Allergies in high-risk schoolchildren after early intervention with cow's milk protein hydrolysates: 10-year results from the German Infant Nutritional Intervention (GINI) study. 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. Extensively and partially hydrolysed preterm formulas in the prevention of allergic diseases in preterm infants: a randomized, double‐blind trial The diagnostic significance of IgG cow's milk protein antibodies re-evaluated 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. Long-term prevention of allergic diseases by using protein hydrolysate formula in at-risk infants. Cumulative incidence of atopic disorders in high risk infants fed whey hydrolysate, soy, and conventional cow milk formulas. The long-term effect of a partial whey hydrolysate formula on the prophylaxis of atopic disease 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 Prebiotic‐supplemented partially hydrolysed cow's milk formula for the prevention of eczema in high‐risk infants: a randomized controlled trial Safety of casein hydrolysate formula in children with cow milk allergy. Effect of feeding whey hydrolysate, soy and conventional cow milk formulas on incidence of atopic disease in high risk infants. Use of hypoallergenic formula in the prevention of atopic disease among Asian children. Gastric emptying in healthy newborns fed an intact protein formula, a partially and an extensively hydrolysed formula. An extensively hydrolysed cow's milk formula improves clinical symptoms of gastroesophageal reflux and reduces the gastric emptying time in infants. Extensively and partially hydrolysed infant formulas for allergy prophylaxis Protein hydrolysate formula maintains homeostasis of plasma amino acids in preterm infants. Effects of a dietary and environmental prevention programme on the incidence of allergic symptoms in high atopic risk infants: three years follow‐up Comparison of an elemental with a hydrolysed whey formula in intolerance to cows' milk. The timing and duration of a sensitive period in human flavor learning: a randomized trial. Vegetable acceptance by infants: effects of formula flavors. Symptomatology and growth in infants with cow's milk protein intolerance using two different whey-protein hydrolysate based formulas in a Primary Health Care setting. Does Early Diet Have an Effect on Subsequent Macromolecular Absorption and Serum IgE? Sensitive period in flavor learning: effects of duration of exposure to formula flavors on food likes during infancy. 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
 Allergy development and macromolecular absorption in infants with different feeding regimens during the first three days of life. A three‐year prospective follow‐up 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. Nutritional evaluation of protein hydrolysate formulas. Gastric Electrical Activity and Gastric Emptying in Preterm Newborns Fed Standard and Hydrolysate Formulas Palatability of hydrolysates and Other substitution formulas for cow's milk-allergic children: a comparative study of taste, smell, and texture evaluated by healthy volunteers. Infant regulation of intake: the effect of free glutamate content in infant formulas. Do infants with cystic fibrosis need a protein hydrolysate formula? A prospective, randomized, comparative study. Higher urinary excretion of essential amino acids in preterm infants fed protein hydrolysates Nutritional evaluation of various protein hydrolysate formulae in term infants during the first month of life Effects of cow milk versus extensive protein hydrolysate formulas on infant cognitive development Nutritional evaluation of protein hydrolysate formulas in healthy term infants: plasma amino acids, hematology, and trace elements. Plasma amino acid concentrations in term-born infants fed a whey predominant or a whey hydrolysate formula. Hydrolyzed infant formula and early β-cell autoimmunity: a randomized clinical trial. Nutritional Value of a Rice-Hydrolysate Formula in Infants with Cows' Milk Protein Allergy: A Randomized Pilot Study Cow's milk IgE and IgG antibody responses to cow's milk formulas Breast-feeding and the development of cows' milk protein allergy. Efficacy and safety of hydrolyzed cow milk and amino acid-derived formulas in infants with cow milk allergy. Avoidance of Cow's Milk-Based Formula for At-Risk Infants Does Not Reduce Development of Celiac Disease: A Randomized Controlled Trial. [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]. Lower Calcium Absorption in Infants Fed Casein Hydrolysate- and Soy Protein-Based Infant Formulas Containing Palm Olein Versus Formulas without Palm Olein Development of immune response to cow's milk proteins in infants receiving cow's milk or hydrolyzed formula. An extensively hydrolysed casein-based formula for infants with cows' milk protein allergy: tolerance/hypo-allergenicity and growth catch-up. Hydrolysed protein accelerates the gastrointestinal transport of formula in preterm infants Short- and long-term effects of feeding hydrolyzed protein infant formulas on growth at < or = 6 y of age: results from the German Infant Nutritional Intervention Study. Challenge confirmation of late-onset reactions to extensively hydrolyzed formulas in infants with multiple food protein intolerance. Gastric emptying in infants with or without gastro-oesophageal reflux according to the type of milk. Supplementary feeding in maternity hospitals and the risk of cow's milk allergy: A prospective study of 6209 infants. The effect of feeding four different formulae on stool weights in prolonged dehydrating infantile gastroenteritis. 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 Preventive effect of feeding high-risk infants a casein hydrolysate formula or an ultrafiltrated whey hydrolysate formula. A prospective, randomized, comparative clinical study. Do prebiotics reduce the number of fever episodes in healthy children in their first year of life: a randomised controlled trial. Preventive effect of hydrolyzed infant formulas persists until age 6 years: long-term results from the German Infant Nutritional Intervention Study (GINI). Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes: The TRIGR Randomized Clinical Trial Long-term effects of hydrolyzed protein infant formulas on growth--extended follow-up to 10 y of age: results from the German Infant Nutritional Intervention (GINI) study. Effect of a partially hydrolyzed whey infant formula at weaning on risk of allergic disease in high-risk children: a randomized controlled trial. Evaluation of Infant Feeding in Acute Gastroenteritis Hypoallergenicity of an extensively hydrolyzed whey formula. The nutritional value of a whey hydrolysate formula compared with a whey-predominant formula in healthy infants. Partial Protein-Hydrolyzed Infant Formula Decreased Food Sensitization but Not Allergic Diseases in a Prospective Birth Cohort Study Colic and the effect of changing formulas: a double-blind, multiple-crossover study. Comparison of a partially hydrolyzed infant formula with two extensively hydrolyzed formulas for allergy prevention: a prospective, randomized study. Dietary manipulation of beta cell autoimmunity in infants at increased risk of type 1 diabetes: a pilot study Certain hydrolyzed formulas reduce the incidence of atopic dermatitis but not that of asthma: three-year results of the German Infant Nutritional Intervention Study. Infantile colic: crying time reduction with a whey hydrolysate: A double-blind, randomized, placebo-controlled trial. Safety and efficacy of a new extensively hydrolyzed formula for infants with cow's milk protein allergy. Effectiveness of casein hydrolysate feedings in infants with colic Neonatal jaundice and diet. 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 Comparison of Breast, Cow, and Soy Feedings in the Prevention of Onset of Allergic Disease Long-term safety assessment in children who received hydrolyzed protein formulas with Lactobacillus rhamnosus GG: a 5-year follow-up Reduction of crying episodes owing to infantile colic: a randomized controlled study on the efficacy of a new infant formula Early diet of preterm infants and development of allergic or atopic disease: randomised prospective study. A Comparative Evaluation of Whey Hydrolysate and Whey-Predominant Formulas Cost-effectiveness of using an extensively hydrolysed formula compared to an amino acid formula as first-line treatment for cow milk allergy in the UK. Dietary treatment of infant colic: a double-blind study. Effectiveness of massage, sucrose solution, herbal tea or hydrolysed formula in the treatment of infantile colic. Correlation between early neonatal diet and atopic symptoms up to 5-7 years of age in very low birth weight infants: follow-up of randomized, double-blind study. Growth and Tolerance of Healthy Term Infants Receiving Hydrolyzed Infant Formulas Supplemented With Lactobacillus rhamnosus GG: Randomized, Double-Blind, Controlled Trial Soluble Adhesion Molecules and Oral Antigen Feeding in Infants “Minor” feeding problems during the first months of life: effect of a partially hydrolysed milk formula containing fructo‐ and galacto‐oligosaccharides Allergic reactions to raw, pasteurized, and homogenized/pasteurized cow milk: a comparison Acidic Oligosaccharides from Pectin Hydrolysate as New Component for Infant Formulae: Effect on Intestinal Flora, Stool Characteristics, and pH Growth, Tolerance and Biochemical Measures in Healthy Infants Fed a Partially Hydrolyzed Rice Protein-Based Formula: A Randomized, Blinded, Prospective Trial Hypoallergenicity and effects on growth and tolerance of a new amino acid-based formula with docosahexaenoic acid and arachidonic acid. Tolerance of a standard intact protein formula versus a partially hydrolyzed formula in healthy, term infants Allergic symptoms up to 4–6 years of age in children given cow milk neonatally A prospective study Growth and bone mineral status of discharged very low birth weight infants fed different formulas or human milk. Gastric Emptying Using Three Different Formulas in Infants with Gastroesophageal Reflux Dietary intervention in infancy and later signs of beta-cell autoimmunity. Development of atopic disease after early administration of cow milk formula Formula Tolerance in Postbreastfed and Exclusively Formula-fed Infants Effects of prolonged exposure to partially hydrolyzed milk protein. Overview of Reviews The prevention of eczema in infants and children: an overview of Cochrane and non-Cochrane reviews. Resource implications and budget impact of managing cow milk allergy in the UK Milk formulas in acute gastroenteritis and malnutrition: a randomized trial. Clinical Response to 2 Commonly Used Switch Formulas Occurs within 1 Day A non-hydrolyzed, fermented milk formula reduces digestive and respiratory events in infants at high risk of allergy Maternal consumption of dairy products during pregnancy and lactation, and the development of cow's milk antibodies in the offspring. Exposure of infants to phyto-oestrogens from soy-based infant formula [Incidence and symptoms of cow's milk protein intolerance following acute gastroenteritis in young infants. Effect of a hypoallergenic diet]. Optimal Growth and Lower Fat Mass in Preterm Infants Fed a Protein-enriched Postdischarge Formula Immune Status of Infants Fed Soy-Based Formulas With or Without Added Nucleotides for 1 Year: Part 1: Vaccine