title: Hydrolysed protein accelerates the gastrointestinal transport of formula in preterm infants Evaluation of pancreatic function development after hydrolyzed protein-based and soy-based formulas in unweaned 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? Early diet of preterm infants and development of allergic or atopic disease: randomised prospective study. Effect of an allergy prevention programme on incidence of atopic symptoms in infancy Association between breast feeding and asthma in 6 year old children: findings of a prospective birth cohort study Effect of environmental factors on the development of allergic disorders in infancy. Soy allergy in infants and children with IgE-associated cow's milk allergy. Incidence and prognosis of asthma and wheezing illness from early childhood to age 33 in a national British cohort Comparison of an elemental with a hydrolysed whey formula in intolerance to cows' milk. Hypoallergenicity of an extensively hydrolyzed whey formula. Challenge confirmation of late-onset reactions to extensively hydrolyzed formulas in infants with multiple food protein intolerance. Supplementary feeding in maternity hospitals and the risk of cow's milk allergy: A prospective study of 6209 infants. Long-term prevention of allergic diseases by using protein hydrolysate formula in at-risk infants. 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. Incidence and prevalence of asthma among adult Finnish men and women of the Finnish Twin Cohort from 1975 to 1990, and their relation to hay fever and chronic bronchitis. Influence of maternal food antigen avoidance during pregnancy and lactation on incidence of atopic eczema in infants Multicentre trial on feeding low birthweight infants: effects of diet on early growth. Infant feeding, wheezing, and allergy: a prospective study. Breast-feeding and the development of cows' milk protein allergy. Extensively and partially hydrolysed infant formulas for allergy prophylaxis Effect of allergen avoidance in infancy on allergic manifestations at age two years. Effects of a dietary and environmental prevention programme on the incidence of allergic symptoms in high atopic risk infants: three years follow‐up The effect of brief neonatal exposure to cows' milk on atopic symptoms up to age 5 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. Plasma amino acid concentrations in term-born infants fed a whey predominant or a whey hydrolysate 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 Factors influencing the relation of infant feeding to asthma and recurrent wheeze in childhood Intolerance of cow's milk and chronic constipation in children 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. Role of food protein intolerance in infants with persistent distress attributed to reflux esophagitis. 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 Infant feeding and allergy. Allergenicity of goat's milk in children with cow's milk allergy. Dietary modifications versus dicyclomine hydrochloride in the treatment of severe infantile colics 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 Cow's milk protein intolerance in infants under 1 year of age: A prospective epidemiological study WEIGHT-GAIN INHIBITION BY LACTOSE IN AUSTRALIAN ABORIGINAL CHILDREN: A Controlled Trial of Normal and Lactose Hydrolysed Milk The diagnostic significance of IgG cow's milk protein antibodies re-evaluated Evidence of very delayed clinical reactions to cow's milk in cow's milk‐intolerant patients 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. Prevalence of asthma symptoms among adults aged 20-44 years in Canada. Effects of maternal diet during late pregnancy and lactation on the development of atopic diseases in infants up to 18 months of age—in‐vivo results The effect of genetic and environmental factors on the prevalence of allergic disorders at the age of two years Individualized protein fortification of human milk for preterm infants: comparison of ultrafiltrated human milk protein and a bovine whey fortifier. Comparison of Breast, Cow, and Soy Feedings in the Prevention of Onset of Allergic Disease Efficacy and safety of hydrolyzed cow milk and amino acid-derived formulas in infants with cow milk allergy. [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]. The long-term effect of a partial whey hydrolysate formula on the prophylaxis of atopic disease Allergic reactions to raw, pasteurized, and homogenized/pasteurized cow milk: a comparison Hydrolyzed lactalbumin‐based oral rehydration solution for acute diarrhoea in infants Soluble Adhesion Molecules and Oral Antigen Feeding in Infants Prospective, controlled, multi-center study on the effect of an amino-acid-based formula in infants with cow's milk allergy/intolerance and atopic dermatitis. 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. Hypoallergenicity and efficacy of an amino acid-based formula in children with cow's milk and multiple food hypersensitivities. A Comparative Evaluation of Whey Hydrolysate and Whey-Predominant Formulas Safety of casein hydrolysate formula in children with cow milk allergy. 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
   A DOUBLE-BLIND CONTROLLED CROSSOVER TRIAL OF AN ANTIGEN-AVOIDANCE DIET IN ATOPIC ECZEMA The natural history of intolerance to soy and extensively hydrolyzed formula in infants with multiple food protein intolerance. 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. Allergy development and macromolecular absorption in infants with different feeding regimens during the first three days of life. A three‐year prospective follow‐up Food and drug reactions, wheezing, and eczema in preterm infants. 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. Latent anaphylactic sensitisation of infants of low birth weight to cows' milk proteins. Effect of environmental manipulation in pregnancy and early life on respiratory symptoms and atopy during first year of life: a randomised trial Development of atopic disease after early administration of cow milk formula Environmental factors and symptoms in infants at high risk of allergy. Allergy to soy formula and to extensively hydrolyzed whey formula in infants with cow's milk allergy: a prospective, randomized study with a follow-up to the age of 2 years. Are all wheezing disorders in very young (preschool) children increasing in prevalence? 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. Influence of maternal diet during lactation and use of formula feeds on development of atopic eczema in high risk infants.
