title: [Preventative effect of a whey hydrolyzed formula (Nestle, NAN H.A.) on the development of allergic symptoms in infants]. Hydrolysed protein accelerates the gastrointestinal transport of formula in preterm infants Randomised controlled trial of brief neonatal exposure to cows’ milk on the development of atopy Does Early Diet Have an Effect on Subsequent Macromolecular Absorption and Serum IgE? Effectiveness of massage, sucrose solution, herbal tea or hydrolysed formula in the treatment of infantile colic. Primary prevention of asthma and atopy during childhood by allergen avoidance in infancy: a randomised controlled study Effect of an allergy prevention programme on incidence of atopic symptoms in infancy [Prevention of allergy in infants. A prospective study of 159 high-risk children]. Association between breast feeding and asthma in 6 year old children: findings of a prospective birth cohort study Long-term safety assessment in children who received hydrolyzed protein formulas with Lactobacillus rhamnosus GG: a 5-year follow-up Effect of a partially hydrolyzed whey infant formula at weaning on risk of allergic disease in high-risk children: a randomized controlled trial. Growth of Healthy Term Infants Fed Partially Hydrolyzed Whey-Based Infant Formula Incidence and prognosis of asthma and wheezing illness from early childhood to age 33 in a national British cohort The Trial to Reduce IDDM in the Genetically at Risk (TRIGR) study: recruitment, intervention and follow-up Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes: The TRIGR Randomized Clinical Trial Nutritional evaluation of protein hydrolysate formulas in healthy term infants: plasma amino acids, hematology, and trace elements. Hydrolyzed infant formula and early β-cell autoimmunity: a randomized clinical trial. Avoidance of Cow's Milk-Based Formula for At-Risk Infants Does Not Reduce Development of Celiac Disease: A Randomized Controlled Trial. Paracetamol use in early life and asthma: prospective birth cohort study Dietary intervention in infancy and later signs of beta-cell autoimmunity. Caesarean section and gastrointestinal symptoms, atopic dermatitis, and sensitisation during the first year of life Extensively hydrolyzed protein formula reduces acid gastro-esophageal reflux in symptomatic preterm infants. Maternal dietary antigen avoidance during pregnancy or lactation, or both, for preventing or treating atopic disease in the child. Tolerance of a standard intact protein formula versus a partially hydrolyzed formula in healthy, term infants Supplementary feeding in maternity hospitals and the risk of cow's milk allergy: A prospective study of 6209 infants. Effect of exclusive breast-feeding and early solid food avoidance on the incidence of atopic dermatitis in high-risk infants at 1 year of age. Prebiotic‐supplemented partially hydrolysed cow's milk formula for the prevention of eczema in high‐risk infants: a randomized controlled trial Certain hydrolyzed formulas reduce the incidence of atopic dermatitis but not that of asthma: three-year results of the German Infant Nutritional Intervention Study. Long-term prevention of allergic diseases by using protein hydrolysate formula in at-risk infants. Cumulative incidence of atopic disorders in high risk infants fed whey hydrolysate, soy, and conventional cow milk formulas. Preventive effect of feeding high-risk infants a casein hydrolysate formula or an ultrafiltrated whey hydrolysate formula. A prospective, randomized, comparative clinical study. Five-year follow-up of high-risk infants with family history of allergy who were exclusively breast-fed or fed partial whey hydrolysate, soy, and conventional cow's milk formulas. Cow's milk IgE and IgG antibody responses to cow's milk formulas Early infant feeding and type 1 diabetes Transforming growth factor-beta1 in mothers' colostrum and immune responses to cows' milk proteins in infants with cows' milk allergy. Breast-feeding and the development of cows' milk protein allergy. Extensively and partially hydrolysed infant formulas for allergy prophylaxis Growth in preterm infants fed either a partially hydrolyzed whey or an intact casein/whey preterm infant formula Effect of allergen avoidance in infancy on allergic manifestations at age two years. The timing and duration of a sensitive period in human flavor learning: a randomized trial. Effects of a dietary and environmental prevention programme on the incidence of allergic symptoms in high atopic risk infants: three years follow‐up The prevalence and natural course of food protein-induced enterocolitis syndrome to cow's milk: a large-scale, prospective population-based study. Application effect of extensively hydrolyzed milk protein formula and follow-up in preterm children with a gestational age of less than 34 weeks: study protocol for a randomized controlled trial Multifaceted allergen avoidance during infancy reduces asthma during childhood with the effect persisting until age 18 years The effect of brief neonatal exposure to cows' milk on atopic symptoms up to age 5 Removal of Bovine Insulin From Cow's Milk Formula and Early Initiation of Beta-Cell Autoimmunity in the FINDIA Pilot Study. Effects of cow milk versus extensive protein hydrolysate formulas on infant cognitive development Dietary manipulation of beta cell autoimmunity in infants at increased risk of type 1 diabetes: a pilot study Maternal compliance with nutritional recommendations in an allergy preventive programme The development and prediction of atopy in high-risk children: follow-up at age seven years in a prospective randomized study of combined maternal and infant food allergen avoidance. Dietary treatment of infant colic: a double-blind study. Early allergic sensitizations and their relevance to atopic diseases in children aged 6 years: results of the GINI study. Prediction of allergy from family history and cord blood IgE levels. A follow-up at the age of 5 years. Cord blood IgE. IV. Plasma amino acid concentrations in term-born infants fed a whey predominant or a whey hydrolysate formula. Growth of Healthy Term Infants Fed an Extensively Hydrolyzed Casein-Based or Free Amino Acid–Based Infant Formula Improved general health status in an unselected infant population following an allergen-reduced dietary intervention programme: the ZUFF-STUDY-PROGRAMME
  Part II: infant growth and health status to age 6 months Effect of allergen avoidance on development of allergic disorders in infancy Gastric Electrical Activity and Gastric Emptying in Preterm Newborns Fed Standard and Hydrolysate Formulas Development of nasal basophilic cells and nasal eosinophils from age 4 months through 4 years in children of atopic parents. A randomized controlled study on the effectiveness of a multifaceted intervention program in the primary prevention of asthma in high-risk infants. Comparison of a partially hydrolyzed infant formula with two extensively hydrolyzed formulas for allergy prevention: a prospective, randomized study. [Effects of extensively hydrolyzed protein formula on feeding and growth in preterm infants: a multicenter controlled clinical study]. Hydrolyzed protein accelerates feeding advancement in very low birth weight infants. The effect of maternal avoidance of eggs, cow's milk, and fish during lactation on the development of IgE, IgG, and IgA antibodies in infants. The nutritional value of a whey hydrolysate formula compared with a whey-predominant formula in healthy infants. Nutritional Efficacy of Preterm Formula With a Partially Hydrolyzed Protein Source: A Randomized Pilot Study Hypoallergenicity and effects on growth and tolerance of a new amino acid-based formula with docosahexaenoic acid and arachidonic acid. Preventive effect of hydrolyzed infant formulas persists until age 6 years: long-term results from the German Infant Nutritional Intervention Study (GINI). Sensitive period in flavor learning: effects of duration of exposure to formula flavors on food likes during infancy. Early exposure to cow's milk protein is protective against IgE-mediated cow's milk protein allergy. Whey hydrolysate compared with cow's milk‐based formula for weaning at about 6 months of age in high allergy‐risk infants: effects on atopic disease and sensitization The Canadian asthma primary prevention study: outcomes at 2 years of age. Correlation between early neonatal diet and atopic symptoms up to 5-7 years of age in very low birth weight infants: follow-up of randomized, double-blind study. Growth, Tolerance and Biochemical Measures in Healthy Infants Fed a Partially Hydrolyzed Rice Protein-Based Formula: A Randomized, Blinded, Prospective Trial Cow's milk protein intolerance in infants under 1 year of age: A prospective epidemiological study Growth of Healthy Term Infants Fed Ready-to-Feed and Powdered Forms of an Extensively Hydrolyzed Casein-Based Infant Formula Extensively and partially hydrolysed preterm formulas in the prevention of allergic diseases in preterm infants: a randomized, double‐blind trial WEIGHT-GAIN INHIBITION BY LACTOSE IN AUSTRALIAN ABORIGINAL CHILDREN: A Controlled Trial of Normal and Lactose Hydrolysed Milk Nitrogen utilization and bone mineralization in very low birth weight infants fed partially hydrolyzed preterm formula. Partial Protein-Hydrolyzed Infant Formula Decreased Food Sensitization but Not Allergic Diseases in a Prospective Birth Cohort Study Higher urinary excretion of essential amino acids in preterm infants fed protein hydrolysates The diagnostic significance of IgG cow's milk protein antibodies re-evaluated Nutritional evaluation of various protein hydrolysate formulae in term infants during the first month of life The effect of hydrolyzed cow's milk formula for allergy prevention in the first year of life: the German Infant Nutritional Intervention Study, a randomized double-blind trial. Importance of the first meal on the development of cow's milk allergy and intolerance. Use of hypoallergenic formula in the prevention of atopic disease among Asian children. Effect of cow's milk exposure and maternal type 1 diabetes on cellular and humoral immunization to dietary insulin in infants at genetic risk for type 1 diabetes. Finnish Trial to Reduce IDDM in the Genetically at Risk Study Group. Reduction of crying episodes owing to infantile colic: a randomized controlled study on the efficacy of a new infant formula Randomized Double-Blind Study of the Nutritional Efficacy and Bifidogenicity of a New Infant Formula Containing Partially Hydrolyzed Protein, a High &bgr;-Palmitic Acid Level, and Nondigestible Oligosaccharides Gastric emptying in healthy newborns fed an intact protein formula, a partially and an extensively hydrolysed formula. Long-term effects of hydrolyzed protein infant formulas on growth--extended follow-up to 10 y of age: results from the German Infant Nutritional Intervention (GINI) study. Comparison of Breast, Cow, and Soy Feedings in the Prevention of Onset of Allergic Disease The association of atopic dermatitis in infancy with immunoglobulin E food sensitization. Effect of feeding whey hydrolysate, soy and conventional cow milk formulas on incidence of atopic disease in high risk infants. [Does the hydrolysis of proteins change the acceptability and the digestive tolerance of milk for infants? The results of a comparative and randomized prospective study]. Hydrolysed proteins in preterm formula: influence on plasma aminoacids, blood fatty acids and insulinaemia The long-term effect of a partial whey hydrolysate formula on the prophylaxis of atopic disease Period-specific growth, overweight and modification by breastfeeding in the GINI and LISA birth cohorts up to age 6 years Soluble Adhesion Molecules and Oral Antigen Feeding in Infants Soy consumption is not a risk factor for peanut sensitization. Infantile colic: crying time reduction with a whey hydrolysate: A double-blind, randomized, placebo-controlled trial. Development of immune response to cow's milk proteins in infants receiving cow's milk or hydrolyzed formula. Parental counseling compared with elimination of cow's milk or soy milk protein for the treatment of infant colic syndrome: a randomized trial. A Comparative Evaluation of Whey Hydrolysate and Whey-Predominant Formulas Improved general health status in an unselected infant population following an allergen reduced dietary intervention programme The ZUFF-STUDY-PROGRAMME
  Part I: study design and 6-month nutritional behaviour
   Effects of brief early exposure to partially hydrolyzed and whole cow milk proteins. Cow's milk‐specific cellular and humoral immune responses and atopy skin symptoms in infants from atopic families fed a partially (pHF) or extensively (eHF) hydrolyzed infant formula Protein hydrolysate formula maintains homeostasis of plasma amino acids in preterm infants. Effect of maternal diet during lactation on development of bovine insulin-binding antibodies in children at risk for allergy. Effects of prolonged exposure to partially hydrolyzed milk protein. Allergies in high-risk schoolchildren after early intervention with cow's milk protein hydrolysates: 10-year results from the German Infant Nutritional Intervention (GINI) study. Allergy development and macromolecular absorption in infants with different feeding regimens during the first three days of life. A three‐year prospective follow‐up Short- and long-term effects of feeding hydrolyzed protein infant formulas on growth at < or = 6 y of age: results from the German Infant Nutritional Intervention Study. Allergen avoidance in infancy and allergy at 4 years of age A low allergen diet is a significant intervention in infantile colic: results of a community-based study. Effect of combined maternal and infant food-allergen avoidance on development of atopy in early infancy: a randomized study. Manchester Asthma and Allergy Study: low-allergen environment can be achieved and maintained during pregnancy and in early life. Early life risk factors for current wheeze, asthma, and bronchial hyperresponsiveness at 10 years of age. Effect of environmental manipulation in pregnancy and early life on respiratory symptoms and atopy during first year of life: a randomised trial Development of immunoglobulin G and immunoglobulin E antibodies to cow's milk proteins and ovalbumin after a temporary neonatal exposure to hydrolyzed and whole cow's milk proteins. Growth and Tolerance of Healthy Term Infants Receiving Hydrolyzed Infant Formulas Supplemented With Lactobacillus rhamnosus GG: Randomized, Double-Blind, Controlled Trial Influence of maternal diet during lactation and use of formula feeds on development of atopic eczema in high risk infants. Specific antibodies to cow’s milk proteins in infants: effect of early feeding and diagnosis of cow’s milk allergy
abstract: We examined the prevent effect of a whey hydrolyzed formula ( NAN H.A. ) on the development of  allergic disease from new born infants . A hundred thirty three pregnant women were divided into the  NAN H.A.  group and the  control group . Mothers , who agreed to use the whey hydrolyzed formula to their infant , were classified into the NAN H.A. group . We examined laboratory date such as IgE levels of these infants as well as clinical symptoms for evaluating of the preventive effect of NAN H.A. The serum IgE levels from infants of the NAN H.A. group were lower than those of the control group . The incidance of the infants who showed allergic clinical symptoms was significant lower in the NAN H.A. group . The odds ratio to skin symptom at 3 years of age with multiple logistic regression was 5.32 between the control group and the NAN H.A. group ( p < 0.05 ) . It was 6.68 between mother 's history of allergy was positive and negative ( p < 0.02 ) . These results suggest that NAN H.A. can prevent the development of allergic symptoms in infants Vomiting , large gastric residuals and abdominal distension are common in very immature infants on formula feeding . The present trial investigated whether a protein hydrolysate formula reduces the gastrointestinal transit time in preterm infants . Fifteen preterm infants ( median gestational age 29 ( 24–32 ) wk , birthweight 1241 ( 660–1900 ) g , postnatal age 18 ( 5–54 ) d ) on full enteral feeds ( > 150 ml/kg*d ) were enrolled . It was hypothesized that the gastrointestinal transit time is at least 2 h shorter when protein hydrolysate formula is fed compared with st and ard preterm formula . In a r and omized cross‐over design study , each formula was fed for 5 d. On days 4 and 9 the gastrointestinal transit time was estimated using carmine red . The protein hydrolysate formula had a markedly shorter gastrointestinal transit time ( 9.8 h ) than the st and ard formula ( 19 h ) ( p= 0.0022 , two‐sided Mann‐Whitney U test ) OBJECTIVE To determine the effect of brief early exposure to cows ’ milk on  atopy in the first 2 years of life . DESIGN Double blind , placebo controlled , r and omised feeding intervention trial ( Bokaal study ) . SETTING Dutch midwifery practice s. PARTICIPANTS 1533 breast fed neonates . INTERVENTION Exposure to cows ’ milk protein ( n = 758 ) or a protein free placebo ( n = 775 ) during the first 3 days of life . MAIN OUTCOME MEASURES Clinical atopic disease and any positive radioallergosorbent ( RAST ) tests at 1 year of age . RESULTS Atopic disease in the first year was found in 10.0 % ( cows ’ milk)v 9.3 % ( placebo ) of the children , with a relative risk of 1.07 ; in the second year , atopic disease was found in 9.6 % v 10.2 % , respectively , with a relative risk of 0.94 . Per protocol analysis showed similar results . Any RAST positive test was found in 9.4 % ( cows ’ milk)v 7.9 % ( placebo ) of children , with a relative risk of 1.19 . Stratified analysis for high family risk of allergy showed a doubled incidence of atopic disease but no effect from the intervention . CONCLUSION Early and brief exposure to cows ’ milk in breast fed children does not increase the risk of atopic disease in the first 2 years A group of 130 healthy term infants were r and omly assigned at birth to one of three feeding regimens for the first 3 days of life : human milk ( HM ) , cow-milk formula ( CMF ) , or a casein hydrolysate formula ( CHF ) . The formula-fed infants received no human milk during the study days . After day 3 , all infants were exclusively breast-fed . Blood sample s were taken at 4 days and at 2 and 4 months of age during outpatient visits . Macromolecular absorption was analyzed 60 min after a feed of human milk by measuring the serum α-lactalbumin ( S-αLA ) concentrations by a competitive radioimmunoassay . Total serum IgE ( S-lgE ) was assayed by radioimmu-noassay . The median S-IgE value was significantly lower at 2 months of age in the CHF group than in the HM group . The values remained significantly lower , even at 4 months of age , in the CHF group than in either the HM or the CMF group . The median S-αLA concentration at 2 months of age was significantly higher in the CHF group than in either the HM group or the CMF group . No significant differences could be found between the CMF and HM groups at any time . One infant in the HM group and one infant in the CMF group developed infantile colic . Two infants in the CHF group developed symptoms of cow-milk allergy . All other infants were healthy at 4 months of age AIM AND OBJECTIVE The aim of the study was to evaluate the effectiveness of massage , sucrose solution , herbal tea or hydrolysed formula , each used individually in the treatment of infantile colic . BACKGROUND The term colic describes a group of symptoms that occur frequently in infants , consisting of paroxysmal abdominal pain and severe crying . Infant colic is of importance for both parents and the community health services that provide families with care , and is therefore an important clinical problem that is amenable to nursing interventions . DESIGN This prospect i ve and r and omised-controlled study involved 175 infants in Turkey . METHODS Data were gathered by using Wessel criteria ; parents wrote a daily structured diary , recording the onset and duration of crying . Patients were assigned r and omly into four different intervention groups ( massage , sucrose solution , herbal tea and hydrolysed formula ) and control group .  Duration of crying following each intervention was recorded in the diary by parents for a one week period . RESULTS There was a significant reduction in crying hours per day in all intervention groups . The difference between mean duration of total crying ( hours/day ) before and after the intervention infants in hydrolysed formula group was found higher than massage , sucrose and herbal tea group . The difference between mean duration of total crying(hours/day ) before and after the intervention infants in massage group was found lower than other intervention groups and all groups . CONCLUSION Our findings demonstrated that varied interventions such as administration of massage , sucrose solution , herbal tea and hydrolysed formula are effective in the treatment of colic . The difference between mean duration of total crying ( hours/day ) before and after the intervention in hydrolysed formula group was found higher than other intervention groups . Hydrolysed formula was the most effective in reducing the duration of crying ( hours/day ) when compared with the other intervention groups . Massage intervention yielded the least symptomatic improvement among all the interventions . RELEVANCE TO CLINICAL PRACTICE Colic treatment models used in this study can be used by nurses in neonatal and primary healthcare setting s as an aid to families for the treatment of infantile colic Background : Recent increases in the prevalence of asthma and atopy emphasise the need for devising effective methods for primary prevention in children at high risk of atopy . Method : A birth cohort of genetically at risk infants was recruited in 1990 to a r and omised controlled study . Allergen avoidance measures were instituted from birth in the prophylactic group ( n=58 ) . Infants were either breast fed with mother on a low allergen diet or given an extensively hydrolysed formula . Exposure to house dust mite was reduced by the use of an acaricide and mattress covers . The control group ( n=62 ) followed st and ard advice as normally given by the health visitors . At age 8 , all 120 children completed a question naire and 110 ( 92 % ) had all assessment s ( skin prick test , spirometry , and bronchial challenges ) . Results : In the prophylactic group eight children ( 13.8 % ) had current wheeze compared with 17 ( 27.4 % ) in the control group ( p=0.08 ) . Respective figures were eight ( 13.8 % ) and 20 ( 32.3 % ) for nocturnal cough ( p=0.02 ) and 11 of 55 ( 20.0 % ) and 29 of 62 ( 46.8 % ) for atopy ( p=0.003 ) . After adjusting for confounding variables , the prophylactic group was found to be at a significantly reduced risk for current wheeze ( odds ratio ( OR ) 0.26 ( 95 % confidence interval ( CI ) 0.07 to 0.96 ) ) , nocturnal cough ( OR 0.22 ( 95 % CI 0.06 to 0.83 ) ) , asthma as defined by wheeze and bronchial hyperresponsiveness ( OR 0.11 ( 95 % CI 0.01 to 1.02 ) ) , and atopy ( OR 0.21 ( 95 % CI 0.07 to 0.62 ) ) . Conclusion : Strict allergen avoidance in infancy in high risk children reduces the development of allergic sensitisation to house dust mite . Our results suggest that this may prevent some cases of childhood asthma A total of 105 “ high‐risk ” infants born in 1988 were studied prospect ively from birth to 18 months of age . The infants were recommended breastfeeding and /or hypoallergenic formula ( Nutramigen or Profylac ) combined with avoidance of solid foods during the first 6 months of life . All mothers had unrestricted diet . Avoidance of daily exposure to tobacco smoke , furred pets and dust‐collecting material s in the bedroom were advised . This prevention group was compared with a control group consisting of 54 identically defined “ high‐risk ” infants born in 1985 in the same area . All infants had either severe single atopic predisposition combined with cord blood IgE ≥ 0.5 KU/1 or biparental atopic predisposition . The control group had unrestricted diet and was not advised about environmental factors . Apart from the prevention programme and year of birth the prevention group and the control group were comparable . The parents were highly motivated and compliance was good . The rate of participation was 97 % , and 85 % followed the dietary measures strictly . The cumulative prevalence of atopic symptoms was significantly lower at 18 months in the prevention group ( 32 % ) , as compared with the control group ( 74 % ) ( p<0.01 ) , due to reduced prevalence of recurrent wheezing ( 13 % , versus 37 % ; p<0.01 ) , atopic dermatitis ( 14 % versus 31 % ; p<0.01 ) , vomiting/diarrhoea ( 5 % versus 20 % ; p<0.01 ) and infantile colic ( 9 % versus 24 % ; p<0.01 ) . The cumulative prevalence of food allergy was significantly lower in the prevention group ( 6 % versus 17 % ; p<0.05 ) . In both high‐risk groups daily exposure to tobacco smoke increased the risk of recurrent wheezing significantly ( p<0.01 ) . The main difference between the prevention group and the control group was the diet . Thus , feeding with breastmilk and /or hypoallergenic formula combined with avoidance of solid foods until the age of 6 months appeared to reduce the cumulative prevalence of atopic symptoms during the first 18 months of life A total of 105 infants at " high risk " for developing allergy born in 1988 were studied prospect ively from birth to 18 months of age . The infants were recommended breastfeeding and /or hypoallergenic formula ( Nutramigen or Profylac ) combined with avoidance of solid foods the first six months of life . All mothers had unrestricted diet . Avoidance of daily exposure to tobacco smoking , furred pets and dust collecting material s in the bedroom was advised . This prevention group was compared to a control group consisting of 54 identically defined " high-risk " infants born in 1985 in the same area . All the infants had either severe single atopic predisposition combined with cord blood IgE > or = 0.5 KU/l or biparental atopic predisposition . The control group had unrestricted diet and was not advised about environmental factors . The cumulative incidence of atopic symptoms was significantly lower at 18 months in the prevention group ( 32 % ) compared with the control group ( 74 % ) ( p < 0.01 ) , due to reduced incidence of recurrent wheezing ( 13 % versus 37 % ; p < 0.01 ) , atopic dermatitis ( 14 % versus 31 % ; p < 0.01 ) , vomiting/diarrhoea ( 5 % versus 20 % ; p < 0.01 ) and infantile colic ( 9 % versus 24 % ; p < 0.01 ) . The cumulative incidence of food-allergy was significantly lower in the prevention group ( 6 % versus 17 % ; p < 0.05 ) . In both high-risk groups exposure to daily tobacco smoking increased the risk of recurrent wheezing significantly ( p < 0.01 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Abstract Objectives : To investigate the association between the duration of exclusive breast feeding and the development of  asthma related outcomes in children at age 6 years . Design : Prospect i ve cohort study . Setting : Western Australia . Subjects : 2187 children ascertained through antenatal clinics at the major tertiary obstetric hospital in Perth and followed to age 6 years . Main outcome measures : Unconditional logistic regression to model the association between duration of exclusive breast feeding and outcomes related to asthma or atopy at 6 years of age , allowing for several important confounders : sex , gestational age , smoking in the household , and early childcare . Results : After adjustment for confounders , the introduction of milk other than breast milk before 4 months of age was a significant risk factor for all asthma and atopy related outcomes in children aged 6 years : asthma diagnosed by a doctor ( odds ratio 1.25 , 95 % confidence interval 1.02 to 1.52 ) ; wheeze three or more times since 1 year of age ( 1.41 , 1.14 to 1.76 ) ; wheeze in the past year ( 1.31 , 1.05 to 1.64 ) ; sleep disturbance due to wheeze within the past year ( 1.42 , 1.07 to 1.89 ) ; age when doctor diagnosed asthma ( hazard ratio 1.22 , 1.03 to 1.43 ) ; age at first wheeze ( 1.36 , 1.17 to 1.59 ) ; and positive skin prick test reaction to at least one common aeroallergen ( 1.30 , 1.04 to 1.61 ) . Conclusion : A significant reduction in the risk of childhood asthma at age 6 years occurs if exclusive breast feeding is continued for at least the 4 months after birth . These findings are important for our underst and ing of the cause of childhood asthma and suggest that public health interventions to optimise breast feeding may help to reduce the community burden of childhood asthma and its associated traits . Key messages Asthma is the leading cause of admission to hospital in Australian children and its prevalence is increasing Whether breast feeding protects against asthma or atopy , or both , is controversial Asthma is a complex disease , and the relative risks between breast feeding and asthma or atopy are unlikely to be large ; this suggests the need for investigation in a large prospect i ve birth cohort with timely assessment of atopic outcomes and all relevant exposures Exclusive breast feeding for at least 4 months is associated with a significant reduction in the risk of asthma and atopy at age 6 years and with a significant delay in the age at onset of wheezing and asthma being diagnosed by a doctor Public health interventions to promote an increased duration of exclusive breast feeding may help to reduce the morbidity and prevalence of childhood asthma  and Abstract Extensively hydrolyzed ( EH ) formula with Lactobacillus rhamnosus GG ( LGG ) was demonstrated to alleviate cow ’s milk allergy ( CMA ) symptoms and promote faster acquisition of tolerance to cow ’s milk protein . We previously demonstrated that partially hydrolyzed ( PH ) and EH formulas with LGG supported normal growth in healthy-term infants through 120 days of age . The objective of the current study was to evaluate growth , development , and specific adverse events through 5 years of age in participants from that cohort who continued receiving study formula . Infants who completed a double-blind , r and omized growth and tolerance study were eligible to continue receiving the assigned study formula through 1 year of age ( control : EH casein formula , EHF , or one of two investigational formulas : EH casein formula with LGG ( EHF-LGG ) or a PH formula with LGG ( PHF-LGG ) ) and participate in follow-up through 5 years of age . Anthropometric measures , behavior development , and specific adverse events were recorded . No significant differences in achieved weight and height or behavioral development outcomes at 3 or 5 years of age were observed among study groups . Few statistically significant differences in the incidence of specific infection-related events through years 3 or 5 were observed among study groups , none of which were considered clinical ly relevant . Conclusion : Extensively and partially hydrolyzed formulas with LGG were associated with normal growth and development and long-term safety through 5 years of age . What is Known:• Infants with cow ’s milk allergy often experience allergic manifestations that can lead to poor nutrition status and poor growth.