findings implying that early nutrition programmes the subsequent health of the child to the risk of developing atopic disease . Sponsorship : Academy of Finl and and National Technology Agency . European Journal of Clinical Nutrition ( 2000 ) 54 , Background and Objective : Feeding long-chain polyunsaturated fatty acids ( LCP ) influences immunity in adults ; however , less is known about their effect during development . The aim of the study was to determine the effect of feeding LCP on immunity in healthy infants during the first 4 months of life . Patients and Methods : Formula-fed infants were r and omized at ≤14 days of age to st and ard term formula ( Formula ) or formula containing LCP ( Formula+LCP ) . Infants exclusively fed human milk ( HM ) were included for comparison . At 16 weeks of age , blood was collected and phenotypes , the ability to proliferate and produce cytokines ( interleukin [IL]-2 , IL-4 , IL-6 , IL-10 , IL-12 , interferon [IFN]-γ , tumor necrosis factor [TNF]-α , TGF-β ) after incubation with phytohemaglutinin ( PHA ) , β-lactoglobulin , or soy protein were measured . Results : Feeding LCP result ed in a higher than and more similar proliferation rate to PHA in HM-fed infants , possibly because of a greater TH1 type cytokine response and a higher percentage of antigen mature ( CD45RO+ ) cells ( P < 0.05 ) . The response to β-lactoglobulin did not differ among groups . After incubation with soy protein Formula+LCP , compared with Formula produced less IL-2 and more TNF-α and had a higher percentage of CD8 + and a lower percentage of CD20 + ( CD20+CD54 + ) cells poststimulation ( P < 0.05 ) . Both formula groups produced less IL-2 after PHA , had a lower percentage of CD80 + cells , and a higher percentage of CD54 + cells after incubation with food proteins ( P < 0.05 ) . Conclusions : Formula-fed infants , at low risk for allergy , respond differently to mitogen and food proteins ex vivo than those fed HM . Feeding LCP altered some of these differences in the direction that is hypothesized to confer immune benefits Background The tissue accretion of long-chain polyunsaturated fatty acids is compromised in infants born prematurely . Human milk contains long-chain polyunsaturated fatty acids , but most preterm infant formulas do not . The long-term effects of preterm formula supplemented with arachidonic acid and docosahexaenoic acid , in proportions typical of those in human milk , were therefore investigated . Methods In this double-blind , r and omized study , 288 preterm infants received experimental formula ( n = 77 ) , unsupplemented ( control ) formula ( n = 78 ) , or human milk ( n = 133 ) until 48 weeks postconceptional age ( PCA ) .  Term formula , without supplemental long-chain polyunsaturated fatty acids , was administered from 48 to 92 weeks PCA to formula-fed infants and to infants weaned from human milk .  Anthropometric and fatty acid data were assessed by using analysis of variance . Results At 92 weeks PCA , no statistically significant anthropometric measurement differences were found except for midarm circumference , which was smaller in human milk – fed infants than in those fed formula . Phospholipid concentrations were similar in the experimental and human milk – fed groups , and docosahexaenoic acid levels were significantly greater than in the control group . The types and incidences of adverse events were similar among the feeding groups . Conclusions The results of this study demonstrate the efficacy and long-term safety of preterm formula supplemented with long-chain polyunsaturated fatty acids The need for a dietary supply of docosahexaenoic acid ( DHA ) and arachidonic aid ( AA ) in term infants was evaluated in a double-masked r and omized clinical trial of the effects of supplementation of term infant formula with DHA ( 0.35 % of total fatty acids ) or with DHA ( 0.36 % ) and AA(0.72 % ) on visual acuity development . One hundred and eight healthy term infants were enrolled in the study ; 79 were exclusively formula-fed from birth ( r and omized group ) and 29 were exclusively breast-fed ( gold st and ard group ) . Infants were evaluated at four time points during the first 12 mo of life for blood fatty acid composition , growth , sweep visual evoked potential(VEP ) acuity , and forced choice preferential looking acuity . Supplementation of term infant formula with DHA or with DHA and AA during the first 4 mo of life yields clear differences in total red blood cell ( RBC ) lipid composition . Supplementation of term infant formula with DHA or with DHA and AA also yields better sweep VEP acuity at 6 , 17 , and 52 wk of age but not at 26 wk of age , when acuity development reaches a plateau . The RBC lipid composition and sweep VEP acuity of supplemented infants was similar to that of human milk-fed infants , whereas the RBC lipid composition and sweep VEP acuity of unsupplemented infants was significantly different from human milk-fed infants . Differences in acuity among diet groups were too subtle to be detected by the forced choice preferential looking protocol . Infants in all diet groups had similar rates of growth and tolerated all diets well . Thus , early dietary intake of preformed DHA and AA appears necessary for optimal development of the brain and eye of the human infant OBJECTIVE To investigate the effect of reducing the n-6/n-3 fatty acid ratio in maternal nutrition on the maternal and cord blood leptin axis and their association with infant body composition up to 2 years . DESIGN AND METHODS 208 healthy pregnant women were r and omized to either a dietary intervention to reduce the n-6/n-3 fatty acid ratio from 15th week of gestation until 4 months postpartum or a control group .  Leptin , soluble leptin receptor and free leptin index were determined in maternal and cord plasma and related to infant body composition assessed by skinfold thicknesses up to 2 years . RESULTS The intervention had no effect on either the maternal or fetal leptin axis . Maternal leptin in late pregnancy was inversely related to infant weight and lean body mass ( LBM ) up to 2 years , after multiple adjustments . Cord leptin was positively related to weight , body fat , and LBM at birth , and inversely associated with weight , BMI , fat mass , and LBM at 2 years and weight gain up to 2 years . The contribution of cord leptin to infant outcomes was overall stronger compared with maternal leptin . CONCLUSIONS Both , maternal and fetal leptin were associated with subsequent infant anthropometry with a greater impact of fetal leptin ABSTRACT : A direct influence of dietary long-chain polyunsaturated fatty acids ( LC-PUFA ) on the developmental quotient ( DQ ) of the healthy term infant remains unexplored . To test this hypothesis , we design ed a prospect i ve study of three types of diet . Twentynine infants received a LC-PUFA-supplemented formula , 31 received a st and ard infant formula , and 30 infants were breastfed exclusively .  Neurodevelopmental response was measured by the Brunet-Lézine psychomotor development lest at 4 mo . The fatty acid status was also assessed among three diet subgroups ( 59 subjects ) at 4 mo . Formula-fed infants who received LC-PUFA supplementation scored significantly higher ( p < 0.01 ) on the Brunet-Lézine scale than infants who received the st and ard formula . Breast-fed infants also performed better than those fed the st and ard formula . Arachidonic acid and docosahexaenoic acid levels in circulating lipids and erythrocyte phospholipids were higher among breast-fed infants and among the group fed the arachidonic- and docosahexaenoic acid-supplemented formula . These findings are suggestive that formula supplementation with one or both of these fatty acids can benefit term infants in neurodevelopmental performance Objective : To assess the effects of dietary long chain polyunsaturated fatty acid ( LCPUFA ) supplementation on auditory brainstem maturation of healthy term newborns during the first 16 weeks of life by measuring brainstem auditory evoked potentials ( BAEPs ) . Design : Throughout the 16 week study period , infants in the formula A group ( n = 28 ) were assigned to be fed exclusively with the same formula supplemented with DHA , and infants in the formula B group ( n = 26 ) were assigned to receive only a DHA unsupplemented but otherwise similar formula . During the study period , the first 26 consecutive infants to be fed exclusively on their mother ’s milk for at least the first 16 weeks of life were chosen as the control group . BAEP measurements were performed twice : at the first and 16th week of age . Results : There were no significant differences among the study and control groups in the BAEP measurements performed at the study entry . At 16 weeks of age , all absolute wave and interpeak latencies in the study and control groups had significantly decreased . The decreases were significantly greater in the formula A and control groups than in the formula B group . Conclusions : Infants fed on human milk or a formula supplemented with LCPUFAs during the first 16 weeks of life show more rapid BAEP maturation than infants fed on a st and ard formula . Although the clinical importance and long term effects of these findings remain to be determined , routine supplementation of formulas with LCPUFAs should be considered OBJECTIVE We tested the hypothesis that balanced addition of long-chain polyunsaturated fatty acid ( LCPUFA ) to preterm formula during the first weeks of life would confer long-term neurodevelopmental advantage in a double-blind , r and omized , controlled trial of preterm formula with and without preformed LCPUFA . METHODS The participants were 195 formula-fed preterm infants ( birth weight < 1750 g , gestation < 37 weeks ) from 2 UK neonatal units and 88 breast milk-fed infants . Main outcome measures were Bayley Mental Developmental Index ( MDI ) and Psychomotor Developmental Index ( PDI ) at 18 months and Knobloch , Passamanick and Sherrard 's Developmental Screening Inventory at 9 months ' corrected age . Safety outcome measures were anthropometry at 9 and 18 months , tolerance , infection , necrotizing enterocolitis , and death . RESULTS There were no significant differences in developmental scores between r and omized groups , although infants who were fed LCPUFA-supplemented formula showed a nonsignificant 2.6-point ( 0.25 st and ard deviation ) advantage in MDI and PDI at 18 months , with a greater ( nonsignificant ) advantage ( MDI : 4.5 points ; PDI : 5.8 points ) in infants below 30 weeks ' gestation . LCPUFA-supplemented infants were shorter than control infants at 18 months ( difference in length st and ard deviation score : 0.44 ; 95 % confidence interval : 0.08 - 0.8 ) . No other significant short- or long-term differences in safety outcomes were observed . Breastfed infants had significantly higher developmental scores at 9 and 18 months than both formula groups and were significantly heavier and longer at 18 months than LCPUFA-supplemented but not control infants . CONCLUSIONS With the dose , duration , and preparation of LCPUFA used , efficacy was not demonstrated , although an advantage in later neurodevelopment can not be excluded by global tests of development up to 18 months , particularly in infants below 30 weeks ' gestation . The surprising effect of LCPUFA-supplemented formula on growth 18 months beyond the intervention period needs to be confirmed in other studies using similar supplementation strategies . Additional follow-up of this cohort is critical at an age when more specific tests of cognitive function are possible It has been recommended to supplement formulas for preterm infants with n-3 and n-6 long-chain polyunsaturated fatty acids ( LCP ) to improve growth , visual acuity , and neurodevelopmental performance . However , large amounts of LCP may increase lipid peroxidation and oxidative stress in preterm infants . We investigated if , under high supplementation of natural tocopherols , LCP addition to formula can be performed safely without causing tocopherol depletion in cell membranes . Thirty-one healthy preterm infants with gestational ages from 28 to 32 weeks were evaluated in a prospect i ve , r and omized study from birth to day 42 . Nine infants received an n-3 and n-6 LCP-enriched formula ( A ) , eleven infants a st and ard formula ( B ) , and eleven infants breast milk ( control group ) . Alpha- and gamma-tocopherol extracts were added to both formulas , amounting to five times the value in breast milk ( 2.3 mg/dL in both formulas versus 0.45 mg/dL in breast milk ) . Erythrocyte arachidonic acid ( AA ) and docosahexaenoic acid ( DHA ) in the phosphatidylethanolamine fraction were similar in the three groups over the study period , whereas a significant reduction of erythrocyte AA and DHA could be detected in the phosphatidylcholine fraction in all three groups from day 14 onwards , when compared to respective cord blood values , with lowest values in the st and ard formula group . Amazingly , levels of alpha- and gamma-tocopherol were higher in plasma , erythrocytes , platelets , monocytes , and polymorphonuclear leukocytes with LCP supplementation as compared to st and ard formula and breast milk from day 7 onwards , whereas in buccal mucosal cells , this was not the case until day 42 . Gammatocopherol uptake in the LCP-supplemented group was also significantly higher in all cell fractions studied from day 7 onwards . We therefore hypothesize that the LCP supplementation used in formula A improves tocopherol solubility and stability in biological membranes . Under high-dose vitamin E addition to n-3 and n-6 LCP-supplemented formula , no evidence for tocopherol depletion and furthermore , high accumulation of tocopherols , can be detected in healthy preterm infants Because docosahexaenoic acid ( DHA ) may be an essential nutrient for the visual and early cognitive development of preterm infants , DHA enrichment of preterm formulas has been recommended . This r and omized trial was design ed to study the n-6 and n-3 fatty acid status of healthy preterm infants fed a formula enriched with a low eicosapentaenoic-fish oil until 4 mo corrected age compared with that of infants fed a st and ard formula .  A reference group of breast-fed infants was studied concurrently . The fatty acid content of red blood cell ( RBC ) phospholipid was assessed at enrollment , hospital discharge , expected term , and 3 and 6 mo postterm . The DHA content of RBC phospholipid was higher in infants fed the enriched versus the st and ard formula at hospital discharge , expected term , and 3 and 6 mo postterm . However , compared with infants fed the st and ard formula , infants fed the enriched formula had also higher RBC phospholipid eicosapentaenoic content ( 0.69 ± 0.15%versus 0.25 ± 0.12 % , p < 0.001 ) , and lower RBC phospholipid arachidonic acid content ( 15.1 ± 0.93%versus 18.8 ± 0.89%;p < 0.001 ) . We conclude that supplementing preterm infants with low-eicosapentaenoic fish oil is effective in improving DHA status , but results in worsening of n-6 fatty acid status . We speculate that preterm infants may require a dietary supply of arachidonic acid as well as DHA if the same fatty acid status as that of breast-fed infants is to be achieved The 209 mothers to be , enrolled in a r and omized , prospect i ve , allergy-prevention study from allergy-prone families , totally abstained from cow 's milk and egg  from gestational week 28 to delivery . This article presents the development of allergic disease at 5 years of age in their children , compared with the development of allergic disease in the children of the control mothers who took normal food throughout pregnancy . The prevalence of allergic disease could be evaluated in 198 children ( 95 % ) .  Allergic disease was monitored with  question naires , skin prick testing , serum-IgE determinations , and physical examination . Eczema , allergic rhinoconjunctivitis , and asthma was equally common in the groups . Persistent food intolerance to egg was significantly more common in children of the mothers receiving the diet . This long-term follow-up confirms our previous findings that maternal elimination diet during late pregnancy does not prevent the development of allergic disease in the genetically predisposed child Objective : To evaluate α-linolenic acid ( ALA ) ( 18∶3 n-3 ) and linolenic acid ( LA ) ( 18∶2 n-6 ) in cholesterol esters ( CE ) as markers of ALA and LA dietary intakes in preterm infants . Subjects : Forty-five preterm infants : two groups fed different formulas , the third fed human milk .  