abstract: 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 ) AIMS Different protein sources could determine differences in the maturation of the exocrine pancreas in humans during the first months after birth ; however , no studies have been carried out in man to evaluate the effect of a hydrolyzed protein diet on exopancreatic function . Our aim was therefore to determine the effect of two different milk formulas on pancreatic secretion in patients with cow 's milk protein allergy ( CMPA ) . METHODS We selected 12 infants ( median age , 3.0 months ) , fed for 6 weeks with a hydrolyzed casein-based formula , and 14 infants ( median age , 3.0 months ) who received a soy-protein based formula over the same period . As controls , two groups of age-matched infants with no gastrointestinal disease and receiving a free diet  were studied . In the patients with CMPA a secretin-cerulein test was performed at the commencement of the diet and after 6 weeks ; in the controls the same test was performed only once . Enzyme concentrations and outputs of trypsin , chymotrypsin , lipase , and phospholipase were assayed . RESULTS No significant difference was observed between the two groups of patients with CMPA for any of the enzymes studied , either at base line or after 6 weeks of diet . No difference was recorded between CMPA patients and age-matched controls on a free diet either . In both CMPA groups there was a significant increase over basal values in trypsin , chymotrypsin , and lipase concentrations after 6 weeks . Furthermore , there was a significant positive correlation between the age of the patients and enzyme concentrations . Mean daily weight gain was 27.4 + /- 3.9 g with hydrolyzed casein and 27.2 + /- 3.5 g in soyfed patients . CONCLUSIONS It is suggested that the diets with different protein content used in subjects with CMPA did not determine any difference in the stimulation of proteolytic and lipolytic pancreatic enzymes 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 OBJECTIVE --To study the effect of early diet on the development of allergic reactions in infants born preterm . DESIGN --Two r and omised prospect i ve trails . In trail A infants were r and omly allocated banked donor milk or preterm formula as their sole diet or ( separately r and omised ) as a supplement to their mother 's expressed breast milk . In trial B infants were allocated term or preterm formula . A blind follow up examination was done 18 months after the expected date of birth . SETTING --Neonatal units of hospitals in Cambridge , Ipswich , King 's Lynn , Norwich , and Sheffield . Outpatient follow up . PARTICIPANTS --777 Infants with a birth weight less than 1850 g born during 1982 to 1984 . MAIN OUTCOME MEASURES --Development of eczema , allergic reactions to food or drugs , and asthma or wheezing by nine and 18 months after term . Whenever possible the observations were confirmed by rechallenge or clinical examination . RESULTS --At 18 months after term there was no difference in the incidence of allergic reactions between dietary groups in either trial . In the subgroup of infants with a family history of atopy , however , those in trial A who received preterm formula rather than human milk had a significantly greater risk of developing one or more allergic reactions ( notably eczema ) by 18 months ( odds ratio 3.6 ; 95 % confidence interval 1.4 to 9.1 ) . CONCLUSIONS --Feeding neonates on formulas based on cows ' milk , including those with a high protein content , did not increase the overall risk of allergy . Nevertheless , in the subgroup with a family history of atopy early exposure to cows ' milk increased the risk of a wide range of allergic reactions , especially eczema 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 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 A total of 1167 infants were followed for 1 year in a population -based prospect i ve study to assess the effect of environmental factors on the development of  allergic disorders .  Some of these environmental factors are interdependent . Mothers who formula fed their infants  smoked more often ( p less than 0.001 ) and tended to belong to lower social classes ( p less than 0.01 ) . Logistic regression analysis was performed to adjust for these confounding variables . Maternal smoking adversely affected the prevalence of asthma ( p = 0.003 ) defined as three or more separate episodes of wheezing and total allergy ( p = 0.02 ) . Infants in lower socioeconomic groups developed asthma significantly more often ( p = 0.03 ) than infants born in higher socioeconomic groups . There was a nonsignificant trend for infants born in summer to develop asthma more than infants born in winter ( p = 0.08 ) . No effect of these factors was observed on eczema , food intolerance , or on the subgroup of infants with definite allergy ( clinical disorder with positive skin prick test [ SPT ] ) . Exposure to animal d and er did not influence the prevalence of clinical disorder , but positive SPT reaction to cat d and er was more prevalent in infants who were exposed to cats and /or dogs ( p = 0.04 ) . Positive SPT to house dust mite occurred significantly more often in infants who were formula fed ( p = 0.05 ) . The environmental factors had a profound effect on the prevalence of asthma but not on other allergic disorders OBJECTIVES To determine the prevalence of soy allergy in IgE-associated cow 's milk allergy ( CMA ) . STUDY DESIGN Children < 3.5 years with documented IgE-associated CMA ( n = 93 ) were evaluated for soy allergy by double-blind , placebo-controlled food challenge , open challenge , or convincing previous history of an anaphylactic reaction to soy .  Children tolerant to soy at entry received soy formula and were followed up for 1 year . RESULTS Of this IgE-associated CMA cohort ( ages 3 to 41 months ) , 14 % ( 95 % CI = 7 . 7%-22.7 % ) were determined to have soy allergy , 12 definitely at entry and 1 possibly after 1 year of soy ingestion . The latter child experienced severe failure to thrive at enrollment and exhibited improved growth while receiving soy during follow-up but was diagnosed with eosinophilic esophagitis at study completion . Improved growth ( P < .05 ) occurred in the non-soy-allergic cohort ingesting soy formula ( 579 31 mL/d ) during the year of follow-up . CONCLUSIONS Soy allergy occurs in only a small minority of young children with IgE-associated CMA . As such , soy formula may provide a safe and growth-promoting alternative for the majority of children with IgE-associated CMA shown to be soy tolerant at the time of introduction of soy formula 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 In a double blind study , 40 infants with cows ' milk intolerance of various causes were r and omised to receive a nutritionally complete formula in which nitrogen was supplied either as whey hydrolysate or amino acids .  The median age of infants was 10 weeks ( range 36 weeks ' gestation to 108 weeks ' postnatal age ) . After a median follow up period of 25 weeks there was no significant difference in dietary intake between the formulas . Twenty four weeks after entry , weight and weight for length improved equally on both formulas . Plasma albumin improved significantly on the hydrolysed whey formula but not in the amino acid group . Both milks were palatable and normal intakes of formula were maintained . Biochemical and haematological indices remained within normal limits . There was no difference in stool frequency and vomiting between the two formulas . Two infants developed a probable allergic colitis while receiving hydrolysed whey . Amino acid formula may have a role in the management of atopic infants with severe cows ' milk intolerance who have already reacted to whey or casein hydrolysate formula Several different protein hydrolysate-based infant formulas have been promoted as hypoallergenic and considered suitable for the dietary management of cow 's milk allergy ( CMA ) . Accepting that none of the hydrolysate-based products is completely safe , the American Academy of Pediatrics ( AAP ) recommends that these formulas should be tested in a double-blind placebo-controlled setting and tolerated by at least 90 % of children with proven CMA . In principle , this recommendation is also endorsed by the European Society of Paediatric Gastroenterology and Nutrition ( ESPGAN ) and the European Society of Paediatric Allergy and Clinical Immunology ( ESPACI ) . In this two-center study , 32 children with proven CMA were tested with the extensive hydrolysate whey formula Nutrilon Pepti , for comparison with Profylac ( extensive ) and Nan HA ( partial ) whey hydrolysate products .  