• Providing partially hydrolyzed ( PH ) and EH formulas with or without LGG in infants can support normal growth in healthy-term infants . What is New:• This study provides long-term safety data for the first 5 years of life on the use of extensively and partially hydrolyzed formulas with LGG when fed through 1 year of age.• Extensively and partially hydrolyzed formulas with LGG are associated with normal growth , development , and long-term safety through 5 years of age BACKGROUND Partially hydrolyzed whey formula ( pHWF ) has been recommended for infants with a family history of allergic disease at the cessation of exclusive breast-feeding to promote oral tolerance and prevent allergic diseases . OBJECTIVE To determine whether feeding infants pHWF reduces their risk of allergic disease . METHODS A single-blind ( participant ) r and omized controlled trial was conducted to compare allergic outcomes between infants fed a conventional cow 's milk formula , a pHWF , or a soy formula . Before birth , 620 infants with a family history of allergic disease were recruited and r and omized to receive the allocated formula at cessation of breast-feeding . Skin prick tests to 6 common allergens ( milk , egg , peanut , dust mite , rye grass , and cat d and er ) were performed at 6 , 12 , and 24 months . The primary outcome was development of allergic manifestations ( eczema and food reactions ) measured 18 times in the first 2 years of life . RESULTS Follow-up was complete for 93 % ( 575/620 ) at 2 years and 80 % ( 495/620 ) at 6 or 7 years of age . There was no evidence that infants allocated to the pHWF ( odds ratio , 1.21 ; 95 % CI , 0.81 - 1.80 ) or the soy formula ( odds ratio , 1.26 ; 95 % CI , 0.84 - 1.88 ) were at a lower risk of allergic manifestations in infancy compared with conventional formula . There was also no evidence of reduced risk of skin prick test reactivity or childhood allergic disease . CONCLUSION Despite current dietary guidelines , we found no evidence to support recommending the use of pHWF at weaning for the prevention of allergic disease in high-risk infants Partially hydrolyzed formulas ( pHF ) represent a significant percentage of the infant formula market . A new whey-based , palm olein oil (PO)–free pHF was developed and a masked , r and omized , parallel growth study was conducted in infants fed this formula or a commercially available whey-based pHF with PO . Infants between 0 and 8 days were to be enrolled and studied to 119 days of age . Growth and tolerance of infants were evaluated . Mean weight gain from 14 to 119 days of age was similar between groups . There were no significant differences between groups in weight , length , head circumference ( HC ) , or length or HC gains . Infants fed the new PO-free pHF had significantly softer stools than those fed the PO-containing formula except at 119 days of age . This study demonstrates that whereas growth of infants fed different formulas during the first 4 months of life may be similar , infants may tolerate individual formulas differently Abstract Objective : To describe the incidence and prognosis of wheezing illness from birth to age 33 and the relation of incidence to perinatal , medical , social , environmental , and lifestyle factors . Design : Prospect i ve longitudinal study . Setting : Engl and , Scotl and , and Wales . Subjects : 18 559 people born on 3 - 9 March 1958 . 5801 ( 31 % ) contributed information at ages 7 , 11 , 16 , 23 , and 33 years . Attrition bias was evaluated using information on 14 571 ( 79 % ) subjects . Main outcome measure : History of asthma , wheezy bronchitis , or wheezing obtained from interview with subjects ' parents at ages 7 , 11 , and 16 and reported at interview by subjects at ages 23 and 33 . Results : The cumulative incidence of wheezing illness was 18 % by age 7 , 24 % by age 16 , and 43 % by age 33 . Incidence during childhood was strongly and independently associated with pneumonia , hay fever , and eczema . There were weaker independent associations with male sex , third trimester antepartum haemorrhage , whooping cough , recurrent abdominal pain , and migraine . Incidence from age 17 to 33 was associated strongly with active cigarette smoking and a history of hay fever . There were weaker independent associations with female sex , maternal albuminuria during pregnancy , and histories of eczema and migraine . Maternal smoking during pregnancy was weakly and inconsistently related to childhood wheezing but was a stronger and significant independent predictor of incidence after age 16 . Among 880 subjects who developed asthma or wheezy bronchitis  from birth to age 7 , 50 % had attacks in the previous year at age 7 ; 18 % at 11 , 10 % at 16 , 10 % at 23 , and 27 % at 33 . Relapse at 33 after prolonged remission of childhood wheezing was more common among current smokers and atopic subjects . Conclusion : Atopy and active cigarette smoking are major influences on the incidence and recurrence of wheezing during adulthood . Key messages Incidence of wheezing illness at all ages was strongly and consistently related to a history of hay fever or eczema ( atopy ) . Associations with maternal smoking during pregnancy , abdominal pain , and migraine were largely confined to those without atopy Active smoking was a powerful and potentially avoidable risk factor for wheeze starting in adult life among both atopic and non-atopic subjects A quarter of the children with a history of asthma or wheezy bronchitis by age 7 reported wheeze in the past year at age 33 Recurrence of wheezing after prolonged remis- sion during late adolescence was strongly associ- ated with atopy and cigarette smoking Aims /hypothesisThe Trial to Reduce  IDDM  in the Genetically at Risk ( TRIGR ) study was design ed to establish whether weaning to a highly hydrolysed formula in infancy subsequently reduces the risk of type 1 diabetes . Methods The study population comprises newborn infants who have first-degree relatives with type 1 diabetes and meet the increased risk HLA inclusion , but not exclusion criteria . The study is being performed in 15 countries in three continents . First-degree relatives of patients with type 1 diabetes were identified from diabetes clinics , diabetes registries , and from other endocrinology or obstetrics offices and websites . HLA typing was performed at birth from cord or heel stick blood , and the results sent to the study ’s Data Management Unit within 2 weeks for communication of eligibility to the clinical study centre . All mothers recruited were encouraged to breastfeed . The intervention lasted for 6 to 8 months , and weaning formulas based on hydrolysed casein and st and ard cow ’s milk were compared . Results TRIGR recruited 5,606 infants , of whom 2,160 were enrolled as eligible participants , 6 % more than the target of 2,032 . Of those enrolled , 80 % were exposed to the study formula . The overall retention rate over the first 5 years is 87 % , with protocol compliance at 94 % . The r and omisation code will be opened when the last recruited child turns 10 years of age , i.e. in 2017 . Conclusions /interpretationThe TRIGR experience demonstrates the feasibility and successful implementation of an international dietary intervention study . TRIGR is the first ever primary prevention trial for type 1 diabetes and , if completed successfully , will provide a definite answer to the research question .Trial registration Clinical Trials.gov NCT00179777 Funding The study was funded by the National Institute of Child Health and Development ( NICHD ) and National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK ) , National Institutes of Health ( NIH ) ( grant numbers HD040364 , HD042444 and HD051997 ) , Canadian Institutes of Health Research , the Juvenile Diabetes Research Foundation International and the Commission of the European Communities ( specific RTD programme ‘ Quality of Life and Management of Living Re sources ’ , contract number QLK1 - 2002 - 00372 ‘ Diabetes Prevention ’ . Other funding came from the EFSD/JDRF/Novo Nordisk Focused Research Grant , Academy of Finl and , Dutch Diabetes Research Foundation and Finnish Diabetes Research Foundation ) Importance Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility . There are no intact proteins in extensively hydrolyzed formulas . Objective To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children . Design , Setting , and Participants An international double-blind r and omized clinical trial of 2159 infants with human leukocyte antigen – conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries ; 1081 were r and omized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula .  The follow-up of the participants ended on February 28 , 2017 . Interventions The participants received either a casein hydrolysate or a conventional adapted cow ’s milk formula supplemented with 20 % of the casein hydrolysate . The minimum duration of study formula exposure was 60 days by 6 to 8 months of age . Main Outcomes and Measures Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria . Secondary outcomes included age at diabetes diagnosis and safety ( adverse events ) . Results Among 2159 newborn infants ( 1021 female [ 47.3 % ] ) who were r and omized , 1744 ( 80.8 % ) completed the trial . The participants were observed for a median of 11.5 years ( quartile [ Q ] 1-Q3 , 10.2 - 12.8 ) . The absolute risk of type 1 diabetes was 8.4 % among those r and omized to the casein hydrolysate ( n = 91 ) vs 7.6 % among those r and omized to the conventional formula ( n = 82 ) ( difference , 0.8 % [ 95 % CI , −1.6 % to 3.2 % ] ) . The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group , duration of breastfeeding , duration of study formula consumption , sex , and region while treating study center as a r and om effect was 1.1 ( 95 % CI , 0.8 to 1.5 ; P = .46 ) . The median age at diagnosis of type 1 diabetes was similar in the 2 groups ( 6.0 years [ Q1-Q3 , 3.1 - 8.9 ] vs 5.8 years [ Q1-Q3 , 2.6 - 9.1 ] ; difference , 0.2 years [ 95 % CI , −0.9 to 1.2 ] ) . Upper respiratory infections were the most common adverse event reported ( frequency , 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group ) . Conclusions and Relevance Among infants at risk for type 1 diabetes , weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years . These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes . Trial Registration clinical trials.gov Identifier : BACKGROUND Protein hydrolysate formulas are used for infants with food allergy . Most studies of such formulas focus on their effect on allergy and rarely evaluate their capacity to provide normal nutritional status . OBJECTIVE We compared plasma aminograms , serum urea nitrogen , and trace element status in breastfed infants , infants fed hydrolysate formulas , and infants fed milk formula .  DESIGN From 6 wk to 6 mo of age , infants were breastfed or fed regular milk formula ( RF ) , 1 of 2 casein-hydrolysate formulas ( CH-1 or CH-2 ) , or whey-hydrolysate formula ( WH ) .  Anthropometric measures were taken monthly , and blood sample s were collected at 6 wk and 6 mo . Plasma amino acids , serum urea nitrogen , hematologic indexes , plasma zinc , and plasma copper were analyzed . RESULTS There were no significant differences in hemoglobin , serum transferrin receptor , copper , or zinc among groups . Serum ferritin was significantly lower in infants fed the CH formulas than in the other groups . Infants fed CH-2 had significantly higher serum urea nitrogen than did all other groups . Plasma threonine , valine , phenylalanine , methionine , and tryptophan were significantly higher in the hydrolysate formula groups than in the breastfed group . Plasma tyrosine was significantly lower in infants fed the CH formulas than in the breastfed group , whereas arginine was significantly higher in the WH group than in all other groups . Plasma proline was lower , whereas threonine and tryptophan were higher , in the WH group than in the CH groups . CONCLUSIONS The iron status of infants fed CH formula was lower than that of all other groups . The amounts of amino acids provided by hydrolysate formulas appear excessive compared with regular formula , which is reflected by high serum urea nitrogen ( CH-2 ) and high plasma amino acid concentrations . A reduced and more balanced amino acid content of hydrolysate formulas may be beneficial IMPORTANCE The disease process leading to clinical type 1 diabetes often starts during the first years of life . Early exposure to complex dietary proteins may increase the risk of β-cell autoimmunity in children at genetic risk for type 1 diabetes .  Extensively hydrolyzed formulas do not contain intact proteins . OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of diabetes-associated autoantibodies in young children . DESIGN , SETTING , AND PARTICIPANTS A double-blind r and omized clinical trial of 2159 infants with HLA-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries ; 1078 were r and omized to be weaned to the extensively hydrolyzed casein formula and 1081 were r and omized to be weaned to a conventional cows ' milk-based formula .  The participants were observed to April 16 , 2013 . INTERVENTIONS The participants received either a casein hydrolysate or a conventional cows ' milk formula supplemented with 20 % of the casein hydrolysate . MAIN OUTCOMES AND MEASURES : Primary outcome was positivity for at least 2 diabetes-associated autoantibodies out of 4 analyzed . Autoantibodies to insulin , glutamic acid decarboxylase , and the insulinoma-associated-2 ( IA-2 ) molecule were analyzed using radiobinding assays and islet cell antibodies with immunofluorescence during a median observation period of 7.0 years ( mean , 6.3 years ) . RESULTS The absolute risk of positivity for 2 or more islet autoantibodies was 13.4 % among those r and omized to the casein hydrolysate formula ( n = 139 ) vs 11.4 % among those r and omized to the conventional formula ( n = 117 ) . The unadjusted hazard ratio for positivity for 2 or more autoantibodies among those r and omized to be weaned to the casein hydrolysate was 1.21 ( 95 % CI , 0.94 - 1.54 ) , compared with those r and omized to the conventional formula , while the hazard ratio adjusted for HLA risk , duration of breastfeeding , vitamin D use , study formula duration and consumption , and region was 1.23 ( 95 % CI , 0.96 - 1.58 ) . There were no clinical ly significant differences in the rate of reported adverse events between the 2 groups . CONCLUSIONS AND RELEVANCE Among infants at risk for type 1 diabetes , the use of a hydrolyzed formula , when compared with a conventional formula , did not reduce the incidence of diabetes-associated autoantibodies after 7 years . These findings do not support a benefit from hydrolyzed formula . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00179777 BACKGROUND & AIMS Feeding during the first months of life might affect risk for celiac disease .  Individuals with celiac disease or type 1 diabetes have been reported to have high titers of antibodies against cow 's milk proteins . Avoidance of cow 's milk-based formula for infants with genetic susceptibility for type 1 diabetes reduced the cumulative incidence of diabetes-associated autoantibodies . We performed a r and omized controlled trial in the same population to study whether weaning to an extensively hydrolyzed formula reduced the risk of celiac disease autoimmunity or celiac disease . METHODS We performed a double-blind controlled trial of 230 infants with HLA-defined predisposition to type 1 diabetes and at least 1 family member with type 1 diabetes . The infants were r and omly assigned to groups fed a casein hydrolysate formula ( n = 113 ) or a conventional formula ( control , n = 117 ) whenever breast milk was not available during the first 6 - 8 months of life . Serum sample s were collected over a median time period of 10 years and analyzed for antibodies to tissue transglutaminase ( anti-TG2A ) using a radiobinding assay , to endomysium using an immunofluorescence assay , and antibodies to a deami date d gliadine peptide using an immunofluorometry assay . Duodenal biopsies were collected if levels of anti-TG2A exceeded 20 relative units . Cow 's milk antibodies were measured during the first 2 years of life . RESULTS Of the 189 participants analyzed for anti-TG2A , 25 ( 13.2 % ) tested positive . Of the 230 study participants observed , 10 ( 4.3 % ) were diagnosed with celiac disease . We did not find any significant differences at the cumulative incidence of anti-TG2A positivity ( hazard ratio , 1.14 ; 95 % confidence interval , 0.51 - 2.54 ) or celiac disease ( hazard ratio , 4.13 ; 95 % confidence interval , 0.81 - 21.02 ) between the casein hydrolysate and cow 's milk groups . Children who developed celiac disease had increased titers of cow 's milk antibodies before the appearance of anti-TG2A or celiac disease . CONCLUSIONS In a r and omized controlled trial of 230 infants with genetic risk factors for celiac disease , we did not find evidence that weaning to a diet of extensively hydrolyzed formula compared with  cow 's milk-based formula would decrease the risk for celiac disease later in life . Increased titers of cow 's milk antibody before anti-TG2A and celiac disease indicates that subjects with celiac disease might have increased intestinal permeability in early life . Clinical Trials.gov Number : NCT00570102 Objective To determine if use of paracetamol in early life is an independent risk factor for  childhood asthma .  Design Prospect i ve birth cohort study . Setting Melbourne Atopy Cohort Study . Participants 620 children with a family history of allergic disease , with paracetamol use prospect ively documented on 18 occasions from birth to 2 years of age , followed until age 7 years . Main outcome measures The primary outcome was childhood asthma , ascertained by question naire at 6 and 7 years . Secondary outcomes were infantile wheeze , allergic rhinitis , eczema , and skin prick test positivity . Results Paracetamol had been used in 51 % ( 295/575 ) of children by 12 weeks of age and in 97 % ( 556/575 ) by 2 years . Between 6 and 7 years , 80 % ( 495/620 ) were followed up ; 30 % ( 148 ) had current asthma . Increasing frequency of paracetamol use was weakly associated with increased risk of childhood asthma ( crude odds ratio 1.18 , 95 % confidence interval 1.00 to 1.39 , per doubling of days of use ) . However , after adjustment for frequency of respiratory infections , this association essentially disappeared ( odds ratio 1.08 , 0.91 to 1.29 ) . Paracetamol use for non-respiratory causes was not associated with asthma ( crude odds ratio 0.95 , 0.81 to 1.12 ) . Conclusions In children with a family history of allergic diseases , no association was found between early paracetamol use and risk of subsequent allergic disease after adjustment for respiratory infections or when paracetamol use was restricted to non-respiratory tract infections . These findings suggest that early paracetamol use does not increase the risk of asthma BACKGROUND Early exposure to complex dietary proteins may increase the risk of beta-cell autoimmunity and  type 1 diabetes in children with genetic susceptibility . We tested the hypothesis that supplementing breast milk with highly hydrolyzed milk formula would decrease the cumulative incidence of diabetes-associated autoantibodies in such children . METHODS In this double-blind , r and omized trial , we assigned 230 infants with HLA-conferred susceptibility to type 1 diabetes and at least one family member with type 1 diabetes to receive either a casein hydrolysate formula or a conventional , cow's-milk-based formula ( control ) whenever breast milk was not available during the first 6 to 8 months of life . Autoantibodies to insulin , glutamic acid decarboxylase ( GAD ) , the insulinoma-associated 2 molecule ( IA-2 ) , and zinc transporter 8 were analyzed with the use of radiobinding assays , and islet-cell antibodies were analyzed with the use of immunofluorescence , during a median observation period of 10 years ( mean , 7.5 ) . The children were monitored for incident type 1 diabetes until they were 10 years of age . RESULTS The unadjusted hazard ratio for positivity for one or more autoantibodies in the casein hydrolysate group , as compared with the control group , was 0.54 ( 95 % confidence interval [ CI ] , 0.29 to 0.95 ) , and the hazard ratio adjusted for an observed difference in the duration of exposure to the study formula was 0.51 ( 95 % CI , 0.28 to 0.91 ) . The unadjusted hazard ratio for positivity for two or more autoantibodies was 0.52 ( 95 % CI , 0.21 to 1.17 ) , and the adjusted hazard ratio was 0.47 ( 95 % CI , 0.19 to 1.07 ) . The rate of reported adverse events was similar in the two groups . CONCLUSIONS Dietary intervention during infancy appears to have a long-lasting effect on markers of beta-cell autoimmunity -- markers that may reflect an autoimmune process leading to type 1 diabetes . ( Clinical Trials.gov number , NCT00570102 . ) Aims : To investigate the effect of caesarean section on gastrointestinal symptoms , atopic dermatitis , and sensitisation to nutritional allergens in infants . Methods : A total of 865 healthy full term neonates with parental history of allergy participating in the prospect i ve German Infant Nutritional Intervention Program ( GINI ) were exclusively breast fed during the first four months of life and had a one year follow up . Data were obtained by follow up visits at age 1 , 4 , 8 , and 12 months , weekly diaries for the first six months , and measurement of total and specific IgE at birth and 12 months . Results : Infants born by  caesarean section  ( 147/865 , 17 % ) had a greater risk of diarrhoea ( ORadj 1.46 , 95 % CI 1.022 to 2.10 ) and sensitisation to food allergens , both in adjusted ( ORadj 2.06 , 95 % CI 1.123 to 3.80 ) and stratified analyses ( by cord blood IgE ) . Caesarean delivery was not associated with colicky pain and atopic dermatitis . Conclusion : Caesarean delivery might be a risk factor for diarrhoea and sensitisation in infants with family history of allergy . Further research in this area seems warranted as choosing caesarean section becomes increasingly popular BACKGROUND Gastro-esophageal reflux ( GER ) is diagnosed frequently in preterm infants . Pharmacological treatment of GER has some potential side effects . Conservative treatment of GER should be the first-line approach and should include body positioning and diet modifications . Formula-fed preterm infants experience frequently symptoms of feeding intolerance . Hydrolyzed protein formula ( HPF ) is often used in these infants due to their effects on gastrointestinal motility . AIMS To investigate the role of an extensively HPF ( eHPF ) on GER indexes in formula-fed preterm infants with symptoms of both GER and feeding intolerance . STUDY DESIGN R and omized crossover trial . SUBJECTS Preterm infants ( gestational age ≤33 weeks ) with symptoms of feeding intolerance ( large gastric residuals , abdominal distension and constipation ) and GER ( frequent regurgitations and /or postpr and ial desaturations ) . OUTCOME MEASURES GER indexes detected by 24-h combined multichannel intraluminal impedance and pH monitoring . GER indexes detected after 4 feeds of an eHPF were compared to those detected after 4 feeds of a st and ard preterm formula ( SPF ) by Wilcoxon signed ranks test . A p<0.05 was considered statistically significant . RESULTS eHPF significantly reduced the number of GERs detected by pH monitoring ( p=0.036 ) and also the reflux index ( p=0.044 ) compared to SPF . No differences in impedance bolus exposure indexes nor in GER height were detected . CONCLUSIONS The use of an eHPF should be evaluated for reducing esophageal acid exposure in preterm infants with feeding intolerance and symptoms of GER . Future research should focus on the evaluation of an eHPF adequate for preterm infants in improving clinical symptoms of GER BACKGROUND Some breastfed infants with atopic eczema benefit from elimination of cow milk , egg , or other antigens from their mother 's diet . Maternal dietary antigens are also known to cross the placenta . OBJECTIVES To assess the effects of prescribing an antigen avoidance diet during pregnancy or lactation , or both , on maternal and infant nutrition and on the prevention or treatment of atopic disease in the child . SEARCH METHODS We search ed the Cochrane Pregnancy and Childbirth Group 's Trials Register ( 6 July 2012 ) . SELECTION CRITERIA All r and omized or quasi-r and omized comparisons of maternal dietary antigen avoidance prescribed to pregnant or lactating women . We excluded trials of multimodal interventions that included manipulation of the infant 's diet other than breast milk or of non-dietary aspects of the infant 's environment . DATA COLLECTION AND ANALYSIS We extracted data from published reports , supplemented by additional information received from the trialists we contacted . MAIN RESULTS The evidence from five trials , involving 952 participants , does not suggest a protective effect of maternal dietary antigen avoidance during pregnancy on the incidence of atopic eczema during the first 18 months of life . Data on allergic rhinitis or conjunctivitis , or both , and urticaria are limited to a single trial each and are insufficient to draw meaningful inferences . Longer-term atopic outcomes have not been reported . The restricted diet during pregnancy was associated with a slightly but statistically significantly lower mean gestational weight gain , a non-significantly higher risk of preterm birth , and a non-significant reduction in mean birthweight . The evidence from two trials , involving 523 participants , did not observe a significant protective effect of maternal antigen avoidance during lactation on the incidence of atopic eczema during the first 18 months or on positive skin-prick tests to cow milk , egg , or peanut antigen at one , two , or seven years . One crossover trial involving 17 lactating mothers of infants with established atopic eczema found that maternal dietary antigen avoidance was associated with a non-significant reduction in eczema severity . AUTHORS ' CONCLUSIONS Prescription of an antigen avoidance diet to a high-risk woman during pregnancy is unlikely to reduce substantially her child 's risk of atopic diseases , and such a diet may adversely affect maternal or fetal nutrition , or both . Prescription of an antigen avoidance diet to a high-risk woman during lactation may reduce her child 's risk of developing atopic eczema , but better trials are needed . Dietary antigen avoidance by lactating mothers of infants with atopic eczema may reduce the severity of the eczema , but larger trials are needed Background Parents who perceive common infant behaviors as formula intolerance-related often switch formulas without consulting a health professional . Up to one-half of formula-fed infants experience a formula change during the first six months of life . Methods The objective of this study was to assess discontinuance due to study physician-assessed formula intolerance in healthy , term infants . Infants ( 335 ) were r and omized to receive either a st and ard intact cow milk protein formula ( INTACT ) or a partially hydrolyzed cow milk protein formula ( PH ) in a 60 day non-inferiority trial . Discontinuance due to study physician-assessed formula intolerance was the primary outcome . Secondary outcomes included number of infants who discontinued for any reason , including parent-assessed . Results Formula intolerance between groups ( INTACT , 12.3 % vs. PH , 13.7 % ) was similar for infants who completed the study or discontinued due to study physician-assessed formula intolerance . Overall study discontinuance based on parent- vs. study physician-assessed intolerance for all infants ( 14.4 vs.11.1 % ) was significantly different ( P = 0.001 ) . Conclusion This study demonstrated no difference in infant tolerance of intact vs. partially hydrolyzed cow milk protein formulas for healthy , term infants over a 60-day feeding trial , suggesting nonst and ard partially hydrolyzed formulas are not necessary as a first-choice for healthy infants . Parents frequently perceived infant behavior as formula intolerance , paralleling previous reports of unnecessary formula changes . Trial Registration clinical trials.gov : BACKGROUND Early feeding with cow 's milk ( CM ) may increase the risk of cow 's milk allergy ( CMA ) . OBJECTIVE We sought to examine prospect ively whether supplementary feeding of CM at the maternity hospital would increase the risk when compared with feeding with pasteurized human milk or hydrolyzed formula . METHODS We studied 6209 unselected healthy , full-term infants , of whom 5385 ( 87 % ) required supplementary milk while in the hospital . The infants were r and omly assigned to receive CM formula ( 1789 infants ) , pasteurized human milk ( 1859 infants ) , or whey hydrolysate formula ( 1737 infants ) . The comparison group ( 824 infants ) was composed of infants who were exclusively breast-fed . The infants were followed for 18 to 34 months for symptoms suggestive of CMA . The primary endpoint was a challenge-proven adverse reaction to CM after a successful CM elimination diet . RESULTS The cumulative incidence of CMA in the infants fed CM was 2.4 % compared with 1.7 % in the pasteurized human milk group ( odds ratio [ OR ] , 0.70 ; 95 % confidence interval [ CI ] , 0 . 