Design : ALA and LA dietary intakes were precisely recorded in each infant to accurately determine the cumulative amount of ingested ALA and LA during two intervals : ( i ) between the second day after the first significant formula intake ( D0 ) and the fifteenth day ( D15 ) ; and ( ii ) between D0 and the first day of the 37th week of post-conception age ( W37 ) . The corresponding amounts of ingested ALA and LA were related to ALA and LA levels determined by capillary column gas – liquid chromatography in plasma cholesterol esters at D15 and W37 , respectively . Results : ALA in CE was very significantly correlated to D0–D15 and D0–W37 ALA intakes ( 0.66 ; P=0.0001 and 0.70 ; P=0.0001 ) , respectively . LA in CE was weakly correlated to D0–D15  LA intakes ( 0.03 ; P=0.01 ) and whatever the group ( human milk or enriched formula ) the correlation was lost at W37 . Conclusion : In preterm infants  , ALA in CE can be considered as representative of ALA dietary intakes , whereas LA in CE appears as a poor marker of LA intakes . European Journal of Clinical Nutrition ( 2000 ) 54 , Objectives : Long-chain polyunsaturated fatty acid ( LC-PUFA ) enrichment of preterm infant formulas is recommended to meet high dem and s. Dietary LC-PUFA may inhibit endogenous LC-PUFA synthesis , thus limiting their benefit . We investigated effects of different docosahexaenoic acid ( DHA ) intakes on plasma and erythrocyte fatty acids and endogenous LC-PUFA synthesis in preterm infants . Methods : Forty-two preterm infants ( birth weight 1000–2200 g ) were r and omized double-blind to  preterm formulas with & ggr;-linolenic acid ( 0.4 % ) and arachidonic acid ( AA , 0.1 % ) but different DHA contents ( A : 0.04 % , B : 0.33 % , C : 0.52 % ) ; 24 received human milk ( HM : 0.51 % AA , 0.38 % DHA , nonr and omized ) . Blood was sample d on study days 0 , 14 , and 28 . Uniformly 13C-labeled linoleic acid ( 2 mg/kg ) and & agr;-linolenic acid ( 1 mg/kg ) were applied orally on day 26 and blood sample s collected 48 hours later . Results : On day 28 , group A had the lowest and group C the highest plasma phospholipid concentrations of eicosapentaenoic acid and DHA . Erythrocyte phospholipid DHA was lowest in group A , but comparable in groups B , C , and HM . Plasma and erythrocyte AA were lower in formula groups than in HM . DHA intake had no effect on DHA synthesis . LC-PUFA synthesis was lower in HM infants . Conclusions : DHA supply dose dependently increased plasma DHA . Formula DHA levels of 0.33 % matched plasma DHA status of infants fed HM . LC-PUFA synthesis was lower in infants fed HM than formulas with different DHA and low AA contents . With the LC-PUFA supplementation used , DHA in formulas did not inhibit AA or DHA synthesis Objective To determine if improvements in cognitive outcome detected at 18 months ’ corrected age ( CA ) in infants born <33 weeks ’ gestation receiving a high-docosahexaenoic acid ( DHA ) compared with st and ard-DHA diet were sustained in early childhood . Design Follow-up of a multicentre r and omised controlled trial . R and omisation was stratified for sex , birth weight ( < 1250 vs ≥1250 g ) and hospital . Setting Five Australian tertiary hospitals from 2008 to 2013 . Participants 626 of the 657 participants r and omised between 2001 and 2005 were eligible to participate .  Interventions High-DHA ( ≈1 % total fatty acids ) enteral feeds compared with st and ard-DHA ( ≈0.3 % total fatty acids ) from age 2–4 days until term CA . Primary outcome Full Scale IQ of the Wechsler Abbreviated Scale of Intelligence ( WASI ) at 7 years CA . Prespecified subgroup analyses based on the r and omisation strata ( sex , birth weight ) were conducted . Results 604 ( 92 % of the 657 originally r and omised ) consented to participate ( 291 high-DHA , 313 st and ard-DHA ) . To address missing data in the 604 consenting participants ( 22 for primary outcome ) , multiple imputation was performed . The Full Scale IQ was not significantly different between groups ( high-DHA 98.3 , SD 14.0 , st and ard-DHA 98.5 , SD 14.9 ; mean difference adjusted for sex , birthweight strata and hospital −0.3 , 95 % CI −2.9 to 2.2 ; p=0.79 ) . There were no significant differences in any secondary outcomes . In prespecified subgroup analyses , there was a significant sex by treatment interaction on measures of parent-reported executive function and behaviour . Scores were within the normal range but girls receiving the high-DHA diet scored significantly higher ( poorer outcome ) compared with girls receiving the st and ard-DHA diet . Conclusions Supplementing the diets of preterm infants with a DHA dose of approximately 1 % total fatty acids from days 2–4 until term CA showed no evidence of benefit at 7 years ’ CA . Trial registration number Australian New Zeal and Clinical Trials Registry : ACTRN12606000327583 Long-chain ( LC ) polyunsaturated fatty acids ( PUFA ) ( LCP ) are considered conditionally essential nutrients for low birth weight infants ( LBWI ) . Therefore , enrichment of LBWI formulae with metabolites both linoleic ( omega-6 ) and alpha-linolenic ( omega-3 ) acids at levels typical for human milk has been recommended . However , previous feeding trials with LCP-enriched formulae evaluated only a dietary supplementation with omega-3 LCP from fish oils alone or with both omega-3 and omega-6 LCP at levels considerably lower than usual human milk contents . We studied the effects of an LBWI formula providing the major omega-3 and omega-6 LCP , docosahexaenoic and arachidonic acids , in amounts similar to those in average human milk . Twenty-seven LBWIs were enrolled in this study when they tolerated full enteral feeding ( > or = 130 ml milk/kg/day ) . Infants either received their own mother 's milk  ( n = 8 , birthweight 1218 + /- 146 g , gestational age 30.2 + /- 1.5 weeks , mean + /- SD ) fortified with protein and minerals ( FM-85 , Nestle Ag , Munchen , Germany ; dosage 5 g/100 ml milk ) or were r and omly assigned to blinded batches of an LBWI formula ( Prematil , Milupa AG , Friedrichsdorf , Germany ) without LCP ( n = 10 , 1280 + /- 229 g , 31.1 + /- 3.1 weeks ) or with LCP ( n = 9 , 1253 + /- 334 g , 30.4 + /- 3.3 wks . ) . During the study period of 21 days , the three feeding groups did not differ in growth and feeding tolerances as assessed by occurrence of gastric residuals , spitting , or abdominal distention ; however , firms stools were noted more frequently in the two formula groups . ( ABSTRACT TRUNCATED AT 250 WORDS ABSTRACT : Red blood cell ( RBC ) phospholipids of infants fed human milk compared with formula have more arachidonic acid ( AA ) and docosahexanoic acid ( DHA ) . The addition of low levels of marine oil to infant formula with 0.6 to 2.0 % α-linolenic acid ( LLA , 18:3n-3 ) prevented declines in DHA in formula-fed infants ; however , the feeding trials were short ( 4 to 6 wk ) , LLA concentrations were low compared with current formulas ( 3.0 to 5.0 % LLA ) , and the formulas were unstable . Trials with stable formulas were necessary to determine if dietary DHA could maintain phospholipid DHA after discharge from the hospital and , in fact , if it was necessary with higher intakes of LLA . The results of acute ( 4 wk ) and extended ( to 79 wk postconception ) feeding of such formulas on RBC and plasma phospholipid AA and DHA are reported here . Control formulas were identical to commercially available formulas . Experimental formulas differed only in the addition of small amounts of marine oil  . DHA in RBC and plasma phosphatidylethanolamine ( PE ) declined during four weeks of feeding but not if marine oil provided DHA ( 0.2 % or 0.4 % ) and plasma phospholipid AA ( g/100 g ) decreased with time and marine oil feeding . Extended feeding with marine oil accounted for half the DHA in RBC and plasma phosphatidylethanolamine at equilibrium ; however , RBC ( g/100 g ) and plasma AA ( g/100 g ; mg/L plasma ) decreased progressively until late infancy and were depressed further by marine oil . We conclude that 1 ) AA and DHA decline in RBC and plasma phospholipids of preterm infants when only their n-6 and n-3 fatty acid precursors are consumed ; and 2 ) marine oil can maintain cord concentrations of RBC phosphatidylethanolamine DHA but further reduces AA OBJECTIVE : To test the hypothesis that long-chain polyunsaturated fatty acid ( LCPUFA ) supplementation in infancy would improve cognition into later childhood ( after 9 years ) at both general and specific levels . METHODS : A comprehensive cognitive battery was completed by 107 formerly preterm infants ( mean age : 128 months ) . As infants , they had been assigned r and omly to receive LCPUFA-supplemented ( N = 50 ) or control ( N = 57 ) formula , between birth and 9 months ; the docosahexaenoic acid level ( DHA ) in the supplemented formulas was 0.5 % . In addition to r and omized comparisons , we planned supplementary analyses to examine the effects of both gender and feeding group ( those receiving some maternal breast milk versus those receiving none ) . RESULTS : There were no significant differences between r and omized diet groups on any cognitive measure . There was significant interaction between gender and supplementation ; girls only showed beneficial effects of LCPUFAs on literacy . Significant interaction also occurred between feeding group and supplementation ; increases of 0.7 SD in verbal IQ , full-scale IQ , and memory scores were found for the LCPUFA group , but only for infants who received only formula and no maternal breast milk . CONCLUSIONS : The results of this post–9-year cognitive follow-up study in a r and omized trial of LCPUFA-supplemented formula for preterm infants suggest no overall group effects but indicate that gender-specific and diet-specific effects may exist . The data provide some evidence that LCPUFAs are a key factor in the cognitive benefits of breast milk . Caution is advised in data interpretation because of the small groups used OBJECTIVE The purpose of this study was to determine the effect of docosahexaenoic acid supplementation on plasma phospholipid docosahexaenoic acid content and indices of depression and information processing for women who breast-feed . STUDY DESIGN Mothers who planned to breast-feed their infants were assigned r and omly in a double-masked fashion to receive either docosahexaenoic acid ( approximately 200 mg/d ) or placebo for the first 4 months after the delivery . Major outcome variables included plasma phospholipid fatty acid patterns and scores on a self-rating question naire of current depression symptoms . A structured clinical interview of depression , scores on another self-rating question naire of depression symptoms , and a laboratory measure of information processing were obtained in subgroups of the total population . RESULTS Plasma phospholipid contents of docosahexaenoic acid at baseline were 3.15 + /- 0.78 and 3.31 + /- 0.70 ( mg/dL of total fatty acids ) in the docosahexaenoic acid and placebo groups , respectively . After 4 months , the plasma phospholipid docosahexaenoic acid content of the docosahexaenoic acid group was 8 % higher ( 3.40 + /- 0.97 mg/dL ) , whereas that of the placebo group was 31 % lower ( 2.27 + /- 0.87 mg/dL ) . Despite the higher plasma phospholipid docosahexaenoic acid content of the supplemented group after 4 months , there was no difference between groups in either self-rating or diagnostic measures of depression ; information processing scores of the two groups also did not differ . CONCLUSION Docosahexaenoic acid supplementation ( approximately 200 mg/d ) for 4 months after the delivery prevented the usual decline in plasma phospholipid docosahexaenoic acid content of women who breastfeed but did not influence self-ratings of depression , diagnostic measures of depression , or information processing We investigated whether n-3 LCPUFA affected  immune function in late infancy and explored effect-modification by single nucleotide polymorphisms ( SNPs ) and links to intestinal microbiota . Infants ( n=105 ) were r and omized to fish oil ( FO , 1.2g/d n-3 LCPUFA ) or sunflower oil (SO)-supplements from age 9 - 18 months .  Immune function was assessed by ex vivo cytokine production in stimulated blood and plasma immunoglobulin E ( IgE ) . We genotyped functional SNPs in PPARG2 and COX2 and analyzed fecal microbiota by 16S-rRNA terminal restriction fragment length polymorphism . FO compared to SO reduced Lactobacillus paracasei-stimulated IL-6 at 18 months ( P=0.03 , n=104 ) . This effect was most pronounced among infants wild-type for PPARG2-Pro12Ala and /or COX2-T8473C ( P<0.05 ) . Predominant bacterial fragments were associated with 18 months IgE in all infants ( P=0.004 ) ( bp100 ) and with IL-6 production among infants weaned before 9 months ( P=0.047 ) ( bp102 ) . Thus , FO  reduced IL-6 in a genotype-modified manner . The microbiota was partly linked to IL-6 and IgE , not directly to FO OBJECTIVE To compare the effects of the exogenous supply of long-chain polyunsaturated fatty acids ( LCP ) and cholesterol on the lipid and fatty acid status in full-term , 4-month old infants . METHODS Twenty-three infants received a st and ard infant formula  while twenty-one were given a formula enriched with LCP and cholesterol in a prospect i ve , r and omized study . The composition of the two formulas differed only in fat quality . A group of fifteen breastfed infants fed was used as reference . No one was complemented with solid foods before blood sampling at 4 months of life . RESULTS Differences in total-cholesterol and low-density lipoprotein-cholesterol ( LDL-C ) levels between feeding groups were mainly gender-related . Dietary cholesterol tended to increase LDL-C plasma levels . The breastfed and the enriched formula-fed groups had higher levels of circulating LCP than the group that received the st and ard formula . In the erythrocytes of infants fed the st and ard formula , C22:6 n-3 levels were less than 50 % those of the breastfed and the enriched formula-fed ones . Higher C20:4 n-6 levels were found in the erythrocytes of the enriched formula-fed group . CONCLUSIONS Formula-fed , full-term infants maintain a lipid and fatty acid status close to that of breastfed infants when supplied with dietary LCP and cholesterol BACKGROUND The prevalence of atopic dermatitis ( AD ) , a chronic skin disease , has increased substantially in recent decades , and different factors have been implicated in its etiology . Although dietary habits are being investigated , few conclusive findings have been reported . Nevertheless , increased consumption of polyunsaturated fatty acids ( PUFA ) and a diet poor in antioxidants have been related to AD . OBJECTIVES The objectives of this study were to investigate the association between AD , the intake of different foods , and the effect of a Mediterranean diet among Spanish schoolchildren aged 6 to 7 . METHODS We performed a cross-sectional study with 20 106 schoolchildren aged 6 - 7 years from 10 different areas of Spain . The participation rate was 76.50 % . The prevalence of AD was assessed using the International Study of Asthma and Allergies in Childhood question naire and the criteria of the Spanish Academy of Dermatology . To calculate the Mediterranean diet score , we classified food into 2 groups : Mediterranean food , including fruit , seafood , vegetables , pulses , cereals , pasta , rice , and potatoes ; and non-Mediterranean food , including meat , milk , and fast food . RESULTS Milk was negatively associated with AD . Butter and nuts also were negatively associated , although statistical significance was only reached when these foods were consumed 3 or more times a week . CONCLUSIONS We found no association between the  Mediterranean diet score  and AD and a positive association between AD and obesity n-3 long-chain polyunsaturated fatty acids ( n-3 LCPUFA ) , from fish oil ( FO ) , in rodents have been shown to reduce adipogenesis . Evidence of an effect on adipose tissue mass in humans is limited , and no studies have specifically aim ed to eluci date this in infancy . To explore whether n-3 LCPUFA intake affects adipose tissue growth , we r and omly allocated 154 healthy infants to daily supplementation with FO or sunflower oil ( SO ) from 9 to 18 mo of age and measured z-score changes in various anthropometric assessment s of body size and skinfold thicknesses and plasma adipokine concentrations . Among the 133 completing infants , erythrocyte n-3 PUFA increased more in those receiving FO than in infants receiving SO [ 12.2 ± 0.7 ( mean ± SE ) versus 2.0 ± 0.4 fatty acid percentage ( FA% ) , p < 0.001 ] with a concomitant larger decrease in n-6 PUFA ( −8.9 ± 0.7 versus −0.9 ± 0.6 FA% , p < 0.001 ) . We found no association between FO  consumption relative to  SO consumption and any of the anthropometric measures related to the size of the fat mass , but infants in the FO group had a lower skinfold ratio ( triceps/subscapular ) at 18 mo than those in SO group ( p = 0.02 ) . Our findings do not support the hypothesis that dietary n-3 LCPUFA is important for infant fat mass , but future studies testing this specifically are warranted One hundred and sixty‐two women with respiratory allergy to animal d and ers and /or pollens were r and omly allocated to a diet consisting of either a very low ingestion of hens ' egg and cows ' milk or a daily ingestion of one hens ' egg and about 11 of cows ' milk during the last 3 months of pregnancy .  