Skin-prick tests ( SPTs ) were , respectively , positive to the three hydrolysate formulas in 19 % , 15 % , and 32 % of children . After oral challenge it was concluded that 97 % ( 95 % CI : 85 - 100 % ) of the children tolerated  Nutrilon Pepti , 94 % ( 95 % CI : 75 - 100 % ) tolerated Profylac , and 64 % ( 95 % CI : 37 - 81 % ) tolerated Nan HA . This study demonstrates that the extensive hydrolysates Nutrilon Pepti and Profylac are well tolerated in a population of children with proven CMA and that both products can be considered safe for their intended use . This study confirms that a very small number of children react even to extensively hydrolyzed formulas . SPT prior to oral exposure to the hydrolysate-based formulas can indicate whether a child is at risk of showing reactions to the product . Introduction of new products to these children should be carried out under a doctor 's supervision . However , the majority of the SPT-positive children did tolerate the two extensively hydrolyzed whey-based formulas tested BACKGROUND Many infants with cow 's milk protein intolerance have adverse reactions to soy , casein and whey hydrolysate formula and to other foods . The recent development of Neocate , a hypoallergenic , nutritionally complete infant formula composed of individual amino acids and other nutrients , has enabled these infants to be stabilized . OBJECTIVE We observed the effect of food challenges in infants with reported hypersensitivity to hypoallergenic formulas . METHODS Eighteen infants ( median age , 7 1/2 months ) were given Neocate formula for 2 months and then underwent a 7-day double-blind placebo-controlled challenge with the formula previously best tolerated . RESULTS In 12 of the 18 infants irritability , vomiting , diarrhea , and /or eczema flares developed during the formula challenge . In two patients symptoms developed immediately , but in the remainder adverse reactions evolved within 7 days ( range , 4 to 7 days ) . Adverse reactions were to soy formula ( six patients ) , whey hydrolysate ( two ) , and casein hydrolysate ( four ) . When infants were 12 months of age , parents reported adverse reactions after the ingestion of other low allergen foods ( median , six ; from a panel of 10 such foods ) . CONCLUSION A group of infants with late-onset adverse reactions to soy , extensively hydrolyzed casein , and whey formulas and to other foods has been identified . Neocate formula proved to be an effective substitute formula for these patients 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 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 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 STUDY OBJECTIVES To examine the prevalence of asthma and hay fever  , and the incidence and temporal relationships of asthma , hay fever , and chronic bronchitis  among adult twins during a 15-year period . DESIGN Prospect i ve cohort study . PARTICIPANTS A population of 11,540 Finnish adult men and women , initially 18 to 45 years of age , who returned a health question naire in 1975 , 1981 , and 1990 as part of the Finnish Twin Cohort study . METHODS Age-st and ardized prevalences and cumulative incidences among individuals were calculated for asthma , hay fever , and chronic bronchitis . The incidence of asthma among subjects with and without hay fever or chronic bronchitis was analyzed in the entire cohort as well as in twin pairs discordant for incident asthma . RESULTS The prevalence of asthma increased slightly from 1975 ( 2.0 % in men and 2.2 % in women ) to 1990 ( 2.9 % in men and 3.1 % in women ) . The prevalence of hay fever showed a larger increase in men and women ( from 6.8 % and 9.8 % to 11.8 % and 15.3 % , respectively ) . Compared with figures for 1976 to 1981 , no significant increase in asthma incidence occurred from 1982 to 1990 , whereas the incidence of hay fever was lower during the latter period among men ( incidence rate ratio , 0.7 ; 95 % confidence interval , 0.6 to 0.9 ) as was the incidence of chronic bronchitis among women ( incidence rate ratio , 0.7 ; 95 % confidence interval , 0.6 to 0.9 ) . Hay fever and chronic bronchitis were usually diagnosed before asthma . Both diseases increased the risk of asthma significantly on the basis of analyses of all individuals and of discordant twin pairs . CONCLUSIONS The pattern of increase in asthma and hay fever prevalence with time was similar , and hay fever was a strong predictor of asthma . These diseases showed no significant increase in incidence Abstract . One hundred and twenty‐one women with history of a previous child with atopic disease were r and omly allocated during the next pregnancy to antigen avoidance or control groups . Dietary advice consisted of almost complete exclusion of milk and dairy products , egg , fish , beef and peanut throughout pregnancy and lactation . A total of 109 completed the study . Maternal antigen avoidance was associated with reduced occurrence of atopic eczema and the skin involvement was less extensive and milder . The beneficial effect was observed mainly in the breast‐fed group . Among the fifty‐five who completed the trial of antigen avoidance , seventeen infants developed atopic eczema , five out of thirty‐five who were breast‐fed and twelve out of twenty who were formula‐fed . Among the offspring of fifty‐four control mothers given no dietary restriction , eczema was observed in twenty‐four infants , eleven out of thirty‐six breast‐fed and thirteen of eighteen formula‐fed . Avoidance of common dietary allergens during pregnancy and lactation enhanced the preventive beneficial effect of exclusive breast feeding on the incidence of atopic eczema among infants at high risk A large multicentre study on the short and long term clinical and developmental outcome of infants r and omised to different diets is being undertaken . This report represents an interim analysis of the early postnatal growth performance of an unselected population of 194 preterm infants ( gestation , mean ( SD ) 31 . 0 ( 2 . 