44 - 1.12 ) and 1.5 % in the whey hydrolysate group ( OR , 0.61 ; 95 % CI , 0 . 38 - 1.00 ) . In the comparison group , CMA developed in 2.1 % of the infants . Among the infants who required supplementary feeding at hospital , both exposure to CM while in the hospital ( OR , 1.54 ; 95 % CI , 1.04 - 2.30 ; P = .03 ) and obvious parental atopy ( OR , 2.32 ; 95 % CI , 1.53 - 3.52 ; P < .001 ) increased the risk of CMA . CONCLUSIONS Our data indicate that feeding of CM at maternity hospitals increases the risk of CMA when compared with feeding of other supplements , but exclusive breast-feeding does not eliminate the risk The aim of this study was to assess the preventive effect of exclusive breast-feeding and early solid food avoidance on  atopic dermatitis ( AD ) in infancy . This study is part of a dietary clinical trial in a prospect i ve cohort of healthy term newborns at risk of atopy . It was recommended to breast-feed for at least 4 months and to avoid solid food in the same time-period . Eight hundred and sixty-five infants exclusively breast-fed , and 256 infants partially or exclusively formula-fed , were followed-up until the end of the first year following birth . AD and sensitization to milk and egg were considered as study end-points . The 1-year incidence of AD was compared between the two study groups . Adjusted odds ratios ( OR ) with 95 % confidence intervals ( CI ) were calculated by multiple logistic regression . The incidence of AD was calculated in relation to age at introduction of solid food and amount of food given . In the breast-fed group , the adjusted OR for AD was 0.47 ( 95 % CI 0.30 - 0.74 ) . The strongest risk factor was the occurrence of AD in the subject 's core family . The risk of infants with AD to be sensitized to milk was four times higher , and to egg eight times higher , than in infants without AD . Age at first introduction of solid food and diversity of solid food showed no effect on AD incidence . We conclude that in infants at atopic risk , exclusive breast-feeding for at least 4 months is effective in preventing AD in the first year of life Prevention guidelines for infants at high risk of allergic disease recommend hydrolysed formula if formula is introduced before 6 months , but evidence is mixed . Adding specific oligosaccharides may improve outcomes BACKGROUND Recommendations for primary prevention of allergic diseases in high-risk children include feeding with hydrolyzed formulas if breast-feeding is insufficient . OBJECTIVE The primary objective of the German Infant Nutritional Intervention study was to investigate the allergy preventive effect of 3 hydrolyzed formulas compared with cow 's milk formula in the first 3 years of life in a r and omized , double-blind trial . METHODS Between 1995 and 1998 , 2252 newborns with atopic heredity were allocated to a group receiving cow 's milk formula , partially or extensively hydrolyzed whey formula , or extensively hydrolyzed casein formula as a milk substitute for the first 4 months if breast-feeding was insufficient . Main outcome parameters were allergic manifestations , atopic dermatitis ( AD ) , and asthma . RESULTS After 3 years , 396 of 2252 children ( 17.6 % ) had dropped out . Breast-fed infants without formula feeding during the intervention ( n = 889 ) were considered separately . A significant reduction of the incidence of AD was achieved with the extensively hydrolyzed casein formula in the intention-to-treat ( ITT ; n = 1363 ) and per protocol ( PP ; n = 904 ) analyses ( ITT : population odds ratio [ 95 % CI ] , 0.67 [ 0.45 - 0.99 ] ; PP : adjusted odds ratio [ OR(adj ) ] , 0.53 [ 0.32 - 0.88 ] ) , and with the partially hydrolyzed whey formula in the PP analysis ( ITT : population odds ratio , 0.76 [ 0.52 - 1.11 ] ; PP : OR(adj ) , 0.60 [ 0.37 - 0.97 ] ) . None of the formulas reduced the incidence of asthma . CONCLUSION The risk for AD , but not for asthma , can be reduced with certain cow 's milk hydrolyzates in high-risk infants when breast-feeding is insufficient . CLINICAL IMPLICATION S Early nutritional intervention in high-risk children has significant influence on the incidence of AD , but not of asthma This prospect i ve , long-term study assessed the effects of a protein hydrolysate formula on allergy prevention in infants with a family history of allergy . Infants were r and omly assigned to receive either the  hydrolysate formula ( n = 92 ) or an adapted cow milk formula  ( n = 85 ) alone or with breast-feeding for 4 months . The groups did not differ in family allergy history scores or cord blood IgE levels . After 4 months , total IgE levels and allergic reactions did not differ significantly between groups , although the hydrolysate group had a lower prevalence of eczema . At 12 months of age , neither IgE levels nor allergic reactions were significantly different . At 2 years of age , however , 18 allergic reactions had occurred in the hydrolysate group and 31 had occurred in the control group ; the differences were significant for eczema ( p < 0.001 ) but not for asthma . At 4 years of age , allergic signs were found in 11 children in the hydrolysate group and in 17 children in the control group ; the difference was significant only for eczema ( p < 0.01 ) . These results suggest that early feeding of a protein hydrolysate formula to infants at risk for allergies had a long-term preventive effect on the prevalence of eczema but not of asthma A recent increase in the prevalence of atopic disorders and the enormous costs of management of atopic patients have prompted attempts at prevention . We have examined the effect of exclusive breast feeding and of feeding different infant formulas on incidence of atopic disease in a prospect i ve r and omized controlled study . Seventy-two infants were recruited into each of the following groups : cow milk whey hydrolysate formula ( NAN/HA ) conventional cow milk formula ( Similac ) , soy-based formula ( Isomil ) , and exclusive breast feeding for greater than 4 months .  The cumulative incidence of atopic eczema , recurrent wheezing , rhinitis , gastrointestinal symptoms , and colic were noted . Skin prick tests and radioallergosorbent tests for IgE antibodies to milk and soy were performed . At 12 and 18 months of age , the incidence of atopic eczema as also that of all atopic symptoms was significantly lower and similar in the breast-fed and whey hydrolysate groups , compared with the cow milk and soy formula groups . IgE antibodies were detected more often in the cow milk and soy formula groups , especially the former . Among symptomatic infants , fewer skin positive prick tests were seen in the soy group compared with the cow milk group . Our observations show that among infants at high risk of developing atopic disease because of positive family history , exclusive breast feeding or whey hydrolysate formula is associated with a lower incidence and thus a delay in the occurrence of allergic disorders compared with groups fed conventional cow milk or soy formulas In a prospect i ve study of a 1-year birth cohort of 158 high-risk infants the effect of feeding breastmilk , a casein hydrolysate ( Nutramigen ) or a new ultrafiltrated whey hydrolysate ( Profylac ) on the development of cow milk protein allergy/intolerance ( CMPA/CMPI ) was assessed and compared . All the infants had biparental or severe single atopic predisposition , the latter combined with cord blood IgE > or = 0.5 kU/L. At birth all infants were r and omized to Nutramigen or Profylac , which was used when breastfeeding was insufficient or not possible during the first 6 months of life . During the same period this regimen was combined with avoidance of solid foods and cow milk protein . All mothers had unrestricted diets and were encouraged to do breastfeeding only . Moreover , avoidance of daily exposure to tobacco smoking , furred pets and dust-collecting material s in the bedroom was advised . The infants were followed prospect ively from birth to 18 months of age . All possible atopic symptoms were registered and controlled elimination/challenge studies were performed when symptoms suggested CMPA/CMPI . A total of 154 ( 97 % ) were followed up and 141 followed the diet strictly . Eighty-eight ( 62 % ) of the infants were breastfed for at least 6 months , 20 ( 14 % ) were breastfed exclusively , 59 and 62 had varying amounts of Nutramigen or Profylac respectively . CMPA/CMPI was diagnosed in 1/20 , 1/59 and 3/62 in the breastfed , the Nutramigen and Profylac groups respectively , but 1 of the latter also had Nutramigen . None of the infants showed reactions against  Nutramigen or Profylac . In 4 infants symptoms were provoked by breastmilk when the mother ingested cow milk and in 1 only by cow milk . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Allergy is a common cause of illness . The effect of feeding different infant formulas on the incidence of atopic disease and food allergy was assessed in a prospect i ve r and omized double-blind study of high-risk infants with a family history of atopy . METHODS 216 high-risk infants whose mothers had elected not to breast-feed were r and omized to receive exclusively a partial whey hydrolysate formula or a conventional cow 's milk formula or a soy formula until 6 months of age . Seventy-two high risk infants breast-fed for > or = 4 months were also studied . RESULTS Follow-up until 5 years of age showed a significant lowering in the cumulative incidence of atopic disease in the breast-fed ( odds ratio 0.422 [ 0.200 - 0.891 ] ) and the whey hydrolysate ( odds ratio 0.322 [ 0.159 - 0.653 ) groups , compared with the conventional cow 's milk group . Soy formula was not effective ( odds ratio 0.759 [ 0.384 - 1.501 ] ) . The occurrence of both eczema and asthma was lowest in the breast-fed and whey hydrolysate groups and was comparable in the cow 's milk and soy groups . Similar significant differences were noted in the 18 - 60 month period prevalence of eczema and asthma . Eczema was less severe in the whey hydrolysate group compared with the other groups . Double-blind placebo-controlled food challenges showed a lower prevalence of food allergy in the whey hydrolysate group compared with the other formula groups . CONCLUSIONS Exclusive breast-feeding or feeding with a partial whey hydrolysate formula is associated with lower incidence of atopic disease and food allergy . This is a cost-effective approach to the prevention of allergic disease in children For comparison of the antigenicity and allergenicity of three cow 's milk formulas , serum IgE antibodies to cow 's milk , β‐lactoglobulin and casein , and IgG antibodies to β‐lactoglobulin were analyzed in 94 infants with a family history of allergy . They were participating in a r and omized trial comparing the allergy prophylactic effect of feeding an extensively hydrolyzed ( N ) , a partially hydrolyzed ( PH ) , and a regular cow 's milk formula ( RM ) .  Only infants who had been formula‐fed for 3 months or more were included . IgE antibodies to cow 's milk proteins were more common in the RM group ( 22/34 ) than in the N ( 2/31 ) and PH groups ( 3/29 ) . There was a strong correlation between sensitization to cow 's milk and β‐lactoglobulin ( r=0.85 , P<0.001 ) . The IgG responses to β‐lactoglobulin were low in the N group , intermediate in the PH group , and high in the RM group . High responses , as well as detection of IgE antibodies , were associated with development of atopic disease . The low antigenicity and allergenicity of the extensively hydrolyzed formula support its use in allergy prophylaxis . The partial hydrolysate seemed to be less suitable for this purpose Background Infant feeding practice s , particularly the type of milk feeding , have been associated with the development of type 1 diabetes . Aim of the study We studied the relationship between early infant feeding ( during the first year of life ) and diabetes in a large population -based cohort . Methods In 1994–1995 , 6,209 healthy full-term newborns participated in a study examining the effect of supplementary feeding , on development of allergy to cow ’s milk , in maternity hospitals . All supplements in the maternity hospitals were known . Mothers recorded the feeding of infants prospect ively at home . In August 2006 , from a nationwide diabetes registry , 45 children from our cohort were listed as having type 1 diabetes . Results The distribution of cases was similar in the r and omized feeding groups : 9/1,789 in the group that received adapted cow ’s milk-based formula ; 12/1,737 in those who received extensively hydrolyzed formula ; 16/1,859 in those who received banked human milk ; and 8 among those 824 exclusively breast-fed in the hospital . When children who had received cow ’s milk-based formula in the maternity hospital were compared with those without such exposure , less number of children in the former group had diabetes by age 8 ( P = 0.026 ) , but by the end of the follow-up ( 11.5 years ) the difference disappeared ( P = 0.16 ) . Length of breast-feeding and introduction of cereals and other solid foods were similar among those developing type 1 diabetes and those remaining healthy , while early regular daily feeding with cow ’s milk-based formula tended to associate with lower risk for type 1 diabetes ( OR 0.66 ; 95 % confidence interval 0.38–1.13 ; P = 0.08 ) . Conclusions In an extended , secondary analysis of a population -based cohort , very early exposure to cow ’s milk is not a risk factor for type 1 diabetes ; it may in fact diminish its appearance before age 8 BACKGROUND Breast milk contains immune factors that compensate for the underdeveloped defenses of the gut of the newborn infant . OBJECTIVE We sought to study the importance of these factors in the immune responses of infants with cows ' milk allergy ( CMA ) to the proteins in cows ' milk ( CM ) . METHODS We prospect ively followed the development of CMA in 6209 healthy infants and collected sample s of colostrum from mothers .  Sample s from mothers of infants with CMA and from control subjects were analyzed for immunoglobulins , CM-specific antibodies , and cytokines . In infants with CMA , correlations between the concentration of transforming growth factor (TGF)-beta1 in colostrum and the extent of the immune response to CM proteins were studied . RESULTS The concentration of TGF-beta1 in colostrum sample s from mothers of infants with IgE-mediated CMA ( n = 65 ) was lower ( mean , 589 pg/mL ; 95 % confidence interval [ CI ] , 413 - 840 ) than from mothers of infants with non-IgE-mediated CMA ( n = 37 ; mean , 1162 pg/mL ; 95 % CI , 881 - 1531 ; t = 2.57 , P = .012 ) . In 126 control subjects the mean concentration was 807 pg/mL ( 95 % CI , 677 - 963 ) . In the infants with CMA ( n = 96 - 100 ) , the concentration of TGF-beta1 in colostrum was positively correlated with IgA antibodies to beta-lactoglobulin and IgG antibodies to alpha-casein and whole formula and negatively with the diameter of a skin prick test response to CM and lymphocyte stimulation indices to alpha-casein and beta-lactoglobulin . CONCLUSIONS In an infant prone to having CMA , the TGF-beta1 content of mother 's colostrum may promote IgG-IgA antibody production and inhibit IgE- and cell-mediated reactions to CM Early feeding with cows ' milk ( CM ) may cause cows ' milk allergy ( CMA )  . Breast milk contains many immune factors which compensate for the undeveloped defence mechanisms of the gut of the newborn infant . We studied the effect of supplementary CM feeding at the maternity hospital on the subsequent incidence of CMA , the effects of formula and breast feeding on the subsequent immunologic types of CMA , and the importance of immune factors present in colostrum in the immune responses of infants with CMA . In a cohort of 6209 infants , 824 were exclusively breast-fed and 87 % required supplementary milk while in the maternity hospital : 1789 received CM formula , 1859 pasteurized human milk , and 1737 whey hydrolysate formula . The cumulative incidence of CMA , verified by a CM elimination-challenge test , was 2.4 % in the CM , 1.7 % in the pasteurized human milk and 1.5 % in the whey hydrolysate group . Among these infants , exposure to CM at hospital and a positive atopic heredity increased the risk of CMA . Of the exclusively breast-fed infants , 2.1 % had CMA . Risk factors for the development of IgE-mediated CMA were : exposure to CM at hospital , breast-feeding during the first 8 weeks at home either exclusively or combined with infrequent exposure to small amounts of CM and long breast-feeding . The content of transforming growth factor-beta1 ( TGF-beta1 ) in colostrum from mothers of infants with IgE-mediated CMA was lower than from mothers of infants with non-IgE-mediated CMA . In infants with CMA , TGF-beta1 in colostrum negatively correlated with the result of skin prick test and the stimulation of peripheral blood mononuclear cells to CM , but positively with infants ' IgA and IgG antibodies to CM proteins . Feeding of CM formula at maternity hospital increases the risk of CMA , but exclusive breast-feeding does not eliminate the risk . Prolonged breast-feeding exclusively or combined with infrequent exposure to small amounts of CM during the first 8 weeks induces the development of IgE-mediated CMA . Colostral TGF-beta1 may inhibit IgE- and cell mediated reactions and promote IgG-IgA antibody production to CM in infants prone to developing CMA The allergy preventive effect of extensively ( N ) and partially ( PH ) hydrolysed cows ’ milk formulas compared with a regular formula ( RM ) was assessed in 155 infants with a family history of allergy . No cows ’ milk was given during the first nine months of life and no egg and fish  up to 12 months of age . Breast feeding mothers avoided the same foods . At weaning the infants were r and omised to one of the formula groups . The cumulative incidence of atopic symptoms at 18 months was 51 , 64 , and 84 % in the N , PH , and RM groups , respectively . From 6 to 18 months there were significantly less cumulative atopic symptoms in the N group compared with the RM group , and significantly less than the PH group up to 6 ( N = 25 % ; PH = 46 % ) and 9 months ( N = 34 % , PH = 58 % ) . At 9 months significantly fewer infants in the N group ( 10 % ) than in the PH group ( 33 % ) had a positive skin prick test to eggs . The findings support an allergy preventive effect of an extensively hydrolysed formula , but not of a partially hydrolysed formula , during the first 18 months of life of high risk infants Objective : To compare feeding tolerance , nutrient intake and growth in preterm infants ( ⩽32 weeks , ⩽1750 g ) fed either a st and ard nonhydrolyzed whey – casein ( nHWC ) or a partially hydrolyzed whey ( pHW ) preterm infant formula .  Study Design : In this double-blind r and omized controlled trial infants were fed either formula for at least 3 weeks . Intake was monitored daily , serum chemistries and growth weekly . Data were analyzed using analysis of covariance . Result : A total of 80 infants were enrolled , 72 completed the study . No differences were noted in demographic characteristics . No differences were detected in feeding tolerance , intakes ( 118±21 vs 119±14 ; nHWC vs pHW ) or growth weight , 28±1.5 vs 28±1.6 g per day ; length , 1.0±0.7 vs 1.0±0.6 cm per week ; head circumference , 0.9±0.4 vs 1.0±0.44 cm per week ) . At the end of study , blood urea nitrogen ( 5.2±3.1 < 6.7±2.3 mg per 100 ml , nHWC < pHW ) , total serum proteins ( 4.7±0.4 > 4.4±0.5 g per 100 ml ) and albumin ( 2.7±0.3 > 2.6±0.4 g per 100 ml ) differed . Conclusion : A pHW preterm infant formula was not associated with improved feeding tolerance , enteral intake or growth but differences in serum chemistries . These are unlikely to be clinical ly relevant because values were well within normal limits for preterm infants , whereas growth was identical in both groups and paralleled that ‘ in utero ’ BACKGROUND One hundred twenty children , identified before birth as being at high risk for atopy , were prenatally assigned to prophylactic or control groups . METHODS The infants in the prophylactic group either received breast milk from mothers on an exclusion diet or an extensively hydrolyzed formula . Their bedrooms and living rooms were treated repeatedly with an acaricide , and they used polyvinyl-covered mattresses with vented head areas . The infants in the control group were fed conventionally , and no environmental control was recommended . RESULTS A significant advantage , first demonstrated at 1 year of age , persists for children in the prophylactic group . They have less of any allergy or eczema , but the reduced prevalence of asthma is no longer significant . Only three children in the prophylactic group had positive skin prick test results compared with 16 in the control group , suggesting a significant reduction in sensitization . CONCLUSION A dual approach to allergen avoidance , focusing on foods and aeroallergens , appears to be beneficial in selected high-risk infants . Avoidance of potent allergens in early life increases the threshold for sensitization in these high-risk infants . Whether sensitization has been avoided or merely deferred has yet to be proved BACKGROUND By using the response to protein hydrolysate formula ( PHF ) as a model system , we discovered the existence of a sensitive period , before 4 mo , when exposure determines the hedonic tone to flavors . OBJECTIVE We aim ed to characterize the timing and duration of this sensitive period . DESIGN Healthy infants , whose parents had chosen formula feeding , were r and omly assigned into 1 of 6 groups at age 0.5 mo : 2 control groups , one fed cow milk-based formula ( CMF ) and the other fed PHF for 7 mo ; 2 groups fed PHF for either 1 or 3 mo beginning at 1.5 mo and CMF otherwise ; and 2 groups fed PHF for 1 mo beginning at either 2.5 or 3.5 mo and CMF otherwise . Brief access taste tests were conducted monthly , and complete " meals " of both formulas occurred at the end of the study . RESULTS Three months of PHF exposure led to acceptance similar to that at 1 mo of exposure . Although these infants were more accepting than were infants with no exposure , they were less accepting than were infants with 7 mo of exposure , which suggests a dosing effect . The time when flavor experiences began was also significant . Among infants exposed to PHF for 1 mo , those who were first fed PHF at 3.5 mo rejected PHF relative to CMF more than did infants exposed at younger ages . CONCLUSION The general principles observed are likely of broader significance , indicating a fundamental feature of mammalian development and reflecting the importance of familiarizing infants with flavors that their mothers consume and transmit to breast milk . This trial was registered at clinical trials.gov as NCT00994747 ABSTRACT A prospect i ve case‐control study is presented to assess an allergy prevention programme in children up to 36 months of age . Infants born at three maternity hospitals were followed from birth : 279 infants with high atopic risk ( intervention group ) were compared with 80 infants with similar atopic risk but no intervention ( non‐intervention group ) . The intervention programme included dietary measures ( exclusive and prolonged milk feeding diet followed by a hypoantigenic weaning diet ) and environmental measures ( avoidance of parental smoking in the presence of the babies , day care > 2 years of life ) . Mothers in this group who had insufficient breast milk were r and omly assigned to one of two coded formulas : either a hydrolysed milk formula ( Nidina HA , Nestlé ) or a conventional adapted formula ( Nan , Nestlé ) . Other environmental measures remained the same as for the breastfeeding mothers . The non‐intervention group were either breastfed or received the usual Italian milk feeding and weaning diet , without environmental advice . The main outcome measures were anthropometric measurements and allergic disease manifestations . Normal anthropometric data were observed both in the intervention group and in the nonintervention group . The