One hundred and sixty‐three infants were followed prospect ively up to 18 months of age when the cumulated incidence of atopic disease in each child was evaluated blindly . No significant differences in the distribution of atopic disease were found among the infants in relation to the maternal diet during late pregnancy . The numbers of skin‐prick tests positive to ovalbumin , ovomucoid , β‐lactoglobulin and cows ' milk were likewise not influenced by differences in the maternal diet during late pregnancy . Genetic factors rather than maternal diet during the perinatal period probably have a greater effect on the incidence of atopic diseases during early infancy BACKGROUND Early life exposures may be important in the development of asthma and allergic disease . OBJECTIVE To test house dust mite ( HDM ) avoidance and dietary fatty acid modification , implemented throughout the first 5 years of life , as interventions to prevent asthma and allergic disease . METHODS We recruited newborns with a family history of asthma antenatally and r and omized them , separately , to HDM avoidance or control and to dietary modification or control . At age 5 years , they were assessed for asthma and eczema and had skin prick tests for atopy . RESULTS Of 616 children r and omized , 516 ( 84 % ) were evaluated at age 5 years . The HDM avoidance intervention result ed in a 61 % reduction in HDM allergen concentrations ( microg/g dust ) in the child 's bed but no difference in the prevalence of asthma , wheeze , or atopy ( P > .1 ) . The prevalence of eczema was higher in the active HDM avoidance group ( 26 % vs 19 % ; P = .06 ) . The ratio of omega-6 to omega-3 fatty acids in plasma was lower in the active diet group ( 5.8 vs 7.4 ; P < .0001 ) . However , the prevalence of asthma , wheezing , eczema , or atopy did not differ between the diet groups ( P > .1 ) . CONCLUSION Further research is required to establish whether other interventions can be recommended for the prevention of asthma and allergic disease . CLINICAL IMPLICATION S House dust mite avoidance measures and dietary fatty acid modification , as implemented in this trial during infancy and early childhood , did not prevent the onset of asthma , eczema , or atopy in high-risk children The effect of genetic and environmental factors on the prevalence of allergic disorders in early childhood was determined in a prospect i ve follow‐up study . Information was available on 1174 children at the age of 2 years . Two‐hundred and seventy‐five were considered to have an allergic disorder . The prevalence varied from 3.2 % for rhinitis to 10.9 % , for asthma . At 2 years 60 children reacted positively on skin‐prick test ( SPT ) . Multivariate logistic regression analysis was used to obtain adjusted odds ratios ( 95 % confidence interval ) for each factor . For asthma , positive family history , male sex , low birth‐weight , maternal smoking and season of birth were significant risk factors . For eczema , positive family history was the only significant risk factor . For rhinitis , lower socio‐economic group and autumn birth were significant . Maie sex and low birth‐weight were significant for skin test positivity . Positive family history and low birth‐weight were significant risk factors for any allergy . Low birth‐weight was also a significant risk for skin test reactivity to house dust mite . Genetic and environmental factors have a profound effect on the development of allergic disorders in the first two years of life Background : Extrauterine growth restriction is common among very low birth weight infants ( VLBW , BW < 1,500 g ) . Optimal postnatal nutrient supply is essential to limit growth restriction and ensure adequate growth and neurodevelopment . Objectives : We compared an enhanced postnatal nutrient supply to a st and ard supply and evaluated the effects on growth velocity , head circumference growth and cerebral maturation - the latter by magnetic resonance diffusion tensor imaging ( DTI ) . We hypothesized increased growth velocity , head circumference growth and decreased mean diffusivity ( MD ) in cerebral white matter ( WM ) areas , suggesting improved cerebral maturation among infants on the enhanced nutrient supply . Methods : In this r and omized controlled trial , infants on the enhanced nutrient supply received increased amounts of energy , protein , fat , essential fatty acids and vitamin A until discharge . DTI was performed close to term equivalent age . Outcomes were growth velocity , head circumference growth and WM mean diffusivity . Results : Among the 50 included infants , 14 in the intervention group and 11 controls underwent a successful DTI . Infants on the enhanced diet achieved improved growth velocity ( 16.5 vs. 13.8 g/kg/day , p = 0.01 ) and increased head circumference ( Δz score : 0.24 vs. -0.12 , p = 0.15 ) . A significantly lower MD was seen in a large WM area such as the superior longitudinal fasciculi ( 1.19 × 10 - 3 vs. 1.24 × 10 - 3 mm2/s , p = 0.04 , adjusted for age when scanned ) . Conclusions : Enhanced nutrient supply to VLBW infants is associated with improved growth velocity , increased head circumference growth and decreased regional WM mean diffusivity , suggesting improved maturation of cerebral connective tracts The influence of dietary long chain polyunsaturated fatty acid ( LCP ) supply , and especially of docosahexaenoic acid ( DHA ) , on evoked potential maturation , was studied in 58 healthy preterm infants using flash visual evoked potentials ( VEPs ) , flash electroretinography ( ERG ) , and brainstem acoustic evoked potentials ( BAEPs )  at 52 weeks of postconceptional age . At the same time , the fatty acid composition of red blood cell membranes was examined . The infants were fed on breast milk ( n = 12 ) , a preterm formula supplemented with LCP ( PF-LCP ) ( n = 21 ) , or a traditional preterm formula ( PF ) ( n = 25 ) . In the breast milk and PF-LCP groups the morphology and latencies of the waves that reflect the visual projecting system were similar ; in the PF group the morphology was quite different and the wave latencies were significantly longer . This could mean that the maturation pattern of VEPs in preterm infants who did not receive LCP was slower . Moreover , a higher level of erythrocyte LCP , especially DHA , was found in breast milk and PF-LCP groups compared with the PF group . ERG and BAEP recordings were the same in all three groups . These results suggest that a well balanced LCP supplement in preterm formulas can positively influence the maturation of visual evoked potentials in preterm infants when breast milk is not available In view of the importance of long-chain polyunsaturated fatty acids ( LCP ) for growth and development of fetal and infant neural tissue , the influence of the dietary n-3 and n-6 LCP intake on the LCP status of forty-three preterm infants ( birth weight < 1800 g ) was studied . Thirty-one formula-fed infants were r and omly assigned to receive a conventional formula lacking LCP ( n 16 ) , or an 22:6n-3- and 20:4n-6-enriched formula ( n 15 ) ; twelve infants received their own mother 's breast milk .  Fatty acid compositions of plasma and erythrocyte ( RBC ) phospholipids ( PL ) were determined in umbilical venous blood , in weekly postnatal sample s until day 35 of life and , for the formula-fed infants , at 3 months of corrected age . Both in plasma ( P < 0.001 ) and RBC ( P < 0.01 ) PL , the changes with time until day 35 for 22:6n-3 and 20:4n-6 in the two groups of formula-fed infants were significantly different , with higher values , comparable with those of human-milk-fed infants , in the LCP-enriched-formula group . At 3 months of corrected age , differences between the two formula-fed groups were even more pronounced . In conclusion , adding 22:6n-3 and 20:4n-6 to artificial formulas in balanced ratios and in amounts similar to those found in preterm human milk raises both the 22:6n-3 and the 20:4n-6 status of formulated preterm infants to values found for human-milk-fed preterm infants . Additional studies are necessary to evaluate the potentially favourable effects of this combined addition on the neurodevelopmental outcome of preterm infants The nutritional requirements of preterm infants for the long chain polyunsaturated essential fatty acids , arachidonic acid ( AA ) and docosahexaenoic acid ( DHA ) , have not been clearly defined . The present study evaluated preterm infants of less than 2.3 kg birth weight fed a commercial formula ( Preemie SMA ® ) devoid of AA and DHA  and compared this control group with similar infant groups fed one of three formulas containing a range of 0.32 to 1.1 % AA and 0.24 to 0.76 % DHA . An analogous group of infants fed their mothers ' breast milk and a breast milk fortifier  ( when indicated ) was also studied . Erythrocyte membrane phospholipids were isolated from blood sample s collected at 12 d of age and after a further 4 wk of feeding . Infants fed the formula without AA and DHA showed a reduction in AA level in erythrocyte phosphatidylcholine , and a reduced level of DHA in phosphatidylethanolamine in comparison with infants fed breast milk or infant formula containing AA and DHA . Supplementing infant formula with increasing levels of AA and DHA produced a clear dose response in the levels of AA and DHA found in erythrocyte membrane phospholipids . From comparison of membrane phospholipid fatty acid composition it appears that a formula level of 0.32 - 1.1 % AA and 0.24 - 0.76 % DHA provides sufficient levels of these fatty acids to achieve a similar fatty acid composition to that of infants fed human milk for most of the lipid fractions examined The influence of dietary omega-3 fatty acid supply on visual acuity development was evaluated in very low birth weight ( VLBW ) infants using visual-evoked potential ( VEP ) and forced-choice preferential-looking ( FPL ) procedures at 36 and 57 wk postconception . The VLBW infants born at 27 - 33 wk postconception were r and omized to one of three diet groups : corn oil , which provided solely linoleic acid ; soy oil , which provided linoleic and alpha-linolenic acids ; or soy/marine oil ; which was similar to the soy oil formula but also provided preformed long chain omega-3 fatty acids . The VLBW infants in the soy/marine oil group had higher omega-3 levels in erythrocyte membranes and better VEP and FPL acuities at 36 and 57 wk than infants in the corn oil group . The soy oil group had intermediate omega-3 levels in erythrocyte membranes and significantly poorer VEP acuity at 57 wk compared with the soy/marine oil group . Only the soy/marine oil group had acuities comparable to the " gold st and ards " of VLBW infants fed human milk and preterm infants who were born and tested at 35 - 36 wk postconception . In addition , VEP and FPL acuity were poorer in a nonr and omized group of formula-fed full-term infants than in breast-fed full-term infants . The results suggest that dietary omega-3 fatty acid supply may play an important role in early human visual development OBJECTIVE To test the hypothesis that in the premature infant with an enterostomy , early enteral supplementation with Microlipid ( fat supplement ) and fish oil increases enteral fat absorption and decreases the requirement for Intralipid ( intravenous fat emulsion ) . STUDY DESIGN Premature infants ( < 2 months old ) with an enterostomy after surgical treatment for necrotizing enterocolitis or spontaneous intestinal perforation and tolerating enteral feeding at 20 mL/kg/day were r and omized to usual care ( control 18 infants ) or early supplementing enteral fat and fish oil ( treatment 18 infants ) .  Intravenous fat emulsion was decreased as enteral fat intake was increased . Daily weight , ostomy output , and nutrition data were recorded . Weekly 24-hour ostomy effluent was collected until bowel reanastomosis , and fecal fat , fecal liquid , and dry feces were measured . Fat absorption ( g/kg/d ) was calculated by subtracting fecal fat from dietary fat . The fecal liquid and dry feces were reported as mg/g wet stool . Date were analyzed by using ANOVA and mixed-effects model . RESULTS The interval from initial postoperative feeding to bowel reanastomosis varied from 2 to 10 weeks . The treatment group received more  dietary fat  and less  intravenous fat emulsion  and had higher enteral fat absorption , less fecal liquid , and drier feces than the control group . These effects were greater among infants with a high ostomy compared with those with a low ostomy . Enteral fat intake was significantly correlated with fat absorption . CONCLUSION Early enteral fat supplement and fish oil increases fat absorption and decreases the requirement for intravenous fat emulsion .  This approach could be used to promote bowel adaptation and reduce the use of intravenous fat emulsion in the premature infant with an enterostomy BACKGROUND Long-chain polyunsaturated fatty acids ( LCPUFA ) are important for normal visual and brain development . Although present in human milk , LCPUFA have until recently been absent from artificial formulas , and infants may have limited ability to synthesis e LCPUFA . To determine the clinical significance of this relative deficiency of LCPUFA , we undertook a r and omised trial of the relation between LCPUFA supplementation and infant cognitive behaviour . METHODS 44 term infants had been r and omised to a formula supplemented with LCPUFA ( 21 ) or not supplemented with LCPUFA ( 23 ) , which they had taken from birth to age 4 months .  Infant cognitive behaviour was assessed at 10 months of age by a means-end problem-solving test -- the intentional execution of a sequence of steps to achieve a goal . The problem required three intermediate steps to achieve the final goal , uncovering and retrieving a hidden toy . FINDINGS Infants who received LCPUFA-supplemented formula had significantly more intentional solutions than infants who received the no-LCPUFA formula ( median 2.0 vs 0 , p=0.021 ) . Intention scores ( median 14.0 vs 11.5 [ maximum 18 ] ) were also increased in this group ( p=0.035 ) . INTERPRETATION These findings suggest that term infants may benefit from LCPUFA supplementation , and that the effects persist beyond the period of supplementation . Since higher problem-solving scores in infancy are related to higher childhood IQ scores , supplementation with LCPUFA may be important for the development of childhood intelligence BACKGROUND Studies investigating cognitive outcomes following docosahexaenoic acid ( DHA ) supplementation of infant formula yield conflicting results , perhaps due to inadequate dietary concentrations . AIM To determine the optimal DHA concentration in term formula to support cognitive maturation . DESIGN This was a double-masked , r and omized , controlled , prospect i ve trial . A total of 181 infants were enrolled at 1 - 9 days of age and assigned r and omly to receive one of four term infant formulas with one of four levels of docosahexaenoic acid : Control ( 0 % DHA ) , 0.32 % DHA , 0.64 % DHA , or 0.96 % DHA . All DHA-supplemented formulas contained 0.64 % arachidonic acid ( ARA ) .  