Responses, and Morbidity Whey Predominant, Whey Modified Infant Formula with Protein/energy Ratio of 1.8 g/100 kcal: Adequate and Safe for Term Infants From Birth to Four Months Effects of Formula Protein Level and Ratio on Infant Growth, Plasma Amino Acids and Serum Trace Elements I. Cow's Milk Formula Effects of brief early exposure to partially hydrolyzed and whole cow milk proteins. Effects of human milk or formula feeding on the growth, behavior, and protein status of preterm infants discharged from the newborn intensive care unit. Feeding a Formula Supplemented With Long Chain Polyunsaturated Fatty Acids Modifies the “Ex Vivo” Cytokine Responses to Food Proteins in Infants at Low Risk for Allergy Aberrant composition of gut microbiota of allergic infants: a target of bifidobacterial therapy at weaning? Soy allergy following early soy feeding in neonates. Latent anaphylactic sensitisation of infants of low birth weight to cows' milk proteins. Short-term effect of partially hydrolyzed formula on the prevention of development of atopic dermatitis in infants at high risk. A randomised multicentre study of human milk versus formula and later development in preterm infants. Erythrocyte fatty acid composition in term infants fed human milk or a formula enriched with a low eicosapentanoic acid fish oil for 4 months Evaluation of two iron-fortified, milk-based formulas during infancy. Comparative Growth and Biochemical Response of Very Low Birthweight Infants Fed Own Mother's Milk, a Premature Infant Formula, or One of Two Standard Formulas Allergen avoidance in infancy and allergy at 4 years of age The Trial to Reduce IDDM in the Genetically at Risk (TRIGR) study: recruitment, intervention and follow-up Growth and nutrient intake in three- to twelve-month-old infants fed human milk or formulas with varying protein concentrations.
BACKGROUND The long-term effect of nutritional intervention with hydrolysate infant formulas on  allergic manifestations in high-risk children is uncertain . OBJECTIVE We sought to investigate the effect of hydrolysate infant formulas on allergic phenotypes in children with family history of allergies at school age . METHODS We analyzed data from participants of the prospect i ve German Infant Nutritional Intervention study after 10 years of follow-up . At birth , children were r and omly assigned to receive , for the first 4 months , one of 4 blinded formulas as breast milk substitute , if necessary : partially hydrolyzed whey formula ( pHF-W ) , extensively hydrolyzed whey formula ( eHF-W ) , extensively hydrolyzed casein formula ( eHF-C ) , or st and ard cow 's milk formula . Outcomes were parent-reported , physician-diagnosed allergic diseases . Log-binomial regression models were used for statistical analysis . RESULTS The relative risk for the cumulative incidence of any allergic disease in the intention-to-treat analysis ( n = 2252 ) was 0.87 ( 95 % CI , 0.77 - 0.99 ) for pHF-W , 0.94 ( 95 % CI , 0.83 - 1.07 ) for eHF-W , and 0.83 ( 95 % CI , 0.72 - 0.95 ) for eHF-C compared with st and ard cow 's milk formula . The corresponding figures for atopic eczema/dermatits ( AD ) were 0.82 ( 95 % CI , 0.68 - 1.00 ) , 0.91 ( 95 % CI , 0.76 - 1.10 ) , and 0.72 ( 95 % CI , 0.58 - 0.88 ) , respectively . In the per- protocol analysis ( n = 988 ) effects were stronger . The period prevalence of AD at 7 to 10 years was significantly reduced with eHF-C in this analysis , but there was no preventive effect on asthma or allergic rhinitis . CONCLUSION The significant preventive effect on the cumulative incidence of allergic diseases , particularly AD , with pHF-W and eHF-C persisted until 10 years without rebound , whereas eHF-W showed no significant risk reduction . There is insufficient evidence of ongoing preventive activity at 7 to 10 years of age 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 Aim : A r and omized , double‐blind study was conducted to evaluate whether use of protein hydrolysate‐based preterm formulas in infants with an atopic predisposition helps prevent the development of allergic diseases . Methods : Preterm infants ( n= 122 ) with at least one first‐degree relative ( parent or sibling ) with allergic disease were r and omly assigned to receive an extensively or partially hydrolysed preterm formula ( intervention groups ) or a st and ard preterm formula until 4 to 5 mo of age . Infants whose parents preferred that they be breastfed received their mothers ' fortified breast milk . Results : Intention‐to‐treat analysis showed that the overall incidence of allergic diseases did not significantly differ between groups at both 4–5 and 12 mo of age . However , by 12 mo , use of the extensively hydrolysed versus the st and ard preterm formula had significantly reduced the risk of atopic dermatitis . At 4–5 and 12 mo , there was a significantly increased risk of non‐acceptance of the extensively hydrolysed formula compared with the other formulas 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 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 This prospect i ve , long-term study assessed the effects of a protein hydrolysate formula on allergy prevention in infants with a family history of allergy . Infants were r and omly assigned to receive either the  hydrolysate formula ( n = 92 ) or an adapted cow milk formula  ( n = 85 ) alone or with breast-feeding for 4 months . The groups did not differ in family allergy history scores or cord blood IgE levels . After 4 months , total IgE levels and allergic reactions did not differ significantly between groups , although the hydrolysate group had a lower prevalence of eczema . At 12 months of age , neither IgE levels nor allergic reactions were significantly different . At 2 years of age , however , 18 allergic reactions had occurred in the hydrolysate group and 31 had occurred in the control group ; the differences were significant for eczema ( p < 0.001 ) but not for asthma . At 4 years of age , allergic signs were found in 11 children in the hydrolysate group and in 17 children in the control group ; the difference was significant only for eczema ( p < 0.01 ) . These results suggest that early feeding of a protein hydrolysate formula to infants at risk for allergies had a long-term preventive effect on the prevalence of eczema but not of asthma A recent increase in the prevalence of atopic disorders and the enormous costs of management of atopic patients have prompted attempts at prevention . We have examined the effect of exclusive breast feeding and of feeding different infant formulas on incidence of atopic disease in a prospect i ve r and omized controlled study . Seventy-two infants were recruited into each of the following groups : cow milk whey hydrolysate formula ( NAN/HA ) conventional cow milk formula ( Similac ) , soy-based formula ( Isomil ) , and exclusive breast feeding for greater than 4 months .  The cumulative incidence of atopic eczema , recurrent wheezing , rhinitis , gastrointestinal symptoms , and colic were noted . Skin prick tests and radioallergosorbent tests for IgE antibodies to milk and soy were performed . At 12 and 18 months of age , the incidence of atopic eczema as also that of all atopic symptoms was significantly lower and similar in the breast-fed and whey hydrolysate groups , compared with the cow milk and soy formula groups . IgE antibodies were detected more often in the cow milk and soy formula groups , especially the former . Among symptomatic infants , fewer skin positive prick tests were seen in the soy group compared with the cow milk group . Our observations show that among infants at high risk of developing atopic disease because of positive family history , exclusive breast feeding or whey hydrolysate formula is associated with a lower incidence and thus a delay in the occurrence of allergic disorders compared with groups fed conventional cow milk or soy formulas 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 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 Prevention guidelines for infants at high risk of allergic disease recommend hydrolysed formula if formula is introduced before 6 months , but evidence is mixed . Adding specific oligosaccharides may improve outcomes 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 The effect of feeding different infant formulas on incidence of atopic disease was assessed in a prospect i ve double-blind r and omized controlled trial among " high risk " infants with family history of atopy among first-degree relatives . The incidence of atopic eczema , wheezing , rhinitis , gastrointestinal symptoms , and colic was noted and serum IgE antibodies to milk were estimated . Seventy-two infants were recruited into each of the following groups : cow milk whey hydrolysate formula ( NAN/HA ) , conventional cow milk formula ( Similac ) , soy-based formula ( Isomil ) , and exclusive breast feeding for greater than or equal to 4 months .  The number of infants who exited for reasons other than atopy and were excluded from analysis were 4 , 5 , 4 , and 12 in the four groups , respectively . The incidence of one or more symptoms of possible allergic etiology was five of 68 infants fed NAN/HA , 24 of 67 infants fed Similac , 25 of 68 infants fed Isomil , and 12 of 60 breast-fed infants . Among symptomatic infants , skin prick test to milk proteins was positive in four out of five infants fed NAN/HA , 16 of 24 fed Similac , 2 of 25 fed Isomil , and 7 of 12 breast-fed . IgE antibodies to milk were found in 2 of 68 , 9 of 67 , 0 of 68 , and 6 of 60 infants in the four groups , respectively . It is concluded that exclusive breast feeding for more than 4 months is partially protective against the development of atopic disease among high risk infants . ( ABSTRACT TRUNCATED AT 250 WORDS 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 BACKGROUND & AIMS Gastric emptying ( GE ) is influenced by the type of nutrition . The objective of this study was to compare GE in infants fed an intact protein formula ( IPF ) , a partially hydrolysed formula ( PHF ) , and an extensively hydrolysed formula ( EHF ) .  METHODS This was a double-blind , r and omized , cross-over study . Following a fasting period of > or = 3 h , 20 healthy newborns were fed IPF , PHF , and EHF containing 50 microl (13)C-octanoic acid ( OA ) . Breath sample s were taken before feeding and every 15 min for 4 h thereafter . (13)C-OA  breath test was assessed by isotope-ratio mass spectrometry , and GE half-times ( t(1/2 ) ) were determined . RESULTS Seventeen infants with a mean gestational age of 37 wk ( range 28 - 40 wk ) and birth weight of 2698 g ( range 720 - 3690 g ) completed the study . At study initiation , the mean age was 31 d ( range 6 d-13 wk ) and the mean weight was 3466 g ( range 2100 - 5700 g ) . EHF emptied significantly faster than IPF and PHF ( medians 46 vs. 55 and 53 min , respectively , Wilcoxon , P<0.05 for both ) . There was no significant difference between GE of PHF and IPF ( Wilcoxon , P=0.2 ) . CONCLUSIONS EHF may be better tolerated by infants with GE problems BACKGROUND About 20 % of infants fed with breast-milk substitutes  suffer from Gastro Esophageal Reflux ( GER ) and 1/3 of them also show Cow 's Milk Allergy ( CMA ) symptoms . METHODS We planned this study to assess by dynamic echography the usefulness of an Extensively Hydrolysed Cow 's Milk Formula ( eHF ) in infants suffering from GER . Ten infants showing GER symptoms and 10 normal babies , all fed with breast-milk substitutes , were enrolled .  