9 ) weeks ; birthweight , mean ( SD ) 1364 ( 294 ) g ) , both ill and well , examined in two ( of four ) parallel trials . One trial compared banked breast milk with a new preterm formula ( primary trial ) ; the other compared these diets as supplements to maternal milk ( supplement trial ) . A major dietary effect on the number of days taken to regain birthweight and subsequent gains in weight , length , and head circumference was observed in the primary trial . Infants fed banked breast milk  and weighing less than 1200 g at birth took a calculated additional three weeks to reach 2000 g compared with those fed on the preterm formula . A significant influence of diet on body proportions was seen in the relation between body weight , head circumference , and length . Similar though smaller differences in growth patterns were seen in the supplement trial . By the time they reach 2000 g , infants of birthweights 1200 to 1849 g fed on banked breast milk and infants below 1200 g fed on either banked breast milk or maternal milk supplemented ( as necessary ) with banked breast milk , fulfilled stringent criteria for failure to thrive ( weight less than 2 SD below the mean for age ) . Only infants fed the preterm formula as their sole diet had maintained their birth centile by discharge from hospital . The misleading nature of comparisons between extrauterine and intrauterine steady state weight gains is emphasised The determinants of wheezing and allergy were investigated in 453 children with a family history of allergic disease . A r and omised controlled trial examined the effects of withholding cows ' milk protein during the first three months of life and replacing cows ' milk with soya milk . The children were followed up to the age of 7 years . Withholding cows ' milk did not reduce the incidence of allergy or wheezing . Children who had ever been breast fed had a lower incidence of wheeze than those who had not ( 59 % and 74 % respectively ) . The effect persisted to age 7 years in the non-atopics only , the risk of wheeze being halved in the breast fed children after allowing for employment status , sex passive smoking , and overcrowding . Allergic disease was not associated with exposure to tobacco smoke , house dust mite antigen , or cats . Breast feeding may confer long term protection against respiratory infection 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 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 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 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 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 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 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 The relationship between infant feeding and childhood asthma is controversial . This study tested the hypothesis that the relation between breast feeding and childhood asthma is altered by the presence of maternal asthma . METHODS Healthy non-selected newborn infants ( n=1246 ) were enrolled at birth . Asthma was defined as a physician diagnosis of asthma plus asthma symptoms reported on ⩾2 question naires at 6 , 9 , 11 or 13 years . Recurrent wheeze ( ⩾4 episodes in the past year ) was reported by question naire at seven ages in the first 13 years of life . Duration of exclusive breast feeding was based on prospect i ve physician reports or parental question naires completed at 18 months . Atopy was assessed by skin test responses at the age of 6 years . RESULTS The relationship between  breast feeding , asthma , and wheeze differed with the presence or absence of maternal asthma and atopy in the child . After adjusting for confounders , children with asthmatic mothers were significantly more likely to have asthma if they had been exclusively breast fed ( OR 8.7 , 95 % CI 3.4 to 22.2 ) . This relationship was only evident for atopic children and persisted after adjusting for confounders . In contrast , the relation between recurrent wheeze and breast feeding was age dependent . In the first 2 years of life exclusive breast feeding was associated with significantly lower rates of recurrent wheeze ( OR 0.45 , 95 % CI 0.2 to 0.9 ) , regardless of the presence or absence of maternal asthma or atopy in the child . Beginning at the age of 6 years , exclusive breast feeding was unrelated to prevalence of recurrent wheeze , except for children with asthmatic mothers in whom it was associated with a higher odds ratio for wheeze ( OR 5.7 , 95 % CI 2.3 to 14.1 ) , especially if the child was atopic . CONCLUSION The relationship between breast feeding and asthma or recurrent wheeze varies with the age of the child and the presence or absence of maternal asthma and atopy in the child . While associated with protection against recurrent wheeze early in life , breast feeding is associated with an increased risk of asthma and recurrent wheeze beginning at the age of 6 years , but only for atopic children with asthmatic mothers Background : Chronic diarrhea is the most common gastrointestinal symptom of intolerance of cow 's milk among children . On the basis of a prior open study , we hypothesized that intolerance of cow 's milk can also cause severe perianal lesions with pain on defecation and consequent constipation in young children . Methods : We performed a double-blind , crossover study comparing cow 's milk with soy milk in 65 children ( age range , 11 to 72 months ) with chronic constipation ( defined as having one bowel movement every 3 to 15 days ) . All had been referred to a pediatric gastroenterology clinic and had previously been treated with laxatives without success ; 49 had anal fissures and perianal erythoma or edema . After 15 days of observation , the patients received cow 's milk or soy milk for 2 weeks . After a one week washout period , the feedings were reversed . A response was defined as eight or more bowel movements during a treatment period . Results : Forty-four of the 65 children ( 68 percent ) had a response while receiving soy milk .  Anal fissures and pain with defecation resolved . None of the children who received cow 's milk had a response . In all 44 children with a response , the response was confirmed with a double blind challenge with cow 's milk . Children with a response had a higher frequency of coexistent rhinitis , dermatitis , or bronchospasm than those with no response ( 11 of 44 children vs. 1 of 21 , P = 0.05 ) ; they were also more likely to have anal fissures and erythema or edema at base line ( 40 of 44 vs. 9 of 21 , P < 0.001 ) , evidence of inflammation of the rectal mucosa on biopsy ( 26 of 44 vs. 5 of 21 , P = 0.008 ) , and signs of hypersensitivity , such as specific IgE antibodies to cow's-milk antigens ( 31 of 44 vs. 4 of 21 , p < 0.001 ) . Conclusions : In young children , chronic constipation can be a manifestation of intolerance of cow 's milk 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 BACKGROUND Distressed behavior is common in infants and is often attributed to gastroesophageal reflux ( GER ) or food protein intolerance . OBJECTIVE To examine the effect of a hypoallergenic amino acid-based infant formula ( AAF ) on distressed behavior and GER symptoms in infants who failed to respond to extensively hydrolyzed formula and antireflux medications . STUDY DESIGN Nineteen distressed infants ( 9 boys and 10 girls ; median age , 5.0 months ) with presumed GER underwent gastroscopy ( n = 17 ) and esophageal 24-hour pH monitoring ( n = 14 ) . Double-blind placebo-controlled ( DBPC ) formula challenges of AAF versus previously besttolerated formula were conducted . RESULTS Nine infants had histologic evidence of esophagitis , and 9 had inflammatory changes in the stomach and /or duodenum . Symptoms remitted in all infants within 2 weeks of the start of feeding with AAF . On DBPC challenge after a median period of 3 months of receiving AAF , 12 infants were intolerant to active formula ( distress score , 287 vs 580 min/wk , P = . 01 ; symptom score , 23.1 vs 36.1 , P = .03 ) . Seven infants did not relapse and were considered tolerant ( distress score , 470 vs 581 , P = .77 ; symptom score , 29.5 vs 20.2 ; P = .89 ) . CONCLUSION Treatment with AAF may reduce distressed behavior and symptoms of GER in infants with food protein intolerance 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 The effect of withholding cows ' milk was examined in 487 infants at high risk of allergic disease . Before birth they were r and omly allocated either to a control group , most of whom received cows ' milk preparations , or to an intervention group , who were offered a soya based substitute .  