Infants were fed the assigned formulas until 12 months of age . One hundred forty-one children completed the 12-month feeding trial and were eligible for this study .  Cognitive function was assessed in 131 children at 18 months of age using the Bayley Scales of Infant Development II ( BSID II ) . RESULTS There were no diet group differences on the Mental Development Index ( MDI ) , the Psychomotor Development Index ( PDI ) , or the Behavior Rating Scale ( BRS ) of the BSID II . However , when the scores of children who received any of the three DHA-supplemented formulas were combined and compared to control children , a significant difference emerged : the MDI scores of DHA-supplemented children were higher ( 104.1 v. 98.4 ; p=0.02 ) . CONCLUSIONS These results suggest that dietary supplementation of DHA during the first year of life leads to enhanced cognitive development at 18 months of age . DHA concentration of 0.32 % is adequate to improve cognitive function ; higher concentrations did not confer additional benefit BACKGROUND The effect of long-chain polyunsaturated fatty acid ( LCPUFA ) intake on cognitive development is controversial . Most r and omized trials have assessed cognition at 18 mo , although significant development of cognitive abilities ( early executive function ) emerge later . OBJECTIVE The objective was to evaluate cognition beyond 18 mo and longitudinal cognitive change from 18 mo to 6 y in children who were fed variable amounts of docosahexaenoic acid ( 0.32 % , 0.64 % , and 0.96 % of total fatty acids ) and arachidonic acid ( ARA ; 0.64 % ) compared with children who were not fed LCPUFA as infants . DESIGN Eighty-one children ( 19 placebo , 62 LCPUFA ) who participated in a double-blind , r and omized trial of LCPUFA supplementation as infants were re-enrolled at 18 mo and tested every 6 mo until 6 y on age-appropriate st and ardized and specific cognitive tests . RESULTS LCPUFA supplementation did not influence performance on st and ardized tests of language and performance at 18 mo ; however , significant positive effects were observed from 3 to 5 y on rule-learning and inhibition tasks , the Peabody Picture Vocabulary Test at 5 y , and the Weschler Primary Preschool Scales of Intelligence at 6 y. Effects of LCPUFAs were not found on tasks of spatial memory , simple inhibition , or advanced problem solving . CONCLUSIONS The data from this relatively small trial suggest that , although the effects of LCPUFAs may not always be evident on st and ardized developmental tasks at 18 mo , significant effects may emerge later on more specific or fine-grained tasks . The results imply that studies of nutrition and cognitive development should be powered to continue through early childhood . This parent trial was registered at clinical trials.gov as NCT00266825 To determine whether docosahexaenoic acid ( DHA ) supplementation of breast-feeding mothers increases the DHA contents of breast milk and infant plasma phospholipids ( PPs ) , breast-feeding women were r and omly assigned to 3 DHA-supplementation groups ( 170 - 260 mg/d ) or a control group . Group 1 ( n = 6 ) consumed an algae-produced high-DHA triacylglycerol ; group 2 ( n = 6 ) consumed high-DHA eggs ; group 3 ( n = 6 ) consumed a high-DHA , low-eicosapentaenoic acid marine oil ; and group 4 ( n = 6 ) received no supplementation . From before to after supplementation ( 2 and 8 wk postpartum ) , mean ( + /-SD ) maternal PP DHA increased in groups 1 , 2 , and 3 by 1.20 + /- 0.53 , 0.63 + /- 0.82 , and 0.76 + /- 0.35 mol% of fatty acids , respectively ( 23 - 41 % ) , but decreased in group 4 by 0.44 + /- 0.34 mol% ( 15 % ) . Breast-milk DHA of groups 1 , 2 , and 3 increased by 0.21 + /- 0.16 , 0.07 + /- 0.11 , and 0 . 12 + /- 0.07 mol% , respectively ( 32 - 91 % ) but decreased in group 4 by 0.03 + /- 0.04 mol% ( 17 % ) . Mean infant PP DHA in groups 1 , 2 , and 3 increased by 1.63 + /- 0.79 , 0.40 + /- 1.0 , and 0.98 + /- 0.61 mol% , respectively ( 11 - 42 % ) , but only by 0.18 + /- 0.74 mol% ( 5 % ) in group 4 . Correlations between the DHA contents of maternal plasma and breast milk and of milk and infant PPs were significant . Breast-milk and maternal and infant PP 22:5n-6 concentrations were lowest in group 2 . DHA supplementation increases the plasma and breast-milk DHA concentrations of lactating women , result ing in higher PP DHA concentrations in infants The effect of breast-feeding was compared with that of two fat-modified milk formulas in 45 infants ( 15 per group ) studied by assessing  body weight gain  for 4 months and plasma lipids , lipoprotein profiles , fatty acid profiles of plasma and red blood cells , and plasma tocopherol status 3 months after birth . A saturated fat formula with coconut oil/soybean oil ( COCO/SOY ) had a fatty acid content and polyunsaturated/saturated ratio ( P/S , 0.55 ) comparable with that of human milk fat ( P/S , 0.39 ) and had the same fat energy content ( 50 % kcal ) . The second formula , with corn oil/soybean oil ( CORN/SOY ) , was highly unsaturated ( P/S , 4.6 ) , with only 35 % kcal from fat . Energy intake and body weight gain were similar for all groups . Plasma total cholesterol , triglyceride , and phospholipid levels were significantly lower ( greater than 20 % on average ) in infants fed the CORN/SOY formula than in infants fed either the COCO/SOY formula or human milk . Infants fed the CORN/SOY formula also had lower ( 25 % to 35 % ) plasma low-density lipoprotein cholesterol and apolipoprotein B levels and low-density lipoprotein/high-density lipoprotein and apolipoprotein B/apolipoprotein A-I ratios . Plasma , red blood cell , and cholesteryl ester fatty acids from infants fed COCO/SOY contained less 18:1 and more 18:2 ; cholesterol esters in plasma from breast-fed infants had the highest 20:4n-6 levels . Plasma tocopherol levels were higher in infants consuming formulas . The presence of cholesterol in human milk appeared to exp and the low-density lipoprotein pool and exert an " unfavorable " increase in the low-density lipoprotein/high-density lipoprotein ratio . Thus modulation of infant lipoproteins by changing dietary fat and cholesterol is feasible and in keeping with the known response in adults Presently , there is growing interest in long-chain polyunsaturated fatty acids ( LCPUFAs ) , which are considered a major determinant of growth , visual and neural development , and long-term health.1 Two groups of LCPUFAs have received special interest : homologues of linoleic acid ( LA ) of the n-6 series , which are precursors of arachidonic acid ( AA ) , and homologues of α-linolenic acid ( ALA ) of the n-3 series , which are precursors of eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) Background / Aims : The supply of docosahexaenoic acid ( DHA , 22:6ω–3 ) , important for fetal/infant neurodevelopment , depends on the maternal fatty acid ( FA ) status , which may be marginal in central Europe . Therefore , we investigated the effect of a daily vitamin/mineral supplement with and without 200 mg DHA from mid-pregnancy through lactation on the DHA concentrations in maternal and infant red blood cell phospholipids ( RBC% ) , and in breast milk FA ( % ) . Methods : At 21 weeks ’ gestation , 144 women were enrolled into a r and omised , double-blind clinical trial receiving daily : ( 1 ) a basic vitamin-mineral supplement ( Vit/Min group ) , ( 2 ) Vit/Min plus 4.5 g fructo-oligosaccharide ( FOS group ) , or ( 3 ) Vit/Min plus 4.5 g FOS plus 200 mg fish oil-derived DHA ( DHA-FOS group ) . FAs were determined by capillary gas-liquid chromatography . Results : While maternal RBC-DHA% at enrolment was not different , at 37 weeks gestation , and 3 months after delivery RBC-DHA% were significantly higher in the DHA-FOS group . The breast milk DHA% was twice as high in the DHA-FOS group ( 0.50 % ) than in the two others ( 0.25 % ) ( p < 0.001 ) , and the ratio ARA/DHA in the DHA-FOS group was 1.0 ± 0.43 , in the others 2.1 ± 0.43 ( p < 0.001 ) . The RBC-DHA% of the infants in the DHA-FOS group was also significantly higher , and correlated significantly with maternal RBC-DHA% before and 3 months after delivery . Conclusions : In central Europe , a dose of 200 mg/day DHA from mid-pregnancy through lactation seems appropriate to improve the DHA status of mothers and infants Background / objective : Long chain polyunsaturated fatty acids have beneficial effects in preterm neurophysiological development and are semi-essential . Their levels and variation in plasma and red cells in term and preterms are better known than their intestinal absorption . In this paper the absorption of supplemented arachidonic acid ( AA ) and docosahexaenoic acid ( DHA ) is evaluated in a preterm group . Design : Four newborn r and omized groups were studied . Group T comprised 11 terms on regular formula . Preterms : group P ( n=9 ) was on a classic preterm formula . Intervention : groups PA ( n=9 ) and PB ( n=13 ) were on the same formula but PB contained AA and DHA in similar proportion to breast milk . At 20 days a 3 day metabolic balance was taken for Ca , Pi , Mg , total fat and individual fatty acids ( C8–C24 , saturated unsaturated ) . Results : Calcium absorption was ( mean±s.d . ) 51±13 % in terms . In preterms it was respectively 45±18 , 38±11 and 37±21 % . Total fat absorption was 92.0±8.0 % in terms , and from 95.0±2.0 to 91.0±8.0 % in preterms . Absorption of 8:0 , 10:0 and 12:0 showed a very high and constant rate despite significant intake differences ( 715–33 mg/kg/day ) . Linoleic acid and α-linolenic acid were absorbed in the three groups at around 94 % regardless of a greater LA intake in group P. Details of absorption ( mg/kg/day ) were : for AA , intake 17±7 , fecal excretion 5±4 , net retention 12±5 ( 75.0±18 % ) ; for DHA , intake 10±3 , fecal excretion 3±2 , net retention 6±4 ( 62.3±30 % ) . Conclusion : Intestinal absorption of fatty acids is high and is comparable in terms and preterms as regards the studied acids . Longer acids were less well absorbed . The supplemented amounts of AA and DHA  were less well absorbed and probably not impairing calcium absorption . Sponsorship : University of Alicante , University of Miguel Hernández . European Journal of Clinical Nutrition ( 2001 ) 55 , BACKGROUND & AIMS Protein source , macronutrient composition and content of long chain-polyunsaturated fatty acids ( LC-PUFA ) of infant formulae may influence infant growth . We aim ed to assess the effect of a modified infant formula on growth . METHODS In a r and omized , double-blind trial , 213 healthy term infants consumed  isoenergetic study formulae ( intervention formula - IF , control formula - CF ) from the first month of life until the age of 120 days . IF ( 1.89 g protein/100 kcal ) contained α-lactalbumin ( ALAB ) and LC-PUFA , while CF ( 2.30 g protein/100 kcal ) provided st and ard whey and no LC-PUFA . Anthropometry and dietary intake were regularly assessed . A venous blood sample was obtained on day 120 . RESULTS Both formulae were well-accepted without significant differences in health related observations . Weight gain was not statistically different between formula groups ( IF : 30.2 ± 6.3 vs. CF : 28.3 ± 6.5 g/day , mean ± SD , P = 0.06 ) . Length gain was higher in IF ( 0.11 ± 0.02 vs. 0.10 ± 0.02 cm/day , P = 0.02 ) . Energy intake from formula was higher in CF at 90 and 120 days ( IF : 509 ± 117 and 528 ± 123 vs. CF : 569 ± 152 and 617 ± 169 kcal/day , P < 0.01 ) . Protein intake in CF was significantly higher at each assessment . Growth per energy intake was higher in IF compared to CF for weight ( 6.45 ± 2.01 vs. 5.67 ± 2.21 g/100 kcal , P = 0.02 ) and length ( 0.23 ± 0.08 vs. 0.20 ± 0.08 mm/100 kcal , P = 0.04 ) . CONCLUSIONS The modified infant formula with reduced protein content with added ALAB and LC-PUFA , meets infant requirements of protein for adequate growth . The increased energetic efficiency of the new infant formula might result from improved protein composition by added ALAB . Apparently minor differences in composition can markedly affect energetic efficiency for growth . The study was registered at Clinical Trials.gov ( NCT01094080 ) This study examines whether feeding infants formula supplemented with long-chain polyunsaturated fatty acids ( LCPUFA ) improves cognitive function of 9-month-olds . Participants included 229 infants from 3 r and omized controlled trials . Children received either formula supplemented with docosahexaenoic acid and arachidonic acid , or a control formula beginning at 1 - 5 days ( 12-month feeding study ) , or following 6 weeks ( 6-week-weaning study ) or 4 - 6 months of breastfeeding ( 4-to 6-month weaning study ) . Infants were assessed with a 2-step problem solving task . In the 12-month feeding and 6-week weaning studies , supplemented children had more intentional solutions ( successful task completions ) and higher intention scores ( goal -directed behaviors ) than controls . These results suggest that LCPUFA supplementation improves means-end problem solving OBJECTIVE To analyze cytokine responses and the clinical course of septic neonates orally supplemented with docosahexaenoic acid as well as to evaluate fatty acid incorporation into leukocytes . METHODS A quasiexperimental study was conducted in neonates who developed sepsis following a surgical procedure . Selected neonates were r and omly assigned to receive 100 mg docosahexaenoic acid ( G-DHA ) daily or olive oil ( G-OO ) as placebo for 14 d throughout a sepsis episode . At selection ( baseline ) , blood sample s were obtained to determine interleukin-1 (IL-1)β , interleukin-6 ( IL-6 ) , and tumor necrosis factor-α as well as the leucocyte fatty acid profile . Measurements were repeated at 7 ( D7 ) and 14 d ( D14 ) of follow-up . Within- and between-group comparisons were conducted with parametric statistics after logarithmic transformation . Repeated measurement analyses with a general linear model procedure were used , adjusting according to human milk intake , use of anti-inflammatory drugs , and nutritional status . RESULTS Sixty-three neonates were included : 29 in G-DHA group and 34 in G-OO group . Although decreases of cytokines during hospitalization were similar in both groups , there was a greater decrease of IL-1β in the G-DHA group than in the G-OO group after adjusting by confounders ( P = 0.028 ) . Leukocyte docosahexaenoic acid increased from 4.96 ± 2.96 at baseline to 5.52 ± 3.05 and 5.92 ± 2.8 at D7 and D14 , respectively , in the G-DHA group ( P = 0.044 ) . Illness severity was inversely associated with the proportion of docosahexaenoic acid in leukocytes throughout follow-up ( P = 0.034 ) . CONCLUSIONS Oral supplementation with docosahexaenoic acid to neonates  attenuates IL-1β response and the clinical course of sepsis . This may be an additional strategy to further benefit ill neonates even if they are not c and i date s for parenteral nutrition Summary .Long-chain polyunsaturated fatty acids ( LCP ) are considered conditionally essential nutrients for the infant born prematurely , and attempts are being made to match fatty acid profiles of formula and breast fed infants . In this double-blind , r and omized study we investigated the effects of a formula enriched with both n-6 and n-3 LCP on plasma fatty acid profiles , antioxidant status and growth of premature infants . 29 infants received either a formula devoid of LCP or a LCP supplemented formula ( 0.5 g/100 g fat linoleic acid metabolites , 0.8 g/100 g fat α-linolenic acid metabolites ) . 