Clinical symptom scores related to GER were assessed for one week . The Gastric Emptying Time ( GET ) was determined by means of dynamic echography after feeding with cow 's milk-derived formulae and again after a week feeding with eHF in subjects previously showing GER symptoms . RESULTS All infants with a clinical diagnosis for GER showed an abnormally high average GET in comparison to normal subjects ( 205 vs 124 min , p = 0.000 ) . Switching to the eHF led to a significant clinical improvement ( p = 0.0039 ) especially in babies skin-test and RAST positive to cow 's milk , and to a significant decrease toward the normal value of the GET ( 167 min , p < 0.001 ) . CONCLUSIONS The eHF tested improves GER symptoms in infants suffering from this disease . Our experience confirms and supports the use of dynamic echography as a reliable , simple , and non-invasive diagnostic method for infants with an increased GET associated with clinical symptoms of GER 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 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 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 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 BACKGROUND By using the response to protein hydrolysate formula ( PHF ) as a model system , we discovered the existence of a sensitive period , before 4 mo , when exposure determines the hedonic tone to flavors . OBJECTIVE We aim ed to characterize the timing and duration of this sensitive period . DESIGN Healthy infants , whose parents had chosen formula feeding , were r and omly assigned into 1 of 6 groups at age 0.5 mo : 2 control groups , one fed cow milk-based formula ( CMF ) and the other fed PHF for 7 mo ; 2 groups fed PHF for either 1 or 3 mo beginning at 1.5 mo and CMF otherwise ; and 2 groups fed PHF for 1 mo beginning at either 2.5 or 3.5 mo and CMF otherwise . Brief access taste tests were conducted monthly , and complete " meals " of both formulas occurred at the end of the study . RESULTS Three months of PHF exposure led to acceptance similar to that at 1 mo of exposure . Although these infants were more accepting than were infants with no exposure , they were less accepting than were infants with 7 mo of exposure , which suggests a dosing effect . The time when flavor experiences began was also significant . Among infants exposed to PHF for 1 mo , those who were first fed PHF at 3.5 mo rejected PHF relative to CMF more than did infants exposed at younger ages . CONCLUSION The general principles observed are likely of broader significance , indicating a fundamental feature of mammalian development and reflecting the importance of familiarizing infants with flavors that their mothers consume and transmit to breast milk . This trial was registered at clinical trials.gov as NCT00994747 Individual differences in acceptance patterns are evident as early as the child 's first experiences with a particular food . To test hypothesis that the flavor of  formula fed to infants modifies their acceptance of some foods , we conducted a within- and between-subjects design study in which two groups of 6- to 11-month-old infants were tested on two separate days . One group was currently feeding a milk-based formula whereas the other was feeding a protein hydrolysate formula , a particularly unpleasant tasting formula to adults that contains similar flavor notes ( e.g. , sulfur volatiles ) with Brassica vegetables such as broccoli . In counterbalanced order , acceptance of pureed broccoli/cauliflower was determined during one test session and pureed carrots on the other . Although there were no group differences in the amount of carrots consumed , hydrolysate infants consumed significantly less broccoli/cauliflower relative to carrots when compared to those who were currently fed milk based formulas ( F(1,72 df)=4.43 ; p=0.04 ) . The mothers of hydrolysate infants were significantly more likely to report that their infants did not enjoy feeding the broccoli/cauliflower ( 54.2 % ) when compared to mothers of infants being fed milk-based formulas ( 28.0 % ; Chi-Square ( 1 df)=4.79 ; p=0.03 ) . Such findings are consistent with prior research that demonstrated a sensory specific satiety following repeated exposure to a particular flavor in milk . We hypothesize that when infants are experiencing a flavor in milk or formula , in the short term , the preference that develops is specific to the context it is experienced in ( e.g. , milk ) . Over the longer term , the preference may generalize to other context s such as solid foods . Hydrolysate infants were also significantly more likely to be judged by their mothers as being more active ( F(1,69 df)=3.95 ; p=0.05 ) and hesitant ( F(1,69 df)=6.55 ; p=0.01 ) when compared to those infants who were feeding milk-based formulas , a finding that further supports the hypothesis that mother-child dynamics surrounding early feeding impacts upon mothers ' perception of their children 's temperament Both growth and the course of allergic symptoms were evaluated in 79 infants with cow 's milk protein intolerance , aged three months or younger , diagnosed by st and ard elimination/provocation and treated with a whey-hydrolysate based infant formula : Nutrilon Pept or Pepti Junior .  The efficacy of both products , in terms of symptomatology and growth , was compared with each other . The products differ in fat source ( Pepti Junior 50 % of its fat as MCT , Nutrilon Pepti normal LCT fat blend ) and the presence of lactose ( Pepti Junior : lactose free ; Nutrilon Pepti : 40 % of its carbohydrate as lactose ) . The study was part of a large project that aim ed at st and ardising the approach towards cow 's milk protein intolerance in Baby Health Clinics . Nearly 50 Baby Health Clinics participated in this project . In this study , growth and symptomatology ( skin , respiratory tract , gastrointestinal tract ) were monitored during an intervention period of at least 10 weeks . Infants in both feeding groups showed normal growth , and in at least 80 % of the infants an improvement of the overall symptomatology could be seen during the intervention period . Most profound were the decreases in prevalence and severity of eczema and infantile colic . No differences in efficacy were found in this study between the two infant formulas . It was concluded that the exclusive use of either whey hydrolysate based infant formula result ed in an improvement of allergic symptoms and in normal growth in infants diagnosed by elimination/provocation for cow 's milk protein intolerance in a Primary Health Care setting 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 BACKGROUND & AIMS Emerging research has revealed the existence of periods in which the developing brain has heightened sensitivity to environmental influences . We discovered a sensitive period , < 4 months of age , when exposure to the flavor of extensively hydrolyzed protein hydrolysate formulas ( ePHF ) determines its hedonic tone . This formula has pronounced bitter , sour , and savory tastes compared to cow-milk-based formulas ( CMF ) . This study aim ed to determine the effects of duration of exposure during the sensitive period on a food containing an exemplar of the savory flavor . METHODS Formula-fed infants were r and omized into four groups at age 0.5 months : one control group fed the CMF for 8 months , and three groups fed ePHF for 1 , 3 , or 8 months and CMF otherwise . When infants were 8.5 months , their acceptance of a savory and plain broth was measured . RESULTS Infants fed hydrolysate formula for 3 or 8 months , but not 1 month , showed greater acceptance of the savory broth relative to the plain broth ( p < 0.01 ) and consumed it at a faster rate ( p = 0.01 ) . CONCLUSIONS The duration of flavor exposure affects infants ' earliest responses to foods : a 3-month exposure to ePHF shifted the hedonic tone for savory flavor 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 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 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 Growth parameters , biochemical indice of protein metabolism and plasma Amino acid ( AA ) concentrations were investigated during the first month of life in term infants ( n = 61 ) fed various protein hydrolysate formulas ( whey ( WHF , n = 3 ) , soy collagen ( SCHF , n = 1 ) and whey-casein hydrolysate formulas ( WCHF , n = 1 ) ) . In addition , metabolic balance studies were performed in 10 infants fed WHF and in 5 fed WCHF . Comparatively to breast fed infants , growth reduction and decrease in plasma protein concentrations were observed with the use of one of the WHF and in a lesser extent with the SCHF and the WCHF . Plasma amino acid pattern reflected the AA content of the formulas . Whey hydrolysate formulas 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 in breast fed infant . Metabolic balance studies showed a relative reduction in nitrogen absorption and utilisation in the infants fed the WHF and the WCHF . In addition a drastic reduction in fat , calcium and phosphorus absorption was also observed with the use of the WCHF . In preterm infants ( n = 19 ) fed whey predominant hydrolysed preterm formulas ( n = 3 ) , metabolic balance studies an plasma AA concentration were evaluated at the end of the first month of life at 34 weeks of gestation age . Comparatively to similar preterm infants fed conventional preterm formulas , a relative reduction in nitrogen absorption ( 83 % vs 90 % ) and retention ( 64 vs 70 % ) as well as in phosphorus absorption ( 78 vs 89 % ) was observed . Calcium retention was similar ( 48 vs 45 mg/kg/d ) but calcium intake was significantly higher in infants fed hydrolysate formulas 120 vs 91 mg/kg/d . Plasma amino acid concentrations were related to amino acid composition of the formulas . Compared with the st and ard preterm formulas , all three protein hydrolysate formulas led to a significant increase in plasma threonine and a decrease in tyrosine and phenylalanine concentrations . In addition , there was a reduction in plasma histidine , valine , leucine , cystine , methionine and /or tryptophane with some of the hydrolysate formulas used . In conclusion , these studies provide evidence that protein hydrolysed formulas are not equivalent to whole protein formulas in terms of nutritional efficiency for preterm and term infants . Therefore further extensive nutritional studies on growth , biochemical indices of protein metabolism and metabolic balance , including minerals and trace elements , appear to be necessary before maintaining and promoting the use of such formulas for teh potential benefits on atopic disease in preterm and in full-term newborn infants 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 Hydrolyzed formulas used to feed infants with cow 's milk-allergy can be classified as soy based , extensively hydrolyzed ( casein , whey and mixed ) , and amino-acid based . Their unsatisfactory taste is reported by parents and physicians . OBJECTIVE The aim of this study was to ascertain the palatability of these formulas in a double-blind taste test . MATERIAL S AND METHODS Fifty healthy volunteers performed a r and omized-order double-blind test with 12 different milks .  