incidence of allergic manifestations was much lower in the intervention group than in the nonintervention group at 1 year ( 11.5 versus 54.4 % , respectively ) and at 2 years ( 14.9 versus 65.6 % ) and 3 years ( 20.6 versus 74.1 % ) . Atopic dermatitis and recurrent wheezing were found in both the intervention group and the non‐intervention group from birth up to the second year of life , while urticaria and gastrointestinal disorders were only present in the non‐intervention group in the first year of life . Conjunctivitis and rhinitis were present after the second year in both the intervention group and the non‐intervention group . Relapse of the same allergic symptom was less in the intervention group ( 13.0 % ) than in the non‐intervention group ( 36.9 % ) . In comparison to the non‐intervention group , there were fewer intervention group cases with two or more different allergic symptoms ( 8.7 versus 32.6 % ) , and they were more likely to avoid steroid treatment ( 0 versus 10.8 % ) and hospital admission ( 0 versus 6.5 % ) . Babies in the non‐intervention group fed with adapted formula were more likely to develop allergies than breastfed babies in the same group . In the intervention group the breastfed infants had the lowest incidence of allergic symptoms , followed by the infants fed the hydrolysed formula ( ns ) . Infants in the intervention group fed the adapted formula had significantly more allergies than the breastfed and hydrolysed milk fed infants , although less than their counterparts in the non‐intervention group . Of the affected subjects in the intervention group , 80.4 % were RAST and /or Prick positive to food or inhalant allergens . Total serum IgE values detected at birth in the intervention group were not predictive , but at 1 and 2 years of age , IgE values more than 2 SD above the mean in asymptomatic babies were found to predictive for later allergy . In breastfed babies the total IgE level at 1 and 2 years of age was lower than in the other two feeding groups . Of the various factors tested in the non‐intervention group , the following were the most important in the pathogenesis of allergic symptoms : ( i ) formula implementation begun in the first week of life ; ( ii ) early weaning ( < 4 months ) ; ( iii ) feeding beef ( < 6 months ) ; ( iv ) early introduction of cow 's milk ( < 6 months ) ; and ( v ) parental smoking in the presence of the babies and early day care admission ( < 2 years of life ) . All the preventive measures used in this study ( exclusive breastfeeding and /or hydrolysed milk feeding , delayed and selective introduction of solid foods , and environmental advice ) were effective at the third year of follow‐up , greatly reducing allergic manifestations in high atopic risk babies in comparison with those not receiving these interventions BACKGROUND The prevalence and natural history for food protein-induced enterocolitis syndrome ( FPIES ) have not been determined . OBJECTIVE We sought to determine the prevalence , clinical manifestations , and rate of recovery for FPIES in a large-scale , population -based prospect i ve study . METHODS In a prospect i ve study the feeding history of 13,019 infants was obtained . Infants with probable adverse reactions to cow 's milk protein ( CMP )  were clinical ly examined , skin prick tested , and challenged orally . Diagnostic criteria for CMP-induced FPIES included age less than 9 months , delayed recurrent vomiting ( usually with nausea ) , and lethargy after exposure to CMP in the absence of other IgE-mediated symptoms , such as rash , urticaria , and respiratory symptoms . In addition , a positive challenge response to milk result ed in the above-mentioned gastrointestinal symptoms , removal of milk from the diet result ed in the resolution of those symptoms , or both . RESULTS Ninety-eight percent of the cohort participated in the study . The cumulative incidence for FPIES was 0.34 % ( 44/13,019 patients ) . The most common symptoms were recurrent vomiting ( 100 % ) , lethargy ( 77 % ) diarrhea ( 25 % ) , pallor ( 14 % ) , and bloody diarrhea ( 4.5 % ) . All patients had FPIES  within the first 6 months of life . By the age of 3 years , 90 % of the patients had recovered . We did not detect any concomitant reaction to soy . Eight patients with FPIES had IgE-mediated cow 's milk allergy ( IgE-CMA ) . CONCLUSIONS The prevalence of FPIES is significant , and its clinical presentation is distinct from that of IgE-CMA . Most patients with FPIES recover , although a proportion might convert to IgE-CMA . The likelihood for a cross-reactivity to soy in this population was less than previously estimated Background The average incidence of preterm birth in the world is up to 11.1 % , and deaths of preterm children account for more than 50 % of neonatal deaths . Gastrointestinal function of preterm children with a gestational age less than 34 weeks is immaturely developed . For preterm children who can only be fed with formula due to their mothers ’ sickness , choosing a suitable formula can not only meet the high nutritional needs of preterm children , but also solve their low gastrointestinal tolerability , and is thus very important . Methods / Design The study is a prospect i ve , r and omized , single-blind and controlled clinical trial . Preterm children with a gestational age less than 34 weeks meeting the inclusion criteria who can not be breastfed will be included . To demonstrate the application effect of extensively hydrolyzed milk protein formula on the target population , preterm children will be r and omized into two groups , 185 subjects in each group . The observation group will be fed with extensively hydrolyzed milk protein ( 100 % whey protein ) formula , while the control group will be fed with preterm children ’s formula until the children are discharged from the neonatal intensive care unit ( NICU ) . All the formula involved in this study will be from Dumex . After discharge , both groups will be uniformly fed with formula for 0 to 6-month-old infants . For statistical analysis , a chi-square test and Student ’s t test will be applied using SAS 9.4 . Discussion This will be the first r and omized controlled clinical study with long-term observation of the growth and development of preterm children during the NICU stay and at 3-month follow-up after discharge from the NICU . Results from this study will be used to determine whether the extensively hydrolyzed formula is more suitable for the low gastrointestinal tolerability of preterm children , and also whether feeding preterm children who are fed with such formula during the NICU stay with ordinary infant formula after discharge from the NICU would affect the normal growth and development of preterm children in the early stage of their lives . Trial registration This study was registered with the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ) with number ChiCTR-IOR-14005696 , on December 22 , 2014 Background Asthma is a chronic disease that often starts in childhood . The key risk factors are a child 's environment and their genetic characteristics . The aim of this study was to evaluate the efficacy of environmental modification in the first 12 months of life on the prevalence of  asthma in high-risk individuals . Methods Children ( n=120 ) considered at high risk of allergic disorders ( either dual heredity or single heredity and a high cord total IgE ) , were enrolled in a single-blinded , r and omised controlled trial . Infants in the intervention arm were either breast fed with the mother on a low allergen diet or given an extensively hydrolysed formula . Exposure to house dust mite allergen was reduced . The control group followed st and ard advice .  Children were assessed at ages 1 , 2 , 4 , 8 and 18 years for the presence of asthma and atopy . Results At 18 years of age , there was a significantly lower prevalence of asthma in the prevention group compared with the control group ( OR : 0.23 , 95 % CI 0.08 to 0.70 , p=0.01 ) , primarily due to asthma that developed during childhood but persisted until age 18 years . Repeated-measure analysis showed that there was an overall reduction in asthma prevalence from 1 to 18 years ( OR : 0.51 , CI 0.32 to 0.81 , p=0.04 ) . Prevalence of atopy was not significantly different between the two groups at age 18 . Conclusion Comprehensive allergen avoidance in the first year of life is effective in preventing asthma onset in individuals considered at high risk due to heredity . The effect occurs in the early years , but persists through to adulthood Aims : To determine the effect of brief early exposure to cows ' milk on the expression of atopy during the first five years of life . Methods : Follow up analysis of a double blind , placebo controlled , r and omised feeding intervention trial ( BOKAAL study ) . Subjects were 1108 children from 1533 initially r and omised breast fed neonates in the Netherl and s. Atopic disease and prevalence of allergic symptoms at age 1 , 2 , and 5 , and specific IgE at age 1 and 5 were determined . Results : Atopic disease in the first year was found in 10.0 % ( cows ' milk ) versus 9.3 % ( placebo ) of the children , with a relative risk ( RR ) of 1.07 . No differences were found in the second year either . At age 5 , atopic disease was found in 26.3 % ( cows ' milk ) versus 25.0 % ( placebo ) , RR 1.05 . There was no difference in the prevalence of allergic symptoms . Specific IgE to cows ' milk ( RAST positive 2 + or more ) was 5.8 % ( cows ' milk ) versus 4.1 % ( placebo ) at age 1 ( RR 1.43 ) , and 5.3 % versus 3.0 % at age 5 ( RR 1.77 ) . There was no difference in sensitisation to other common allergens between the two groups . Conclusion : Early , brief exposure to  cows ' milk  in breast fed children is not associated with atopic disease or allergic symptoms up to age 5 OBJECTIVE To test whether weaning to a bovine insulin-free cow 's milk formula ( CMF ) reduces type 1 diabetes mellitus-associated autoantibodies in children at genetic risk . DESIGN R and omized , double-blind pilot trial ( Finnish Dietary Intervention Trial for the Prevention of Type 1 Diabetes [ FINDIA ] ) . SETTING Three pediatric hospitals in Finl and from May 15 , 2002 , to November 22 , 2005 . PARTICIPANTS A total of 1113 infants with HLA-conferred susceptibility to type 1 diabetes were r and omly assigned to receive study infant formulas ; 908 children provided at least 1 follow-up blood sample ( last follow-up , June 2009 ) . INTERVENTION The CMF ( n = 389 ) , whey-based hydrolyzed formula ( WHF ) ( n = 350 ) , or whey-based FINDIA formula essentially free of bovine insulin ( n = 365 ) during the first 6 months of life whenever breast milk was not available . MAIN OUTCOME MEASURES Primary outcome was beta-cell autoimmunity monitored at ages 3 , 6 , and 12 months and then annually until age 3 years . Autoantibodies to insulin , the 65-kDa isoform of glutamic acid decarboxylase , and the tyrosine phosphatase-related IA-2 molecule were screened , and islet cell autoantibodies and autoantibodies to zinc transporter 8 were analyzed in infants whose primary screening test results were positive . RESULTS In the intention-to-treat analysis , 6.3 % of children in the CMF group , 4.9 % of those in the WHF group , and 2.6 % of children in the FINDIA group were positive for at least 1 autoantibody by age 3 years . The odds ratios were 0.75 ( 95 % CI , 0.37 - 1.54 ) in the WHF group and 0.39 ( 0.17 - 0.91 ) in the FINDIA group when compared with the CMF group . In the treatment-received analysis , the corresponding odds ratios were 0.81 ( 95 % CI , 0.37 - 1.76 ) and 0.23 ( 0.08 - 0.69 ) . CONCLUSION In comparison with ordinary CMF , weaning to an insulin-free CMF reduced the cumulative incidence of autoantibodies by age 3 years in children at genetic risk of type 1 diabetes mellitus . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01055080 Abstract Little research has focused on infant developmental effects , other than growth , of formulas that differ substantially in the form of protein . To examine development of infants fed formulas differing in free amino acid content , we r and omized 0.5-month-old infants ( n = 79 ) to either a  control group who fed only cow milk formula ( CMF ) during the first 8 months ( CMF8 ) , or to one of two experimental groups : one experimental group fed extensively protein hydrolyzed formula ( EHF ) for 1–3 months during first 4.5 months ( EHF1 - 3 ) of life , and the other fed EHF for 8 months ( EHF8 ) . The Mullen Scales of Early Learning were administered monthly from 1.5 to 8.5 months to assess fine ( FM ) and gross ( GM ) motor control , receptive ( RL ) and expressive ( EL ) language , visual reception ( VR ) , and an early learning composite ( ELC ) . Across the 5.5–8.5-month time period , when compared to CMF8 infants , GM scores in EHF1 - 3 infants averaged 1.5 points higher ( 95 % CI 0.1 , 3.0 ) and in EHF8 infants 2.2 points higher ( 95 % CI 0.3 , 4.0 ) . Similarly , VR scores averaged 1.9 points higher ( 95 % CI 0.1 , 3.8 ) in EHF1 - 3 infants and 2.2 points higher ( 95 % CI −0.2 , 4.5 ) in EHF8 infants . EHF8 infants ’ RL scores averaged 1.8 points lower ( 95 % CI 0.1 , 3.6 ) than CMF8 infants . These data suggest that the form of protein in infant formula may impact cognitive development and that the higher free amino acid content in breast milk may be a contributing factor to the differential cognitive development between breastfed and CMF-fed infants . Clinical Trial Registration : clinical trials.gov NCT00994747 Aims /hypothesisWe aim ed to assess the feasibility of a dietary intervention trial with weaning to hydrolysed formula in infants at increased risk of type 1 diabetes and to study the effect of the intervention on the emergence of diabetes-associated autoantibodies in early childhood . Methods We studied 242 newborn infants who had a first-degree relative with type 1 diabetes and carried risk-associated HLA-DQB1 alleles . After exclusive breastfeeding , the infants underwent a double-blind , r and omised pilot trial of either casein hydrolysate ( Nutramigen ; Mead Johnson ) or conventional cow ’s milk-based formula  until the age of 6–8 months . During a mean observation period of 4.7 years , autoantibodies to insulin , anti-glutamic acid decarboxylase and insulinoma-associated antigen-2 were measured by radiobinding assays , and islet cell antibodies ( ICA ) by immunofluorescence . Results The feasibility of screening and identifying a cohort of first-degree relatives with HLA-conferred disease susceptibility , enrolling them in a dietary intervention trial and following them for seroconversion to autoantibody positivity is established . The cumulative incidence of autoantibodies was somewhat smaller in the casein hydrolysate vs control formula group , suggesting the need for a larger well-powered study . After adjustment for duration of study formula feeding , life-table analysis showed a significant protection by the intervention from positivity for ICA ( p=0.02 ) and at least one autoantibody ( p=0.03 ) . Conclusions /interpretationThe present study provides the first evidence ever in man , despite its limited power , that it may be possible to manipulate spontaneous beta cell autoimmunity by dietary intervention in infancy Aims : To assess maternal compliance with nutritional recommendations in an allergy preventive programme , and identify factors influencing compliance behaviour . Methods : R and omised double-blind intervention study on the effect of infant formulas with reduced allergenicity in healthy , term newborns at risk of atopy . Maternal compliance with dietary recommendations concerning milk and solid food feeding was categorised . Results : A total of 2252 newborns were r and omised to one of four study formulas . The drop out rate during the first year of life was 13.5 % ( n = 304 ) . The rates of high , medium , and low compliance to milk feeding during weeks 1–16 were 83.4 % , 4.0 % , and 7.5 % ; the corresponding rates to solid food feeding during weeks 1–24 were 60.0 % , 12.1 % , and 22.9 % . In 5.1 % of subjects no nutritional information was available . Low compliance was more frequent among non-German parents , parents with a low level of education , young mothers , smoking mothers , and those who weaned their infant before the age of 2 months . Conclusions : Evaluation of allergy preventive programmes should take into account non-compliance for assessing the preventive effectiveness on study outcome BACKGROUND The natural history of allergic disease and its potential for prevention merit close examination because of the explosive worldwide increase in the prevalence and morbidity of atopic disorders . This study examines the development of atopy at age 7 years in 165 children in a high-risk cohort , previously reported from birth to age 4 years . METHODS In this prospect i ve , r and omized , controlled study of food allergen avoidance in infancy , the prophylactic-treated group consisted of infants whose mothers avoided cow 's milk , egg , and peanut during the last trimester of pregnancy and lactation and who , themselves ,  avoided cow 's milk until age 1 year ( casein hydrolysate supplementation before age 1 ) , egg until age 2 years , and peanut and fish until age 3 years . The control group consisted of maternal/infant pairs who followed st and ard feeding practice s. RESULTS Despite a significant reduction in food allergy and milk sensitization before age 2 years , none of the following differed between the groups at age 7 years : food allergy , atopic dermatitis , allergic rhinitis , asthma , any atopic disease , lung function , food or aeroallergen sensitization , serum IgE level , or presence of nasal eosinophils or nasal basophilic cells .  Children with food allergy by 4 years evidence d higher 7-year ( current ) prevalences of allergic rhinitis and asthma ( p < 0.01 ) . Atopic diseases/parameters at age 7 years were shown , by multivariate analysis ( p < 0.05 ) , to be associated with several genetic and environmental risk factors ( male gender , maternal nonwhite ethnicity and asthma , and household smoking ) , as well as predictive atopic markers during infancy ( elevated serum IgE level ; egg , cow 's milk , and peanut sensitization ; and nasal eosinophils and nasal basophilic cells ) . CONCLUSIONS These findings help to : ( 1 ) eluci date the natural history of atopic disease in high-risk children ; ( 2 ) document the progression of allergy from atopic dermatitis , food allergy , and food sensitization to respiratory allergy and aeroallergen sensitization despite food allergy prevention in infancy ; ( 3 ) identify allergy predictive markers ; and ( 4 ) exp and our appreciation of the interactions of genetic and environmental factors in the development of atopy The possible role of cows milk intolerance in the aetiology of infant colic was evaluated in 19 babies presenting to their health visitor or general practitioner in one town . Over a three week period a st and ard modified cows milk formula was compared with a soya milk formula on a double blind basis . The duration of colic symptoms was significantly reduced during the week on soya milk ( P less than 0.01 ) , with 11 out of 19 babies fulfilling the diagnostic criteria for cows milk intolerance . Four babies whose symptoms failed to improve either spontaneously or with soya milk were given a hydrolysed protein milk with a positive response in two , confirmed by challenge testing . Thus in 13 out of 19 babies ( 68 % ) the symptoms of infant colic resolved almost completely with dietary change BACKGROUND Only a few studies have analyzed the value of early sensitization in predicting the development of atopic disease . The relevance of low immunoglobulin ( Ig ) E antibody levels in this respect also remains unclear . OBJECTIVE To investigate the relevance of sensitization in 12-month-old children in the development of atopic disease by the age of 6 years . METHODS We analyzed data for 1290 children with a positive family history of atopy from the prospect i ve , multicenter German Infant Nutritional Intervention ( GINIplus ) study and investigated the relationship between the presence of detectable specific IgE antibodies  at the age of 12 months and the development of atopic disease by the age of 6 years . RESULTS In all , 10.9 % of children analyzed developed sensitization . At the age of 6 years , 20.6 % of children with early sensitization had eczema compared to 9.4 % of those without ( odds ratio [ OR ] , 2.31 ; 95 % confidence interval [ CI ] , 1.42 - 3.74 ) . The corresponding figures were 15.4 % vs 7.3 % for allergic rhinitis ( OR , 2.22 ; CI , 1.31 - 3.78 ) and 10.2 % vs 2.6 % ( OR , 3.93 ; 95 % CI , 1.98 - 7.76 ) for asthma . Children with early sensitization to aeroallergens had the greatest risk of subsequent atopic disease . Early sensitization did not increase risk in children without eczema within the first year of life . Very low specific IgE levels ( 0.18 - 0.34 kU/L ) were not significantly associated with any of the outcomes analyzed . CONCLUSION Sensitization to common food allergens and to aeroallergens in particular during the first year of life was found to be a strong predictor for the development of atopic disease by the age of 6 years in children with a positive family history of atopy Screening of total IgE in 1189 cord blood sample s was conducted by Phadebas IgE PRIST  in a one-year birth cohort 1983 - 1984 in Viborg , Denmark . 113 children with cord blood IgE levels > or = 0.5 kU/l and 138 children chosen at r and om among those with cord blood IgE levels < 0.5 kU/l were seen at a follow-up at 5 years of age . Based upon history and physical examination a diagnosis of definite atopy or no atopy was established . Allergy ( IgE mediated ) was defined as atopic disease combined with increased total IgE levels at 5 years of age . The cumulative prevalence of atopic disease was not influenced by cord blood IgE levels or atopic predisposition . Cord blood IgE levels had a low sensitivity as a predictor of atopic disease . A statistically significant correlation between serum levels of IgE at birth and at 5 years was however found ( p < 0.001 ) , and a significantly greater number of children with elevated cord blood IgE levels developed allergic disease before 5 years of age ( p < 0.01 ) . A cut-off limit of 0.3 kU/l was superior to the originally suggested limit of 0.5 kU/l . A total IgE level > 63 kU/l ( geometric mean + 1 SD ) at the age of 5 years can be regarded as being an elevated level . A cord blood IgE level > or = 0.3 kU/l in combination with atopic predisposition was predictive of allergic disease , especially allergic bronchial asthma . With regard to allergic disease , the positive predictive value was 26 % , the sensitivity 33 % and the rate ratio for development of allergic disease 4 . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Hydrolysates are used in the treatment and prevention of cows milk protein allergy . Hydrolysis might alter the plasma level of amino acids . METHODS Forty-five infants were included in a double-blind prospect i ve study and were r and omized in two groups : one receiving a whey predominant formula ( n = 20 ) and the second group receiving a whey hydrolysate formula ( n = 25 ) . Weight and length gain was evaluated up to the age of 13 weeks , when blood was sample d for determination of fasting plasma amino acids . RESULTS Four infants of the hydrolysate group dropped out because refusal to ingest the formula . Weight and length gain at 13 weeks of age were extremely comparable . Significant differences in plasma concentrations were observed for a number of nonessential and essential amino acids ( p = .035 to .0001 ) . Threonine and lysine were both higher in the hydrolysate group , and aspartic acid , cystine , methionine , tyrosine , phenylalanine , histidine , and arginine were lower in the hydrolysate group . CONCLUSIONS These differences in plasma amino acid levels have to be regarded with care because all concentrations were within normal ranges , with the exception of threonine . Weight and length gain of the hydrolysate and the whey predominant formula were identical A masked , r and omized , parallel growth study was conducted in infants fed an amino acid – based formula ( AF ) or an extensively hydrolyzed casein-based formula ( HF ) . Infants were enrolled between 0 and 9 days and studied to 112 days of age .  Growth , formula intake , stool patterns , and serum albumin concentrations were assessed . There were no significant differences between groups in weight , length , or head circumference , gains in weight or length , or study formula intake . The number of stools parents rated as being formed , and the mean daily number of stools were greater in the HF than in the AF group at 14 and 28 days of age . Mean serum albumin concentrations were not significantly different between groups and were within the normal range . This study demonstrates that AF supports normal growth of infants comparable to that of infants fed HF during the critical first 4 months of life Summary Aim of the study . An allergen-reduced dietary intervention programme with strict dietary requirements was implemented over the first four months of life in an unselected population -based infant cohort and compared to a non-intervention cohort ( the ZUFF study ) . Recommendations for the dietary programme in the intervention cohort were extended , but not strictly implemented , until the end of month six . The intervention was based on breastfeeding , a moderate whey hydrolysate formula ( pHF ) , and delayed introduction of weaning foods with a high allergenicity . This study was a prospect i ve , controlled , and unblinded study , the first to assess the effects of an allergen-reduced , pHF-based early nutritional programme in a broad unselected infant population . Because overall healthy development of the infant is a major objective of any nutritional programme , the study evaluated the effects of the dietary intervention on infant growth and general health status rather than specific allergic manifestations . Part I of this paper gave results for nutritional behaviour only , and Part II gives results for growth and general health status during the intervention period through the sixth month of life . Methods . Assignment of study infants was to demographically comparable intervention ( Z ) or control ( FF ) cohorts according to place of birth . In the intervention cohort ( Z=564 ) , the recommended dietary regimen was breastfeeding and – if exclusive breastfeeding was not possible – supplementation with a moderately hydrolysed , allergen-reduced infant formula ( pHF ) . Weaning foods were delayed until four months of age or later in case of weaning foods with high allergenicity . In the control cohort ( FF=566 ) , there was no specific intervention . Imbalances between cohorts in confounding ( adjuvant ) factors that could influence health related outcomes were integrated as covariates into the logistic regression of the main analyses . Growth parameters included weight , length , head circumference , BMI , and Z scores ( SDS ) . General health status was assessed by clinical ly significant findings in gastrointestinal , respiratory , or skin symptoms . Results . Growth at 6 weeks and at 3 and 6 months was similar for Z and FF . Significantly fewer Z than FF infants had clinical ly noteworthy health findings at 3 months ( Z=27 % versus FF=37 % , odds ratio=0.63 , CI=0.48–0.82 ) and 6 months ( Z=33 % versus FF=49 % , odds ratio=0.51 , CI=0.40–0.66 ) . This corresponds to a 30 % reduction in overall health concerns at 6 months for the intervention cohort . At 3 and 6 months , differences between cohorts in most measures of general health status were strongly influenced by a lower incidence of skin symptoms in the Z cohort . Within FF , there were fewer exclusively breastfed ( eBF ) infants with health problems at 3 months compared with those who were partially ( pBF ) or non-breastfed ( nBF ) ( eBF=31 % , pBF=40 % , nBF=39 % , p<0.05 ) . In contrast , in the Z intervention cohort , the number of infants with health concerns was similar for exclusively breastfed infants and for those in whom mother 's milk was supplemented or replaced by pHF ( eBF=29 % , pBF=25 % , nBF=26 % , ns ) . In a sub analysis of overall health findings in infants without a family risk of allergies , there were again significantly fewer Z than FF infants with any health or any skin problem . Conclusion .An allergen-reduced dietary recommendation that includes a moderate whey hydrolysate infant formula ( pHF ) has no negative effects on growth parameters up to 6 months of life in an infant population unselected for atopic risk . The dietary intervention produced improvements in general health status when compared with a control cohort that received infant formula with unhydrolysed proteins ( IF ) , and high allergenic weaning foods at an earlier age . The difference between cohorts was principally due to fewer adverse skin findings . In infants following our allergen-reduced feeding recommendation , 3-month general health status was comparable between those who were exclusively breastfed and those in whom breastfeeding was supplemented or replaced by pHF . Our results demonstrate that a pHF feeding recommendation during the first 4 to 6 months of life – when exclusive breestfeeding is not possible – is a safe and feasible regimen not only in high-allergic risk population s but in general unselected infant population . The general use of pHF formula in non- or partly breastfed infants could therefore be considered an important contribution to optimised infant nutrition There is much evidence that the development of allergic disorders may be related to early exposure of allergens , including those in breastmilk . We have tried to find out whether avoidance of food and inhaled allergens in infancy protects against the development of  allergic disorders in high-risk infants . In a prenatally r and omised , controlled study 120 infants with family history of atopy and high ( greater than 0.5 kU/l ) cord-blood concentrations of total IgE were allocated r and omly to prophylactic and control groups . In the prophylactic group ( n = 58 ) , lactating mothers  avoided allergenic foods ( milk , egg , fish , and nuts ) and avoided feeding their infants these foods and soya , wheat , and orange  up to the age of 12 months ; the infants ' bedrooms and living rooms were treated with an acaricidal powder and foam every 3 months , and concentrations of Dermatophagoides pteronyssinus antigen(Der p l ) in dust sample s were measured by enzyme-linked immunosorbent assay . In the control group ( n = 62 ) , the diet of mothers and infants was unrestricted ; no acaricidal treatment was done and Der p l concentrations were measured at birth and at 9 months . A paediatric allergy specialist unaware of group assignment examined the infants for allergic disorders at 10 - 12 months . Odds ratios were calculated by logistic regression analysis for various factors with control for other confounding variables . At 12 months , allergic disorders had developed in 25 ( 40 % ) control infants and in 8 ( 13 % ) of the prophylactic group ( odds ratio 6.34 , 95 % confidence intervals 2.0 - 20.1 ) . The prevalences at 12 months of asthma ( 4.13 , 1.1 - 15.5 ) and eczema ( 3.6 , 1.0 - 12.5 ) were also significantly greater in the control group .  