17 breast fed infants served as a control group . At study entry as well as two and four weeks later , plasma and urine sample s were collected , growth data obtained and food tolerance was documented . At the end of the four week study period , plasma docosahexaenoic acid ( DHA ) levels of supplemented infants were significantly higher than those of unsupplemented infants and similar to those of infants fed human milk . Plasma n-6 LCP concentrations including arachidonic acid ( AA ) were similar between groups . The plasma α-tocopherol levels of breast fed and supplemented infants were similar and tended to be lower than in infants fed the formula devoid of LCP . Urinary malondialdehyde ( MDA ) excretion of formula fed infants was significantly higher compared to infants fed human milk , but did not differ between the two formula groups . Parameters of growth and milk tolerance did not differ between groups . Our results demonstrate that plasma LCP levels similar to those of breast fed infants can be achieved with the LCP supplemented formula used in this trial , without evidence of adverse effects of the LCP enrichment Objectives : To determine the effect of increasing docosahexaenoic acid ( DHA , 22 : 6 n-3 ) in breast milk on infant fatty acid profiles . A secondary aim was to examine aspects of neural development . Design and Setting Double blind , placebo controlled study of infants recruited from postnatal wards at Flinders Medical Centre . Subjects : Fifty-two healthy term infants who were breast fed for at least 12 weeks and were from middle class families . Intervention : Breast milk with DHA concentrations that ranged from 0.1–1.7 % of total fatty acids . This was achieved by supplementation of the maternal diet for the first 12 weeks post partum . Results : Breast milk DHA was related to infant plasma ( r=0.89 , P<0.001 ) and erythrocyte ( r=0.88 , P<0.001 ) phospholipids in a saturable curvilinear manner so that breast milk DHA above 0.8 % of total fatty acids result ed in little further increase in infant plasma or erythrocyte DHA levels . The rise in plasma and erythrocyte DHA was approximated by a fall in total n-6 polyunsaturated fatty acids . We could detect no relationship between visual evoked potential acuity ( measured at 12 and 16 weeks ) of infants by either the dietary grouping or the DHA status of individuals . A stepwise multiple regression showed that infant erythrocyte DHA at 12 weeks and home stimulation were the only independent factors associated with Bayley 's MDI at 1 y ( adjusted model r2=0.18 , P<0.005 ) ; while at 2 y gender and social score of the spouse were the only significant predictors of Bayley 's MDI ( adjusted model r2=0.22 , P<0.005 ) . Conclusions : Increasing breast milk DHA levels caused a dose dependent saturable increase in infant plasma and erythrocyte phospholipid DHA . There were no long-term effects of infant DHA status on indices of neurodevelopment . Sponsorship : Financial support was provided by Martek Biosciences , MD , USA and the National Health and Medical Research Council , Australia Objective To test the hypothesis that consumption of infant formulas containing long-chain polyunsaturated fatty acids ( LCPUFAs ) by preterm infants would favourably influence growth , body composition and blood pressure ( BP )  at age 10 years . Methods This was a follow-up study of a preterm cohort ( < 35 weeks and birth weight < 2000 g ) r and omly assigned to unsupplemented or LCPUFA-supplemented formulas to 9 months post term . The setting was a research clinic at Yorkhill Hospital for Sick Children , Glasgow , UK . A total of 107 children aged 9–11 years who participated in the original r and omised controlled trial ( 45 % follow-up ) took part . Main outcome measures were : ( 1 ) anthropometry , ( 2 ) body composition and ( 3 ) BP . Results There were no differences in growth or BP between r and omised groups for the whole cohort . However , girls who had received LCPUFA-supplemented formula were heavier ( 42.20 ( SD 9.61 ) vs 36.94 ( 9.46 ) kg , p=0.05 ) , had greater skin fold thicknesses ( biceps 10.7 ( 3.3 ) vs 8.5 ( 3.6 ) mm , p=0.03 ; suprailiac 16.7 ( 8.2 ) vs 12.0 ( 7.5 ) mm , p=0.03 ) and higher BP ( mean 82.2 ( 8.4 ) vs 78.1 ( 6.2 ) mm Hg , p=0.04 : systolic 111.4 ( 10.1 ) vs 105.9 ( 9.0 ) mm Hg , p=0.04 : diastolic 64.8 ( 8.4 ) vs 61.1 ( 5.4 ) mm Hg , p=0.05 ) . Differences in weight SD score ( 0.85 ( 95 % CI 0.13 to 1.58 ) , p=0.02 ) , Ln sum of skin fold thicknesses ( 0.27 ( 0.02 to 0.52 ) , p=0.04 ) and BP ( mean 4.6 mm Hg ( 0.43 to 8.84 ) , p=0.03 ; systolic 6.1 ( 0.45 to 11.7 ) , p=0.04 ) remained after adjustment for prer and omisation confounders . Differences in BP were not significant following adjustment for current weight . Conclusions Girls born preterm and r and omised to LCPUFA-supplemented formula showed increased weight , adiposity and BP at 9–11 years , which might have adverse consequences for later health . No effects were seen in boys . Long-term follow-up of other LCPUFA supplementation trials is required to further investigate this finding BACKGROUND The Childhood Asthma Prevention Study was a r and omized controlled trial conducted in children with a family history of asthma in whom  omega-3 fatty acid supplementation and restriction of dietary omega-6 fatty acids did not prevent asthma , eczema , or atopy at age 5 years . OBJECTIVE We sought to examine the relation of all measures of omega-3 and omega-6 polyunsaturated fatty acids with outcomes at age 5 years in the whole birth cohort , regardless of r and omization group . METHODS Plasma fatty acids were measured at 18 months , 3 years , and 5 years . Compliance with the fatty acid supplements was estimated every 6 months . Dietary intake  was assessed at 18 months by means of weighed-food record and at 3 years by means of food-frequency question naire . At age 5 years , 516 children were examined for wheeze and eczema  ( question naire ) and atopy ( skin prick tests , n = 488 ) . Multiple logistic regression was used to evaluate associations between exposures and outcomes . RESULTS Plasma levels of omega-3 or omega-6 fatty acids were not associated with wheeze , eczema , or atopy at age 5 years ( P = .11-.96 ) . Overall , fatty acid exposure , measured as plasma levels , dietary intake , and compliance with supplements , was not associated with any respiratory or allergic outcomes ( P = .35-.59 ) . CONCLUSION This observational analysis of the cohort , using the full range of observed variation in omega-3 and omega-6 fatty acid exposure , supports the negative findings of the r and omized controlled trial . CLINICAL IMPLICATION S Modification of dietary polyunsaturated fatty acids in early childhood is not helpful in preventing atopy and asthma Adiponectin has potent insulin-sensitizing effects , improves lipid metabolism , and potentially protects against the development of metabolic syndrome . Thus , increasing adiponectin levels in preterm infants at risk for developing metabolic syndrome may be of special interest . The aim of this study was to examine the effects of dietary long-chain polyunsaturated fatty acids ( LCPUFA ) on serum adiponectin and lipid concentrations in preterm infants . Adiponectin and lipid levels of 60 healthy preterm infants [ gestational age 32.7 ( 1.9 ) wk ] r and omly assigned to be fed either 1 ) a formula containing LCPUFA [ arachidonic and docosahexanoic ] ( + LCPUFA group ) or 2 ) the same formula without LCPUFA ( −LCPUFA/control group ) , were determined at mean ( SD ) 33.8 ( 11.7 ) d. Adiponectin and HDL-C concentrations were significantly higher in the + LCPUFA group than in controls ( p = 0.002 and p = 0.01 , respectively ) ; whereas , triglyceride levels were lower ( p = 0.06 ) . Adiponectin correlated positively with HDL-C levels and negatively with triglyceride levels in the + LCPUFA group but not in the controls . In conclusion , circulating adiponectin concentrations were higher in preterm infants fed a formula containing LCPUFA than infants fed an LCPUFA-free formula and they correlated with lipidemic profile OBJECTIVES To determine the effect of alpha-linolenic acid ( ALA ) intake ( or the dietary linoleic acid [LA]/ALA ratio ) on the growth and visual function of term infants . STUDY DESIGN Normal term infants were assigned r and omly and in masked fashion at birth to receive formulas with approximately 16 % of total fatty acids as LA and 0.4 % , 1.0 % , 1.7 % , or 3.2 % of fatty acids as ALA ( LA/ALA ratios of 44 , 18.2 , 9.7 , and 4.8 ) for the first 4 months of life . The fatty acid pattern of plasma phospholipids was determined shortly after birth and at approximately 21 , 60 , and 120 days of age . Anthropometric data were obtained at the same times and also at approximately 240 days of age . Transient visual evoked responses ( VERs ) were measured at approximately 120 and 240 days of age . For comparisons , anthropometric and VER data also were obtained in infants who were exclusively breast-fed for the first 4 months of life . RESULTS Infants who received the formula with 3.2 % ALA ( LA/ALA ratio , 4.8 ) had higher plasma concentrations of phospholipid docosahexaenoic acid ( DHA ) but lower concentrations of arachidonic acid at 21 , 60 , and 120 days of age . Mean weight of this group at 120 days of age was 760 gm less ( p < 0.05 ) than the mean weight of the group that received the formula with 0.4 % ALA ( LA/ALA ratio , 44 ) . Despite differences in plasma phospholipid DHA contents among groups , neither VER latency nor amplitude differed significantly among formula groups or between any formula group and age-matched , breast-fed infants . CONCLUSIONS The highest versus the lowest ALA intake ( or the lowest vs the highest LA/ALA ratio ) result ed in higher plasma phospholipid DHA content from 21 to 120 days of age but was not associated with improved visual function as assessed by transient VER . Moreover , mean body weight of infants who received the highest versus lowest ALA intake was less at 120 days ( p < 0.05 ) . These data suggest that the lower LA/ALA ratios currently recommended for infant formulas should not be adopted until the effect of such ratios on growth are evaluated more completely The effects of dietary docosahexaenoic acid ( DHA ) supply during infancy on later cognitive development of healthy term infants were evaluated in a r and omized clinical trial of infant formula milk supplemented with 0.35 % DHA or with 0.36 % DHA and 0.72 % arachidonic acid ( AA ) , or control formula which provided no DHA or AA .  Fifty-six 18-month-old children ( 26 male , 30 female ) who were enrolled in the trial within the first 5 days of life and fed the assigned diet to 17 weeks of age were tested using the Bayley Scales of Infant Development , 2nd edition ( BSID-II ) ( Bayley 1993 ) at the Retina Foundation of the Southwest , Dallas , TX . These children had also been assessed at 4 months and 12 months of age for blood fatty-acid composition , sweep visual evoked potential ( VEP ) acuity , and forced-choice preferential looking ( FPL ) acuity ( Birch et al. 1998 ) . Supplementation of infant formula with DHA+AA was associated with a mean increase of 7 points on the Mental Development Index ( MDI ) of the BSID-II . Both the cognitive and motor subscales of the MDI showed a significant developmental age advantage for DHA- and DHA+AA-supplemented groups over the control group . While a similar trend was found for the language subscale , it did not reach statistical significance . Neither the Psychomotor Development Index nor the Behavior Rating Scale of the BSID-II showed significant differences among diet groups , consistent with a specific advantage of DHA supplementation on mental development . Significant correlations between plasma and RBC-DHA at 4 months of age but not at 12 months of age and MDI at 18 months of age suggest that early dietary supply of DHA was a major dietary determinant of improved performance on the MDI The adipokine visfatin has been proposed to exert insulin-mimicking effects and to play a role in the development of metabolic syndrome . Preterm infants are at risk for the later development of insulin resistance and , possibly , for other components of metabolic syndrome . Dietary long-chain polyunsaturated fatty acids ( LCPUFAs ) during the perinatal period may reduce the risk of metabolic syndrome . The authors ' objective was to study the circulating concentrations of visfatin in preterm infants and to examine associations of visfatin with anthropometric measurements , metabolic indices , and dietary LCPUFAs . Serum visfatin concentrations were determined by enzyme-linked immunosorbent assay at mean ( SD ) 33.8 ( 11.7 ) days of life in 60 healthy preterm infants ( gestational age , 32.7 [ 1.9 ] weeks ) r and omly assigned to be fed since birth either a formula containing LCPUFA ( arachidonic and docosahexaenoic acid ) ( + LCPUFA group ) or the same formula without LCPUFA ( -LCPUFA group ) . Associations of visfatin with anthropometric parameters , serum glucose , insulin , homeostasis model assessment index of insulin resistance , blood lipids , and adiponectin levels were examined . Serum visfatin levels were significantly higher in the + LCPUFA than in the -LCPUFA group ( P < .001 ) and correlated positively with body weight z score ( β = 0.31 , P = .02 ) , total cholesterol ( β = 0.34 , P = .01 ) , high-density lipoprotein cholesterol ( HDL-C ) ( β = 0.47 , P < .001 ) , and adiponectin levels ( β = 0.29 , P = .03 ) , but not with indices of insulin sensitivity . In multiple regression analysis , HDL-C and dietary LCPUFAs correlated independently with serum visfatin levels . Circulating visfatin levels in preterm infants are independently associated with HDL-C levels and dietary LCPUFAs . Whether the higher visfatin levels in the + LCPUFA preterm infant group are beneficial for the later health of these infants remains to be determined OBJECTIVE To test the efficacy and safety of long-chain polyunsaturated fatty acid ( LCPUFA ) supplementation with gamma-linolenic acid , a precursor of arachidonic acid , and docosahexaenoic acid in preterm infants . STUDY DESIGN Preterm ( < 35 weeks , < or = 2000 g birth weight ) infants ( n=238 ) r and omly assigned to unsupplemented or LCPUFA-supplemented formula to 9 months after term . The main outcome measure was the Bayley Mental and Psychomotor Indexes ( MDI , PDI ) at 18 months after term . Safety outcome measures were anthropometry ( 9 and 18 months ) , feed tolerance , infection , and clinical complications . RESULTS There were no significant differences in neurodevelopment between groups overall . In preplanned subgroup analyses , LCPUFA-supplemented boys had significantly higher Bayley MDI than did control boys ( difference , 5.7 points ; 95 % CI , 0.3 to 11.1 ; P=.04 ) . LCPUFA-supplemented infants showed significantly greater weight gain ( difference , 310 g ; 95 % CI , 30 to 590 g ; P=.03 ) and length gain ( difference , 1.0 cm ; 95 % CI , 0.02 to 1.9 ; P=.05 ) between birth and 9 months , with greater effect in boys ( weight difference at 9 months , 510 g ; 95 % CI , 80 to 930 g ; P=.02 ; length difference at 18 months , 1.8 cm ; 95 % CI , 0.1 to 1.8 ; P=.03 ) . CONCLUSIONS This trial , using the strategy of providing gamma-linolenic acid as a source of arachidonic acid , showed efficacy for growth and for neurodevelopment in boys , with no adverse effects . These data have important implication s for LCPUFA-supplementation strategy in preterm infants STUDY DESIGN The Infant Fish Oil Supplementation Study is a double-blind r and omised controlled trial investigating whether the incidence of allergic disease can be reduced and developmental outcomes enhanced through supplementation with omega-3 fatty acids .  