Eczema and wheezing occurred to a similar extent in the two groups during the first year of life , although napkin rash , diarrhoea , and oral thrush were commoner in the intervention group , especially during the first three months . Breast feeding for any length of time was associated with a reduced incidence of wheezing and diarrhoea BACKGROUND Cow 's milk allergy ( CMA ) is a common disease of infancy and childhood . An appropriate cow 's milk ( CM ) substitute is necessary for feeding babies with CMA .  CM substitutes are soy formulas and casein- or whey-based extensively hydrolyzed formulas . In several countries , including Italy , goat 's milk ( GM ) formulas are available , and some physicians recommend them for feeding babies with CMA . OBJECTIVE We sought to investigate , in vitro and in vivo , the allergenicity of GM in 26 children with proven IgE-mediated CMA . METHODS All the children underwent skin tests with CM and GM ; detection of specific serum IgE to CM and GM ; and double-blind , placebo-controlled , oral food challenges ( DBPCOFCs ) with fresh CM , GM , and , as placebo , a soy formula ( Isomil , Abbott , Italy ) . CAP inhibition and immunoblotting inhibition assays were also carried out in 1 of 26 and 4 of 26 children with positive RAST results to both CM and GM , respectively . RESULTS All the children had positive skin test responses and CAP results to both CM and GM , all had positive DBPCOFC results to CM , and 24 of 26 had positive DBPCOFCs to GM . In CAP inhibition tests , preincubation of serum with CM or GM strongly inhibited IgE either to CM or to GM . In immunoblotting inhibition assays , preincubation with CM completely extinguished reactivity to GM , whereas GM partially inhibited reactivity to CM . CONCLUSIONS These data strongly indicate that GM is not an appropriate CM substitute for children with IgE-mediated CMA . A warning on the lack of safety of GM for children with CMA should be on the label of GM formulas to prevent severe allergic reactions in babies with CMA This study examined 120 infants , aged 3–12 weeks , with severe colics and compared the results of a specific hypoallergenic diet ( group A ) with those of pharmacological treatment ( group B ) . Non‐breastfed group A infants  received soy milk and if unresponsive , hydrolyzed milk formulas ;  mothers of breast‐fed infants  received a diet without cow 's milk , eggs or fish .  Breast‐fed and non‐breast‐fed group B infants received dicyclomine hydrochloride 3 mg/kg/day . Results , based on quantitative measurements of crying . indicated that in breast‐fed infants there was no significant improvement between group A ( 62.5 % ) and group B ( 66.6 % ) infants . Among formula‐fed infants , comparison of positive results using soy milk ( 65.9 % ) with positive results using dicyclomine ( 53.3 % ) was not significant ; positive results using soy milk and hydrolyzed milk formulas in non‐responders to soy milk , provided an improvement in 95.4 % of cases . Pharmacological treatment provided an improvement in 53.3 % ) of cases . The diffcrence was significant ( p<0.01 ) 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 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 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 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 Background : In patients with cow 's milk protein intolerance ( CMPI ) , delayed clinical reactions to cow 's milk ( CM ) ingestion may be misdiagnosed if the clinical symptoms are not “ classical ” and there is a long time lapse between ingestion of CM and the clinical reaction . The aim was to evaluate the clinical outcome of CMPI in a cohort of CM‐intolerant children , with particular attention to the occurrence of clinical manifestations beyond 72 h after CM challenge 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 BACKGROUND Reported prevalence rates of asthma vary within and between countries around the world . These differences suggest environmental factors in addition to genetic factors in the cause of the disease and may provide clues for preventive strategies . We examined the variability of asthma-related symptoms and medication use among adults in 6 sites across Canada ( Vancouver , Winnipeg , Hamilton , Montreal , Halifax and Prince Edward Isl and ) and compared our findings with those from sites that had participated in a recent European survey . METHODS We used the same sampling strategy and st and ardized question naire as those used in the European Community Respiratory Health Survey ( ECRHS ) . The 6 Canadian sites were selected to represent different environments with respect to climate , air pollution and occupational exposure . Community-based sample s of 3000 to 4000 people aged 20 - 44 years were r and omly selected in each site . Subjects were asked to complete the question naire by mail between March 1993 and November 1994 . Prevalence rates ( and 95 % confidence intervals [ CIs ] ) of asthma symptoms , self-reported asthma attacks and use of asthma medication were compared across the Canadian sites and with sites that had participated in the ECRHS . RESULTS The overall response rate of those selected to receive the question naire was 86.5 % ( range 74.5%-92.8 % ) . The prevalence rates of most asthma symptoms varied significantly among the Canadian sites . For instance , 21.9 % ( Montreal ) to 30.4 % ( Halifax ) of the men and 24.0 % ( Vancouver ) to 35.2 % ( Halifax ) of the women reported wheezing in the year before the survey . Depending on the site , 4.4 % to 6.3 % of the men and 5.2 % to 9.5 % of the women reported an asthma attack in the last year , and 4.0 % to 6.1 % of the men and 4.9 % to 9.7 % of the women were currently using asthma medication . Prevalence rates of symptoms , asthma attacks and medication use did not change with age , but they were higher among women than among men . Compared with the results from the ECRHS sites , those from the Canadian sites were among the highest . INTERPRETATION Significant variation in the prevalence of asthma symptoms , asthma attacks and use of asthma medication between Canadian sites and international sites suggests environmental influences . Different combinations of factors in different sites may be responsible for the high prevalence rates and should be the subject of further research to guide clinical management and public health intervention One hundred and sixty‐two women with respiratory allergy to animal d and ers and /or pollens were r and omly allocated to a diet consisting of either a very low ingestion of hens ' egg and cows ' milk or a daily ingestion of one hens ' egg and about 11 of cows ' milk during the last 3 months of pregnancy .  One hundred and sixty‐three infants were followed prospect ively up to 18 months of age when the cumulated incidence of atopic disease in each child was evaluated blindly . No significant differences in the distribution of atopic disease were found among the infants in relation to the maternal diet during late pregnancy . The numbers of skin‐prick tests positive to ovalbumin , ovomucoid , β‐lactoglobulin and cows ' milk were likewise not influenced by differences in the maternal diet during late pregnancy . Genetic factors rather than maternal diet during the perinatal period probably have a greater effect on the incidence of atopic diseases during early infancy The effect of genetic and environmental factors on the prevalence of allergic disorders in early childhood was determined in a prospect i ve follow‐up study . Information was available on 1174 children at the age of 2 years . Two‐hundred and seventy‐five were considered to have an allergic disorder . The prevalence varied from 3.2 % for rhinitis to 10.9 % , for asthma . At 2 years 60 children reacted positively on skin‐prick test ( SPT ) . Multivariate logistic regression analysis was used to obtain adjusted odds ratios ( 95 % confidence interval ) for each factor . For asthma , positive family history , male sex , low birth‐weight , maternal smoking and season of birth were significant risk factors . For eczema , positive family history was the only significant risk factor . For rhinitis , lower socio‐economic group and autumn birth were significant . Maie sex and low birth‐weight were significant for skin test positivity . Positive family history and low birth‐weight were significant risk factors for any allergy . Low birth‐weight was also a significant risk for skin test reactivity to house dust mite . Genetic and environmental factors have a profound effect on the development of allergic disorders in the first two years of life BACKGROUND To improve the nutritional management of pre-term infants , a new individualized human milk fortification system based on presupplementation milk protein analyses was evaluated . METHODS In an open , prospect i ve , r and omized multicenter study , 32 healthy preterm infants ( birth weights , 920 - 1750 g ) were enrolled at a mean of 21 days of age ( range , 9 - 36 days ) when tolerating exclusive enteral feedings of 150 ml/kg per day . All infants were fed human milk and were r and omly allocated to fortification with a bovine whey protein fortifier ( n = 16 ) or ultrafiltrated human milk protein ( n = 16 ) . All human milk was analyzed for protein content before fortification with the goal of a daily protein intake of 3.5 g/kg . During the study period ( mean , 24 days ) daily aliquots of the fortified milk were obtained for subsequent analyses of the protein content . RESULTS Both fortifiers were well tolerated , and growth gain in weight , length , and head circumference , as well as final prepr and ial concentrations of serum urea , transthyretin , transferrin , and albumin were similar in both groups . The ultimate estimated protein intake was equivalent in both groups ( mean 3.1+/-0.1 g/kg per day ) . Serum amino acid profiles were similar in both feeding groups , except for threonine ( significantly higher in the bovine fortifier group ) and proline and ornithine ( significantly higher in the human milk protein group ) . CONCLUSIONS Protein analyses of the milk before individual fortification provides a new tool for an individualized feeding system of the preterm infant . The bovine whey protein fortifier attained biochemical and growth results similar to those found in infants fed human milk protein exclusively with the corresponding protein intakes 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 determine the antigenicity , nutritional adequacy , and growth-promoting efficacy of protein hydrolysate or amino acid-derived formulas in infants with cow milk allergy . STUDY DESIGN Several protein hydrolysate or amino acid-derived formulas were grade d for beta-lactoglobulin content and skin reactivity in 74 atopic children with cow milk allergy proved by a double-blind , placebo-controlled challenge . A r and omized , prospect i ve follow-up study of 9 months included 22 infants with a mean age of 6 months ( 95 % confidence interval , 4 to 7 ) , who were fed an extensively hydrolyzed whey formula ( group We ) , and 23 infants with a mean age of 17 ( 95 % confidence interval , 4 to 7 ) months , who were given an amino acid-derived formula ( group AA ) . RESULTS Both formulas were clinical ly and biochemically tolerated . The mean concentration of essential amino acids in plasma was lower in group We but higher in group AA compared with values for breast-fed control infants ( p = 0.001 ) . There was a different trend between the groups in weight ( p = 0.09 ) and length ( p = 0.006 ) . Growth was promoted in group AA during the follow-up ; it was constant during the first months , followed by a gradual decline in rate in group We . In both groups , atopic eczema improved significantly and progressively , and a downward trend was found in serum total and milk-specific IgE concentrations , proving the efficacy of both formulas . CONCLUSIONS Extensively hydrolyzed formulas are safe and effective for most infants ; an amino acid-derived formula may be preferable for infants with multiple food allergies , especially for the maintenance of normal growth 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 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 Five children aged 12‐40 months with IgE‐mediated adverse reactions to cow milk ( immediate onset clinical pattern of cow milk allergy ) were orally challenged double‐blind in r and om order with three different milk preparations processed from the same batch of milk 1 ) raw untreated cow milk , 2 ) pasteurized cow milk , 3 ) homogenized and pasteurized cow milk , and 4 ) Nutramigen ® (a commercial hypoallergenic infant formula based on hydrolysed casein ) as placebo .  Skin prick tests with the same preparations were also performed . On oral challenge the three different processed milk types provoked significant and similar allergic reactions in each child , and no adverse reactions followed the challenge with placebo ( Nutramigen ) . Skin prick test with the same milk products were positive in all children and comparable to the results with an extract of purified raw cow milk protein ( Soluprickreg ; ) , whereas Nutramigen did not elicit any skin reactions . A tendency towards a lower threshold of reaction and larger skin reactions induced by the processed milk preparations might indicate an increased ability of pasteurized and homogenized/pasteurized milk to evoke allergic reactions in patients allergic to milk The addition of different organic substrates to st and ard glucose oral rehydration solution ( G‐ORS ) has been shown to improve the intestinal absorption of sodium and water , and thereby decrease stool losses . Therefore , we evaluated , in infants with acute diarrhoea , the safety and efficacy of three oral rehydration solutions ( ORS ) which had the same concentrations of electrolytes ( with sodium 60 mmol/l ) but different substrates of proteins and carbohydrates . One solution ( LAD‐ORS ) contained hydrolyzed lactalbumin ( LAD ) with maltodextrin and sucrose , a second ( MS‐ORS ) was identical but without LAD and a third ( G‐ORS ) was st and ard glucose ORS . The three solutions were compared in a double‐blind , r and omized trial in 74 hospitalized well‐nourished children in Panama and the United States . All three oral rehydration solutions were equally efficacious and safe in these children , 54 % of whom were infected with rotavirus . There was no suggestion that hydrolyzed lactalbumin or maltodextrin provided any advantage over glucose‐ORS  in terms of stool output or in duration of diarrhoea . We conclude that all three solutions are efficacious in the therapy of acute diarrhoea in infants 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 Cow 's milk allergy/intolerance is treated by complete avoidance of cow 's milk proteins . Because cow 's milk is an important food for infants , its avoidance may lead to an increased risk of growth impairment . Whilst there is evidence for the beneficial effects of extensively hydrolyzed cow 's milk formulate ( eHF ) in infants with cow 's milk allergy/intolerance , little is known about the effects of amino-acid-based formulae ( AA ) in such infants . We therefore performed a prospect i ve , controlled , multi-center trial to study the efficacy of AA in comparison with eHF , on the growth and clinical symptoms of 73 infants ( median age 5.7 months ) with cow 's milk allergy/intolerance and atopic dermatitis . Cow 's milk allergy/intolerance was proven in all infants by double-blind , placebo-controlled food-challenge . We observed a significant improvement in the SCORAD index in both groups , from a mean of 24.6 , at entry , to a mean of 10.7 ( p < 0.0001 ) after 6 months . In the AA group there was a significant increase in the length st and ard deviation score ( p < 0.04 ) , whilst there was no difference in the eHF group . The weight-for-length values were stable in both groups . The energy intake during the study was similar in both groups . Both an AA and eHF result ed in a significant clinical improvement in infants with an early onset of symptoms of cow 's milk allergy/intolerance . Feeding an AA result ed in improved growth compared with feeding eHF , despite similar dietary intakes , and may therefore be considered as a beneficial alternative in infants with severe cow 's milk allergy intolerance 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 OBJECTIVE To determine the hypoallergenicity and efficacy of a pediatric amino acid-based formula ( AAF ) , EleCare , for children with cow 's milk allergy ( CMA ) and multiple food allergies ( MFA ) . STUDY DESIGN Hypoallergenicity was determined by performing blinded oral food challenges in 31 consecutive children with documented CMA .  