Parental smoking was a significant risk factor for total allergy at 12 months whether only one parent smoked ( 3.97 , 1.2 - 13.6 ) or both parents smoked ( 4.72 , 1.2 - 18.2 ) Background Because infant formulas containing hydrolyzed cow milk protein are used to reduce feeding intolerance and to improve gastric emptying , the effect on gastrointestinal motility of a hydrolysate formula was compared with that of a st and ard preterm formula . Methods Thirty-six preterm newborns with a gestational age of 32.2 ± 2.3 weeks were assigned r and omly to st and ard formula or hydrolyzed formula .  Cutaneous electrogastrography and ultrasound examination of gastric emptying were performed simultaneously to evaluate gastrointestinal motility before and after the test meal . All recording sessions were performed 1 week after infants had reached full enteral feeding . Results No significant difference in gastrointestinal symptoms was noted in the newborns fed the different formulas . In particular , regurgitation and vomiting were observed in 78 % versus 64 % of preterm newborns after st and ard and hydrolyzed formula , respectively ( Fisher exact test , not significant ) . No differences were found in terms of gastric electrical activity and gastric emptying time between the two groups . Conclusions It seems unnecessary to use hydrolysate formulas to improve motility in preterm infants BACKGROUND The importance of the inflammatory response in allergic disease has warranted investigation of two of the more integral cells in the pathogenesis of allergic rhinitis , namely , nasal basophilic cells ( NBCs ) and nasal eosinophils ( NEs ) . In the present study the natural history of NBCs and NEs was studied from birth through 4 years of age in infants of atopic parents to better underst and their relationship to the development of various atopic disorders . METHODS During a prospect i ve , r and omized , controlled trial of the effect of maternal and infant food avoidance on the development of atopic disorders in 288 infants of atopic parents , NBCs and NEs were determined semiquantitatively on Wright-Geimsa stained nasal mucosal scrapings and related to each other and to various atopic parameters . RESULTS In these infants who are at high risk NBCs developed in both those becoming atopic and those remaining nonatopic , but they occurred with increased frequency and quantity in those children in whom most allergic disorders and food or inhalant sensitization developed . NEs , rare at 4 months in all infants , increased in atopic children from 1 to 4 years , and remained infrequent and nominal in nonatopic children . Levels of NBCs and NEs ( 1 ) correlated with each other strongly , directly , and with increasing magnitude in children from ages 4 months to 4 years and ( 2 ) correlated with log serum IgE levels weakly and moderately in children from ages 2 to 4 years . Stepwise linear regression analyses revealed that allergic rhinitis accounted for most of the variance seen in the level of NBCs and NEs during early childhood , reaching 50 % by age 4 years . Asthma , atopic dermatitis , food allergy , food and inhalant sensitization , serum IgE level , and IgG beta-lactoglobulin level accounted for a small proportion of the variance in NBCs and NEs from ages 4 months to 4 years . CONCLUSIONS These findings help to eluci date the natural history of NBCs and NEs in infants at risk for atopic disorders and document the temporal association of these cells with the development of atopic disease , principally allergic rhinitis 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 The aim of this study was to compare the allergy-preventive effect of a partially hydrolyzed formula with two extensively hydrolyzed formulas , in infants with a high risk for development of allergic disease . High-risk infants from four Danish centres were included in the period from June 1994 to July 1995 . Five-hundred and ninety-five high-risk infants were identified . High-risk infants were defined as having biparental atopy , or a single atopic first-degree relative combined with cord blood immunoglobulin E ( IgE ) > or = 0.3 kU/l . At birth all infants were r and omized to one of three different blinded formulas .  All mothers had unrestricted diets during pregnancy and lactation and were encouraged to breast-feed exclusively . If breast-feeding was insufficient , one of the three formulas , according to r and omization , was given during the first 4 months . It was recommended not to introduce cow 's milk , cow 's milk products . and solid foods until the age of 4 months . After the age of 4 months a normal unrestricted diet and conventional cow 's milk-based formula were given when needed . All infants were followed-up prospect ively with interview and physical examination at the age of 6 , 12 , and 18 months , and if any possible atopic symptoms were reported . If food allergy was suspected , controlled elimination/challenge procedures were performed in a hospital setting . Of 550 infants included in the study , 514 were seen at all visits and 36 were excluded owing to noncompliance . Of 478 infants who completed the study , 232 were exclusively breast-fed , 79 received an extensively hydrolyzed casein formula ( Nutramigen ) , 82 an extensively hydrolyzed whey formula ( Profylac ) , and 85 a partially hydrolyzed whey formula ( Nan HA ) , during the first 4 months of life . These four groups were identical in regard to atopic predisposition , cord blood IgE , birthplace , and gender . Exclusively breast-fed children were exposed less to tobacco smoke and pets at home and belonged to higher social classes , whereas the three formula groups were identical concerning environmental factors . The frequency of breast-feeding was high ; only eight ( 2 % ) children were not breast-fed at all . The three formula groups were identical in regard to duration of breast-feeding and age at introduction of formula and solid foods . No significant differences were found in the three groups of infants receiving formula milk regarding the cumulative incidence of atopic dermatitis or respiratory symptoms . The cumulative incidence of parental-reported cow 's milk allergy was significantly higher in children fed partially hydrolyzed formula ( Nan HA ) compared with extensively hydrolyzed formula ( Nutramigen or Profylac ) at 12 and 18 months ( NanHA , 7.1 % ; Nutramigen , 2.5 % ; Profylac , 0 % ; p=0.033 ) . The cumulative incidence of confirmed cow 's milk allergy was 1.3 % ( three of 232 ) in exclusively breast-fed infants , 0.6 % ( one of 161 ) in infants fed extensively hydrolyzed formula ( Nutramigen or Profylac ) , and 4.7%(four of 85 ) in infants fed partially hydrolyzed formula ( Nan HA ) . Partially hydrolyzed formula was found to be less effective than extensively hydrolyzed formula in preventing cow 's milk allergy , 0.6 % vs. 4.7 % ( p=0.05 ) , but because of the small number of cases the results should be interpreted with caution . Compared with other similar studies the frequency ofatopic symptoms was low , even though the dietetic intervention did not include either maternal diet during lactation or dietary restrictions to the children after the age of 4 months OBJECTIVE To study the effects of extensively hydrolyzed protein formula ( eHF ) on the feeding and growth in preterm infants through a multicenter controlled clinical study . METHODS Preterm infants admitted to eight upper first-class hospitals in China between February 2012 and December 2013 were r and omly selected . They were divided into two observation groups and two control groups . The first observation group consisted of preterm infants with a gestational age of < 32 weeks , who were fed with eHF for 10 - 14 days after birth and then with st and ard preterm formula ( SPF ) until discharge . The second observation group consisted of preterm infants with a gestational age of 32 - 34 weeks , who were fed with SPF after birth , but were switched to eHF ( 7 - 14 days ) if suffering feeding intolerance at 6 - 8 days after birth . The two control groups with corresponding gestational ages kept to be fed with SPF after birth . Clinical data were recorded to compare feeding condition , physical growth , blood biochemical indices , and major complications between different groups . RESULTS A total of 328 preterm infants were enrolled . Preterm infants with a gestational age of < 32 weeks in the observation group had a significantly shorter meconium evacuation time than in the corresponding control group ( P<0.05 ) . They also had significantly lower levels of serum total bilirubin at weeks 1 and 2 after birth compared with the control group ( P<0.05 ) . The observation group needed more time in reaching enteral nutrition ( EN ) basic energy uptake of 50 kcal/(kg·d ) , partial parenteral nutrition ( PPN ) , hospitalization , and corrected gestational age at discharge compared with the controlled infants ( P<0.05 ) . There was no difference in the incidence of extrauterine growth retardation ( EUGR ) at discharge between the two groups ( P>0.05 ) . Preterm infants with a gestational age of 32 - 34 weeks in the observation group had significantly lower serum total bilirubin levels at 2 weeks after birth compared with the corresponding control group ( P<0.05 ) . They required more time in achieving EN basic energy and PPN than in the control group ( P<0.05 ) . There was no difference in the incidence of EUGR at discharge between the two groups ( P>0.05 ) . CONCLUSIONS For preterm infants  , eHF can improve gastrointestinal motility , accelerate bilirubin metabolism and excretion and does not increase the incidence of EUGR BACKGROUND Feeding intolerance is common in very low birth weight ( VLBW ; < 1500 g ) infants .  Hydrolyzed protein preterm infant formula ( HPF ) has been shown to accelerate the gastrointestinal transit of formula . The aim of this study was to investigate whether HPF improves early feeding tolerance compared with st and ard preterm infant formula ( SPF ) . We hypothesized that HPF would accelerate early enteral feeding advancement . METHODS Primary outcome was the time from initiation of milk feeds until full feeds ( 150 mL/kg birth weight/d ) were achieved in infants who received < 10 % human milk ( HM ) to exclude HM as a confounder . Because the availability of HM was not predictable at the time of enrollment , all eligible VLBW infants ( n = 129 ) were r and omly assigned in a r and omized , controlled trial to receive HPF or SPF if HM was not available . Infants who received > 10 % HM ( n = 42 ) were excluded . Milk bolus feeding every 2 to 3 hours was started at the discretion of the attending physician and advanced by 16 mL/kg/d . Prepr and ial gastric residuals were tolerated up to 5 mL/kg ; otherwise , feedings were reduced or withheld . Data are shown as median ( 5th and 95th percentile ) . RESULTS Forty-six and 41 ( HPF vs SPF ) infants received < 10 % HM . There was no significant difference with regard to birth weight , gestational age , and onset of milk feeds ( day 3 [ 1 - 8 ] vs 4 [ 2 - 6 ] ) . The time from initiation of milk feeds to full feeds was significantly shorter with HPF feeding ( 10 [ 9 - 27 ] vs 12 [ 9 - 28 ] days ) . CONCLUSION HPF improved the feeding tolerance and enabled a more rapid establishment of full enteral feeding in VLBW infants compared with SPF Serum levels of IgE , IgE antibodies to egg white ( EW ) and cow 's milk ( CM )  , IgG , and IgA antibodies to ovalbumin ( OA ) and beta-lactoglobulin ( BLG ) were measured in a group of 115 infants with a family history of atopy/allergy at birth and at 3 , 6 , 9 , 12 , and 18 months of age . The mothers of 65 infants  avoided eggs , CM , and fish during the first 3 months of lactation ( maternal antigen avoidance diet , D group ) , whereas the remaining 50 mothers  had no diet restrictions ( no maternal antigen avoidance diet , ND group ) . CM was introduced after 6 months of age and EW after 9 months . The only statistically significant difference between the D and ND group infants was a lower rate of specimens with IgE antibodies to EW and /or CM in the infants at 3 months of age ( p = 0.008 ) . IgE antibodies to EW and /or CM appeared in 62 infants during the study period and often during complete breast-feeding . In 40 of the infants , IgE antibodies appeared before the introduction of EW and CM into the diet . The IgE concentrations of the D and the ND group infants were similar . Cord-blood IgE was a poor predictor of atopy/allergy ; for example , only seven of 103 infants with double heredity for atopy/allergy had values above the 90th percentile of our normal reference . The concentrations of IgG antibodies to OA and BLG were similar in the two groups . The levels decreased significantly ( p less than 0.001 ) from birth to 6 months of age , indicating a passive placental transfer . ( ABSTRACT TRUNCATED AT 250 WORDS Forty-five healthy infants were included in a double-blind r and omized prospect i ve study comparing the nutritional value of two formulas . One group received a whey-predominant formula ( n = 20 ) ; the other group received a whey hydrolysate formula ( n = 25 ) . Four infants of the whey hydrolysate group were dropped because they refused the formula . Although the mean daily volume intake was smaller with the whey hydrolysate formula compared with the whey-predominant formula ( p < 0.001 ) , the weight gain in the two groups after 13 weeks was identical ( 27.2 g/day in both groups ; the mean difference in weight gain between the groups after 13 weeks was only 8 g ) . Length gain at 13 weeks was 10.4 cm in the whey-predominant formula group and 10.8 cm in the whey hydrolysate formula group ( p = NS ) . After 13 weeks , blood was sample d for hemoglobin , hematocrit , red blood cell count , white blood cell count , lymphocytes , glycemia , proteins , albumin , prealbumin , calcium , phosphorus , urea , creatinine , iron , iron-binding capacity , zinc , and vitamins A and E. Except for the iron-binding capacity , zinc , urea ( in plasma as well as in urine ) ( all three were higher in the whey hydrolysate group ) , no significant differences were found . According to these results , exclusive feeding of the whey hydrolysate formula from birth to 3 months of age to healthy infants appears to result in an adequate nutritional status , as assessed at 3 months of age Background Decreased nitrogen levels , calcium intestinal absorption rates , and plasma amino acid imbalances were reported for preterm infants who were fed partially hydrolyzed preterm formulas . In this pilot study , we evaluated a new formula with modified nitrogen and calcium sources . Methods During their second week of life , 16 preterm infants were r and omly assigned to one of two groups : 9 were fed the  new partially hydrolyzed formula and 7 were fed a conventional formula . Nutrient balance was performed at the end of the first month of life . Amino acid concentrations and anthropometric parameters were measured at theoretical term . Results Birth weight and gestational age ( mean ± SD ) were similar in the two groups ( 28.9 ± 7.0 weeks and 1183 ± 242 g vs. 27.7 ± 1.0 weeks and 1139 ± 162 g ) . Median nitrogen absorption rates ( 85 % vs. 89%;P = 0.03 ) and biological values ( 59 % vs. 69%;P = 0.13 ) were lower for infants who were fed the new formula than for those fed the conventional formula . After correction for difference in nitrogen intake , there was no significant difference in nitrogen retained between the two groups ( P = 0.11 ) . Plasma amino acid concentrations were also similar in the two groups . Median calcium absorption tended to be higher in the new-formula group than in the conventional-formula group ( 54 % vs. 45 % , P = 0.19 ) . At theoretical term , infants fed the conventional formula were heavier than infants fed the new formula ( 3559 ± 362 g vs. 3193 ± 384 g , P = 0.04 ) . Conclusions Because nitrogen content is 10 % higher in hydrolyzed-protein formula than in entire-protein formula , appropriate nitrogen retention , plasma amino acid profile , and mineral use can be achieved with the new partially hydrolyzed formula . Further studies with larger groups are needed to evaluate the effect on growth OBJECTIVE In study 1 , to compare the effect on growth in healthy infants of a new amino acid-based formula ( AAF )  and a control extensively hydrolyzed formula ( EHF ) , with both docosahexaenoic acid ( DHA ) and arachidonic acid ( ARA ) at levels similar to those in human milk worldwide . In study 2 , to evaluate the hypoallergenicity of this new AAF in infants and children with confirmed cow 's milk allergy ( CMA ) . STUDY DESIGN In study 1 , a total of 165 healthy , full-term , formula-fed infants r and omly received the  new AAF or control formula .  Anthropometric measurements , tolerance , and adverse events were recorded throughout the study . Plasma amino acid profiles were evaluated in a subset of the infants . In study 2 , the hypoallergenicity of the new AAF was evaluated in 32 infants and children using a double-blind , placebo-controlled food challenge ; an open challenge ; and a 7-day feeding . RESULTS In study 1 , overall growth , tolerance , and safety outcomes were similar in both groups . In study 2 , 29 of the 32 subjects completed both challenges ; no allergic reaction was seen in any of the 32 subjects . CONCLUSIONS The new AAF with DHA and ARA at levels similar to those in human milk worldwide is hypoallergenic . It also is safe and supports growth in healthy , term infants BACKGROUND The long-term effect of nutritional intervention with hydrolyzed infant formulas on allergy development has not been sufficiently evaluated . OBJECTIVE We performed a follow-up of the German Infant Nutritional Intervention study until 6 years of life to investigate the long-term allergy-preventive effect of 3 hydrolyzed infant formulas compared with cow 's milk formula ( CMF ) in a r and omized , double-blind trial . METHODS Between 1995 and 1998 , 2252 newborns with atopic heredity were r and omly assigned at birth to receive one of 4 blinded formulas : partially or extensively hydrolyzed whey formula , extensively hydrolyzed casein formula , or CMF as milk substitute for the first 4 months when breast-feeding was insufficient . The cohort was followed from birth until 6 years of age with yearly question naires . Outcomes were physician-diagnosed allergic diseases ( atopic dermatitis , food allergy , allergic urticaria , asthma , and hay fever/allergic rhinitis ) . Log-binomial regression modeled with generalized estimation equations was used for the statistical analysis . RESULTS In the intent-to-treat analysis the relative risk of a physician 's diagnosis of allergic manifestation ( AM ) compared with CMF was 0.82 ( 95 % CI , 0.70 - 0.96 ) for partially hydrolyzed whey formula , 0.90 ( 95 % CI , 0.78 - 1.04 ) for extensively hydrolyzed whey formula , and 0.80 ( 95 % CI , 0.69 - 0.93 ) for extensively hydrolyzed casein formula . The corresponding figures for atopic eczema were 0.79 ( 95 % CI , 0.64 - 0.97 ) , 0.92 ( 95 % CI , 0.76 - 1.11 ) , and 0.71 ( 95 % CI , 0.58 - 0.88 ) , respectively . In the per- protocol analysis all effects were stronger and significant . No significant effect on other AMs was found . CONCLUSION The data confirm a long-term allergy-preventive effect of hydrolyzed infant formulas on AM and atopic eczema until 6 years of age BACKGROUND & AIMS Emerging research has revealed the existence of periods in which the developing brain has heightened sensitivity to environmental influences . We discovered a sensitive period , < 4 months of age , when exposure to the flavor of extensively hydrolyzed protein hydrolysate formulas ( ePHF ) determines its hedonic tone . This formula has pronounced bitter , sour , and savory tastes compared to cow-milk-based formulas ( CMF ) . This study aim ed to determine the effects of duration of exposure during the sensitive period on a food containing an exemplar of the savory flavor . METHODS Formula-fed infants were r and omized into four groups at age 0.5 months : one control group fed the CMF for 8 months , and three groups fed ePHF for 1 , 3 , or 8 months and CMF otherwise . When infants were 8.5 months , their acceptance of a savory and plain broth was measured . RESULTS Infants fed hydrolysate formula for 3 or 8 months , but not 1 month , showed greater acceptance of the savory broth relative to the plain broth ( p < 0.01 ) and consumed it at a faster rate ( p = 0.01 ) . CONCLUSIONS The duration of flavor exposure affects infants ' earliest responses to foods : a 3-month exposure to ePHF shifted the hedonic tone for savory flavor BACKGROUND The diversity in the perceived prevalence , recovery , and risk factors for cow 's milk allergy ( CMA ) necessitated a large-scale , population -based prospect i ve study . OBJECTIVE We sought to determine the prevalence , cross-reactivity with soy allergy , and risk factors for the development of CMA . METHODS In a prospect i ve study the feeding history of 13,019 infants was obtained by means of telephone interview ( 95.8 % ) or question naire ( 4.2 % ) . Infants with probable adverse reactions to milk were examined , skin prick tested , and challenged orally . RESULTS Ninety-eight percent of the cohort participated in the study . The cumulative incidence for IgE-mediated CMA was 0.5 % ( 66/13,019 patients ) . The mean age of cow 's milk protein ( CMP ) introduction was significantly different ( P < .001 ) between the healthy infants ( 61.6 + /- 92.5 days ) and those with IgE-mediated CMA ( 116.1 + /- 64.9 days ) . Only 0.05 % of the infants who were started on regular CMP formula within the first 14 days versus 1.75 % who were started on formula between the ages of 105 and 194 days had IgE-mediated CMA ( P < .001 ) . The odds ratio was 19.3 ( 95 % CI , 6.0 - 62.1 ) for development of IgE-mediated CMA among infants with exposure to CMP at the age of 15 days or more ( P < .001 ) . Sixty-four patients with IgE-mediated CMA tolerated soy , and none had a proved allergy to soy . CONCLUSIONS IgE-mediated CMA is much less common than generally reported . Early exposure to CMP as a supplement to breast-feeding might promote tolerance . Finally , soy is a reasonable feeding alternative in patients with IgE-mediated CMA Ninety-one high atopy-risk infants were prospect ively followed up to 18 months of age with regard to the development of allergic/atopic manifestations and sensitization . They were r and omized into one of two feeding groups , i.e. , a hydrolyzed , ultrafiltered cow 's milk whey formula , Profylac ( n = 32 ) , or an ordinary cow 's milk formula ( n = 39 ) , for 12 months , started after exclusive breast-feeding for 0 - 9 ( median 6.0 ) months . Lactating mothers avoided milk , egg , and fish , as did the infants up to 12 months of age . Twenty of the 91 infants were breast-fed exclusively for more than 9 months and regarded as a control group . All infants were followed-up by question naires , physical examinations , skin prick tests  , and determination of serum total IgE and cow ' milk-specific IgE. The frequency of allergic/atopic disease was similar in the three groups . However , all three infants who developed cow 's milk allergy with skin symptoms belonged to the cow 's milk formula group . The skin prick test with whey hydrolysate was negative in all , while with cow 's milk it was positive in eight infants . Growth was similar in the three groups . The study comprises too few infants to allow us to make statistically based statements . However , the difficulties encountered and the limited effects obtained by the use of whey hydrolysate at weaning at about 6 months of age made us conclude that we can spare high atopy-risk families this extra burden BACKGROUND Avoidance of individual risk factors have not been successful in preventing the development of asthma . OBJECTIVE We sought to determine the effectiveness of a multifaceted intervention program in primary prevention of asthma in high-risk infants . METHODS We identified 545 high-risk infants on the basis of an immediate family history of asthma . Families were r and omized into intervention or control groups . Intervention measures included avoidance of house dust mite , pet allergen , and environmental tobacco smoke . Breast-feeding was encouraged with formula supplementation if necessary , and introduction of solid foods was delayed . RESULTS At 2 years of age , 19.5 % of the children had asthma , and 14.7 % had atopy ( positive skin test response to one or more common allergens ) . Significantly fewer children had asthma in the intervention group compared with in the control group ( 16.3 % vs 23.0 % ) , with 60 % less persistent asthma at 2 years . There was a 90 % reduction for recurrent wheeze in the intervention group compared with that seen in the control group . Exposure to maternal environmental tobacco smoke during pregnancy or the first year was a risk factor for asthma at 2 years of age . A positive skin test response , particularly to food , at 12 months predicted asthma at 2 years . There was no significant difference for atopy between the intervention and control groups , but daycare reduced atopy at 2 years . CONCLUSION This multifaceted intervention program during a window of opportunity in the first year of life was effective in preventing  asthma  in high-risk children at 2 years of age . Future studies with this cohort at school age are important The influence of early feeding on the risk of atopic diseases has been studied in full-term newborns , not in very low birth weight infants ( VLBW ) . The study evaluated effect of early feeding of VLBW infants with either cow 's milk-based formula ( CMF ) or extensively hydrolyzed milk formula ( HF ) on incidence of atopic diseases and markers of atopy at 5 - 7 years of age . This was a follow-up of the r and omized , double-blind study evaluating the influence of different enteral feeding protocol s on the early morbidity of VLBW infants . In the original study 80 children were r and omly allocated into 2 groups receiving during first month of life HF ( experimental group ) or CMF ( control group ) . At the age of 5 - 7 years , 62 children among 74 available ( 84 % ) with mean birthweight 1124 g were evaluated according to st and ardized ISAAC ( International Study of Asthma and Allergies in Childhood ) protocol . Total IgE level , specific IgE , lymphocyte CD4+CCR4+/CD4+CXCR3 + ratio and skin prick tests ( SPT ) were done . Prevalence of obvious allergic diseases was not significantly different between the studied groups ( HF : 12/33 ; CMF : 6/29 ; RR [ relative risk ] HF vs CMF : 1.76 ; 95%CI [ confidence interval ] : 0.76 - 4.09 ) . Comparison of atopic status across groups revealed similar rate of positive markers of atopy : IgE ( RR : 2.57 95%CI : 0.91 - 8,08 ) , SPT ( RR : 5.13 ; 95%CI : 0.93 - 31.6 ) , lymphocyte CD4+CCR4+/CD4+CXCR3 + ratio ( OR : 2.32 ; 95%CI : 0.78 - 7.53 ) in the both studied groups . Based on the carried out follow-up study we were unable to confirm the usefulness of hydrolyzed formula in prevention of allergy in an unselected cohort of very low birth weight infants Objective : To evaluate growth , tolerance and plasma biochemistries in infants fed an experimental rice protein-based infant formula .  