Infants at high risk of developing allergic disease will be r and omised to receive either fish oil or olive oil supplements until 6 months of age and followed up at six postnatal clinic visits to assess allergy outcomes and infant neurodevelopment . INTERVENTION Study groups to consist of a treatment group allocated to receive 650 mg of fish oil daily ( 250 - 280 mg docosahexaenoic acid and at least 60 mg eicosapentaenoic acid and a placebo group ( olive oil ) from birth to 6 months of age . OUTCOMES Allergy outcomes will be assessed by clinical history , clinical assessment s and allergen skin prick tests at the 12 , 30 and 60 month visits . Neurodevelopmental assessment s to be conducted at 18 months , and language question naires at 12 , 18 and 30 months . Sample s will be collected from mothers antenatally , from infants at birth , and at clinic visits from 6 months onwards for immunological assessment s. Fatty acid composition to be measured in erythrocytes and plasma ( at birth and after the supplementation period ) to assess the effect of the intervention on fatty acid status . Information on medical history , diet and other lifestyle factors at an antenatal clinic visit and postnatal clinic visits will also be collected . CONCLUSION This study is design ed to examine clinical ly relevant effects of a novel , non-invasive and potentially low cost approach to reduce the incidence of allergic disease and facilitate neurodevelopment during early childhood BACKGROUND The visual and mental development of preterm infants improved after feeding them milk enriched with docosahexaenoic acid ( DHA ) in amounts matching the fetal accretion rate . OBJECTIVE The objective was to evaluate whether feeding preterm infants milk with a higher DHA content than that used in current practice influences language or behavior in early childhood . DESIGN This was a follow-up study in a subgroup of infants enrolled in the DINO ( Docosahexaenoic acid for the Improvement in Neurodevelopmental Outcome ) trial . In a double-blind r and omized controlled trial , infants born at <33 wk of gestation were fed milk containing 1 % of total fatty acids as DHA ( higher-DHA group ) or approximately 0.3 % DHA ( control group ) until reaching full-term equivalent age . The longer-term effects of the intervention on language , behavior , and temperament were measured by using the MacArthur Communicative Development Inventory ( MCDI ) at 26-mo corrected age , the Strengths and Difficulties Question naire ( SDQ ) , and the Short Temperament Scale for Children ( STSC ) between 3- and 5-y corrected age . RESULTS Mean ( + /-SD ) MCDI scores did not differ significantly ( adjusted P = 0.8 ) between the higher-DHA group ( 308 + /- 179 , n = 60 ) and the control group ( 316 + /- 192 , n = 67 ) per the Vocabulary Production subscale . Composite scores on the SDQ and STSC did not differ between the higher-DHA group and the control group [ SDQ Total Difficulties : higher-DHA group ( 10.3 + /- 6.0 , n = 61 ) , control group ( 9.5 + /- 5.5 , n = 64 ) , adjusted P = 0.5 ; STSC score : higher-DHA group ( 3.1 + /- 0.7 , n = 61 ) , control group ( 3.0 + /- 0.7 , n = 64 ) , adjusted P = 0.3 ] . CONCLUSIONS Feeding preterm infants milk containing 3 times the st and ard amount of DHA did not result in any clinical ly meaningful change to language development or behavior when assessed in early childhood . Whether longer-term effects of dietary DHA supplementation can be detected remains to be assessed . This trial was registered with the Australia and New Zeal and Clinical Trial Registry at www.anzctr.org.au as 12606000327583 Polyunsaturated fatty acids ( PUFA ) are vital for the normal development of the brain and the eye retina in infancy . Breast milk contains significant amounts of PUFA , and compensates for their low production in infancy . Only recently a few companies with worldwide product distribution have started to enrich infant formula with PUFA . We evaluated the safety and clinical efficacy of a locally made PUFA-enriched infant formula , produced for the first time in Israel . 50 normal , full term infants participated in a prospect i ve , r and omized double-blind study . Half received a regular whey-predominant infant formula ( Materna Plus ) , and the other half a PUFA-enriched formula ( Materna Premium ) , both produced in Israel , for 30 days . Evaluation included physical examination , growth parameters , stool analysis , daily parental question naires regarding infant behavior and defecation , and developmental assessment . There were no significant differences on comparing growth parameters , infant behavior , attacks of restlessness , gas severity , or stool characteristics in the 2 groups . There were no side effects or abnormal stool findings in either group , and no differences in developmental assessment at 3 months of age . We conclude that the locally-produced PUFA-enriched infant formula is safe and clinical ly efficient . We assume that the lack of any effect on developmental indices is due to the relatively short exposure to the PUFA-enriched diet . Nevertheless , based on the recent literature , there is no doubt that PUFA supplementation is vital in improving infant brain and eye development BACKGROUND Docosahexaenoic acid ( DHA ) intake throughout the first year of life is associated with neurodevelopmental and neuropsychological benefits . Few studies have evaluated the role of DHA intakes on age at achievement of gross motor milestones . OBJECTIVE The objective was to assess the effects of DHA supplementation throughout the first year of life on the achievement of four gross motor milestones in healthy infants . DESIGN In this multicenter prospect i ve , r and omized , double-blind , placebo-controlled trial , 1160 healthy neonates were assigned to receive supplementation with either 20 mg liquid DHA ( n = 580 ) or placebo ( n = 580 ) orally once daily throughout the first year of life . The primary endpoint was the time at achievement of 4 gross motor milestones ( sitting without support , h and s- and -knees crawling , st and ing alone , and walking alone ) . All analyses were performed on an intention-to-treat basis . RESULTS The time to achievement of sitting without support was shorter ( P < 0.001 ) in infants who received DHA [ median : 26 wk ; interquartile range ( IQR ) : 24 - 29 wk ] than in those who received placebo ( 27 wk ; 26 - 31 wk ) . No significant difference between infants who received DHA or placebo was found for h and s- and -knees crawling [ 39 wk ( 34 - 44 wk ) compared with 40 wk ( 35 - 44 wk ) , respectively ] , st and ing alone [ 49 wk ( 43 - 55 wk ) compared with 49 wk ( 44 - 57 wk ) , respectively ] , and walking alone [ 55 wk ( 50 - 60 wk ) compared with 56 wk ( 52 - 61 wk ) , respectively ] . CONCLUSIONS Despite the 1-wk advance in sitting without support associated with DHA supplementation , no demonstrable persistent effects of DHA supplementation on later motor development milestones were found . Thus , the long-term clinical significance of the 1-wk change in sitting without support , if any , remains unknown . This trial is registered at ( clinical trials.gov ) as NCT00610922 BACKGROUND n-3 Fatty acid supplementation in adults results in cardiovascular benefits . However , the cardiovascular effects of n-3 supplementation in early childhood are unknown . OBJECTIVE The objective was to evaluate blood pressure ( BP ) and arterial structure and function in 8-y-old children who had participated in a r and omized controlled trial of dietary n-3 and n-6 modification over the first 5 y of life . DESIGN The children ( n = 616 ; 49 % girls ) were r and omly assigned antenatally to active ( n = 312 ; increase in n-3 intake and decrease in n-6 intake ) or control ( n = 304 ) diet interventions implemented from the time of weaning or introduction of solids until 5 y of age . At age 8.0 + /- 0.1 y , BP , carotid intima-media thickness , carotid artery distensibility , augmentation index , and brachial pulse wave velocity were measured in 405 of these children . Venous blood was collected for measurement of plasma fatty acids , lipoproteins , high-sensitivity C-reactive protein , and asymmetric dimethylarginine . Plasma fatty acid concentrations were also assessed during the intervention . RESULTS Plasma concentrations of n-3 fatty acids were higher and of n-6 were lower in the active than in the control diet group at 18 mo and 3 and 5 y ( P < 0.0001 ) . Concentrations of n-3 and n-6 fatty acids were similar at 8 y. At 8 y of age , no significant differences were found in BP , carotid intima-media thickness , carotid artery distensibility , augmentation index , asymmetric dimethylarginine , high-sensitivity C-reactive protein , or lipoproteins between diet groups . CONCLUSION A dietary supplement intervention to increase n-3 and decrease n-6 intakes from infancy until 5 y does not result in significant improvements in arterial structure and function at age 8 y. This trial was registered at the Australian Clinical Trials Registry as ACTRN012605000042640 The objective of this study was to assess the relation between observed levels of omega-3 fatty acids in plasma and symptoms of asthma and atopy in children at 18 months of age . A total of 616 women at risk of having a child who would develop asthma because of a family history were recruited from the antenatal clinics of six hospitals in Sydney , Australia . Families were r and omized to either active omega-3 supplemented or control group . The active group received a daily tuna fish oil supplement and omega-3-rich margarines and cooking oils and the control group received a placebo supplement with polyunsaturated margarines and cooking oils . When the children were 18 months of age an assessment of symptoms was carried out by a research nurse blinded to treatment group allocation . Atopy was measured by skin prick tests , blood was collected to determine serum immunoglobulin E ( IgE ) , and plasma fatty acid concentrations . A total of 376 children ( 61.0 % of total recruited ) completed an assessment at 18 months and had blood taken to determine plasma fatty acid concentrations . Omega-3 fatty acid levels were expressed in quintiles of exposure ' as treated ' without reference to treatment group allocation . Wheeze ever , doctor visits for wheeze , bronchodilator use and nocturnal coughing were significantly reduced in children in the higher exposure quintiles . Serum IgE was reduced in the highest quintile but not significantly so . There was no difference in diagnosed asthma or atopy between the exposure quintiles . Although wheeze at this age may not be a good indicator of asthma in later childhood , it is encouraging that some symptoms have been reduced in children with high omega-3 fatty acid concentrations in plasma BACKGROUND Studies investigating the effects of docosahexaenoic acid ( DHA ) in infant formula on language development yield conflicting results . No study to date has investigated the effects of DHA in infant formula on school readiness . AIM To determine the effects of different dietary concentrations of DHA provided during the first 12 months of life on language development and school readiness . DESIGN This was a double-masked , r and omized , controlled , prospect i ve trial . A total of 182 infants were enrolled at 1 - 9 days of age and assigned r and omly to receive infant formula with one of four levels of DHA : control ( 0 % DHA ) , 0.32 % DHA , 0.64 % DHA , or 0.96 % DHA . All formulas with DHA also contained 0.64 % arachidonic acid .  One hundred forty-one children completed the 12-month feeding trial and were eligible for this study . Consent was obtained from 131 participants .  School readiness was assessed at 2.5 years using the Bracken Basic Concept Scale-Revised ( BBCS-R ) and receptive vocabulary was assessed at 2 and 3.5 years using the Peabody Picture Vocabulary Test-Third Edition ( PPVT-III ) . RESULTS There were no diet group differences on any of the BBCS-R subscales . On the PPVT-III , the control group had higher raw scores and st and ard scores than both the 0.32 % and 0.96 % groups at 2 years of age . These differences were not evident at 3.5 years . CONCLUSIONS Dietary DHA during the first year of life did not enhance school readiness or language development . Children who consumed infant formula with 0.32 % and 0.96 % DHA showed lower receptive vocabulary scores than controls at 2 but not 3.5 years of age We investigated whether supplementation with arachidonic acid ( 20:4 omega 6 ; AA ) , or a combination of AA and docosahexaenoic acid ( 22:6 omega 3 ; DHA ) would affect  human milk polyunsaturated fatty acid ( PUFA ) composition . Ten women were daily supplemented with 300 mg AA  , eight with 300 mg AA , 110 mg eicosapentaenoic acid ( 20:5 omega 3 ; EPA ) and 400 mg DHA , for one week and eight women served as unsupplemented controls . Milk sample s were collected on days 0 , 1 and 7 . The fatty acid composition of the milk was analyzed by capillary gas chromatography with flame ionisation detection . Supplementation with AA alone had no effect on breastmilk AA , but tended to reduce EPA and DHA levels . Administration of a combination of AA , EPA and DHA tended to increase both milk AA and long chain PUFA (LCPUFA)omega 3 content . A larger simultaneous increase of milk AA , DHA and EPA than observed in the present study can probably be accomplished by the use of a combination of a lower LCPUFA omega 6/LCPUFA omega 3 ratio and higher AA , EPA and DHA dosages BACKGROUND We tested whether addition of n-3 and n-6 long-chain polyunsaturated fatty acids ( LCPUFA ) to infant-formula milk during the first 6 months promotes long-term cognitive and motor development , without adverse consequences . METHODS We did a double-blind , r and omised , controlled , efficacy and safety trial of formula with and without LCPUFAs , with an additional breastfed reference group , in four hospitals in two cities in the UK . The participants were 447 healthy full-term babies . 309 were fed formula ( 155 without LCPUFAs )  and 138 were breastfed for at least 6 weeks . The main outcome measures were : Bayley Mental and Psychomotor Development Indices ( MDI , PDI ) at 18 months ( primary efficacy outcome ) and Knobloch , Passamanick , and Sherrards test at 9 months ( secondary outcome ) . Principal safety outcomes were : infection , atopy , growth , and gastrointestinal tolerance . FINDINGS Babies fed formula with and without LCPUFA did not differ in cognitive or motor development , growth , infection , atopy or tolerance . The mean ( 95 % CI ) MDI was 0.5 ( -2.7 to 3.8 ) units and the PDI 0.6 ( -1.8 to 3.0 ) units higher in the supplementation group . Formula-fed infants had similar developmental scores to the breastfed reference group after adjustment for higher social class and maternal education in the latter . INTERPRETATION There was no evidence of a beneficial or adverse effect on cognitive and motor development or growth up to 18 months . Although no significant differences in safety outcomes were observed , we suggest such data should be collected in future LCPUFA trials . Our trial does not provide support for addition of LCPUFA to st and ard infant formula but we are now doing further follow-up of this cohort This study evaluated preterm infants of less than 2.3 kg birth weight fed commercial formula ( Preemie SMA ® ) devoid of arachidonic acid ( AA ) and docosahexaenoic acid ( DHA ) and compared this control group with similar infant groups fed one of three formulas containing a range of 0.32—1.1 % AA and 0.24—0.75 % DHA  in the fat component of the formula . An analogous group of infants fed on their mothers ' breast milk and a breast milk fortifier  was also studied . Individual lipoprotein fractions were isolated from blood sample s collected at 12 d of age and after a further 4 wk of feeding . The fatty acid content of individual lipid components , isolated from each lipoprotein fraction was quantitatively determined in order to identify change in marker pools of essential fatty acid . The high density lipoproteins ( HDL ) and low density lipoproteins ( LDL ) phospholipid and cholesterol ester fractions contain most of the AA and DHA found in the lipoprotein fractions ( total of 0.49 % and 0.35 % , respectively ) . Infants fed a formula without AA and DHA showed a reduction in AA level in the phospholipid fraction of all lipoproteins and in the HDL and LDL cholesterol ester fraction . A reduced level of DHA was also observed primarily in the lipoprotein phospholipid fraction in comparison with infants fed breast milk or infant formula containing AA and DHA . Supplementing infant formula with increasing levels of AA and DHA produced a clear dose response in the level of AA found in the HDL and LDL phospholipid fraction . From comparison of the fatty acid levels present in the lipoproteins it appears that a formula level of 0.49 % AA and 0.35 % DHA provides sufficient levels of these fatty acids to achieve a similar fatty acid content to that of infants fed breast milk for the major lipoprotein fractions examined . □ Diet , fatty acid , infant , Healthy newborn infants were either breast-fed or r and omly design ated  to receive a st and ard formula , formula plus cholesterol , or formula plus gamma-linolenic acid at birth . At 0 , 7 , and 30 days of life , the following variables were measured : cholesteryl esters ( cholesteryl arachidonate , cholesteryl