The taste , smell , smell , and texture of each formula were evaluated o n scales ranging from 1 ( worst ) t o 5 ( best ) . The Pearson correlation coefficient between the peptide weight of each formula and the score obtained for each evaluated attribute was calculated . RESULTS The soy formulas and rice formula had the best taste scores , followed by the whey hydrolysates ; the mixed hydrolysates and the casein hydrolysates had the lowest taste scores . Individually the most palatable formula was mixed hydrolysate 1 , by total score . We found a statistically significant correlation between peptide weight , reflecting the degree of hydrolysis of each formula , and the scores obtained for taste , texture , and overall palatability . CONCLUSION The palatability of formulas is determined by the amount of bitter peptides obtained through hydrolysis . Flavorings and sweeteners may also contribute to palatability . Further studies are needed in order to determine how to modify the organoleptic properties of these products with the purpose of improving their palatability BACKGROUND We recently discovered that infants r and omly assigned to a formula high in free amino acids ( extensive protein hydrolysate formula ; ePHF )  during infancy consumed less formula to satiation and gained less weight than did infants fed an isocaloric formula low in free amino acids ( cow milk formula ; CMF ) . OBJECTIVE Because ePHF and CMF differ markedly in concentrations of free glutamate , we tested the hypothesis that the higher glutamate concentrations in ePHF promote satiation and satiety . DESIGN In this counterbalanced , within-subject study , infants < 4 mo of age ( n = 30 ) visited our laboratory for 3 sets of 2 consecutive infant-led formula meals over 3 test days . Infants were fed 1 of 3 isocaloric formulas during each first meal : CMF , ePHF , or CMF with added free glutamate to approximate concentrations in ePHF ( CMF+glu ) . When infants signaled hunger again , they were fed a second meal of CMF . From these data , we calculated satiety ratios for each of the 3 formulas by dividing the intermeal interval by the amount of formula consumed during that particular first meal . RESULTS Infants consumed significantly less  CMF+glu  ( P < 0.02 ) and  ePHF  ( P < 0.04 ) than CMF during the first meals . They also showed greater levels of satiety after consuming CMF+glu  or ePHF : satiety ratios for CMF+glu ( P < 0.03 ) and ePHF ( P < 0.05 ) were significantly higher than for CMF . CONCLUSION These findings suggest a role of free glutamate in infant intake regulation and call into question the cl aim that formula feeding impairs infants ' abilities to self regulate energy intake OBJECTIVES We compared the nutritional benefits of a protein hydrolysate and a conventional infant formula in infants newly diagnosed with cystic fibrosis ( CF ) . STUDY DESIGN Twenty-three infants with CF ( < 6 months of age ) and pancreatic insufficiency were r and omized to receive a hydrolysate formula ( Alimentum ) or a cow 's milk-based formula ( Similac ) . Each patient was monitored at 1 month and then every 3 months for 1 year . RESULTS Eighteen patients ( 8 Alimentum , 10 Similac ) completed the study . At entry , the age distribution and clinical characteristics of each group were comparable . Energy intake with each formula was the same at 1 and 3 months , but at 6 and 12 months the hydrolysate-fed infants had higher age-adjusted energy intake . There were no differences in fecal energy or fecal fat at entry or throughout the study . Although the hydrolysate-fed infants were slightly more malnourished at diagnosis , growth velocity and nutritional status of infants with CF in each group were the same throughout the study . CONCLUSIONS The results of this r and omized study fail to support the use of a hydrolyzed formula for the routine care of infants newly diagnosed with CF Aim : Protein hydrolysates have been introduced in preterm formulae , but it is not clear whether they are needed for the feeding of preterm infants . We design ed a r and omized , controlled trial to test the effects of a preterm formula with hydrolysed cow 's milk proteins on short‐term growth and urinary and plasma amino acids levels . Methods : Infants with a birthweight 1750 g and gestational age 34 wk fed a conventional preterm infant formula ( formula B ) or a hydrolysed formula ( formula A ) .  Weight was measured daily ; length , head circumference , mid‐arm circumference and total skinfold thickness were measured weekly . Blood and urine were analysed for amino acid concentrations at start , 14 and 28 d. Results : Twenty‐one infants met the criteria for r and omization . The daily feeding volumes were : formula A 172.8±5.6 vs formula B 170.1±2.8 ml/kg/d . Infants fed with formula A showed slower weight gain ( 17.4±3.4 vs 20.5±3.3 g/kg/d ; p=0.045 ) and lower mean change in Z‐scores for weight ( −0.18±0.16 vs 0.00±0.09 ; p=0.009 ) and for head circumference ( −0.06±0.13 vs 0.06±0.13 ; p=0.049 ) . After 14 d , infants receiving formula A had statistically significant higher urinary levels of essential amino acids compared to infants receiving formula The 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 Abstract Little research has focused on infant developmental effects , other than growth , of formulas that differ substantially in the form of protein . To examine development of infants fed formulas differing in free amino acid content , we r and omized 0.5-month-old infants ( n = 79 ) to either a  control group who fed only cow milk formula ( CMF ) during the first 8 months ( CMF8 ) , or to one of two experimental groups : one experimental group fed extensively protein hydrolyzed formula ( EHF ) for 1–3 months during first 4.5 months ( EHF1 - 3 ) of life , and the other fed EHF for 8 months ( EHF8 ) . The Mullen Scales of Early Learning were administered monthly from 1.5 to 8.5 months to assess fine ( FM ) and gross ( GM ) motor control , receptive ( RL ) and expressive ( EL ) language , visual reception ( VR ) , and an early learning composite ( ELC ) . Across the 5.5–8.5-month time period , when compared to CMF8 infants , GM scores in EHF1 - 3 infants averaged 1.5 points higher ( 95 % CI 0.1 , 3.0 ) and in EHF8 infants 2.2 points higher ( 95 % CI 0.3 , 4.0 ) . Similarly , VR scores averaged 1.9 points higher ( 95 % CI 0.1 , 3.8 ) in EHF1 - 3 infants and 2.2 points higher ( 95 % CI −0.2 , 4.5 ) in EHF8 infants . EHF8 infants ’ RL scores averaged 1.8 points lower ( 95 % CI 0.1 , 3.6 ) than CMF8 infants . These data suggest that the form of protein in infant formula may impact cognitive development and that the higher free amino acid content in breast milk may be a contributing factor to the differential cognitive development between breastfed and CMF-fed infants . Clinical Trial Registration : clinical trials.gov NCT00994747 BACKGROUND Protein hydrolysate formulas are used for infants with food allergy . Most studies of such formulas focus on their effect on allergy and rarely evaluate their capacity to provide normal nutritional status . OBJECTIVE We compared plasma aminograms , serum urea nitrogen , and trace element status in breastfed infants , infants fed hydrolysate formulas , and infants fed milk formula .  DESIGN From 6 wk to 6 mo of age , infants were breastfed or fed regular milk formula ( RF ) , 1 of 2 casein-hydrolysate formulas ( CH-1 or CH-2 ) , or whey-hydrolysate formula ( WH ) .  Anthropometric measures were taken monthly , and blood sample s were collected at 6 wk and 6 mo . Plasma amino acids , serum urea nitrogen , hematologic indexes , plasma zinc , and plasma copper were analyzed . RESULTS There were no significant differences in hemoglobin , serum transferrin receptor , copper , or zinc among groups . Serum ferritin was significantly lower in infants fed the CH formulas than in the other groups . Infants fed CH-2 had significantly higher serum urea nitrogen than did all other groups . Plasma threonine , valine , phenylalanine , methionine , and tryptophan were significantly higher in the hydrolysate formula groups than in the breastfed group . Plasma tyrosine was significantly lower in infants fed the CH formulas than in the breastfed group , whereas arginine was significantly higher in the WH group than in all other groups . Plasma proline was lower , whereas threonine and tryptophan were higher , in the WH group than in the CH groups . CONCLUSIONS The iron status of infants fed CH formula was lower than that of all other groups . The amounts of amino acids provided by hydrolysate formulas appear excessive compared with regular formula , which is reflected by high serum urea nitrogen ( CH-2 ) and high plasma amino acid concentrations . A reduced and more balanced amino acid content of hydrolysate formulas may be beneficial 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 IMPORTANCE The disease process leading to clinical type 1 diabetes often starts during the first years of life . Early exposure to complex dietary proteins may increase the risk of β-cell autoimmunity in children at genetic risk for type 1 diabetes .  Extensively hydrolyzed formulas do not contain intact proteins . OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of diabetes-associated autoantibodies in young children . DESIGN , SETTING , AND PARTICIPANTS A double-blind r and omized clinical trial of 2159 infants with HLA-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries ; 1078 were r and omized to be weaned to the extensively hydrolyzed casein formula and 1081 were r and omized to be weaned to a conventional cows ' milk-based formula .  The participants were observed to April 16 , 2013 . INTERVENTIONS The participants received either a casein hydrolysate or a conventional cows ' milk formula supplemented with 20 % of the casein hydrolysate . MAIN OUTCOMES AND MEASURES : Primary outcome was positivity for at least 2 diabetes-associated autoantibodies out of 4 analyzed . Autoantibodies to insulin , glutamic acid decarboxylase , and the insulinoma-associated-2 ( IA-2 ) molecule were analyzed using radiobinding assays and islet cell antibodies with immunofluorescence during a median observation period of 7.0 years ( mean , 6.3 years ) . RESULTS The absolute risk of positivity for 2 or more islet autoantibodies was 13.4 % among those r and omized to the casein hydrolysate formula ( n = 139 ) vs 11.4 % among those r and omized to the conventional formula ( n = 117 ) . The unadjusted hazard ratio for positivity for 2 or more autoantibodies among those r and omized to be weaned to the casein hydrolysate was 1.21 ( 95 % CI , 0.94 - 1.54 ) , compared with those r and omized to the conventional formula , while the hazard ratio adjusted for HLA risk , duration of breastfeeding , vitamin D use , study formula duration and consumption , and region was 1.23 ( 95 % CI , 0.96 - 1.58 ) . There were no clinical ly significant differences in the rate of reported adverse events between the 2 groups . CONCLUSIONS AND RELEVANCE Among infants at risk for type 1 diabetes , the use of a hydrolyzed formula , when compared with a conventional formula , did not reduce the incidence of diabetes-associated autoantibodies after 7 years . These findings do not support a benefit from hydrolyzed formula . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00179777 This study was design ed to assess whether a rice-hydrolysate formula allows normal growth and adequate metabolic balance in infants with cows ' milk protein allergy . Infants ( seven females , nine males ; aged 6–14 months ) were r and omly assigned to receive a rice-hydrolysate formula ( n = 8) or a soy formula ( control group , n = 8) . St and ardized growth indices ( Z scores ) and biochemical parameters were evaluated during a 6-month treatment period . Infants in both groups showed normal growth patterns during the study , and no adverse reactions were seen . Mean plasma biochemical parameters were within the normal ranges , and did not differ between groups . In conclusion , rice-hydrolysate formula may be a nutritionally suitable alternative for infants with cows ' milk protein allergy . Larger studies , with satisfactory power , should be undertaken to confirm these findings For comparison of the antigenicity and allergenicity of three cow 's milk formulas , serum IgE antibodies to cow 's milk , β‐lactoglobulin and casein , and IgG antibodies to β‐lactoglobulin were analyzed in 94 infants with a family history of allergy . They were participating in a r and omized trial comparing the allergy prophylactic effect of feeding an extensively hydrolyzed ( N ) , a partially hydrolyzed ( PH ) , and a regular cow 's milk formula ( RM ) .  Only infants who had been formula‐fed for 3 months or more were included . IgE antibodies to cow 's milk proteins were more common in the RM group ( 22/34 ) than in the N ( 2/31 ) and PH groups ( 3/29 ) . There was a strong correlation between sensitization to cow 's milk and β‐lactoglobulin ( r=0.85 , P<0.001 ) . The IgG responses to β‐lactoglobulin were low in the N group , intermediate in the PH group , and high in the RM group . High responses , as well as detection of IgE antibodies , were associated with development of atopic disease . The low antigenicity and allergenicity of the extensively hydrolyzed formula support its use in allergy prophylaxis . The partial hydrolysate seemed to be less suitable for this purpose 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 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 BACKGROUND & AIMS Feeding during the first months of life might affect risk for celiac disease .  Individuals with celiac disease or type 1 diabetes have been reported to have high titers of antibodies against cow 's milk proteins . Avoidance of cow 's milk-based formula for infants with genetic susceptibility for type 1 diabetes reduced the cumulative incidence of diabetes-associated autoantibodies . We performed a r and omized controlled trial in the same population to study whether weaning to an extensively hydrolyzed formula reduced the risk of celiac disease autoimmunity or celiac disease . METHODS We performed a double-blind controlled trial of 230 infants with HLA-defined predisposition to type 1 diabetes and at least 1 family member with type 1 diabetes . The infants were r and omly assigned to groups fed a casein hydrolysate formula ( n = 113 ) or a conventional formula ( control , n = 117 ) whenever breast milk was not available during the first 6 - 8 months of life . Serum sample s were collected over a median time period of 10 years and analyzed for antibodies to tissue transglutaminase ( anti-TG2A ) using a radiobinding assay , to endomysium using an immunofluorescence assay , and antibodies to a deami date d gliadine peptide using an immunofluorometry assay . Duodenal biopsies were collected if levels of anti-TG2A exceeded 20 relative units . Cow 's milk antibodies were measured during the first 2 years of life . RESULTS Of the 189 participants analyzed for anti-TG2A , 25 ( 13.2 % ) tested positive . Of the 230 study participants observed , 10 ( 4.3 % ) were diagnosed with celiac disease . We did not find any significant differences at the cumulative incidence of anti-TG2A positivity ( hazard ratio , 1.14 ; 95 % confidence interval , 0.51 - 2.54 ) or celiac disease ( hazard ratio , 4.13 ; 95 % confidence interval , 0.81 - 21.02 ) between the casein hydrolysate and cow 's milk groups . Children who developed celiac disease had increased titers of cow 's milk antibodies before the appearance of anti-TG2A or celiac disease . CONCLUSIONS In a r and omized controlled trial of 230 infants with genetic risk factors for celiac disease , we did not find evidence that weaning to a diet of extensively hydrolyzed formula compared with  cow 's milk-based formula would decrease the risk for celiac disease later in life . Increased titers of cow 's milk antibody before anti-TG2A and celiac disease indicates that subjects with celiac disease might have increased intestinal permeability in early life . Clinical Trials.gov Number : NCT00570102 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 Objective : Quantitative balance studies were performed to compare fat and calcium absorption in healthy , full term infants fed casein hydrolysate-based ( CHF ) and soy protein-based ( SPF ) infant formulas with or without palm olein ( PO ) .  Previous studies have reported that PO significantly reduced absorption of both fat and calcium in cow ’s milk-based formulas in which most of the calcium is inherent in the milk protein . In both SPF and CHF virtually all calcium is added as calcium salts . Methods : Two r and omized , blinded , crossover balance studies were conducted in normal term infants using a three-day home balance method . One study evaluated 10 infants fed commercially available CHF with or without PO , and the other study evaluated 12 infants fed commercially available SPF with or without PO .  Fat and calcium absorption were determined based on the weight of formula intake , weight of stools , and measured calcium and fat in formula and stools . Results : Fat and calcium intake did not differ between the groups fed CHF . However , infant ’s calcium and fat absorption was less , 41 ± 6 % ( Mean ± SEM ) and 92.0 ± 0.8 % , respectively , when fed CHF with PO compared to 66 ± 5 % and 96.6 ± 1.1 % , respectively , when fed CHF without PO , ( p < 0.01 ) . For infants fed SPF , fat and calcium intake did not differ between the feeding groups . Mean calcium absorption was also significantly less when infants were fed SPF with PO , 22 ± 3 % , than when fed SPF with no PO , 37 ± 4 % ( p < 0.05 ) . Fat absorption did not differ between the two SPFs . Conclusion : This study demonstrates that PO , as the predominant fat , is associated with significantly lower absorption of calcium from infant formulas in which calcium salts are the source of calcium . These findings corroborate previous reports of this negative effect of PO in cow milk-based infant formulas in which most of the calcium is a component of the cow milk protein source 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 Children with cows ' milk protein allergy ( CMPA ) are at risk of insufficient length and weight gain , and the nutritional efficacy of hypo-allergenic formulas should be carefully assessed . In 2008 , a trial assessed the impact of probiotic supplementation of an extensively hydrolysed casein-based formula ( eHCF ) on acquisition of tolerance in 119 infants with CMPA . First analysis of the study results showed that the studied formula allowed improvement of food-related symptoms . The scoring of atopic dermatitis ( SCORAD ) index was assessed at r and omisation and after 6 months of feeding . A post hoc analysis was performed using WHO growth software 's nutritional survey module ( WHO Anthro version 3.2.2 ) . All infants who were fed the study formula tolerated it well . The SCORAD index significantly improved from r and omisation to 6 months of feeding with the study formula . Anthropometric data indicated a significant improvement in the weight-for-age , length-for-age and weight-for-length z scores , as well as in the restoration of normal BMI . The probiotic supplementation did not show any impact on these parameters . The present data showed that this eHCF was clinical ly tolerated and significantly improved the SCORAD index and growth indices 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 ) BACKGROUND The short- and long-term effects of feeding with hydrolyzed formulas on growth are uncertain . OBJECTIVE Our aim was to investigate the potential differences in body mass index ( BMI ) over the first 6 y of life between infants fed with partially hydrolyzed whey ( pHF-W ) , extensively hydrolyzed whey ( eHF-W ) , extensively hydrolyzed casein ( eHF-C ) , or cow-milk formula ( CMF ) and infants exclusively breastfed for the first 16 wk of life . DESIGN We established a prospect i ve , r and omized , double-blind trial of full-term neonates with atopic heredity in the German birth cohort followed by the German Infant Nutritional Intervention Study through the first 6 y of life . Intention-to-treat and per- protocol analyses of absolute and World Health Organization-st and ardized BMI trajectories for 1840 infants ( pHF-W : n = 253 ; eHF-W : n = 265 ; eHF-C : n = 250 , CMF : n = 276 ; breastfed : n = 796 ) were performed . RESULTS No significant differences in absolute or World Health Organization-st and ardized BMI trajectories were found among the pHF-W , eHF-W , CMF , and breastfed groups during the 6-y follow-up . However , in the eHF-C group , both intention-to-treat and per- protocol analyses showed a significantly slower sex-adjusted BMI gain through the 8th to 48th week of life ( -0.1 to -0.2 lower BMI z score ) but not beyond . Analyses of weight and length revealed that this difference is due to a slightly diminished weight gain in the first year of life because growth in length did not differ among study groups for the entire follow-up . CONCLUSIONS To our knowledge , this is the first r and omized trial investigating both short- and long-term effects of partially and extensively hydrolyzed formula ( pHF-W , eHF-W , eHF-C ) , CMF , and breastfeeding on growth in one trial . Feeding with eHF-C led to a transient lower weight gain in the first year of life . No long-term consequences of different formulas on BMI were observed 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 The present study was design ed to determine the effects of milk composition and the influence of  gastro-oesophageal reflux ( GOR )  on gastric emptying .  Cineoesogastrocintigraphy ( COGS ) was performed in 201 infants between 0 - 1 year of age in order to detect GOR , and provided a means of estimation of the gastric emptying ( GE ) .  