Design : R and omized , blinded , 16 week parallel feeding trial of 65 healthy infants fed either an experimental partially hydrolyzed rice protein-based infant formula fortified with lysine and threonine ( RPF , n = 32 ) , or a st and ard intact cow ’s milk protein-based formula ( CMF , n = 33 ) as a control . Assessment s occurred at enrollment ( average 2 days ) , 2 , 4 , 8 , and 16 weeks of age . Results : Growth as indicated by weight , length , and head circumference was not different between the 2 formula groups . All plasma biochemistries for both groups were within reference normal range . However , RPF group had lower phosphorus and urea nitrogen , lower essential amino acids except threonine , which was higher , and lower ratio of essential ( including semi-essential ) to non-essential amino acids . Differences in the concentrations and ratios of amino acids became less as feeding progressed with age . Plasma total protein , albumin , prealbumin , calcium , magnesium , and alkaline phosphatase were not different between groups . Conclusion : Healthy infants fed an experimental partially hydrolyzed rice protein-based formula  had normal growth , tolerance , and plasma biochemistry comparable to those of infants fed a st and ard intact milk protein-based formula , despite some differences in amino acid profiles Incidence and clinical manifestation of cow 's milk protein intolerance ( CMPI ) were studied in 1158 unselected newborn infants followed prospect ively from birth to 1 year of age . No food changes were required in 914 infants who were used as healthy controls . When CMPI was suspected ( 211 infants ) , diagnostic dietary interventions according to a st and ard protocol were performed . After exclusion of lactose intolerance , two positive cow 's milk elimination/challenge tests were considered diagnostic of CMPI . Two hundred and eleven symptomatic infants were examined for possible CMPI . A large group of 80 infants improved on a lactose reduced formula . In 87/211 infants CMPI was excluded ( sick controls ) . Finally CMPI was proven in 26 infants . The calculated incidence rate for CMPI was 2.8 % . The principal symptoms in infants with CMPI were gastrointestinal , dermatological and respiratory in 50 % , 31 % and 19 % respectively . A positive family history for atopy ( first or second degree relatives ) was more frequent in either CMPI infants ( 65 % ) , or sick controls ( 63 % ) when compared to either healthy controls ( 35 % ) or infants improving on a low lactose formula ( 51 % ) . Differences between patients with CMPI and sick controls were only found for the presence of atopy in at least 2 first degree relatives [ ( 5/26 in CMPI infants and 4/87 in sick controls ( P<0.05 ) ] and for multiorgan involvement [ 10/26 infants with CMPI as opposed to 12/87 in the sick control group ( P<0.02 ) ] . These statistical differences are too weak to be of clinical value Extensively hydrolyzed formulas present a complex matrix subject to adverse conditions during manufacture that could influence growth and tolerance of infants fed these formulas . A masked , r and omized , parallel growth study was conducted in infants fed a ready-to-feed ( RTF ) or powdered ( PWD ) form of an extensively hydrolyzed casein-based formula . Infants were enrolled between 0 and 9 days and studied to 112 days of age .  Growth , formula intake , and stool patterns were assessed . There were no significant differences between groups in weight , length , head circumference , or their respective gains . Tolerance was similar between groups except that the RTF group had greater formula intakes and passed more stools/day compared to the PWD group . This study demonstrates that the PWD formulation of this RTF formula supports similar growth and tolerance in infants during the first 4 months of life Aim : A r and omized , double‐blind study was conducted to evaluate whether use of protein hydrolysate‐based preterm formulas in infants with an atopic predisposition helps prevent the development of allergic diseases . Methods : Preterm infants ( n= 122 ) with at least one first‐degree relative ( parent or sibling ) with allergic disease were r and omly assigned to receive an extensively or partially hydrolysed preterm formula ( intervention groups ) or a st and ard preterm formula until 4 to 5 mo of age . Infants whose parents preferred that they be breastfed received their mothers ' fortified breast milk . Results : Intention‐to‐treat analysis showed that the overall incidence of allergic diseases did not significantly differ between groups at both 4–5 and 12 mo of age . However , by 12 mo , use of the extensively hydrolysed versus the st and ard preterm formula had significantly reduced the risk of atopic dermatitis . At 4–5 and 12 mo , there was a significantly increased risk of non‐acceptance of the extensively hydrolysed formula compared with the other formulas Weight-gain in 35 slightly undernourished Australian Aboriginal infants was studied in hospital ( 49 admissions ) during a blind controlled trial of a pre-hydrolysed low-lactose milk preparation and reconstituted full-cream milk powder . Infants fed the lactose hydrolysed milk gained 70 % more weight than those receiving normal milk . Better weight-gains were achieved in those on the lactose hydrolysed milk irrespective of percentage st and ard weight for age , the presence of diarrhoea on admission to the trial , and stool sugar concentrations . The use of low-lactose milk should be considered in nutritional aid programmes for undernourished children throughout the world Partialy hydrolyzed formulas have been proposed for term and preterm infants , but decreased nitrogen and calcium intestinal absorption rates , together with plasma amino acid imbalances have been reported in preterm infants . We evaluated a new formula with modified nitrogen and calcium sources ( glycerophosphate ) . During their second week of life , 16 preterm infants were r and omly assigned to 1 of 2 groups : 9 were fed the new partially hydrolyzed formula  and 7 a  conventional formula . A nutrient balance was performed at the end of the first month of life . Amino acid concentrations and whole-body mineralization were measured at the end of study period ( theoretical term ) .  Birth weight and gestational age ( mean + /- SD ) were similar in the 2 groups ( 28.9 + /- 7.0 wks and 1,183 + /- 242 g v 27.7 + /- 1.0 wks and 1,139 + /- 162 g ) . Median nitrogen absorption rate ( 85 % v 89 % ; P = .03 ) was lower in infants fed the new formula than in those fed the conventional one . After correction for difference in nitrogen intake , there was no significant difference in N retained between the 2 groups ( P = .11 ) . Plasma amino acid concentrations were also similar in the 2 groups . At theoretical term , median bone mineral content was not significantly different between the 2 groups ( 50 g/kg v 55 g/kg ; P = .17 ) and it was close to the reference values obtained in term neonates just after birth . As long as nitrogen content is 10 % higher in protein hydrolyzed formula than in entire protein formula , appropriate nitrogen retention , plasma amino acid profile can be achieved with the new partially hydrolyzed formula . In both groups , bone mineralization at theoretical term was close to the mineralization observed term neonates just after birth Background : Exposure to cow ’s milk protein in early infancy could lead to increased rates of allergic diseases later in life . We investigated whether feeding a protein-hydrolyzed formula ( HF ) in the first 6 months of life decreased allergic diseases up to 36 months later . Methods : Newborns who had at least 1 first-degree family member with a history of atopy and could not breast-feed were enrolled . They were fed with HF or cow ’s milk infant formula ( CM ) for at least 6 months via an open-label protocol and were monitored prospect ively at 6 , 18 and 36 months of age to assess allergy sensitization and allergic diseases . Results : A total of 1,002 infants were enrolled and 679 infants were consistently fed the same formula for the first 6 months of life ( 345 HF and 334 CM ) . The percentage of food sensitization ( especially to milk protein ) was significantly lower in the HF group than in the CM group at 36 months ( 12.7 vs. 23.4 % , p = 0.048 ) . There was no significant difference in the prevalence of aeroallergen sensitization between the groups . Occurrence of allergic diseases during the first 3 years of life was significantly correlated with aeroallergen sensitization , but not to food allergen sensitization , parental atopy or feeding types . Conclusions : Infants fed with HF during the first 6 months of life had a significantly lower percentage of sensitization to milk protein allergens , but not allergic diseases during the first 3 years of life . Avoidance of cow ’s milk protein alone in infancy is not enough to decrease rates of allergic diseases Aim : Protein hydrolysates have been introduced in preterm formulae , but it is not clear whether they are needed for the feeding of preterm infants . We design ed a r and omized , controlled trial to test the effects of a preterm formula with hydrolysed cow 's milk proteins on short‐term growth and urinary and plasma amino acids levels . Methods : Infants with a birthweight 1750 g and gestational age 34 wk fed a conventional preterm infant formula ( formula B ) or a hydrolysed formula ( formula A ) .  Weight was measured daily ; length , head circumference , mid‐arm circumference and total skinfold thickness were measured weekly . Blood and urine were analysed for amino acid concentrations at start , 14 and 28 d. Results : Twenty‐one infants met the criteria for r and omization . The daily feeding volumes were : formula A 172.8±5.6 vs formula B 170.1±2.8 ml/kg/d . Infants fed with formula A showed slower weight gain ( 17.4±3.4 vs 20.5±3.3 g/kg/d ; p=0.045 ) and lower mean change in Z‐scores for weight ( −0.18±0.16 vs 0.00±0.09 ; p=0.009 ) and for head circumference ( −0.06±0.13 vs 0.06±0.13 ; p=0.049 ) . After 14 d , infants receiving formula A had statistically significant higher urinary levels of essential amino acids compared to infants receiving formula The effect of different feeding regimens , notably the use of hydrolysed cow 's milk formulas , on the development of allergic reactions and the development of cow 's milk protein-IgG antibodies is still disputed . We prospect ively compared the development of allergic manifestations and cow 's milk protein-IgG antibodies in a total of 702 infants who were divided into six groups:1.exclusively breast milk for at least 4 weeks (n=206).2.Breast milk plus initial partially hydrolysed formula (n=104).3.Breast milk plus extensively hydrolysed formula (n=50).4.Breast milk plus initial conventional cow 's milk formula (n=73).5.Conventional cow 's milk with or without breast milk throughout (n=187).6.Extensively hydrolysed cow 's milk formula for 2 months , followed by conventional cow 's milk (n=82).Cow 's milk protein antibodies were determined by an indirect immuno-fluorescent test . Antibody titres rose slowly in groups 1 , 3 and 6 . Children in group 5 showed two high peaks . There were no significant differences in the frequency and type of allergic manifestations between the groups . Introduction of cow 's milk formula during the first trimenon result ed in elevated antibody titres in all breast fed infants compared with introduction at a later date . Conclusion : In contrast to a previous study from the same laboratory , there is no diagnostic significance of cow 's milk protein-IgG antibodies for allergic manifestations . The occurrence of these antibodies is a physiological phenomenon : the shorter the breast feeding period and the earlier cow 's milk formula is introduced , the higher the antibody levels The aim of the study was to compare , during the first month of life , growth parameters , biochemical indices of protein metabolism and plasma amino acid concentrations in newborn infants fed either human milk ( n = 23 ) , three different whey hydrolysate formulae ( WHF 1 , n = 13 ; WHF 2 , n = 10 ; WHF 3 , n = 13 ) , a soy-collagen hydrolysate formula ( SCHF n = 18 ) or a whey-casein hydrolysate formula ( WCHF , n = 20 ) .  Growth parameters and the various protein concentrations determined in the infants fed WHF 1 and WHF 2 were similar to the values observed with human milk . With WHF 3 , growth in weight , length and head circumference and serum total protein concentrations were reduced significantly whereas blood urea nitrogen was increased . With SCHF , growth in weight and length as well as serum total protein and transferrin concentration were decreased significantly , whereas serum IgG concentration was increased . With WCHF growth in length and serum transferrin concentration were decreased compared to the human milk group . In the various groups , the plasma amino acid pattern reflected the amino acid content of the formula . Whey hydrolysate formula induced mainly an increase in threonine and a decrease in tyrosine concentrations .  Soy-collagen hydrolysate formula led to an increase of non-essential amino acids , such as glycine and hydroxyproline , and a decrease in plasma lysine and cystine .  Whey-casein hydrolysate formula induced a plasma amino acid pattern close to the profile observed with human milk . Nevertheless , the plasma concentrations of most of the various amino acids were higher . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND The potential of extensively or partially hydrolyzed formulas to reduce the risks for allergies is controversial . OBJECTIVE We sought to assess the preventive effect of differently hydrolyzed formulas compared with cow 's milk formula ( CMF ) in high-risk infants . METHODS Between 1995 and 1998 , 2252 infants with a hereditary risk for atopy were enrolled in the German Infant Nutritional Intervention Study and r and omly assigned at birth to one of 4 blinded formulas : CMF , partially hydrolyzed whey formula , extensively hydrolyzed whey formula , and extensively hydrolyzed casein formula ( eHF-C ) . The primary end point at 1 year of age was the presence of allergic manifestation , which was defined as atopic dermatitis ( AD ) , gastrointestinal manifestation of food allergy , allergic urticaria , or a combination of these factors . RESULTS At 12 months per protocol , analysis was performed on 945 infants exposed to study formula : 304 ( 13.5 % ) infants had left the study , 138 ( 6.1 % ) infants were excluded because of noncompliance , and 865 infants were exclusively breast-fed the first 4 months of life . The incidence of allergic manifestation was significantly reduced by using eHF-C compared with CMF ( 9 % vs 16 % ; adjusted OR , 0.51 ; 95 % CI , 0.28 - 0.92 ) , and the incidence of AD was significantly reduced by using eHF-C ( OR , 0.42 ; 95 % CI , 0.22 - 0.79 ) and partially hydrolyzed whey formula ( OR , 0.56 ; 95 % CI , 0.32 - 0.99 ) . Family history of AD was a significant risk factor and modified the preventive effect of the hydrolysates . CONCLUSIONS Prevention of allergic diseases in the first year of life is feasible by means of dietary intervention but influenced by family history of AD . The preventive effect of each hydrolyzed formula needs to be clinical ly evaluated A cohort of 1749 newborns from the municipality of Odense born during 1985 in the University Hospital of Odense were followed prospect ively for the development of cow 's milk allergy (CMA)/cow 's milk protein intolerance ( CMI ) during their first year . The diagnosis of CMA/CMI was based on elimination/open milk challenge procedures according to generally accepted criteria . Thirty nine infants ( 2.2 % ) developed CMA/CMI .  Infants with CMA/CMI were fed cow 's milk formula daily during the first month of life significantly more often than infants in the study population ( p less than .001 ) . All 39 infants with CMA/CMI had ingested cow 's milk formula ( 40 - 830 mL ) neonatally , whereas none of the 210 neonates without supplements of cow 's milk formula  developed CMA/CMI ( p less than .05 ) . Based on a positive skin-prick test ( 2 + or more ) and /or specific serum IgE antibody to cow 's milk ( AL-RAST class 2 or more ) 16 infants were classified as having CMA . In infants solely breast-fed for greater than 1 month CMA was as frequent ( 1 % [ 14/1414 ] as in cow 's milk formula fed infant ( 0.6 % [ 2/335 ] ) . In infants with CMI , a significant majority ( 3.9 % [ 13/335 ] versus 0.7 % [ 10/1414 ] , p less than .001 ) had been cow 's milk formula fed during the first month . These data indicate an association between early cow 's milk formula feeding and development of reproducible adverse reactions to cow 's milk protein . Early neonatal intake of cow 's milk protein is probably a condition of sensitization and later adverse reactions to cow 's milk protein OBJECTIVE To determine the effect of a partially hydrolysed formula on genetically predisposed children , with respect to the development of atopic clinical manifestations and in vitro testing of serum IgE levels ( total and milk-specific ) . METHODS One hundred and ten infants were r and omly assigned to receive either partially hydrolysed formula or st and ard infant formula  , and were prospect ively monitored from birth for clinical atopic symptoms and serum IgE levels . RESULTS Eczema occurred less frequently in infants receiving partially hydrolysed formula . This was significant ( P < 0.05 ) at 3 , 6 , 9 , 12 , 18 and 24 months . However , the significance decreased with time , although it almost reached statistical significance at 30 months by the Kaplan-Meier survival function ( log-rank statistic , 3.46 ; P = 0.063 ) . Although wheezing occurred less frequently in infants receiving partially hydrolysed formula , compared to those receiving st and ard infant formula , the difference did not reach statistical significance ( P > 0.05 ) . CONCLUSIONS Exclusive feeding of hypoallergenic milk formula in the first 4 months of life has a protective effect in terms of the development of atopic dermatitis in the first 2 years of life , compared to feeding with cow 's milk formula Type 1 diabetes is considered to be a T-cell-mediated autoimmune disease in which insulin-producing beta-cells are destroyed . Immunity to insulin has been suggested to be one of the primary autoimmune mechanisms leading to islet cell destruction . We have previously shown that the first immunization to insulin occurs by exposure to bovine insulin ( BI ) in cow 's milk ( CM ) formula . In this study , we analyzed the development of insulin-specific T-cell responses by proliferation test , emergence of insulin-binding antibodies by enzyme immunoassay , and insulin autoantibodies by radioimmunoassay in relation to CM exposure and family history of type 1 diabetes in infants with a first-degree relative with type 1 diabetes and increased genetic risk for the disease . The infants were r and omized to receive either an adapted CM-based formula or a hydrolyzed casein (HC)-based formula  after breast-feeding for the first 6 - 8 months of life . At the age of 3 months , both cellular and humoral responses to BI were higher in infants exposed to CM formula than in infants fully breast-fed ( P = 0.015 and P = 0.007 ) . IgG antibodies to BI were higher in infants who received CM formula than in infants who received HC formula at 3 months of age ( P = 0.01 ) , but no difference in T-cell responses was seen between the groups . T-cell responses to BI at 9 months of age ( P = 0.05 ) and to human insulin at 12 ( P = 0.014 ) and 24 months of age ( P = 0.009 ) as well as IgG antibodies to BI at 24 months of age ( P = 0.05 ) were lower in children with a diabetic mother than in children with a diabetic father or a sibling , suggesting possible tolerization to insulin by maternal insulin therapy . The priming of insulin-specific humoral and T-cell immunity occurs in early infancy by dietary insulin , and this phenomenon is influenced by maternal type 1 diabetes Objectives : The aim of this study was to evaluate the efficacy on crying episodes owing to infantile colic of a new infant formula containing partially hydrolysed whey proteins , prebiotic oligosaccharides ( OS ) , with a high β-palmitic acid content . Design : Prospect i ve r and omized controlled study . Setting : Italy . Subjects : Two hundred and sixty-seven formula-fed infants , aged less than 4 months , with infantile colic , were r and omized to receive either the new infant formula ( study treatment ( ST ) ) or a st and ard formula and simethicone ( 6 mg/kg twice a day ) ( control treatment ( CT ) ) . A question naire was given to parents to evaluate for 14 days the daily number of colic episodes and crying time . Results : Out of the 199 infants who completed the study , 96 were treated with the new formula and 103 were not treated . Infants receiving the new formula had a significant decrease in colic episodes after 1 week ( 2.47±1.94 at day 7 vs 5.99±1.84 at the study entry ) compared to infants receiving the CT ( 3.72±1.98 at day 7 vs 5.41±1.88 at the study entry ) ( P<0.0001 ) . Also at day 14 , the crying episodes were significantly different between the two groups of infants ( 1.76±1.60 in ST vs 3.32±2.06 in CT ) ( P<0.0001 ) . Conclusions : The use of a partially hydrolysed formula supplemented with fructo- and galacto-OS induces a reduction of crying episodes in infants with colic after 7 and 14 days when compared with a st and ard formula and simethicone . Sponsorship : The study was supported by funds from Numico , Italy Objectives The aim of this study was to evaluate the nutritional efficacy and bifidogenic characteristics of a new infant formula containing partially hydrolyzed whey protein , modified vegetable oil with a high & bgr;-palmitic acid content , prebiotic oligosaccharides , and starch . Methods In a double-blind study , healthy formula-fed term infants aged younger than 2 weeks were r and omized to receive either the new infant formula ( NF ) or a st and ard formula ( SF )  until the age of 12 weeks .  Anthropometric measurements were taken at enrollment , 6 weeks , and 12 weeks . In a sub sample of infants , blood sample s were taken at 6 weeks and stool sample s were taken at enrollment and 6 weeks . Blood sample s were analyzed for biochemical measures of protein status and amino acids , and stools were analyzed for total bacteria and bifidobacteria . Mothers completed a feeding diary and question naire at 6 and 10 weeks . Results One hundred fifty-four infants were enrolled in the study ; 102 completed the trial . The growth of infants in both formula groups was in line with published growth curves . During the first 6 weeks , NF girls gained more weight and head circumference than the SF girls . These velocity differences were not maintained throughout the 12-week study period . The NF stools had a higher proportion of bifidobacteria at 6 weeks compared with the SF stools , and they were softer . There were no clinical ly significant differences in the blood biochemical and amino acid values between groups . Both formulas were well tolerated by the infants . Conclusions When compared with a st and ard infant formula , the new formula supported satisfactory growth , led to higher counts of bifidobacteria in the feces , produced blood bio-chemical values typical of formula-fed infants , and was well tolerated BACKGROUND & AIMS Gastric emptying ( GE ) is influenced by the type of nutrition . The objective of this study was to compare GE in infants fed an intact protein formula ( IPF ) , a partially hydrolysed formula ( PHF ) , and an extensively hydrolysed formula ( EHF ) .  