oleate , cholesteryl palmitate , and cholesteryl linoleate ) , high-density lipoprotein ( HDL ) cholesterol , apoproteins ( A-I , A-II , B , C-II , C-III , and E ) , and the cholesterol and apoprotein A-I content of the HDL subfractions HDL-2b , HDL-(2a + 3a ) , and HDL-(3b + 3c ) . Breast-fed infants had higher serum levels of cholesterol , cholesteryl oleate , cholesteryl palmitate , cholesteryl arachidonate , and HDL-2b than had formula-fed infants . Addition of gamma-linolenic acid to formula raised cholesteryl-arachidonate levels , and cholesterol and gamma-linolenic acid raised serum HDL-2b levels compared with those produced by unsupplemented formula . Our data suggest that both exogenous cholesterol and gamma-linolenic acid contribute to the maturation of HDL particles associated with human milk consumption in newborn infants . They may also promote adequate delivery of cholesterol and arachidonic acid to the developing brain OBJECTIVES . Arachidonic acid ( 20:4n-6 ) and docosahexaenoic acid ( 22:6n-3 ) are essential for brain growth and cognitive development . We have reported that supplementing pregnant and lactating women with n-3 very-long-chain polyunsaturated fatty acids promotes higher IQ scores at 4 years of age as compared with maternal supplementation with n-6 polyunsaturated fatty acids . In our present study , the children were examined at 7 years of age with the same cognitive tests as at 4 years of age . We also examined the relation between plasma fatty acid pattern and BMI in children , because an association between arachidonic acid and adipose tissue size has been suggested . METHODS . The study was r and omized and double-blinded . The mothers took 10 mL of cod liver oil or corn oil from week 18 of pregnancy until 3 months after delivery . Their children were tested with the Kaufman Assessment Battery for Children at 7 years of age , and their height and weight were measured . RESULTS . We did not find any significant differences in scores on the Kaufman Assessment Battery for Children test at 7 years of age between children whose mothers had taken cod liver oil ( n = 82 ) or corn oil ( n = 61 ) . We observed , however , that maternal plasma phospholipid concentrations of α-linolenic acid ( 18:3n-3 ) and docosahexaenoic acid during pregnancy were correlated to sequential processing at 7 years of age . We observed no correlation between fatty acid status at birth or during the first 3 months of life and BMI at 7 years of age . CONCLUSION . This study suggests that maternal concentration of n-3 very-long-chain polyunsaturated fatty acids during pregnancy might be of importance for later cognitive function , such as sequential processing , although we observed no significant effect of n-3 fatty acid intervention on global IQs . Neonatal fatty acid status had no influence on BMI at 7 years of age Objective : To investigate whether diet influences the composition of the intestinal microbiota in 10-month-old infants . Patients and Methods : Fecal sample s were collected from sixty-five 10-month-old infants participating in a r and omized 2 × 2 intervention study comparing cow 's milk ( CM ) with infant formula ( IF ) with or without fish oil ( FO ) supplement . Infants r and omized to CM received a daily iron supplement . Bacterial DNA was extracted from the feces . Polymerase chain reaction was performed with primers targeting the V3 and V6–8 region of the 16S rRNA gene and analyzed by denaturing gradient gel electrophoresis ( DGGE ) . Cluster analysis of the DGGE gels was performed by use of the Pearson correlation coefficient . Results : Sample s from infants receiving CM clustered differently than did those from the IF group in the V3-based DGGE gels ( P < 0.001 ) and showed a different distribution with or without FO in the CM group ( P = 0.001 ) but not in the IF group ( P = 0.39 ) . Repeat analysis with the V6–8-based DGGE gels showed the same pattern , although the V3 gels had 2.5 times as many b and s as the V6–8 gels . Conclusions : Consumption of CM or IF has a decisive influence on the composition of the intestinal microbiota .  Supplementation with FO showed an effect on the microbiota only in the CM group . We speculate that these differences could be influenced by the intake of iron and n-3 polyunsaturated fatty acids , respectively Full-field electroretinograms ( ERGs ) were obtained from very-low-birth-weight ( VLBW ) neonates to determine whether omega-3 ( omega-3 ) fatty acids are essential for normal human retinal development . Eighty-one infants born at 30.4 ( st and ard deviation , + /- 1.5 ) wk gestation were , within 10 d of birth , either enrolled to receive mother 's milk ( naturally containing both omega-6 and omega-3 essential fatty acids ) or  r and omized to receive one of the infant formulas . Corn oil-based Formula A contained mainly linoleic acid ( 18:2 omega-6 ) and was low in all omega-3 fatty acids . Soy oil-based Formula B contained ample alpha-linolenic acid ( 18:3 omega-3 ) but no long-chain omega-3 . Formula C , supplemented with both alpha-linolenic acid and marine oils , was comparable to human milk in long-chain omega-3 . Full-field ERGs were obtained in the special care nursery from infants aged 36 and 57 wk postconception . Ten healthy preterm infants born at 35 wk gestation were tested at 36 wk postconception . Significant differences were found among groups in rod ERG function . Post hoc comparisons showed that infants fed Formula A had significantly higher rod thresholds than infants receiving long-chain omega-3 ( human milk , Formula C , and intrauterine ) . Infants receiving Formula B had intermediate thresholds that were significantly higher than those of infants receiving intrauterine nutrition . Analysis of the leading edge of the a-wave showed that b-wave differences originated at the photoreceptor level . Differences were not present in infants at 57 wk postconception . No significant differences among groups were found in cone b-waves at 36 or 57 wk postconception . Oscillatory potentials had significantly longer implicit times at 57 wk postconception in infants fed Formula A than in infants receiving human milk . These findings suggest that retinal function varies with the dietary supply of omega-3 fatty acids in VLBW infants Objective : To study the effect of modified polyunsaturated fatty acid ( PUFA ) profiles of complementary food on long-chain ( LC ) PUFA composition in healthy infants . Design : Double blinded , r and omised , controlled intervention trial . Setting : Dortmund , Germany . Patients : Free-living sample of healthy term infants . Methods : Participants were r and omly assigned within the first 2 months of life . During the intervention period from 4 to 10 months , the control group ( n = 53 ) received commercial complementary meals with corn oil ( 3.4 g/meal ) rich in n-6 linoleic acid ( LA ) , the intervention group ( n = 49 ) received the same meals with rapeseed oil ( 1.6 g/meal ) rich in n-3 alpha-linolenic acid ( ALA ) .  Fatty acid intake was assessed from dietary records throughout the intervention period . Fatty acid proportions ( % of total fatty acid ) in total plasma were analysed before and after the intervention . Results : Plasma fatty acid profiles did not differ between the intervention and control groups before the intervention . During the intervention , the only difference in fatty acid intake between the intervention and control groups was a higher intake of ALA in the intervention group , 21 % deriving from study food and a lower ratio of LA/ALA ( 10.7 vs 14.8 ) . At the end of the intervention , the plasma proportions of total n-3 fatty acids and of n-3 LC-PUFA , but not of ALA , were higher and the ratios of n-6/n-3 fatty acids were lower in the intervention group . Conclusions : Feasible dietary modifications of the precursor fatty acid profile via n-3 PUFA-rich vegetable oil favoured n-3 LC-PUFA synthesis in the complementary feeding period when LC-PUFA intake from breast milk and formula is decreasing BACKGROUND & AIMS High supply of protein and energy has been introduced to very-low-birth-weight infants to improve growth and cognitive development . The aim of this study was to compare two different feeding strategies on postnatal growth and clinical outcome during neonatal hospitalization . METHODS Fifty very-low-birth-weight infants were r and omized to either an enhanced or a st and ard feeding protocol within 24 h after birth . Chi-square and T-tests were applied . RESULTS First week protein , fat and energy supply was significantly higher in the intervention group compared to the control group ( all P < 0.001 ) . After inclusion of 50 patients we observed a higher occurrence of septicemia in the intervention group , 63 % vs. 29 % ( P = 0.02 ) , and no more patients were included . The infants in the intervention group demonstrated improved postnatal growth , but they also disclosed significant electrolyte deviations during the first week of life with hypophosphatemia , hypokalemia and hypercalcemia . First week phosphate nadir was lower in the infants experiencing septicemia ( 1.23 ( 0.50 ) mmol/L ) as compared to the infants without ( 1.61 ( 0.61 ) mmol/L ) ( P = 0.03 ) . CONCLUSION Our study implies that enhanced feeding may induce electrolyte imbalances in VLBW infants , and that deleterious side effects similar to those seen in refeeding syndrome may occur . Clinical Trials.gov , number NCT01103219 and the EudraCT number is 2010 - 020464 - 38 A prospect i ve study in healthy infants predefining both diet fatty acid and cholesterol , from birth to age 1 year , compared response of cholesterol fractions in three groups : r and om assignment to 1 ) monounsaturated-(Hi-Mono ) ( n = 20 ) , or 2 ) polyunsaturated-(Hi-Poly ) ( n = 22 ) fatty acid-enriched diets , or 3 ) non-r and omized selection to breast feeding ( Human Milk ) ( n = 25 ) .  In each group , design ated weaning foods and supplements maintained fatty acid and cholesterol intake similar to that of each group 's defined formulas , with long-term compliance confirmed by plasma phospholipid fatty acid concentrations . By 12 months , total cholesterol was significantly lower in the Hi-Poly group compared to either of the other groups ( P < 0.05 ) . Low density lipoprotein (LDL)- and high density lipoprotein (HDL)-cholesterol concentrations were significantly lower by 12 months in the Hi-Poly group , compared to the Hi-Mono groups . However , at the earlier 4-month interval , total cholesterol and LDL-cholesterol in both Hi-Mono and Hi-Poly groups were not different from each other , although each was significantly lower than the parallel Human Milk-group ( P < 0.05 ) . The Hi-Mono group increased gradually in total and LDL-cholesterol such that , after 12 months ' feedings , all lipid fractions of this Hi-Mono group were no different from those of the Human Milk group . In independent group comparisons , there were no significant differences in HDL-cholesterol concentrations after 4 and 9 months on these diets . Independent of diet , HDL-cholesterol showed a falling trend as an overall time-effect across all groups ( P < 0.001 ) . These data suggest that prolonged feeding of a diet enriched in polyunsaturated acids in early infancy has a significant cholesterol-lowering effect compared to monounsaturates . These differences in total , LDL- , and HDL-cholesterol plasma concentrations between polyunsaturates and monounsaturates were not significantly evident until feedings had continued for a year OBJECTIVES : Impaired fetal growth is an independent cardiovascular risk factor and is associated with arterial wall thickening in children . No preventive strategy has been identified . We sought to determine whether dietary omega-3 fatty acid supplementation during early childhood prevents the association between impaired fetal growth and carotid arterial wall thickening . METHODS : The Childhood Asthma Prevention Study was a r and omized , controlled single-blind trial in 616 children born at term , recruited antenatally from maternity hospitals in Sydney . Participants were r and omized to either a 500-mg-daily fish oil supplement and canola-based margarines and cooking oil ( omega-3 group ) , or a 500-mg-daily sunflower oil supplement and omega-6 fatty acid – rich margarines and cooking oil ( control group ) , from the start of bottle-feeding or 6 months of age until 5 years of age . Carotid intima-media thickness ( IMT ) , a noninvasive measure of sub clinical atherosclerosis , was the primary endpoint of a cardiovascular sub study ( CardioCAPS ) at age 8 years . We examined the association of fetal growth with carotid IMT in children with birth weight < 90th percentile ( omega-3 group [ n = 187 ] , control group [ n = 176 ] ) . RESULTS : In the control group , fetal growth was inversely associated with carotid IMT , but this was prevented in the omega-3 group ( difference between groups of 0.041 mm [ 95 % confidence interval 0.006 , 0.075 ] per kg birth weight , adjusted for gestational age and gender , Pheterogeneity = .02 ) . CONCLUSIONS : The inverse association of fetal growth with arterial wall thickness in childhood can be prevented by dietary omega-3 fatty acid supplementation over the first 5 years of life AIM To determine the effect of neonatal docosahexaenoic acid ( DHA ) supplementation in preterm infants on later respiratory-related hospitalisations . METHODS We enrolled 657 infants in a multicentre , r and omised , controlled trial design ed to study the long-term efficacy of higher dose dietary DHA in infants born <33 weeks ' gestation . Treatment was with high DHA ( ∼1 % ) compared with st and ard DHA ( ∼0.3 % ) in breast milk or formula , given from the first week of life to term equivalent . Parent-reported hospital admissions to 18 months corrected age were recorded . The proportion of children hospitalised for lower respiratory tract ( LRT ) conditions and the mean number of hospitalisations per infant were determined . RESULTS Twenty-three per cent ( 154/657 ) of infants were hospitalised for LRT conditions . Seventy-three per cent ( 173/238 ) of admissions were for bronchiolitis . There was no significant effect of higher DHA on the proportion of infants admitted for LRT conditions ( high DHA 22 % vs. st and ard DHA 25 % , adjusted relative risk 0.92 , 95 % confidence interval ( CI ) 0.68 - 1.24 , P = 0.57 ) or in the mean number of admissions per infant ( high DHA 0.34 , st and ard DHA 0.38 , adjusted ratio of means 0.91 , 95 % CI 0.63 - 1.32 , P = 0.62 ) . The sexes responded differently to treatment ( interaction P = 0.046 ) , with reduced admissions in boys given high DHA , but this was not statistically significant ( high DHA 19 % , st and ard DHA 28 % , adjusted relative risk 0.69 , 95 % CI 0.46 - 1.04 , P = 0.08 ) . CONCLUSIONS Hospitalisation for LRT problems in the first 18 months for preterm infants was not reduced by neonatal supplementation with 1 % DHA Preterm infants fed formulas with docosahexaenoic acid ( DHA , 22:6n-3 ) during the interval equivalent to the last intrauterine trimester and beyond have higher circulating DHA and transiently higher visual acuity compared with infants fed formulas containing linolenic acid . In term infants several nonr and omized studies of infants receiving DHA from human milk suggest a relationship between DHA status and acuity , but the evidence for a cause- and -effect relationship is mixed . In the present study , term infants were r and omly assigned to a st and ard term formula ( n = 20 ) or the same formula with egg yolk lecithin to provide DHA ( 0.1 % ) and arachidonic acid(AA , 20:4n-6 , 0.43 % ) ( n = 19 ) at levels reported in milk of American women . A third group of infants was breast fed for ≥3 mo(n = 19 ) . Grating visual acuity ( Teller Acuity Card procedure ) and plasma and red blood cell ( RBC ) phosphatidylcholine ( PC ) and phosphatidylethanolamine ( PE ) DHA and AA were determined at corrected ages of 2 , 4 , 6 , 9 ( acuity only ) , and 12 mo past term = 40 wk postmenstrual age ( PMA ) . At 2 mo breast-fed infants and infants fed the supplemented formula had higher grating acuity than term infants fed st and ard formula . As in preterm infants , the increase was transient . Plasma PC DHA and AA and RBC PE AA increased by 2 mo in supplemented infants , but RBC PE DHA in supplemented infants was not higher than in controls until 4 mo and beyond . Despite normal intrauterine accumulation of DHA and AA , infants fed formula with 2 % linolenic acid and 0.1 % DHA had better 2-mo visual acuity than infants fed formula with 2 % linolenic acid OBJECTIVE To determine if docosahexaenoic acid ( DHA ) and arachidonic acid ( ARA ) supplementation influences growth or visual acuity of formula-fed premature infants . STUDY DESIGN Double-blind , multi-center study of 194 premature infants given preterm formula with no DHA or ARA ( control ) , 0.15 % energy DHA , or 0.14 % DHA + 0.27 % ARA from single-cell triglycerides for at least 28 days and then fed term formula ( no DHA or ARA ) to 57 weeks postmenstrual age ( PMA ) , with 90 breast-fed term infants as reference . RESULTS Infants fed DHA+ARA formula  gained weight significantly faster ( post-hoc analysis ) during preterm formula feeding than control infants ( 34.7 vs. 30.7 g/d ) and had weights and weight : length ratios not different from term breast-fed infants at 48 and 57 weeks PMA . Infants fed control or DHA formula had lower body weights than term infants . Red blood cell phosphatidylethanolamine ARA was significantly correlated to weight gain during preterm formula feeding and to weight and length at 40 , 48 , and 57 weeks PMA ( r = 0.19 to 0.24 , P = .004-.02 ) . Providing DHA or DHA+ARA during the preterm period had no effect on subsequent visual acuity or incidence of adverse events . CONCLUSIONS Feeding DHA+ARA from single-cell triglycerides enhances weight gain in formula-fed premature infants with no evidence of adverse effects Abstract We compared growth of infants whose mothers either did or did not receive docosahexaenoic acid ( DHA ) supplements during pregnancy and lactation . At 21 weeks ' gestation , 144 women were enrolled into a r and omized , double-blind clinical trial receiving : ( 1 ) a basic supplement consisting of vitamins and minerals ( BS ) , or ( 2 ) BS plus 4.5 g fructooligosaccharide ( BSF ) , or ( 3 ) BSF plus fish oil DHA ( 200 mg ) until the end of the third month of lactation .  