Ninety infants appeared free from GOR and constituted the control group ; 111 had GOR . There infants were fed human milk or various st and ard formulae . In addition , 20 infants fed a whey-hydrolysate formula were tested . An appropriate volume of milk was marked with sulfur-colloid Tc ( 200 microcuries ) . Measurements of gastric radioactivity were made 30 min and 120 min after ingestion . For the whole population , the infants with GOR had slightly more rapid GE after 30 min ( P less than 0.05 ) , but , for the same type of milk , there was no significant difference between GOR and controls . GE did not differ with age or sex , but differed mainly according to the type of milk . In the control group , gastric residual content ( GRC ) at 120 min was 18 + /- 11 per cent with human milk ( n = 7 ) , 16 + /- 21 per cent with whey-hydrolysate formula ( n = 8) , 25 + /- 17 per cent with acidified formula ( n = 13 ) , 26 + /- 19 per cent with whey-predominant formula ( n = 22 ) , 39 + /- 17 per cent with casein-predominant formulae ( n = 20 ) , 47 + /- 19 per cent with follow-up formulae ( n = 16 ) and 55 + /- 19 per cent with cow 's milk ( n = 12 ) . ( ABSTRACT TRUNCATED AT 250 WORDS 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 Prolonged diarrhea following an acute episode of dehydrating gastroenteritis in infants is often treated by the empirical removal of both cow 's milk protein and lactose from the feed , as they both have been implicated in the prolongation of diarrhea . In order to assess the efficacy of this policy and to determine whether there are any advantages in using a lactose-free semi-elemental feed in this situation , infants with prolonged dehydrating gastroenteritis from a developing community in South Africa were studied . Male black children between the ages of 6 weeks and 2 years with prolonged dehydrating gastroenteritis ( requiring intravenous fluids for longer than 72 h to maintain hydration ) were r and omly assigned to receive one of four feeds if the stool weight was greater than 30 g/kg body weight/24 h on the fourth day of admission . The four formula feeds were a partially modified cow 's milk formula ; a lactose-free , casein-containing formula ; a lactose-free , soy-protein-containing formula ; and a lactose-free , whey-hydrolysate-containing formula .  Stool weights were measured for the following 3 days . Seventy-two children were enrolled into the study .  Stool weights were similar in the four groups at the start of the trial , and fell significantly over the trial period in those groups receiving the lactose-free feeds . Mean stool weight in the cow 's milk formula group did not change . Thus , it appears that the continued feeding of a cow 's milk-based lactose-containing formulae to infants with prolonged dehydrating gastroenteritis adversely affects their recovery . ( ABSTRACT TRUNCATED AT 250 WORDS 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 ) 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 The objective of the present study was to assess the effect of adding specific prebiotics to st and ard formula feeding on the number of fever episodes  in the first year of life . In the present r and omised , double-blind , placebo-controlled trial in seven centres in five West European countries , 830 healthy term infants , without a first-degree family history of allergic disease , of mothers who indicated to give only formula feeding were r and omised either to receive a st and ard non-hydrolysed cows ' milk-based formula to which a mixture of specific oligosaccharides was added ( prebiotics group ( PG ) ) , or to receive a similar formula without oligosaccharides ( control group ( CG ) ) . A separate reference group consisted of 300 breast-fed infants . The primary outcome was the number of fever episodes prospect ively documented by the parents . There was no difference in the number of fever episodes between the PG ( median value 1·19 ; 25th-75th percentile 0·09 - 2·34 ) and CG ( 1·16 ; 25th-75th percentile 0·06 - 2·38 ) . The median number of fever episodes in the separate breast-feeding reference group was 1·24 ( 25th-75th percentile 0·51 - 3·45 ) . There was no effect of adding specific prebiotics to st and ard formula feeding in reducing the number of fever episodes in the present study BACKGROUND The long-term effect of nutritional intervention with hydrolyzed infant formulas on allergy development has not been sufficiently evaluated . OBJECTIVE We performed a follow-up of the German Infant Nutritional Intervention study until 6 years of life to investigate the long-term allergy-preventive effect of 3 hydrolyzed infant formulas compared with cow 's milk formula ( CMF ) in a r and omized , double-blind trial . METHODS Between 1995 and 1998 , 2252 newborns with atopic heredity were r and omly assigned at birth to receive one of 4 blinded formulas : partially or extensively hydrolyzed whey formula , extensively hydrolyzed casein formula , or CMF as milk substitute for the first 4 months when breast-feeding was insufficient . The cohort was followed from birth until 6 years of age with yearly question naires . Outcomes were physician-diagnosed allergic diseases ( atopic dermatitis , food allergy , allergic urticaria , asthma , and hay fever/allergic rhinitis ) . Log-binomial regression modeled with generalized estimation equations was used for the statistical analysis . RESULTS In the intent-to-treat analysis the relative risk of a physician 's diagnosis of allergic manifestation ( AM ) compared with CMF was 0.82 ( 95 % CI , 0.70 - 0.96 ) for partially hydrolyzed whey formula , 0.90 ( 95 % CI , 0.78 - 1.04 ) for extensively hydrolyzed whey formula , and 0.80 ( 95 % CI , 0.69 - 0.93 ) for extensively hydrolyzed casein formula . The corresponding figures for atopic eczema were 0.79 ( 95 % CI , 0.64 - 0.97 ) , 0.92 ( 95 % CI , 0.76 - 1.11 ) , and 0.71 ( 95 % CI , 0.58 - 0.88 ) , respectively . In the per- protocol analysis all effects were stronger and significant . No significant effect on other AMs was found . CONCLUSION The data confirm a long-term allergy-preventive effect of hydrolyzed infant formulas on AM and atopic eczema until 6 years of age Importance Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility . There are no intact proteins in extensively hydrolyzed formulas . Objective To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children . Design , Setting , and Participants An international double-blind r and omized clinical trial of 2159 infants with human leukocyte antigen – conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries ; 1081 were r and omized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula .  The follow-up of the participants ended on February 28 , 2017 . Interventions The participants received either a casein hydrolysate or a conventional adapted cow ’s milk formula supplemented with 20 % of the casein hydrolysate . The minimum duration of study formula exposure was 60 days by 6 to 8 months of age . Main Outcomes and Measures Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria . Secondary outcomes included age at diabetes diagnosis and safety ( adverse events ) . Results Among 2159 newborn infants ( 1021 female [ 47.3 % ] ) who were r and omized , 1744 ( 80.8 % ) completed the trial . The participants were observed for a median of 11.5 years ( quartile [ Q ] 1-Q3 , 10.2 - 12.8 ) . The absolute risk of type 1 diabetes was 8.4 % among those r and omized to the casein hydrolysate ( n = 91 ) vs 7.6 % among those r and omized to the conventional formula ( n = 82 ) ( difference , 0.8 % [ 95 % CI , −1.6 % to 3.2 % ] ) . The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group , duration of breastfeeding , duration of study formula consumption , sex , and region while treating study center as a r and om effect was 1.1 ( 95 % CI , 0.8 to 1.5 ; P = .46 ) . The median age at diagnosis of type 1 diabetes was similar in the 2 groups ( 6.0 years [ Q1-Q3 , 3.1 - 8.9 ] vs 5.8 years [ Q1-Q3 , 2.6 - 9.1 ] ; difference , 0.2 years [ 95 % CI , −0.9 to 1.2 ] ) . Upper respiratory infections were the most common adverse event reported ( frequency , 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group ) . Conclusions and Relevance Among infants at risk for type 1 diabetes , weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years . These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes . Trial Registration clinical trials.gov Identifier : BACKGROUND Previous analysis in a prospect i ve , population -based cohort reported reduced weight gain in children fed extensively hydrolyzed casein ( eHF-C ) formula during the first year of life but showed no effect on growth between 1 and 6 y of life . No studies have been conducted in children up to the age of 10 y. OBJECTIVE The objective was to investigate potential differences in body mass index ( BMI ) over the first 10 y of life between infants fed within the intervention period of the first 16 wk of life with partially hydrolyzed whey ( pHF-W ) , extensively hydrolyzed whey ( eHF-W ) , eHF-C , or cow-milk formula ( CMF ) and infants exclusively breastfed ( BF ) within the intervention period . DESIGN This was a prospect i ve , r and omized , double-blind trial in full-term neonates with atopic heredity in the German birth cohort German Infant Nutritional Intervention ( GINI ) followed through the first 10 y of life . Analyses of absolute and World Health Organization (WHO)-st and ardized BMI trajectories for 1840 infants [ pHF-W ( n = 253 ) , eHF-W ( n = 265 ) , eHF-C ( n = 250 ) , CMF ( n = 276 ) , and BF ( n = 796 ) ] were conducted according to intention-to-treat principles . RESULTS Except for the previously reported slower BMI gain in infants fed with eHF-C formula within the first year of life , no significant differences in absolute or WHO-st and ardized BMI trajectories were shown between the pHF-W , eHF-W , eHF-C , CMF , and BF groups thereafter up to the age of 10 y. CONCLUSIONS Extension of the follow-up period from 6 to 10 y for this r and omized controlled trial showed no long-term consequences on BMI for the 4 infant formulas considered . These data need to be confirmed in future studies BACKGROUND Partially hydrolyzed whey formula ( pHWF ) has been recommended for infants with a family history of allergic disease at the cessation of exclusive breast-feeding to promote oral tolerance and prevent allergic diseases . OBJECTIVE To determine whether feeding infants pHWF reduces their risk of allergic disease . METHODS A single-blind ( participant ) r and omized controlled trial was conducted to compare allergic outcomes between infants fed a conventional cow 's milk formula , a pHWF , or a soy formula . Before birth , 620 infants with a family history of allergic disease were recruited and r and omized to receive the allocated formula at cessation of breast-feeding . Skin prick tests to 6 common allergens ( milk , egg , peanut , dust mite , rye grass , and cat d and er ) were performed at 6 , 12 , and 24 months . The primary outcome was development of allergic manifestations ( eczema and food reactions ) measured 18 times in the first 2 years of life . RESULTS Follow-up was complete for 93 % ( 575/620 ) at 2 years and 80 % ( 495/620 ) at 6 or 7 years of age . There was no evidence that infants allocated to the pHWF ( odds ratio , 1.21 ; 95 % CI , 0.81 - 1.80 ) or the soy formula ( odds ratio , 1.26 ; 95 % CI , 0.84 - 1.88 ) were at a lower risk of allergic manifestations in infancy compared with conventional formula . There was also no evidence of reduced risk of skin prick test reactivity or childhood allergic disease . CONCLUSION Despite current dietary guidelines , we found no evidence to support recommending the use of pHWF at weaning for the prevention of allergic disease in high-risk infants Sixty-eight bottle-fed babies under 9 months of age with mild acute gastroenteritis were observed to evaluate current feeding regimens following acute gastroenteritis in infancy . All babies were fed for 24 h with a glucose-electrolyte mixture ( GEM ) and then r and omly assigned to either a gradual re introduction to their normal milk , i.e. , slow re grade ; immediate return to full-strength formula ; or a rapid re grade to a hypoallergenic whey hydrolysate formula . All groups were well matched for age , sex , ethnic origin , nutritional state , and degree of hydration . There was no significance difference in