METHODS This was a double-blind , r and omized , cross-over study . Following a fasting period of > or = 3 h , 20 healthy newborns were fed IPF , PHF , and EHF containing 50 microl (13)C-octanoic acid ( OA ) . Breath sample s were taken before feeding and every 15 min for 4 h thereafter . (13)C-OA  breath test was assessed by isotope-ratio mass spectrometry , and GE half-times ( t(1/2 ) ) were determined . RESULTS Seventeen infants with a mean gestational age of 37 wk ( range 28 - 40 wk ) and birth weight of 2698 g ( range 720 - 3690 g ) completed the study . At study initiation , the mean age was 31 d ( range 6 d-13 wk ) and the mean weight was 3466 g ( range 2100 - 5700 g ) . EHF emptied significantly faster than IPF and PHF ( medians 46 vs. 55 and 53 min , respectively , Wilcoxon , P<0.05 for both ) . There was no significant difference between GE of PHF and IPF ( Wilcoxon , P=0.2 ) . CONCLUSIONS EHF may be better tolerated by infants with GE problems BACKGROUND Previous analysis in a prospect i ve , population -based cohort reported reduced weight gain in children fed extensively hydrolyzed casein ( eHF-C ) formula during the first year of life but showed no effect on growth between 1 and 6 y of life . No studies have been conducted in children up to the age of 10 y. OBJECTIVE The objective was to investigate potential differences in body mass index ( BMI ) over the first 10 y of life between infants fed within the intervention period of the first 16 wk of life with partially hydrolyzed whey ( pHF-W ) , extensively hydrolyzed whey ( eHF-W ) , eHF-C , or cow-milk formula ( CMF ) and infants exclusively breastfed ( BF ) within the intervention period . DESIGN This was a prospect i ve , r and omized , double-blind trial in full-term neonates with atopic heredity in the German birth cohort German Infant Nutritional Intervention ( GINI ) followed through the first 10 y of life . Analyses of absolute and World Health Organization (WHO)-st and ardized BMI trajectories for 1840 infants [ pHF-W ( n = 253 ) , eHF-W ( n = 265 ) , eHF-C ( n = 250 ) , CMF ( n = 276 ) , and BF ( n = 796 ) ] were conducted according to intention-to-treat principles . RESULTS Except for the previously reported slower BMI gain in infants fed with eHF-C formula within the first year of life , no significant differences in absolute or WHO-st and ardized BMI trajectories were shown between the pHF-W , eHF-W , eHF-C , CMF , and BF groups thereafter up to the age of 10 y. CONCLUSIONS Extension of the follow-up period from 6 to 10 y for this r and omized controlled trial showed no long-term consequences on BMI for the 4 infant formulas considered . These data need to be confirmed in future studies It has been reported that the feeding of cow 's milk may enhance the development of atopy in predisposed infants . A prospect i ve study following children from birth through 15 years of age in a private pediatric practice was design ed to determine if the food ingested during the first months of life is related to the development of atopy in the offspring of allergic families . Each of 328 children with a positive family history of allergy was assigned to one of three groups . according to the feeding preference of the parents : 48 were fed breast milk ; 79 , soy-based formula ; and 201 , cow 's milk formula . All groups had egg , citrus , tomato , and wheat restrictions as well as inhalant allergen avoidance . These were compared to a control group of 580 children with no family history of allergy . Breast fed infants were found to have approximately one-half the incidence of atopy of cow 's milk or soy formula fed infants from atopic families when followed for up to 15 years . Soy feeding produced no advantage over cow 's milk in the prophylaxis of allergic disease . There was a threefold increase in clinical ly apparent atopic disease in offspring of allergic families when compared to controls but only a two-fold increase if the infant was breast fed . These results support the hypothesis that breast feeding and delay of exposure to known allergens may reduce the frequency of clinical allergic disease in the offspring of allergic families OBJECTIVE To prospect ively investigate the association of high levels of immunoglobulin E ( IgE ) sensitization to foods and the presence of atopic dermatitis ( judged by reported topical steroid use during the first 16 months of life ) in a birth cohort of 620 Australian children " at risk " of allergic disease because of family history . RESULTS A total of 559 of the children in the cohort were fully evaluated , and the cumulative prevalence of atopic dermatitis was 24 % . More children in the cohort who had atopic dermatitis had strongly positive skin test results ( > or = 4 + , histamine equivalent units , > or = approximately 6-mm wheal ) , consistent with IgE food sensitization to either cow 's milk , egg , or peanut at 6 months ( 22 % vs 5 % , chi(2 ) = 35 ; P < 10(-6 ) ) and at 12 months ( 36 % vs 11 % , chi(2 ) = 41 ; P < 10(-6 ) ) than those without atopic dermatitis . The calculated attributable risk percent for IgE food sensitization as a cause of atopic dermatitis was 65 % and 64 % at these times . In a separate group of infants with severe atopic dermatitis , the equivalent rates of IgE food sensitization at 6 months was 83 % and at 12 months , 65 % . CONCLUSION IgE food sensitization is a major risk factor for the presence of atopic dermatitis in infancy The effect of feeding different infant formulas on incidence of atopic disease was assessed in a prospect i ve double-blind r and omized controlled trial among " high risk " infants with family history of atopy among first-degree relatives . The incidence of atopic eczema , wheezing , rhinitis , gastrointestinal symptoms , and colic was noted and serum IgE antibodies to milk were estimated . Seventy-two infants were recruited into each of the following groups : cow milk whey hydrolysate formula ( NAN/HA ) , conventional cow milk formula ( Similac ) , soy-based formula ( Isomil ) , and exclusive breast feeding for greater than or equal to 4 months .  The number of infants who exited for reasons other than atopy and were excluded from analysis were 4 , 5 , 4 , and 12 in the four groups , respectively . The incidence of one or more symptoms of possible allergic etiology was five of 68 infants fed NAN/HA , 24 of 67 infants fed Similac , 25 of 68 infants fed Isomil , and 12 of 60 breast-fed infants . Among symptomatic infants , skin prick test to milk proteins was positive in four out of five infants fed NAN/HA , 16 of 24 fed Similac , 2 of 25 fed Isomil , and 7 of 12 breast-fed . IgE antibodies to milk were found in 2 of 68 , 9 of 67 , 0 of 68 , and 6 of 60 infants in the four groups , respectively . It is concluded that exclusive breast feeding for more than 4 months is partially protective against the development of atopic disease among high risk infants . ( ABSTRACT TRUNCATED AT 250 WORDS A prospect i ve r and omized study of growth and digestive tolerance in a cohort of 60 healthy infants with no history for allergic disease is reported . A milk-based formula and a formula of identical composition whose proteins had undergone hydrolysis were fed successively to the study infants according to a crossover design , for eight weeks . Intake , weight gain and length gain were comparable and satisfactory with both diets . With the hydrolyzed protein formula , stools were greener in color and significantly more numerous , although both parameters remained within normal limits . The most noteworthy result was the significantly greater rate of regurgitations in the group given the hydrolyzed protein formula , i.e. , 26 % versus 8 % in the group fed a conventional modified milk formula . These results show that use of partial protein hydrolysate formulas is associated with minor digestive adverse effects The data from the present investigation differ from those of the previous study . The new version of hydrolysed protein formula did not induce changes in insulinaemia or in the insulinaemia/glycaemia ratio in pre‐ and postpr and ial sample s when compared with the intact protein formula . The investigation also confirmed that branch chain aminoacids regulate insulin secretion and that the length of chain is insulinotropic for fatty acids , while the degree of unsaturation is not able to reduce insulin secretion in the newborn baby . This could be caused by stimulation of insulin output activated by the C20:5 n 3 ; the effects of fatty acids are probably related more to the variable composition of cell membrane than to the fatty acids circulating levels At the age of 5 years , the prevalence of atopic manifestations was analysed in 58 formula-fed “ at risk ” infants because of a history of atopic disease in at least two first degree relatives . Infants were r and omly assigned to receive either a partial whey-hydrolysate formula ( n : 28 ) or a regular cow 's milk formula ( n : 30 ) during the first 6 months of life ; thereafter , feeding was unrestricted . Only non-breastfed infants were included . The groups did not differ in risk factors or in known confounding factors possibly influencing the incidence of manifestations suggestive of atopic disease . At 6 months , the prevalence of cow 's milk protein ( CMP ) sensitivity was significantly decreased in the hydrolysate group ( 7 % versus 43%;P : 0.002 ) . At the age of 12 ( 21 % versus 53%;P : 0.029 ) , 36 ( 25 % versus 57%;P : 0.018 ) and 60 months ( 29 % versus 60%;P : 0.016 ) there was still a significant difference in the number of atopic manifestations , if calculated cumulatively . There was no difference between the groups if only the new cases after the age of 6 months were considered . Eczema was less frequent in the whey-hydrolysate group , but only during the 1st year of life , suggesting a decreased prevalence of CMP sensitivity . During the first 6 months , diarrhoea of non-infectious origin occurred in 8/30 infants ( 27 % ) of the adapted formula group , and in no infant in the hydrolysate group . “ Colic as single manifestation ” was considered of “ allergic ” origin in 1/28 infants in the hydrolysate group , and in 4/30 infants in the adapted formula group . If gastro-intestinal symptoms such as “ diarrhoea and colic as single manifestation ” are not considered , the number of infants with CMP sensitivity remains only significant for the first 6 months ( P : 0.004 ) . At 12 , 36 and 60 months , differences are not significant ( 0.106 , 0.116 and 0.07 , respectively ) . The results of this study support the hypothesis that allergy prevention is antigen specific . Conclusion If mother 's milk is not available and other studies confirm these results , there might be an indication for partial hydrolysates in infants with a family history of atopy , since these formulae reduce the incidence of CMP sensitivity Children ’s weight/growth development is age-specific and may be influenced by breastfeeding . We therefore assessed velocities of weight , length , body-mass-index and overweight/obesity development from birth up to age 6 years overall and in relation to breastfeeding . The method of this study is based on pooled data of the birth-cohorts GINI-plus and LISA-plus and follows 7,643 healthy full-term neonates in four study -centers in Germany . Up to nine anthropometric measurements are available . Overweight/obesity is percentile-defined according to WHO-Child-Growth-St and ards .  Fully-breastfed  is defined as  breastfed for at least 4 months . Piecewise-linear-r and om-coefficient-models were applied to assess growth trajectories and velocities between 0–3 , 3–6 , 6–12 , 12–24 and beyond 24th months . Velocities for weight- , length- and BMI -development are highest in the first 3 months after birth and diminish , with differing pace , in the periods that follow . For overweight and obesity , peak-velocities are estimated in periods 6–12 and 3–6 months . The difference in the velocity of weight gain for breastfed vs. other children is −18 g/month in the first 3 month , −93 g/month between month 3 and 6 , −14 g/month between month 6 and 12 and −3 g/month beyond the 24th month . Velocities in length are not different between breastfed and non-breastfed children . Over time , a slightly lower risk ( difference < 2 % ) of being overweight was estimated for breastfed children , after adjustment for study -center , socio-economic-status and maternal smoking in pregnancy . Infants fully-breastfed gain less weight , but grow equally in length in the first 12 months of life versus mixed or formula-fed children . The protective effect of breastfeeding on becoming overweight is related to its weight-velocity-modifying-effect in early infancy Oral administration of foreign proteins , e.g. cow 's milk ( CM ) proteins , stimulates the immune system and induces humoral and cellular immune response against these antigens in infants . Up-regulation of adhesion molecules is known to be associated with activation of the immune system . The purpose of the study was to examine whether orally administered CM proteins induce elevation in soluble adhesion molecules , i.e. intercellular adhesion molecule-1 ( ICAM-1 ) and L-selectin , in infants . In a double-blind trial , 10 infants received CM-based formula and 10 infants casein hydrolysate formula until the age of 9 mo . The infants of mothers with insulin-dependent diabetes mellitus ( IDDM ) were recruited into a pilot study of a trial for primary prevention of IDDM by elimination of CM proteins from the diet during early infancy . A cord blood sample and peripheral blood sample s were taken at the ages of 3 , 6 , 9 , and 12 mo of age . The levels of soluble ICAM-1 and L-selectin were measured by ELISA . The levels of soluble ICAM-1 were higher at the ages of 3 , 6 , 9 , and 12 mo in infants who received CM-based formula than in infants who received hydrolyzed formula ( p = 0.05 ) . Instead , no difference was found in the the levels of soluble L-selectin . The levels of soluble ICAM-1 and L-selectin were higher in all infants when compared with the levels reported in adults or to the levels seen in cord blood . Orally fed CM proteins induce an elevation in soluble ICAM-1 in infants . This may reflect the generation of an immune response against these proteins , because ICAM-1 has an important costimulatory role in lymphocyte activation BACKGROUND A recent cohort study suggested that intake of soy milk or soy formula was associated with peanut allergy . If this finding is confirmed , it suggests an avenue for modification of diet as a peanut allergy prevention strategy . OBJECTIVE To investigate the relationship between soy consumption and peanut sensitization in a prospect i ve cohort study of children . METHODS A total of 620 babies with a family history of allergic disease were recruited . Dietary information was obtained from telephone interviews every 4 weeks from birth until 15 months and then again at 18 months and 2 years . Skin prick tests to peanut , milk , and egg were performed at 6 , 12 , and 24 months . A wheal size > or = 3 mm was considered positive for sensitization . RESULTS Children whose parents elected to introduce soy formula or soy milk into their children 's diet were more likely to be sensitized to peanuts at 2 years ( odds ratio , 2.02 ; 95 % CI , 1.04 - 3.92 ; P = .039 ) . However , this relationship was explained by feeding of soy to children who had siblings with milk allergy or were themselves sensitized to milk . After adjusting for these factors , there was no evidence of an association between soy consumption and peanut sensitization ( odds ratio , 1.34 ; 95 % CI , 0.64 - 2.79 ; P = .434 ) . CONCLUSION The association between soy consumption and peanut sensitization is not causal but merely a result of preferential use of soy milk in infants with a personal or family history of cow 's milk allergy . Future studies should take the confounding effects related to dietary modifications by parents into account when investigating the association between diet and childhood allergic diseases OBJECTIVE To determine the effectiveness of whey hydrolysate formula in the treatment of infantile colic in a primary care setting in the Netherl and s. STUDY DESIGN R and omized , double-blind , parallel trial with a 1-week qualification period and a 1-week intervention period . Participants . Forty-three healthy , thriving , formula-fed infants , < 6 months old , crying > 3 hours per day on at least 3 days per week . Infants were r and omized to whey hydrolysate formula ( n = 23 ) or st and ard formula ( n = 20 ) . MAIN OUTCOME MEASURE Difference in duration of crying ( minutes per day ) between qualification week and intervention week . RESULTS Analysis according to the intention to treat principle showed a difference in the decrease of crying duration of 63 minutes per day [ 95 % confidence interval : 1 - 127 minutes per day ] in favor of the whey hydrolysate formula .  Five infants did not complete the trial . The scope of the study was not sufficient to expect significant differences in the subgroup analyses . CONCLUSIONS An extensively hydrolyzed whey formula is effective in reducing the duration of crying in a primary care setting BACKGROUND Development of humoral and cellular immune responses to orally administered antigens in human beings is poorly understood , although antigen administration has been suggested as a treatment for hypersensitivity disorders and autoimmune diseases . OBJECTIVE The purpose of the study was to investigate the development of systemic immune response in infants fed with formula containing whole cow 's milk proteins or hydrolyzed formula containing casein peptides .  METHODS In a double-blind trial , 10 infants received cow 's milk-based formula , and 10 infants received a casein hydrolysate formula until the age of 9 months . Blood sample s were taken at the ages of 6 , 9 , and 12 months . Cellular responses were assessed by proliferation assay of peripheral blood mononuclear cells to cow 's milk proteins ( beta-lactoglobulin , bovine serum albumin , and alpha-casein ) . Humoral responses to the same proteins were measured by ELISA for IgG antibodies . RESULTS Feeding infants with cow 's milk-based formula induced systemic humoral and cellular responses to cow 's milk proteins . T-cell response later declined , supporting the concept of oral tolerization . Exposure to cow 's milk proteins after the age of 9 months result ed in depressed cellular and humoral responsiveness to these proteins . CONCLUSION Our results support the view that induction of oral tolerance in human beings is an age-dependent phenomenon Treating the infant colic syndrome by counseling the  parents  concerning more effective responses to the infant crying is compared to the elimination of soy or cow 's milk protein from the infant 's diet in a r and omized clinical trial . Because symptoms of vomiting and diarrhea are not part of the infant colic syndrome , infants with these gastrointestinal symptoms were excluded from the study .  Dietary changes were accomplished by either feeding the infants a hydrolyzed casein formula or by requiring mothers to eliminate milk from their diets . In phase 1 of the study , the group receiving counseling  ( n = 10 ) had a decrease in crying from 3.21 + /- 1.10 h/d to 1.08 + /- 0.70 h/d ( P = .001 ) . The crying in the group that received dietary changes ( n = 10 ) decreased from 3.19 + /- 0.69 h/d to 2.03 + /- 1.07 h/d ( P = .01 ) , a level still greater than twice normal . The decrease in those receiving counseling was faster and greater than that of those given dietary changes ( P less than .02 ) . In the second phase of the study , group 2 infants were reexposed to cow 's milk or soy protein and the parents received counseling . In this phase , counseling again decreased crying significantly from 2.09 + /- 1.07 h/d to 1.19 + /- 0.60 h/d ( P = .05 ) . No infant in the study who improved with changes in his or her diet had a significant increase in crying , with reexposure to soy or cow 's milk protein . ( ABSTRACT TRUNCATED AT 250 WORDS Whey hydrolysate formulas are a recent and important innovation in infant feeding . This study compared clinical tolerance and acceptability of a whey hydrolysate formula ( WH ) with those of a whey-predominant formula ( WF ) in 45 infants . Four infants ( 16 % ) who refused to drink WH formula  were eliminated from the study . Mean volume intake was significantly lower for WH ( 120 mL/kg/day ) than for WF ( 147 mL/kg/day ; P < .001 ) . Consequently , mean caloric intake was also significantly different : 80 kcal/kg/day ( WF ) vs 97 kcal/kg/day ( WF ; P < .001 ) . Nevertheless , weight gain from birth to 13 weeks of age was nearly identical in both groups ( 171 % for WH vs 178 % for WF ) . No significant differences were noted in duration of feeding , number of pauses during feeding , number of stools per day , or number of regurgitations per day . The lower rate of caloric intake and the dropout rate of 16 % for WH raise questions about the use of WH formula in normal infants , as has become the case in some Western European regions Summary Background : The best nutritional option for newborn infants is mother 's milk . However , some newborn babies may not be exlusively breastfed during the first months of life , potentially leading to reduced overall health status and the early onset of allergic diseases in some infants . Considerable research has been devoted to the development and assessment of infant nutrition programmes , particularly to the prevention of allergies in high-risk infants . However , equal numbers of infants with and without an elevated familial risk of allergies will eventually develop allergic diseases . Therefore , optimizing nutritional programmes for the early infant population as a whole is an important – but as yet insufficiently studied – area of investigation . Moreover , although safe and effective nutrition must primarily support healthy development of the infant , few studies have evaluated the overall health benefits of nutritional interventions , but have focussed on specific allergic manifestations . In animal models , an allergen-reduced moderate whey hydrolysate formula ( pHF , Nestlé Beba HA ) induces the development of oral tolerance towards cow 's milk proteins , without inducing sensitization . In infants with a high risk for allergies , pHF formulae reduce the early onset of allergic disease during the first 5 years of life by approximately 50 % compared with a dietary regimen of unaltered proteins . At present , very little is known about the overall health benefits of such a dietary intervention on the unselected infant population as a whole . Aim of the study : The aim of our prospect i ve , controlled study was to investigate the overall health benefits of an allergen-reduced nutritional programme in a newborn infant population unselected for atopic risk factors . The population in our study was a comparable as possible to the general population of healthy newborn infants . Our study included exclusive breastfeeding , use of a moderate whey hydrolysate formula ( pHF , Nestlé Beba HA ) if infant formula was needed , and delayed introduction of low-allergenic weaning foods . The study included assessment s of compliance with the dietary programme , and evaluated nutritional habits , growth , and overall health status for 24 months . The health evaluation included allergic manifestations but die – by purpose – not define or evaluate them specifically . Part I of this paper gives results for nutritional habits during the first 6 months of life , Part II gives results for growth and general health status for the same time period , Part III will present feeding habits during the second half of the first year of life , and Part IV will present results to 24 months of age . The complete study report is published as a supplement to this journal . Methods : Nuritional assignment was to demographically comparable intervention ( Z ) or control ( FF ) cohorts according to the infant 's place of birth . In the intervention cohort ( Z , n=564 ) , the recommended dietary regimen was breastfeeding and /or the pHF formula , with no weaning food before 4 months of age . In the control cohort ( FF , n=566 ) , there was no intervention . Longitudinal diet groups , defined for 4 months , excluding dropouts and noncompliants , were exclusive breastfeeding ( eBF , Z , n=201 , FF , n=162 ) , partial breastfeeding ( pBF , Z , n=222 , FF , n=311 ) , or non-breastfeeding ( nBF , Z , n=42 , FF , n=62 ) . Imbalances between groups and cohorts in confounding factors that could influence health-related symptoms were integrated as covariates into the main analyses using logistic regression . Nutritional surveillance was carried out using continuous prospect i ve monitoring . Results : The overall rate of breastfeeding , irrespective of partial or excluive breastfeeding or the additional use of weaning foods , was similar in both cohorts at 4 and 6 months . However , from ages 3 to 6 month , significantly more Z than FF infants were excluively breastfed ( p<0.05 ) , and weaning foods were introduced at a significantly later age in Z than FF ( 22 versus 18 weeks ; p<0.0001 ) . Infants in the Z cohort received fewer different kinds of weaning foods compared with FF ( 2 versus 10 ; p<0.0001 ) . Six-month rates of dropout were very low in both groups ( Z=4.3 % , FF=1.8 % ) and compliance with the programme was excellent over the strict intervention period of 4 months ( Z=86.9 % ) until the sixth month . Conclusions : A dietary recommendation that promotes breastfeeding , includes a moderate whey hydrolysate formula ( Nestlé Beba HA ) , and delays the introduction of highly allergenic weaning foods ( an allergen-reduced dietary regimen ) significantly increases breastfeeding and delays weaning in a normal infant population without any compliance problem to the moderate hydroysate formula that is quite often seen in the eHF . The regimen was followed closely , with a high degree of compliance and a low dropout rate compared with previous allergy-prevention studies . Compliance with the dietary regimen was excellent over the 4 months of intervention and throughout the following 2 months Clinical experience ( " the dangerous bottle " ) and experimental evidence indicate that the early life of an infant is particularly important for the development of the immune responses to food antigens . However , the clinical and immunologic consequences of a brief exposure to , or avoidance of , food antigens during the neonatal period in human infants are poorly understood and documented . We present the preliminary results of a prospect i ve controlled study of 256 normal breast-fed infants r and omly assigned to receive ( blind ) either an adapted formula ( Nidina ) or a partially hydrolyzed formula ( Nidal HA ) as a supplement to breast-feeding for a few days when necessary , and to be examined at days 5 , 90 , 150 , and 365 . The results indicated that ( 1 ) the prevalence of clinical symptoms and of total and specific IgE responses was not statistically different in the two groups of infants and ( 2 ) infants fed a hydrolyzed formula had median titers of specific IgG lower than those fed an adapted formula ; the difference was significant for alpha-lactalbumin at day 90 ( p < 0.005 ) and for alpha-lactalbumin ( p < 0.05 ) , casein ( p < 0.05 ) , and hydrolyzed formula ( p < 0.01 ) at day 150 . Humoral immune responses of breast-fed infants to food antigens thus appear to be modulated by early , short-term exposure to them Background : Hydrolyzed milk formulas are recommended to feed infants at high risk of atopy if breast‐feeding is not possible . We studied the specific cellular and humoral immune response to cow 's milk proteins and occurrence of atopic dermatitis under different feeding regimens : two hydrolyzed infant milk formulas ( partially [ pHF ] and extensively hydrolyzed [ eHF ] ) and under exclusive breast‐feeding ( BF ) BACKGROUND Plasma amino acid concentrations were measured in preterm infants who were fed either a new hydrolyzed cow 's milk protein formula or a st and ard preterm infant formula .  It was hypothesized that feeding with the hydrolysate results in prepr and ial amino acid concentrations that are significantly different from the concentrations found when feeding with the st and ard formula . METHODS Fifteen preterm infants , median gestational age , 29 weeks ( range , 24 - 32 weeks ) ; birth weight , 1241 g ( range , 660 - 1900 g ) ; and postnatal age , 18 days ( range , 7 - 54 days ) receiving full enteral feedings ( > 150 ml/kg x day ) , were enrolled . The intervention was r and omized allocation to the formula with hydrolyzed or natural cow 's milk protein ( the whey/casein ratio was 60:40 in both formulas ) . In a crossover design , each formula was fed for 5 days , and plasma amino acids were analyzed on day 4 or 5 of each 5-day period . RESULTS In spite of the 12 % higher amino acid intake with hydrolysate formula , the median individual plasma amino acid concentrations were virtually identical with both formulas , and they were within the 10th and the 90th percentile of the reference of levels in the umbilical cord artery after elective cesarean delivery or of breast-fed newborn infants . The median concentrations of lysine and aspartic acid were higher with hydrolyzed formula feeding ( p<0.05 ; two-tailed Mann-Whitney test ) . With both formulas , single amino acid concentrations were out of the reference values . CONCLUSION Virtually identical plasma amino acid concentration patterns were measured with the new hydrolyzed preterm infant formula and the st and ard preterm infant formula , but longitudinal studies are required before the studied protein hydrolysate can be recommended for preterm feeding in general BACKGROUND The role of exposure to dietary antigens through maternal milk is intriguing , because it may result either in immunization or in tolerance . Exposure to cow 's milk proteins results in antibody formation against bovine insulin in infants at risk for type 1 diabetes . OBJECTIVE To study the appearance of IgG antibodies to bovine and human insulin in infants with an atopic family history whose mothers followed a cow 's milk-free diet during the first 3 months of lactation . METHODS In a prospect i ve cohort study on prevention of food allergies , 123 infants were exclusively breast-fed or received supplementation with a hydrolyzed casein-based formula ( Nutramigen ) until the age of 6 months . The mothers either avoided cow 's milk during the first 3 months of lactation ( diet group ) or had an unrestricted diet ( nondiet group ) . The levels of IgG antibodies to bovine and human insulin were determined by enzyme immunoassay at 3 , 6 , 12 , and 18 months and at 4 years . In addition , cord blood was obtained at birth and a maternal sample at delivery . RESULTS At 3 months , IgG antibodies to bovine insulin were low in both dietary groups ( median levels 0.150 and 0 . 