Infants ' length , weight and head circumference were measured at birth and at 1 , 3 and 21 months . A total of 51 mothers/infants were lost to follow-up by the third month and 24 at 21 months . The two groups not receiving DHA were combined into a control group . Analysis with mixed models adjusted for confounding factors showed a significant time dependent effect for the DHA group on the development of the body mass index ( BMI ) ( P=0.037 ) , and of weight ( P=0.046 ) , but no effect on the development of length ( P=0.537 ) , or of head circumference ( P=0.267 ) . At 21 months , weight of the  DHA group was lower by −601 g ( 95 % CI −171 ; −1030 g ) and BMI was lower by −0.76 kg/m2 ( 95 % CI −0.07 ; −1.46 ) compared to controls . The results indicate that DHA taken by pregnant and lactating mothers may reduce BMI in late infancy BACKGROUND While there is a large body of data on the effects of long-chain polyunsaturated fatty acid supplementation of infant formula on visual and cognitive maturation during infancy , longterm visual and cognitive outcome data from r and omized trials are scarce . AIM To evaluate docosahexaenoic acid ( DHA ) and arachidonic acid (ARA)-supplementation of infant formula on visual and cognitive outcomes at 4 years of age . METHODS Fifty-two of 79 healthy term infants who were enrolled in a single-center , double-blind , r and omized clinical trial of DHA and ARA supplementation of infant formula were available for follow-up at 4 years of age . In addition , 32 breast-fed infants served as a " gold st and ard " . Outcome measures were visual acuity and the Wechsler Preschool and Primary Scale of Intelligence -- Revised . RESULTS At 4 years , the control formula group had poorer visual acuity than the breast-fed group ; the DHA- and DHA+ARA-supplemented groups did not differ significantly from the breast-fed group . The control formula and DHA-supplemented groups had Verbal IQ scores poorer than the breast-fed group . CONCLUSION DHA and ARA-supplementation of infant formula supports visual acuity and IQ maturation similar to that of breast-fed infants OBJECTIVE We tested the hypothesis of whether a pharmacologic , orogastric dose of docosahexaenoic acid ( DHA ) administered during the acute phase of sepsis protects the nutritional status of neonates . METHODS A r and omized , placebo-controlled trial was conducted . Neonates who developed sepsis after a surgical procedure were r and omly assigned to receive daily 100 mg of DHA or 100 mg of olive oil as placebo for 14 d. At selection , illness severity was evaluated and a blood sample was obtained to measure erythrocyte fatty acid composition . Energy intake and type of feeding were recorded daily . Body composition was also determined at selection and after 14 d of follow-up with the deuterium dilution technique . Body composition differences between d 14 and baseline were calculated and compared between groups . Confounders were analyzed in a multiple regression model . RESULTS In all , 16 DHA and 11 placebo cases were followed up . Both groups showed an increase in length and head circumference , but length gain tended to be greater in neonates with DHA ( P = 0.07 ) . The DHA group presented increases in body mass ( 50 g , P = 0.03 ) and fat mass ( 70 g , P = 0.03 ) , whereas infants in the placebo group did not show an increase in any body composition components . Gain in fat mass was positively related with the DHA of erythrocytes and whether or not infants received DHA . CONCLUSIONS Orogastric DHA administered in the acute phase of infection likely protects the nutritional status of neonates with sepsis Background In contrast to human milk , current infant formulas in the United States do not contain ω3 and ω6 long-chain polyunsaturated fatty acids . This may lead to suboptimal blood lipid fatty acid profiles and to a measurable diminution of visual function in developing term infants . The need for docosahexaenoic acid and arachidonic acid supplementation in the infant diet was evaluated in a double-blind , r and omized clinical trial . Methods Healthy term infants were r and omized to diets of ( 1 ) commercial formula , ( 2 ) docosahexaenoic acid – enriched formula ( 0.35 % of total fatty acids ) , or ( 3 ) docosahexaenoic acid– ( 0.36 % ) and arachidonic acid– ( 0.72 % ) enriched formula .  Eighty-seven infants completed the 17-week nutritional trial , and 58 were observed until 52 weeks of life . A reference group was exclusively breast fed for at least 17 weeks ( n = 29 ) . Outcome measures included electroretinographic responses , visual evoked potentials , and blood fatty acid analysis in infants at birth and at 6 , 17 , and 52 weeks of age . Results Commercial formula-fed infants had 30 % to 50 % lower content of docosahexaenoic acid in total red blood cell lipids during the 17-week feeding trial compared with breast-fed infants . Significant differences persisted at the 1-year follow-up . Arachidonic acid content was consistently reduced in the commercial formula group by 15 % to 20 % . Infants fed long-chain polyunsaturated fatty acid – enriched formulas had docosahexaenoic acid and arachidonic acid blood lipid profiles resembling those of human milk-fed infants . Infants receiving this enriched formula had more mature electroretinographic responses than commercial formula-fed infants at 6 weeks of age . Human milk-fed and docosahexaenoic acid-enriched formula-fed infants had better visual acuity than commercial formula-fed infants at both 17 and 52 weeks of age . Early ( 17-week ) fatty acid profiles in blood lipids were correlated with later ( 52-week ) visual function development in study infants . Conclusions Results from this clinical trial demonstrate that long-chain polyunsaturated fatty acid supplementation of formula in term infants produces blood lipid fatty acid profiles that are similar to those observed in breast-fed infants . This supplementation leads to better visual function later in life ( i.e. , 1 year of age ) than that shown by infants fed commercial formula CONTEXT Uncertainty exists about the benefit of dietary docosahexaenoic acid ( DHA ) on the  neurodevelopment of preterm infants . OBJECTIVE To determine the effect of meeting the estimated DHA requirement of preterm infants on neurodevelopment at 18 months ' corrected age . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind controlled trial enrolling infants born at less than 33 weeks ' gestation from April 2001 to October 2005 at 5 Australian tertiary hospitals , with follow-up to 18 months . INTERVENTION High-DHA ( approximately 1 % total fatty acids ) enteral feeds compared with st and ard DHA ( approximately 0.3 % total fatty acids ) from day 2 to 4 of life until term corrected age . MAIN OUTCOME MEASURES Bayley Mental Development Index ( MDI ) at 18 months ' corrected age . A priori subgroup analyses were conducted based on r and omization strata ( sex and birth weight < 1250 g vs > or = 1250 g ) . RESULTS Of the 657 infants enrolled , 93.5 % completed the 18-month follow-up . Bayley MDI scores did not differ between the high- and st and ard-DHA groups ( mean difference , 1.9 ; 95 % confidence interval [ CI ] , -1.0 to 4.7 ) . The MDI among girls fed the high-DHA diet was higher than girls fed st and ard DHA in unadjusted and adjusted analyses ( unadjusted mean difference , 4.7 ; 95 % CI , 0.5 - 8.8 ; adjusted mean difference , 4.5 ; 95 % CI , 0.5 - 8.5 ) . The MDI among boys did not differ between groups . For infants born weighing less than 1250 g , the MDI in the high-DHA group was higher than with st and ard DHA in the unadjusted comparison ( mean difference , 4.7 ; 95 % CI , 0.2 - 9.2 ) but did not reach statistical significance following adjustment for gestational age , sex , maternal education , and birth order ( mean difference , 3.8 ; 95 % CI , -0.5 to 8.0 ) . The MDI among infants born weighing at least 1250 g did not differ between groups . CONCLUSION A DHA dose of approximately 1 % total fatty acids in early life did not increase MDI scores of preterm infants overall born earlier than 33 weeks but did improve the MDI scores of girls . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12606000327583 Long-chain PUFA ( LCPUFA ) supplementation of formula can have beneficial effects on neurodevelopmental outcome in early infancy , but uncertainty exists regarding effects after 6 months . The present study is the first to investigate whether consumption by term infants of formula containing LCPUFA for the first 2 months after birth improves neurological condition of these children at 9 years of age . A prospect i ve , double-blind , r and omised control study was performed in two groups of healthy term infants : a control group with st and ard formula ( n 169 ) and a LCPUFA-supplemented group ( LF ; n 146 ) . A breast-fed group ( BF ; n 159 ) served as a reference . At age 9 years , children were neurologically assessed according to Touwen , result ing in a Neurological Optimality Score and information on severity and type of minor neurological dysfunction ( MND ) . Information on potential confounders was collected at enrollment and follow-up . Multivariate analyses were carried out to evaluate the effect of nutrition while adjusting for confounders . Attrition ( 28 % ) was selective : drop-outs in the LF group were more often boys and had a significantly lower mental developmental index at 18 months . Neurological optimality and severity and type of MND at 9 years did not differ between the two formula groups . Children in the BF group showed significantly less often fine manipulative dysfunction than formula-fed children . In conclusion , LCPUFA supplementation of formula during the first 2 postnatal months in healthy term infants does not alter neurological function at school age . The study confirmed that breast-fed infants have a slightly better neurodevelopmental outcome than formula-fed infants The objective of this study was to evaluate the effect of conventional and long-chain polyunsaturated fatty acids (LCP)-enriched preterm formula on prostanoid formation in preterm infants during their first weeks of life . In a prospect i ve , r and omized , double-blind study , healthy infants received either formula enriched with LCP ( n = 10 ) , st and ard preterm formula(n = 10 ) , or ( expressed ) breast milk ( n = 10 ) . Urine was sample d , and anthropometric measurements were taken at study entry and after the study period of 3 wk . In vivo formation of prostagl and in E2 , thromboxane A2 , and prostacyclin was evaluated by measuring the urinary excretion of the respective index metabolites by gas chromatography-mass spectrometry . There were no significant differences in urinary prostanoid excretion and anthropometric data between the groups at the end of the study period . We conclude that neither conventional formula nor supplementation of a preterm formula with LCP for a period of 3 wk substantially influence prostanoid formation in healthy preterm infants OBJECTIVE . The objective of our study was to evaluate the effect of supplementation with docosahexaenoic acid and arachidonic acid for human milk-fed preterm infants . The primary end point was cognitive development at 6 months of age . METHODS . The study was a r and omized , double-blind , placebo-controlled study among 141 infants with birth weights of < 1500 g. The intervention with 32 mg of docosahexaenoic acid and 31 mg of arachidonic acid per 100 mL of human milk started 1 week after birth and lasted until discharge from the hospital ( on average , 9 weeks ) . Cognitive development was evaluated at 6 months of age by using the Ages and Stages Question naire and event-related potentials , a measure of brain correlates related to recognition memory . RESULTS . There was no difference in adverse events or growth between the 2 groups . At the 6-month follow-up evaluation , the intervention group performed better on the problem-solving subscore , compared with the control group ( 53.4 vs 49.5 points ) . There was also a nonsignificant higher total score ( 221 vs 215 points ) . The event-related potential data revealed that infants in the intervention group had significantly lower responses after the st and ard image , compared with the control group ( 8.6 vs 13.2 ) . There was no difference in responses to novel images . CONCLUSIONS . Supplementation with docosahexaenoic acid and arachidonic acid for very preterm infants fed human milk in the early neonatal period was associated with better recognition memory and higher problem-solving scores at 6 months INTRODUCTION This intervention examined whether fish-oil-supplementation in late infancy modifies free-play test scores and if this is related to blood pressure ( BP ) and mean RR interval . PATIENTS AND METHODS 83 Danish 9-month-old infants were r and omized to ±fish oil ( FO ) ( 3.4±1.1mL/d ) for 3months and 61 of these completed the free-play-test before and after the intervention . RESULTS Most of the free-play scores changed during the intervention , but the intervention affected only the number of looks away from the toy , which was increased in + FO and decreased in -FO ( p=0.037 ) . The increased numbers of looks away were associated with an increase in erythrocyte eicosapentaenoic acid ( r=0.401 , p=0.017 , n=35 ) and were also associated with a decrease in systolic-BP ( r=-0.511 , p<0.001 , n=52 ) . CONCLUSIONS The results indicate that n-3 fatty acid intake also in late infancy can influence brain development and that the cognitive and cardiovascular effects may be related
target: There is no evidence that PUFA supplementation in infancy has an effect on infant or childhood allergy , asthma , dermatitis/eczema or food allergy .
  However , the quality of evidence was very low .
  There was insufficient evidence to determine an effect on allergic rhinitis
background: BACKGROUND Early dietary intakes may influence the development of allergic disease .
  It is important to determine if dietary polyunsaturated fatty acids ( PUFAs ) given as supplements or added to infant formula prevent the development of allergy .
  OBJECTIVES To determine the effect of higher PUFA intake during infancy to prevent allergic disease .