stool frequency or reducing substances , vomiting , and duration of hospital stay between the three groups . Many infants ( 6/24 ) refused to take the whey hydrolysate formula , presumably because of unpalatability . Weight gain was more rapid when full-strength milk was given . Clinical relapse developed in 12 ( 17 % ) of patients . An enteric pathogen was detected in eight of this group and cow 's milk protein intolerance in three ( one from each feeding group ) . No infant had clinical ly significant lactose intolerance , in marked contrast to previous experience at Queen Elizabeth Hospital . In this group of previously healthy , well-nourished babies with mild acute gastroenteritis , there was no advantage in regrading slowly to milk or a hypoallergenic formula . An immediate return to normal formula 24 h after GEM feeding was well tolerated and simpler for parents 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 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 : Exposure to cow ’s milk protein in early infancy could lead to increased rates of allergic diseases later in life . We investigated whether feeding a protein-hydrolyzed formula ( HF ) in the first 6 months of life decreased allergic diseases up to 36 months later . Methods : Newborns who had at least 1 first-degree family member with a history of atopy and could not breast-feed were enrolled . They were fed with HF or cow ’s milk infant formula ( CM ) for at least 6 months via an open-label protocol and were monitored prospect ively at 6 , 18 and 36 months of age to assess allergy sensitization and allergic diseases . Results : A total of 1,002 infants were enrolled and 679 infants were consistently fed the same formula for the first 6 months of life ( 345 HF and 334 CM ) . The percentage of food sensitization ( especially to milk protein ) was significantly lower in the HF group than in the CM group at 36 months ( 12.7 vs. 23.4 % , p = 0.048 ) . There was no significant difference in the prevalence of aeroallergen sensitization between the groups . Occurrence of allergic diseases during the first 3 years of life was significantly correlated with aeroallergen sensitization , but not to food allergen sensitization , parental atopy or feeding types . Conclusions : Infants fed with HF during the first 6 months of life had a significantly lower percentage of sensitization to milk protein allergens , but not allergic diseases during the first 3 years of life . Avoidance of cow ’s milk protein alone in infancy is not enough to decrease rates of allergic diseases This study investigated the effect of changing the formulas of colicky infants and addressed the method ologic flaws of earlier studies . Attention was paid to issues of design ing a blind study , providing a washout period , and measuring and reproducing the effect . In this r and omized , double-blind trial , three changes of formula were made : for each of four 4-day periods , colicky infants alternately received a casein hydrolysate formula ( Nutramigen ) and a formula containing cow milk . Mothers recorded crying in diaries and indicated which crying episodes they considered to have been caused by colic . Nine infants were started on Nutramigen and eight on the cow milk formula .  With the first formula change there was significantly less crying and colic in infants when they were fed Nutramigen than when they were fed cow milk ( p less than 0.01 ) ; with the second change there was less colic when infants were fed Nutramigen ( p less than 0.05 ) but not significantly less crying . By the third change there were no significant differences between formulas . Further analyses demonstrated that there were more clinical ly meaningful positive responses ( a change in crying by at least one third ) to Nutramigen than to cow milk ( p less than 0.05 ) . However , only one subject had a clinical ly meaningful response in colic to all three formula changes . These results demonstrate that in some instances , colic improves with elimination of cow milk formula . However , the effect diminishes with time , and only infrequently is the effect reproducible 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 Aims /hypothesisWe aim ed to assess the feasibility of a dietary intervention trial with weaning to hydrolysed formula in infants at increased risk of type 1 diabetes and to study the effect of the intervention on the emergence of diabetes-associated autoantibodies in early childhood . Methods We studied 242 newborn infants who had a first-degree relative with type 1 diabetes and carried risk-associated HLA-DQB1 alleles . After exclusive breastfeeding , the infants underwent a double-blind , r and omised pilot trial of either casein hydrolysate ( Nutramigen ; Mead Johnson ) or conventional cow ’s milk-based formula  until the age of 6–8 months . During a mean observation period of 4.7 years , autoantibodies to insulin , anti-glutamic acid decarboxylase and insulinoma-associated antigen-2 were measured by radiobinding assays , and islet cell antibodies ( ICA ) by immunofluorescence . Results The feasibility of screening and identifying a cohort of first-degree relatives with HLA-conferred disease susceptibility , enrolling them in a dietary intervention trial and following them for seroconversion to autoantibody positivity is established . The cumulative incidence of autoantibodies was somewhat smaller in the casein hydrolysate vs control formula group , suggesting the need for a larger well-powered study . After adjustment for duration of study formula feeding , life-table analysis showed a significant protection by the intervention from positivity for ICA ( p=0.02 ) and at least one autoantibody ( p=0.03 ) . Conclusions /interpretationThe present study provides the first evidence ever in man , despite its limited power , that it may be possible to manipulate spontaneous beta cell autoimmunity by dietary intervention in infancy BACKGROUND Recommendations for primary prevention of allergic diseases in high-risk children include feeding with hydrolyzed formulas if breast-feeding is insufficient . OBJECTIVE The primary objective of the German Infant Nutritional Intervention study was to investigate the allergy preventive effect of 3 hydrolyzed formulas compared with cow 's milk formula in the first 3 years of life in a r and omized , double-blind trial . METHODS Between 1995 and 1998 , 2252 newborns with atopic heredity were allocated to a group receiving cow 's milk formula , partially or extensively hydrolyzed whey formula , or extensively hydrolyzed casein formula as a milk substitute for the first 4 months if breast-feeding was insufficient . Main outcome parameters were allergic manifestations , atopic dermatitis ( AD ) , and asthma . RESULTS After 3 years , 396 of 2252 children ( 17.6 % ) had dropped out . Breast-fed infants without formula feeding during the intervention ( n = 889 ) were considered separately . A significant reduction of the incidence of AD was achieved with the extensively hydrolyzed casein formula in the intention-to-treat ( ITT ; n = 1363 ) and per protocol ( PP ; n = 904 ) analyses ( ITT : population odds ratio [ 95 % CI ] , 0.67 [ 0.45 - 0.99 ] ; PP : adjusted odds ratio [ OR(adj ) ] , 0.53 [ 0.32 - 0.88 ] ) , and with the partially hydrolyzed whey formula in the PP analysis ( ITT : population odds ratio , 0.76 [ 0.52 - 1.11 ] ; PP : OR(adj ) , 0.60 [ 0.37 - 0.97 ] ) . None of the formulas reduced the incidence of asthma . CONCLUSION The risk for AD , but not for asthma , can be reduced with certain cow 's milk hydrolyzates in high-risk infants when breast-feeding is insufficient . CLINICAL IMPLICATION S Early nutritional intervention in high-risk children has significant influence on the incidence of AD , but not of asthma 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 Cow 's milk protein allergy ( CMPA ) is best treated by complete elimination of cow 's milk from the diet . For infants with CMPA who can not be breast-fed , formulas based on extensively hydrolyzed proteins or on amino acids are the preferred substitutes for cow 's milk-based formulas . In this study , we compared the tolerance and growth of infants with CMPA who were fed a new extensively hydrolyzed formula containing lactose ( eHF ) with those who were fed an amino acid formula ( AAF ) . This was a prospect i ve , multi-center , r and omized , reference-controlled study . Seventy-seven infants < 12 months old with suspected CMPA were enrolled . In 66 of these , CMPA was confirmed by oral challenge in a double-blind , placebo-controlled food challenge ( DBPCFC ) or by a medical history of severe allergic reaction to cow 's milk and a positive skin prick test . These infants were then tested for their reaction to eHF and AAF in a DBPCFC . All infants tolerated both formulas and were r and omized to receive either eHF ( n = 34 ) or AAF ( n = 32 ) for 180 days . Growth ( weight , length , and head circumference ) and tolerance [ skin , gastro-intestinal , and respiratory tract symptoms of allergy ] were evaluated after 30 , 60 , 90 , and 180 days . There were no significant differences between the two groups in any of the growth measurements . Length and head circumference were similar to Euro-growth st and ards , but weight was slightly lower . Gastro-intestinal and respiratory tract symptoms of allergy were also similar in the two groups . However , whereas SCORAD scores for atopic dermatitis remained constant throughout the study in infants-fed eHF , there was a slight decrease in those fed AAF . Infants-fed eHF had significantly fewer incidents of vomiting than infants-fed AAF and a significantly higher frequency of soft stools . The new eHF is safe and well tolerated in infants diagnosed with CMPA This study found that two casein hydrolysate formulas varying in composition were equally effective in managing  colicky symptoms associated with protein sensitivity . Both hydrolysate formulas were associated with a significant , comparable reduction in crying duration and intensity from baseline in 15 of 22 infants with complete data . Subsequent challenge data suggest that the population studied were infants experiencing colicky symptoms due to protein sensitivity . A greater proportion of infants showed a positive reaction ( ≥1.5h of crying/d ) to the protein challenges than the placebo challenge , and crying was rated as more intense during whey and milk protein challenges OBJECTIVE To determine whether an earlier observation , that infants fed a casein-hydrolysate formula ( Nutramigen ) have lower neonatal jaundice levels than those fed st and ard formulas , would be repeated in a larger independent group of infants with more frequent measurements and more rigorous statistical analysis . DESIGN Newborn infants were fed human milk , a st and ard whey-predominant formula ( Enfamil ) , or Nutramigen  ( n = 20 for each group ) during the first 3 weeks of life . Transcutaneous jaundice index was measured daily for the first week of life and every 2 to 3 days thereafter , using a noninvasive jaundice meter . Linear regression models of the data were constructed , vali date d , and compared statistically . SETTING General community hospital with subsequent home visitation . PARTICIPANTS Healthy , term newborn infants selected by convenience , based on time of birth . INTERVENTION Infants were exclusively fed human milk , Enfamil , or