Growth , tolerance , and biochemical response were evaluated during a nonr and omized feeding study with each child serving as his or her own control . RESULTS Thirty-one children ( median age , 23.3 months ; range , 6 months to 17.5 years ) were recruited ; 29 had MFA , 17 had acute reactions and cow 's milk-specific IgE antibody , and 14 had allergic eosinophilic gastroenteritis . At study entry , 23 were receiving another AAF ;  13 had not tolerated extensively hydrolyzed formula .  Eighteen subjects with allergic eosinophilic gastroenteritis and /or MFA were followed up while receiving AAF for a median of 21 months ( range , 7 to 40 months ) , with biochemical analysis performed at 4 months . No statistically significant differences were observed in the change in weight or height National Center for Health Statistics z scores from entry ; the percent of expected growth exceeded 90 % . There was a small decline in percent eosinophils and increase in hemoglobin , hematocrit , and serum ferritin level ( P < .05 ) . Except for small increases in plasma leucine and valine levels ( P < or = .006 ) , the remaining biochemical markers were unchanged . CONCLUSIONS The AAF was hypoallergenic and effective in maintaining normal growth for children with CMA and MFA 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 The purpose of this study was to determine whether a new casein hydrolysate infant formula , Alimentum , could be administered safely to children with cow milk hypersensitivity . The formula was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and with a sensitive enzyme-linked inhibition immunoassay , and it was judged to be safe for clinical trials in children allergic to cow milk . Twenty-five such children underwent double-blind placebo-controlled oral food challenges with 10 gm of powdered cow milk and casein hydrolysate formula .  All children were highly atopic and had positive skin prick reactions to cow milk . No patient reacted to placebo during a double-blind , placebo-controlled food challenge . Two patients lost their allergy to cow milk and did not react during the challenge ; the remaining patients reacted with a variety of cutaneous , respiratory , and gastrointestinal symptoms within 15 to 90 minutes of challenge . All children tolerated the blinded challenge to the casein hydrolysate and were fed the hydrolysate openly without difficulty . We conclude that this casein hydrolysate is generally safe to feed to children with immediate hypersensitivity to cow milk . We recommend that all infant formulas promoted as " hypoallergenic " be tested in milk-allergic patients to assess their allergenic potential , in addition to st and ard nutritional evaluation and animal testing for antigenicity 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 20 out of 36 children ( aged two to eight years ) with atopic eczema completed a twelve-week , double-blind , controlled , crossover trial of an egg and cows ' milk exclusion diet . During the first and third four-week periods , patients on an egg and cows ' milk exclusion diet received a soya-based milk substitute ( trial period ) or an egg and cows ' milk preparation ( control period ) . Response was assessed in terms of eczema activity , number of areas affected , pruritus , sleeplessness , and antihistamine usage while on the two diets . During the middle period patients resumed their normal diet to minimise any carry-over effect .  14 patients  responded more favourably to the antigen-avoidance diet than to the control diet , whereas only 1 responded more favourably to the control diet than the trial diet . Patients experienced more benefit during the first diet period than the second , whatever the nature of the diet . There was no correlation between a positive prick test to egg and cows ' milk antigen and response to the trial diet Infants ( n = 18 ) with intolerance to extensively hydrolyzed formulas and soy who responded to an L-amino acid-based elemental formula ( AAF ) were studied until 3 years of age . By 2 years of age most tolerated non-formula foods , and by 3 years only 3 required AAF .  Growth normalized during AAF feeding in 4 infants with failure to thrive 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 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 Allergic reactions were investigated in 777 preterm infants who were r and omly assigned to early diet and followed up to 18 months post term .  Wheezing or asthma was common ( incidence 23 % ) ; it was associated with neonatal ventilation , maternal smoking , and a family history of atopy and was unexpectedly reduced in babies born by caesarean section . Even in non-ventilated infants , the incidence of subsequent wheezing was 18 % , rising to an estimated 44 % ( using logistic regression ) when the foregoing risk factors ( excluding ventilation ) were present .  Eczema occurred in 151 infants ( 19 % ) and was strongly associated with  multiple pregnancy  ( 30 % incidence in twins or triplets ) . Reactions to cows ' milk ( incidence : 4.4 % from detailed history ; 0.8 % confirmed by challenge ) , other foods ( 10 % ) , and drugs ( 5 % ) were within the range reported in full term infants . Milk and food reactions were associated with multiple pregnancy ( 19 % ) and a family history of atopy . Reactions to drugs were least likely to occur in infants who had been ventilated and were on multiple medications in the neonatal period , suggesting that drug tolerance may have developed . We speculate that preterm infants may be a high risk group for asthma and eczema , which could imply an association between atopy and prematurity 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 Latent systemic anaphylactic sensitisation to cows ' milk was assessed in 61 preterm infants who were r and omly assigned to receive either a special formula for preterm infants based on cows ' milk or banked breast milk or one or other of these as a supplement to maternal milk .  