114 optical density units in the diet and nondiet groups ) . After exposure to dietary insulin , IgG antibodies to bovine insulin increased in both groups , reaching a peak at 12 months in the nondiet group and at 18 months in the diet group . At 18 months , IgG antibodies to bovine insulin were lower in infants in the nondiet group than in infants in the diet group ( 0.287 vs 0.500 , P<.0001 ) . At 4 years , the antibodies no longer differed between the groups . CONCLUSION The exposure to cow 's milk proteins through breast milk during the first 3 months of life result ed in decreased levels of antibodies to dietary bovine insulin at 18 months of age , suggesting a role for breast milk antigens in early tolerance induction Formulas containing proteins with reduced potential to sensitize might be effective in reducing the risk of atopic disease , but such products should be nutritionally adequate . We design ed a r and omized , double-blind study to evaluate nutritional adequacy and sensitization potential of a formula containing partially hydrolyzed whey-predominant milk proteins .  Subjects were term infants enrolled at birth . Infants in group A were fed human milk , and group B received the partially hydrolyzed formula ; group C , fed a formula containing intact whey-predominant milk proteins , served as control subjects . We recorded anthropometric measurements and symptoms of formula intolerance at monthly intervals for 4 months in 205 infants .  Milk IgE and IgG antibodies were measured until 8 months of age in 63 infants .  Daily weight gain was not significantly different among the groups . Gastrointestinal symptoms attributed to feeding intolerance were also comparable . Increases in serum IgG antibodies were significantly greater in group C throughout the study . There were no significant differences in IgE antibodies . Thus a formula containing partially hydrolyzed whey-predominant milk protein promoted adequate growth and induced a lesser priming effect for IgG antibody response than did an intact whey-predominant formula BACKGROUND The long-term effect of nutritional intervention with hydrolysate infant formulas on  allergic manifestations in high-risk children is uncertain . OBJECTIVE We sought to investigate the effect of hydrolysate infant formulas on allergic phenotypes in children with family history of allergies at school age . METHODS We analyzed data from participants of the prospect i ve German Infant Nutritional Intervention study after 10 years of follow-up . At birth , children were r and omly assigned to receive , for the first 4 months , one of 4 blinded formulas as breast milk substitute , if necessary : partially hydrolyzed whey formula ( pHF-W ) , extensively hydrolyzed whey formula ( eHF-W ) , extensively hydrolyzed casein formula ( eHF-C ) , or st and ard cow 's milk formula . Outcomes were parent-reported , physician-diagnosed allergic diseases . Log-binomial regression models were used for statistical analysis . RESULTS The relative risk for the cumulative incidence of any allergic disease in the intention-to-treat analysis ( n = 2252 ) was 0.87 ( 95 % CI , 0.77 - 0.99 ) for pHF-W , 0.94 ( 95 % CI , 0.83 - 1.07 ) for eHF-W , and 0.83 ( 95 % CI , 0.72 - 0.95 ) for eHF-C compared with st and ard cow 's milk formula . The corresponding figures for atopic eczema/dermatits ( AD ) were 0.82 ( 95 % CI , 0.68 - 1.00 ) , 0.91 ( 95 % CI , 0.76 - 1.10 ) , and 0.72 ( 95 % CI , 0.58 - 0.88 ) , respectively . In the per- protocol analysis ( n = 988 ) effects were stronger . The period prevalence of AD at 7 to 10 years was significantly reduced with eHF-C in this analysis , but there was no preventive effect on asthma or allergic rhinitis . CONCLUSION The significant preventive effect on the cumulative incidence of allergic diseases , particularly AD , with pHF-W and eHF-C persisted until 10 years without rebound , whereas eHF-W showed no significant risk reduction . There is insufficient evidence of ongoing preventive activity at 7 to 10 years of age A group of 129 infants were r and omly assigned at birth to one of three feeding regimens : human milk ( HM ) , cow 's milk formula ( CMF ) or a casein hydrolysate formula ( CHF ) during the first 3 days of life . Blood sample s were taken on at 4 days and at 2 , 4 , 8 , 12 and 24 months of age . Macromolecular absorption was analysed by measuring the serum concentration of human α‐lactalbumin ( S‐α‐LA ) with a competitive radioimmunoassay ( RIA ) . Total serum IgE was measured by RIA . A family history of allergy correlated to the proportion of infants with allergic symptoms both at 24 and 36 months of age ( p= 0.03 and p= 0.04 respectively ) . In none of the three groups did correlation exist between the duration of breastfeeding and serum α‐LA , serum IgE , family history of allergy , frequency of allergic symptoms and proportion of infants with infections BACKGROUND The short- and long-term effects of feeding with hydrolyzed formulas on growth are uncertain . OBJECTIVE Our aim was to investigate the potential differences in body mass index ( BMI ) over the first 6 y of life between infants fed with partially hydrolyzed whey ( pHF-W ) , extensively hydrolyzed whey ( eHF-W ) , extensively hydrolyzed casein ( eHF-C ) , or cow-milk formula ( CMF ) and infants exclusively breastfed for the first 16 wk of life . DESIGN We established a prospect i ve , r and omized , double-blind trial of full-term neonates with atopic heredity in the German birth cohort followed by the German Infant Nutritional Intervention Study through the first 6 y of life . Intention-to-treat and per- protocol analyses of absolute and World Health Organization-st and ardized BMI trajectories for 1840 infants ( pHF-W : n = 253 ; eHF-W : n = 265 ; eHF-C : n = 250 , CMF : n = 276 ; breastfed : n = 796 ) were performed . RESULTS No significant differences in absolute or World Health Organization-st and ardized BMI trajectories were found among the pHF-W , eHF-W , CMF , and breastfed groups during the 6-y follow-up . However , in the eHF-C group , both intention-to-treat and per- protocol analyses showed a significantly slower sex-adjusted BMI gain through the 8th to 48th week of life ( -0.1 to -0.2 lower BMI z score ) but not beyond . Analyses of weight and length revealed that this difference is due to a slightly diminished weight gain in the first year of life because growth in length did not differ among study groups for the entire follow-up . CONCLUSIONS To our knowledge , this is the first r and omized trial investigating both short- and long-term effects of partially and extensively hydrolyzed formula ( pHF-W , eHF-W , eHF-C ) , CMF , and breastfeeding on growth in one trial . Feeding with eHF-C led to a transient lower weight gain in the first year of life . No long-term consequences of different formulas on BMI were observed In an attempt to prevent or reduce the manifestations of atopic disease , a group of infants considered to be genetically at high risk of atopy was entered in a prenatally r and omized , controlled study . A prophylactic group ( n= 58 ) was either breast‐fed with their mothers excluding foods regarded as highly antigenic from their diets , or given an extensively hydrolysed formula . In addition , strenuous efforts were made to reduce exposure to the house‐dust mite by application of acaricide to the bedroom and living room carpets and upholstered furniture . A control group ( n= 62 )  was fed conventionally by breast or on formula , and no specific environmental measures were taken . The results ( previously reported ) after 1 year showed significantly less total allergy , asthma , and eczema in the prophylactic group . Similar results were obtained at 2 years although the reduction in asthma no longer achieved statistical significance . However , there was significantly less sensitization , as shown by a battery of skin prick tests ( SPTs ) , to both dietary allergens and aeroallergens in the prophylactic group . A11 the children have now been review ed at the age of 4 years , and SPTs to a wide range of dietary allergens and aeroallergens have been performed . The control group continues to show more total allergy ( odds ratio [ OR ] 2.73 , 95 % confidence interval [ CI ] 1.21–6.13 , P<0.02 ) , definite allergy ( allergic symptoms plus positive SPT ) ( OR 5.6 , CI 1.8–17.9 , P<0.005 ) , and eczema ( OR 3.4 , CI 1.2–10.1 , P<0.05 ) . More control children have positive SPTs ( OR 3.7 , CI 1.3–10.0 , P<0.02 ) . A dual approach to the prevention of allergic disease , avoiding as far as possible sensitization to food and aeroallergens , significantly reduces the risk of atopic disease . This should be reserved for infants considered at very high risk of atopy , and close medical and dietetic supervision must be available BACKGROUND The effect of diet change in 38 bottle-fed and 77 breast-fed " colicky " infants , referred from community-based pediatric facilities was studied over a 1-week period in a double-blind ( within each feeding mode ) , r and omized , placebo-controlled trial . METHODS Bottle-fed infants were assigned to either casein hydrolysate or cow 's milk formula .  All mothers of breast-fed infants were started on an artificial color-free , preservative-free , additive-free diet and also r and omized to an active low allergen diet ( milk- , egg- , wheat- , nut-free ) or a control diet . RESULTS The response to diet was assessed on day 1 and day 8 with the use of a previously vali date d infant distress chart on which parents recorded distress levels . If successful outcome was defined as a reduction in distress of 25 % or more , after adjusting for age and feeding mode , infants on active diet had a significantly higher rate of improvement than those on the control diet ( odds ratio , 2.32 ; 95 % confidence interval , 1.07 - 5.0 ; p = 0.03 ) . Analysis of the day 8 to day 1 distress ratio , again adjusted for age and feeding mode , showed that infants on the active diet had distress reduced by 39 % ( 95 % confidence interval , 26 - 50 ) compared with 16 % ( 95 % confidence interval , 0 - 30 ) for those on the control diet ( p = 0.012 ) . CONCLUSION The results suggest a period of dietary modification with a low allergen diet and appropriate nutritional support should be considered in healthy infants with colic The effect of maternal and infant avoidance of allergenic foods on food allergy was examined in a prenatally r and omized , controlled trial of infants of atopic parents . The diet of the prophylactic-treated group ( N = 103 ) included ( 1 ) maternal avoidance of cow 's milk , egg , and peanut during the third trimester of pregnancy and lactation and ( 2 ) infant use of casein hydrolysate ( Nutramigen ) for supplementation or weaning , and avoidance of solid foods for 6 months ; cow 's milk , corn , soy , citrus , and wheat , for 12 months ; and egg , peanut , and fish , for 24 months . In the control group ( N = 185 ) , mothers had unrestricted diets , and infants followed American Academy of Pediatrics feeding guidelines . The cumulative prevalence of atopy was lower at 12 months in the prophylactic-treated ( 16.2 % ) compared to the control ( 27.1 % ) group ( p = 0.039 ) , result ing from reduced food-associated atopic dermatitis , urticaria and /or gastrointestinal disease by 12 months ( 5.1 % versus 16.4 % ; p = 0.007 ) , and any positive food skin test by 24 months ( 16.5 % versus 29.4 % ; p = 0.019 ) , caused primarily by fewer positive milk skin tests ( 1 % versus 12.4 % ; p = 0.001 ) . The prevalences of allergic rhinitis , asthma , and inhalant skin tests were unaffected . Serum IgE levels in the prophylactic-treated group were marginally lower only at 4 months . Thus , reduced exposure of infants to allergenic foods appeared to reduce food sensitization and allergy primarily during the first year of life BACKGROUND Early exposure to dust mite allergens may be critical for primary sensitization . Reducing exposure may offer a realistic chance for primary prevention of sensitization and asthma , but it is essential to implement measures that can achieve and maintain the low-allergen environment . OBJECTIVE Our purpose was to assess the effectiveness of mite allergen avoidance measures in achieving and maintaining a low-allergen environment during pregnancy and in the first year of life . METHODS The Manchester Asthma and Allergy Study is a prospect i ve , prenatally r and omized study that follows the development of asthma and atopy in a cohort of infants at high risk ( both parents atopic ) who are r and omly allocated to full mite allergen avoidance or to a normal regimen . Avoidance measures comprise ( 1 ) mite-proof covers ( mattress , pillow , and quilt ) for parental bed , ( 2 ) high-filtration vacuum cleaner , ( 3 ) vinyl flooring in infant 's bedroom , ( 4 ) new crib and portable crib mattresses encased in mite-proof material , ( 5 ) benzyl benzoate ( Acarosan ) applied on carpets and soft furniture , ( 6 ) bed linens washed in hot water weekly , and ( 7 ) washable soft toys . Dust sample s from the parental bed , bedroom floor , living room floor , infant 's mattress , and nursery floor were collected between the 10th and 14th weeks of pregnancy , immediately after birth , and then at age 6 months and 1 year , and Der p 1 levels were determined by mAb-based ELISA . RESULTS Recovered Der p 1 from maternal mattress was reduced by 97 . 25 % ( 95 % confidence interval [ CI ] 95.25%-98.41 % ) during the second and third trimesters of pregnancy , with the effect persisting for 6 months ( 98 % reduction , 95 % CI 97.25%-99.1 % ) and 12 months ( 97.6 % reduction , 95 % CI 95.7%-98.6 % ) after the birth ( active vs control , P < .000001 ) . Total Der p 1 from bedroom floor in the active group was reduced by 53.7 % ( 95 % CI 25.7%-71.2 % ) in sample s collected within 4 weeks of the child 's birth , with the percentage reduction being 62 . 8 % ( 95 % CI 39.3%-77.2 % ) at 6 months and 26.5 % ( 95 % CI -24 % to 57.1 % ) at 1 year ( active compared vs control , P < .007 ) . Der p 1 levels in crib mattress and nursery floor in the active group were extremely low ( crib mattresses geometric mean [ 95 % CI ] 2.3 ng [ 1.6 - 3.4 ] at birth , 6.8 ng [ 4.5 - 10 ] at age 6 months , and 15.6 ng [ 9.8 - 24.8 ] at age 1 year [ active vs control , P = .001 ] ; nursery 1 ng [ 0.9 - 1.1 ] at birth , 1.7 ng [ 1.2 - 2.5 ] at age 6 months , and 2 ng [ 1.3 - 3.5 ] at age 1 year [ active vs control , P < .00001 ] ) . The total amount of allergen recovered at age 1 year was 29-fold ( 95 % CI 15.1- to 56.7-fold ) higher in the control group than in the active group . CONCLUSIONS The avoidance measures used in this study achieved and maintained a low mite allergen environment during pregnancy and in the first year of life in homes of infants at risk of atopy STUDY OBJECTIVES We sought to identify early life factors ( ie , first 4 years ) associated with  wheeze , asthma , and bronchial hyperresponsiveness ( BHR ) at age 10 years , comparing their relative influence for these conditions . METHODS Children were seen at birth , and at 1 , 2 , 4 , and 10 years of age in a whole- population birth cohort study ( 1,456 subjects ) . Information was collected prospect ively on genetic and environmental risk factors .  Skin-prick testing  was performed at 4 years of age . Current wheeze ( in the last 12 months ) and currently diagnosed asthma ( CDA ) [ ie , current wheeze and ever-diagnosed asthmatic subject ] were recorded at 10 years of age when BHR was measured at bronchial challenge . Independent significant risk factors for these outcomes were identified by logistic regression . RESULTS Independent significance for current wheeze occurred with maternal asthma ( odds ratio [ OR ] , 2.08 ; 95 % confidence interval [ CI ] , 1.27 to 3.41 ) and paternal asthma ( OR , 2.12 ; 95 % CI 1.29 to 3.51 ) , recurrent chest infections at 2 years ( OR , 3.98 ; 95 % CI , 2.36 to 6.70 ) , atopy at 4 years of age ( OR , 3.69 ; 95 % CI , 2.36 to 5.76 ) , eczema at 4 years of age ( OR , 2.15 ; 95 % CI , 1.24 to 3.73 ) , and parental smoking at 4 years of age ( OR , 2.18 ; 95 % CI , 1.25 to 3.81 ) . For CDA , significant factors were maternal asthma ( OR , 2.26 ; 95 % CI , 1.24 to 3.73 ) , paternal asthma ( OR , 2.30 ; 95 % CI , 1.17 to 4.52 ) , and sibling asthma ( OR , 2.00 ; 95 % CI , 1.16 to 3.43 ) , recurrent chest infections at 1 year of age ( OR , 2.67 ; 95 % CI , 1.12 to 6.40 ) and 2 years of age ( OR , 4.11 ; 95 % CI , 2.06 to 8.18 ) , atopy at 4 years of age ( OR , 7.22 ; 95 % CI , 4.13 to 12.62 ) , parental smoking at 1 year of age ( OR , 1.99 ; 95 % CI , 1.15 to 3.45 ) , and male gender ( OR , 1.72 ; 95 % CI , 1.01 to 2.95 ) . For BHR , atopy at 4 years of age ( OR , 5.38 ; 95 % CI , 3.06 to 9.47 ) and high social class at birth ( OR , 2.03 ; 95 % CI , 1.16 to 3.53 ) proved to be significant . CONCLUSIONS Asthmatic heredity , predisposition to early life atopy , plus early passive smoke exposure and recurrent chest infections are important influences for the occurrence of wheeze and asthma at 10 years of age . BHR at 10 years of age has a narrower risk profile , suggesting that factors influencing wheezing symptom expression may differ from those predisposing the patient to BHR BACKGROUND Asthma places huge dem and s on health-care services , and its prevalence is increasing . Reduction of exposure to environmental allergens could offer a realistic chance for primary prevention . Our aim was to ascertain whether or not living in a low-allergen environment reduces the risk of  asthma and atopic diseases in infants . METHODS We assigned infants to four risk groups according to parental atopic status . We enrolled 291 high-risk couples ( both parents atopic , no pets ) into a prospect i ve , prenatally r and omised , cohort study , and allocated them to environmental manipulation , in which measures to reduce prenatal and postnatal allergen exposure were undertaken ( active HRA ) ( n=145 ) or no intervention ( control HRC ) ( n=146 ) . Two further prospect i ve groups were studied : 161 high-risk infants with pets in the home ( HRP group ) and 168 low-risk infants , whose parents were both non-atopic ( LR group ) . The main outcome measures were signs and symptoms of atopic disease at 1 year of age . FINDINGS 103 families dropped out or were lost to follow up . At age 1 year we followed-up 133 HRA , 118 HRC , 140 HRP , and 126 LR infants . Children in the HRA group were less likely to have respiratory symptoms during the first year of life than those in the HRC group . The most pronounced differences were in the relative risks for severe wheeze with shortness of breath ( relative risk 0.44 [ 95 % CI 0.20 - 1.00 ] ) , prescribed medication for the treatment of wheezy attacks ( 0.58 [ 0.36 - 0.95 ] ) , and wheezing after vigorous playing , crying , or exertion ( 0.18 [ 0.04 - 0.79 ] ) . Probability of respiratory symptoms in HRC and HRP infants was similar , whereas it was much lower in the LR than in the HRC group . Cat ownership was significantly associated with sensitisation to cats ( 24.6 [ 3.04 - 199.05 ] ; p=0.003 ) . INTERPRETATION Environmental manipulation reduces some respiratory symptoms in the first year of life in high-risk infants . Further follow up is needed , however , to ascertain whether living in a low-allergen environment reduces allergy and asthma in later life The ingestion of food antigens usually results in the induction of oral tolerance , but the clinical and immunologic consequences of brief exposure to cow 's milk proteins during the neonatal period are not well-documented . The aim of this work was to study immunoglobulin (Ig)E and IgG responses to cow 's milk proteins and ovalbumin after exposure during the first three days of life in infants who were otherwise exclusively breast-fed . A group of 129 infants was r and omly assigned at birth to one of three feeding regimens : human milk ( HM ) , cow 's milk formula ( CMF ) , or a casein hydrolysate formula ( CHF ) , during the first three days of life . They were then all exclusively breast-fed for a varying period of time and followed for two years . Serum IgG and IgE antibodies to cow 's milk proteins and ovalbumin ( OVA ) were analyzed in blood sample s obtained at birth , at 4 days and at 2 , 4 , 8 , 12 and 24 months of age . The levels of IgG antibodies to beta-lactoglobulin ( IgG-BLG ) and bovine serum albumin ( IgG-BSA ) were higher in the CMF and the HM groups than in the CHF group for up to two years . This was particularly obvious for IgG-BLG in infants who started weaning before two months . The levels of IgG antibodies to casein ( IgG-CAS ) were higher in the CMF group , as compared with the CHF group at 8 and 12 months . The levels of IgG antibodies to OVA were similar in all three feeding groups . The levels of IgE antibodies to CAS or OVA were similar in the three feeding groups . Exposure to cow 's milk during the first three days of life stimulated IgG antibody production to cow 's milk proteins and this was still obvious at 2 years of age , while feeding with a casein hydrolysate during the first three days of life was associated with low levels of IgG antibodies to cow 's milk proteins Healthy , term infants received extensively hydrolyzed casein formula ( EHF ; control ) , the same formula supplemented with Lactobacillus rhamnosus GG ( EHF-LGG ) , or partially hydrolyzed whey : casein ( 60:40 ) formula supplemented with LGG ( PHF-LGG ) , in this double-blind , r and omized , controlled , parallel , prospect i ve study . Anthropometric measures and 24-hour dietary and tolerance recalls were obtained at 30 , 60 , 90 , 120 , and 150 days of age . Blood collected in a subset of infants was analyzed for fatty acid profiles in plasma and red blood cells and for markers of allergic sensitization . Adverse events were recorded throughout the study . Growth rates were not statistically different between EHF and PHF-LGG and between EHF and EHF-LGG from day 14 to day 30 , 120 , or 150 . No relevant differences in formula tolerance , adverse events , or allergic and immune markers were demonstrated between groups . The extensively and partially hydrolyzed formulas supplemented with LGG support normal growth in healthy , term infants and are well tolerated and safe Retraction On 28 October 2015 , The BMJ retracted this article , published in 1989 : Ch and ra RK , Puri S , Hamed A. Influence of maternal diet during lactation and use of formula feeds on development of atopic eczema in high risk infants . BMJ 1989;299:228–30 . The BMJ has retracted the article after receiving a copy of an inquiry into the research of R K Ch and ra , which was conducted by the Memorial University of Newfoundl and and completed in August 1995 . The university did not publish the inquiry report at the time . Nor did it notify the editors of journals that had published articles by Ch and ra that were considered in the report . The BMJ obtained a copy of the report when it came into the public domain as a result of Ch and ra taking and losing a legal action against the Canadian Broadcasting Corporation ( CBC ) , which aired television programmes about Ch and ra in 2006 . The inquiring committee experienced great difficulty with its work , but its final conclusion was that “ scientific misconduct has been committed by Dr Ch and ra . ” It looked at three studies and found that : “ absolutely no raw data ( or files ) of any kind were exhibited ” “ the Committee can not identify anyone who did the recruiting , can not identify anyone who did or remembers a significant amount of work ” “ the coauathors had little or very likely nothing to do with the work ” “ it is unbelievable that there are essentially no hospital records to support the study in question ” “ the committee can not accept that the Carnation study was done anywhere near to completeness or with the accuracy reported in the Annals of Allergy and Journal of Clinical Nutrition , For that matter , the same can probably be said for the Mead Johnson work published in the British Medical Journal . ” When asked by The BMJ in 2015 why it had not published the report in 1995 , Memorial University of Newfoundl and said that the report “ was the product of a flawed investigation process and could not be relied upon . ” In the CBC programmes , however , a university spokesman said that the university had not acted on the report because of legal threats from Ch and ra . The university further told The BMJ : “ In the spirit of being helpful , we acknowledge that over the years serious questions have been raised about the 1989 publication , leading to much controversy . If [ The ] BMJ decides to retract the paper on the basis of evidence apart from the findings of the 1995 report , then we would underst and your decision in this regard . ” The BMJ is retracting the paper because of the 1995 report , and because of the convincing evidence given in the CBC television programmes and the court case that the work of R K Ch and ra is not to be trusted . For more information , see The BMJ 's feature article(1 ) and editorial,(2 ) published on 28 October 2015 Purpose To investigate whether specific IgA , IgG , IgG1 and IgG4 responses to cow ’s milk proteins differ between infants with cow ’s milk allergy and infants with cow ’s milk related symptoms ( control subjects ) , and whether early feeding affects these responses as well as specific IgE. Methods A cohort of 6,209 healthy , full-term infants in a double-blind r and omized trial received , as supplementary feeding at maternity hospitals ( mean duration 4 days ) , either cow ’s milk formula , extensively hydrolyzed whey formula or donor breast milk .  Infants who developed cow ’s milk associated symptoms ( n = 223 ) underwent an open oral cow ’s milk challenge ( mean age 7 months ) , which confirmed cow ’s milk allergy in 111 and was negative in 112 . We measured in sera cow ’s milk specific IgE levels with UniCAP ( Phadia , Uppsala , Sweden ) , and β-lactoglobulin and α-casein specific IgA , IgG1 , IgG4 and IgG levels with enzyme-linked immunosorbent assay . Results Infants with IgE-mediated cow ’s milk allergy had lower β-lactoglobulin and α-casein specific IgG1 , IgG4 and IgG levels ( p < 0.05 ) than infants with non-IgE-mediated cow ’s milk allergy or control subjects . Within the group of infants with cow ’s milk allergy , exposure to cow ’s milk during the first few days after birth led to higher β-lactoglobulin and α-casein specific IgG4 levels ( p < 0.005 ) compared to infants fed with either breast milk or extensively hydrolyzed formula . Conclusions Subdued IgG class responses to cow ’s milk proteins characterized IgE-mediated cow ’s milk allergy . In infants who developed cow ’s milk allergy early exposure to cow ’s milk result ed in a heightened specific IgG4 response
target: We found no evidence to support short-term or prolonged feeding with a hydrolysed formula compared with exclusive breast feeding for prevention of allergic disease .
  Very low- quality evidence indicates that short-term use of an EHF compared with a CMF may prevent infant CMA .
  Further trials are recommended before implementation of this practice .We found no evidence to support prolonged feeding with a hydrolysed formula compared with a CMF for prevention of allergic disease in infants unable to be exclusively breast fed
background: BACKGROUND Infant formulas containing hydrolysed proteins have been widely advocated for preventing allergic disease in infants , in place of st and ard cow 's milk formula ( CMF ) .
  However , it is unclear whether the clinical trial evidence supports this .
  OBJECTIVES To compare effects on allergic disease when infants are fed a hydrolysed formula versus CMF or human breast milk .
  If hydrolysed formulas are effective , to determine what type of hydrolysed formula is most effective , including extensively or partially hydrolysed formula ( EHF/PHF ) .
  To determine whether infants at low or high risk of allergic disease , and whether infants receiving early short-term ( first few days after birth ) or prolonged formula feeding benefit from hydrolysed formulas .