A single sample of venous blood was taken near to the time of discharge from the neonatal intensive care unit , and the histamine release by blood basophils in response to in vitro challenge with cows ' milk and anti-IgE was measured . Compared with the blood from infants fed on human milk , that from infants fed on preterm formula showed a significant increase in histamine release to challenge with cows ' milk , the response being greater in blood from infants of lower birth weight and gestational age . A smaller but significant increase in blood histamine release with anti-IgE challenge was observed in the group fed on preterm formula . Infants of low birth weight fed on preterm formula based on cows ' milk may develop latent systemic sensitisation more rapidly than infants born at term . The clinical importance of this requires further investigation 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 We prospect ively studied the incidence of atopic disease in healthy term infants with a birth weight between ‐1 and ‐2 SD who were fed a cow milk formula during the first few days of life . A total of 216 infants were r and omized to receive either early feeding with formula before normal breastfeeding was started ( n= 112 ) or “ normal feeding ” with breastmilk ( n= 104 ) . Symptoms of allergy developed in 18%% of the infants before 18 months of age in the formula fed group , as compared to 33 % in the breastfed group ( P < 0.05 ) . The difference was confined to the group of infants with a history of allergy in two family members . Thus , 11 % of the formula‐fed infants developed allergy symptoms , as compared to 61 % of the control infants ( P < 0.01 ) . Our study implies that early feeding during the first days of life with a cow milk formula , before the introduction of breastmilk , may reduce the incidence of allergy symptoms before 18 months of age in infants with a family history of allergy STUDY OBJECTIVE : To identify environmental determinants of six symptoms associated with allergic disease in infancy . DESIGN : Infants were participants in a prospect i ve r and omised controlled trial of feeding practice s in families with a history of atopy . SETTING : Infants were recruited in two maternity hospitals in S Wales and followed up in the community for 1 year . PARTICIPANTS : Mothers of 519 infants agreed to participate , but 36 were excluded ( mainly for moving home or failing to attend for follow-up ) , leaving 483 in the study ( 253 male , 230 female ) . Infants were followed up and examined for evidence of allergic disease at 3 , 6 , and 12 months . MEASUREMENTS AND MAIN RESULTS : At each examination , mothers were question ed about episodes of illness in the infant , and the data presented relate to ( reported and observed ) eczema and nasal discharge , and ( reported ) wheeze , prolonged colds , diarrhoea and vomiting . Mothers kept a diary with details of feeding for the first 6 months . All homes were visited by a nurse who took sample s of dust for dust mite antigen analysis . Extensive socio-demographic data were collected . None of the factors studied showed a convincing relationship with eczema . In a multiple logistic regression analysis breast feeding appeared to protect against wheeze , nasal discharge , colds , vomiting and diarrhoea . Having more siblings increased the likelihood of prolonged colds , and ( together with overcrowding ) of wheeze and nasal discharge . Maternal smoking and low social class were associated with wheeze , and house dust antigen with prolonged colds . Respiratory symptoms were associated with some aspects of housing but these could not be distinguished clearly from other social factors . Babies born in Autumn were at increased risk of wheeze , vomiting and diarrhoea . CONCLUSIONS : Environmental factors play an important part in determining risk of symptoms in potentially atopic babies . These factors are in principle open to manipulation OBJECTIVES We conducted a prospect i ve , r and omized study to evaluate the cumulative incidence of allergy or other adverse reactions to soy formula and to extensively hydrolyzed formula up to the age of 2 years in infants with confirmed cow 's milk allergy . STUDY DESIGN Infants ( n = 170 ) with documented cow 's milk allergy were r and omly assigned to receive either a soy formula or an extensively hydrolyzed formula . If it was suspected that the formula caused symptoms , a double-blind , placebo-controlled challenge ( DBPCFC ) with the formula was performed . The children were followed to the age of 2 years , and soy-specific immunoglobulin E antibodies were measured at the time of diagnosis and at the ages of 1 and 2 years . RESULTS An adverse reaction to the formula was confirmed by challenge in 8 patients ( 10 % ; 95 % confidence interval , 4.4%-18.8 % ) r and omly assigned to soy formula and in 2 patients ( 2.2 % ; 95 % confidence interval , 0.3 % to 7.8 % ) r and omly assigned to extensively hydrolyzed formula .  Adverse reactions to soy were similar in IgE-associated and non-IgE-associated cow 's milk allergy ( 11 % and 9 % , respectively ) . IgE to soy was detected in only 2 infants with an adverse reaction to soy . Adverse reactions to soy formula  were more common in younger ( < 6 months ) than in older ( 6 to 12 months ) infants ( 5 of 20 vs 3 of 60 , respectively , P = .01 ) . CONCLUSIONS Soy formula was well tolerated by most infants with IgE-associated and non-IgE-associated cow 's milk allergy . Development of IgE-associated allergy to soy was rare . Soy formula can be recommended as a first-choice alternative for infants > or=6 months of age with cow 's milk allergy BACKGROUND Distinct wheezing disorders co-exist in young ( preschool ) children , some of which ( early transient wheeze and viral wheeze ) are thought to be unrelated to atopy . Investigation of changes in prevalence of wheezing disorders in preschool children could provide important clues about underlying mechanisms responsible for increasing prevalence of asthma in schoolchildren . METHODS Repeated population surveys of the prevalence of respiratory symptoms were done by parent-completed postal question naires in r and om sample s of 1650 ( 1990 ) and 2600 ( 1998 ) caucasian children aged 1 - 5 years living in the county of Leicestershire , UK . FINDINGS The response rates were 86 % ( 1422 of 1650 ) in 1990 and 84 % ( 2127 of 2522 ) in 1998 . Between 1990 and 1998 , there was a significant increase in the prevalance of reported wheeze ever ( 16 % to 29 % , p<0.0001 ) , current wheeze ( 12 % to 26 % , p<0.0001 ) , diagnosis of asthma ( 11 % to 19 % , p<0.0001 ) , treatment for wheeze ( 15 % to 26 % , p<0.0001 ) , and admission for wheeze or other chest trouble ( 6 % to 10 % , p<0.0001 ) . The increase occurred both in children with viral wheeze ( 9 % to 19 % ) and in those with the classic asthma pattern of wheezing with multiple triggers ( 6 % to 10 % ) . There was also an increase in transient early wheezers ( 3 % to 5 % ) , persistent wheezers ( 5 % to 13 % ) , and late-onset wheezers ( 6 % to 8 % ) , and in all severity groups . The increase could not be accounted for by putative household risk factors because these declined between the 2 years . INTERPRETATION The fact that all preschool wheezing disorders increased ( including viral wheeze ) makes it probable that factors unrelated to atopy are implicated in the changing epidemiology of wheeze in childhood 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 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
target: REVIEW ER 'S CONCLUSIONS There is no evidence to support feeding with a hydrolysed formula for the prevention of allergy in preference to exclusive breast feeding .
  In high risk infants who are unable to be completely breast fed , there is evidence that prolonged feeding with a hydrolysed compared to a cow 's milk formula reduces infant and childhood allergy and infant CMA .
background: BACKGROUND Allergies and food reactions are common and may be associated with foods including adapted cow 's milk formulas .
  Formulas containing hydrolysed proteins have been used to treat infants with allergy or food intolerance , and have been advocated for prevention of allergy and food intolerance in infants .
  OBJECTIVES To determine whether use of hydrolysed formulas for infant feeding prevents allergy and food intolerance .
  If hydrolysed formulas are effective , to determine what type of hydrolysed formula is most effective including extensively and partially hydrolysed formulas .
  To determine which infants benefit including infants at low or high risk of allergy and infants receiving early , short term or prolonged formula feeding .