Nutramigen . Formulas were r and omly assigned . MAIN OUTCOME MEASURE Jaundice index , a transcutaneous measurement of jaundice . RESULTS The jaundice index differed significantly among the 3 groups . Paired comparisons showed that the jaundice index of the Nutramigen group was significantly lower than that of the Enfamil group ( on days 6 - 16 ) and the human milk group ( on days 3 - 20 ) . The jaundice index of the Enfamil-fed group was significantly lower than that of the human milk group on days 13 to 19 . CONCLUSIONS Jaundice levels are lower in neonates fed Nutramigen rather than Enfamil and both these groups have lower jaundice levels than breast-fed infants 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 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 Abstract Extensively hydrolyzed ( EH ) formula with Lactobacillus rhamnosus GG ( LGG ) was demonstrated to alleviate cow ’s milk allergy ( CMA ) symptoms and promote faster acquisition of tolerance to cow ’s milk protein . We previously demonstrated that partially hydrolyzed ( PH ) and EH formulas with LGG supported normal growth in healthy-term infants through 120 days of age . The objective of the current study was to evaluate growth , development , and specific adverse events through 5 years of age in participants from that cohort who continued receiving study formula . Infants who completed a double-blind , r and omized growth and tolerance study were eligible to continue receiving the assigned study formula through 1 year of age ( control : EH casein formula , EHF , or one of two investigational formulas : EH casein formula with LGG ( EHF-LGG ) or a PH formula with LGG ( PHF-LGG ) ) and participate in follow-up through 5 years of age . Anthropometric measures , behavior development , and specific adverse events were recorded . No significant differences in achieved weight and height or behavioral development outcomes at 3 or 5 years of age were observed among study groups . Few statistically significant differences in the incidence of specific infection-related events through years 3 or 5 were observed among study groups , none of which were considered clinical ly relevant . Conclusion : Extensively and partially hydrolyzed formulas with LGG were associated with normal growth and development and long-term safety through 5 years of age . What is Known:• Infants with cow ’s milk allergy often experience allergic manifestations that can lead to poor nutrition status and poor growth.• Providing partially hydrolyzed ( PH ) and EH formulas with or without LGG in infants can support normal growth in healthy-term infants . What is New:• This study provides long-term safety data for the first 5 years of life on the use of extensively and partially hydrolyzed formulas with LGG when fed through 1 year of age.• Extensively and partially hydrolyzed formulas with LGG are associated with normal growth , development , and long-term safety through 5 years of age Objectives : The aim of this study was to evaluate the efficacy on crying episodes owing to infantile colic of a new infant formula containing partially hydrolysed whey proteins , prebiotic oligosaccharides ( OS ) , with a high β-palmitic acid content . Design : Prospect i ve r and omized controlled study . Setting : Italy . Subjects : Two hundred and sixty-seven formula-fed infants , aged less than 4 months , with infantile colic , were r and omized to receive either the new infant formula ( study treatment ( ST ) ) or a st and ard formula and simethicone ( 6 mg/kg twice a day ) ( control treatment ( CT ) ) . A question naire was given to parents to evaluate for 14 days the daily number of colic episodes and crying time . Results : Out of the 199 infants who completed the study , 96 were treated with the new formula and 103 were not treated . Infants receiving the new formula had a significant decrease in colic episodes after 1 week ( 2.47±1.94 at day 7 vs 5.99±1.84 at the study entry ) compared to infants receiving the CT ( 3.72±1.98 at day 7 vs 5.41±1.88 at the study entry ) ( P<0.0001 ) . Also at day 14 , the crying episodes were significantly different between the two groups of infants ( 1.76±1.60 in ST vs 3.32±2.06 in CT ) ( P<0.0001 ) . Conclusions : The use of a partially hydrolysed formula supplemented with fructo- and galacto-OS induces a reduction of crying episodes in infants with colic after 7 and 14 days when compared with a st and ard formula and simethicone . Sponsorship : The study was supported by funds from Numico , Italy 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 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 OBJECTIVE To estimate the cost-effectiveness of using an extensively hydrolysed formula ( eHF ; Nutramigen ) compared with an amino acid formula ( AAF ; Neocate ) as first-line treatment for cow milk allergy ( CMA ) in the UK , from the perspective of the National Health Service ( NHS ) . METHOD A decision model was constructed depicting the treatment paths and associated re source use attributable to first-line management of CMA with the two formulae . The model was based on the case records of 145 AAF-treated infants and 150 matched eHF-treated patients from The Health Improvement Network ( THIN ) data base [ a nationally representative data base of patients registered with general practitioners ( GPs ) in the UK ] . The model estimated the costs and consequences of patient management over 12 months following their initial GP visit for CMA . RESULTS Patients presenting with a combination of gastrointestinal symptoms and eczema accounted for 44 % of all patients in both groups . Those with gastrointestinal symptoms alone and eczema alone accounted for up to a further 39 % and 13 % , respectively . Those with  urticaria  and faltering growth  accounted for < 5 % and ≤6 % of all patients , respectively . Patients ' age and weight at presentation was a mean 2.6 - 2.8 months and 4.4 kg , respectively . It took a mean 2.2 months to start a formula after initially seeing a GP . Time to symptom resolution following the start of treatment was 1.2 months in both groups ; hence , the mean number of symptom-free months during the 12 months following the initial GP visit was estimated to be 8.6 months in both groups . Patients treated with an eHF had a mean 13.1 GP visits over the 12 months compared to 17.5 visits made by AAF-treated patients ( p < 0.001 ) . The NHS cost of managing a CMA infant over the first 12 months following initial presentation to a GP was estimated to be £ 1853 and £ 3161 for an eHF-treated and AAF-treated patient , respectively . CONCLUSION Starting treatment for CMA with an eHF was the cost-effective option , as there were no significant differences in clinical outcomes between the two groups . A prospect i ve , r and omized controlled trial would allow a definitive confirmation of these findings The possible role of cows milk intolerance in the aetiology of infant colic was evaluated in 19 babies presenting to their health visitor or general practitioner in one town . Over a three week period a st and ard modified cows milk formula was compared with a soya milk formula on a double blind basis . The duration of colic symptoms was significantly reduced during the week on soya milk ( P less than 0.01 ) , with 11 out of 19 babies fulfilling the diagnostic criteria for cows milk intolerance . Four babies whose symptoms failed to improve either spontaneously or with soya milk were given a hydrolysed protein milk with a positive response in two , confirmed by challenge testing . Thus in 13 out of 19 babies ( 68 % ) the symptoms of infant colic resolved almost completely with dietary change AIM AND OBJECTIVE The aim of the study was to evaluate the effectiveness of massage , sucrose solution , herbal tea or hydrolysed formula , each used individually in the treatment of infantile colic . BACKGROUND The term colic describes a group of symptoms that occur frequently in infants , consisting of paroxysmal abdominal pain and severe crying . Infant colic is of importance for both parents and the community health services that provide families with care , and is therefore an important clinical problem that is amenable to nursing interventions . DESIGN This prospect i ve and r and omised-controlled study involved 175 infants in Turkey . METHODS Data were gathered by using Wessel criteria ; parents wrote a daily structured diary , recording the onset and duration of crying . Patients were assigned r and omly into four different intervention groups ( massage , sucrose solution , herbal tea and hydrolysed formula ) and control group .  Duration of crying following each intervention was recorded in the diary by parents for a one week period . RESULTS There was a significant reduction in crying hours per day in all intervention groups . The difference between mean duration of total crying ( hours/day ) before and after the intervention infants in hydrolysed formula group was found higher than massage , sucrose and herbal tea group . The difference between mean duration of total crying(hours/day ) before and after the intervention infants in massage group was found lower than other intervention groups and all groups . CONCLUSION Our findings demonstrated that varied interventions such as administration of massage , sucrose solution , herbal tea and hydrolysed formula are effective in the treatment of colic . The difference between mean duration of total crying ( hours/day ) before and after the intervention in hydrolysed formula group was found higher than other intervention groups . Hydrolysed formula was the most effective in reducing the duration of crying ( hours/day ) when compared with the other intervention groups . Massage intervention yielded the least symptomatic improvement among all the interventions . RELEVANCE TO CLINICAL PRACTICE Colic treatment models used in this study can be used by nurses in neonatal and primary healthcare setting s as an aid to families for the treatment of infantile colic The influence of early feeding on the risk of atopic diseases has been studied in full-term newborns , not in very low birth weight infants ( VLBW ) . The study evaluated effect of early feeding of VLBW infants with either cow 's milk-based formula ( CMF ) or extensively hydrolyzed milk formula ( HF ) on incidence of atopic diseases and markers of atopy at 5 - 7 years of age . This was a follow-up of the r and omized , double-blind study evaluating the influence of different enteral feeding protocol s on the early morbidity of VLBW infants . In the original study 80 children were r and omly allocated into 2 groups receiving during first month of life HF ( experimental group ) or CMF ( control group ) . At the age of 5 - 7 years , 62 children among 74 available ( 84 % ) with mean birthweight 1124 g were evaluated according to st and ardized ISAAC ( International Study of Asthma and Allergies in Childhood ) protocol . Total IgE level , specific IgE , lymphocyte CD4+CCR4+/CD4+CXCR3 + ratio and skin prick tests ( SPT ) were done . Prevalence of obvious allergic diseases was not significantly different between the studied groups ( HF : 12/33 ; CMF : 6/29 ; RR [ relative risk ] HF vs CMF : 1.76 ; 95%CI [ confidence interval ] : 0.76 - 4.09 ) . Comparison of atopic status across groups revealed similar rate of positive markers of atopy : IgE ( RR : 2.57 95%CI : 0.91 - 8,08 ) , SPT ( RR : 5.13 ; 95%CI : 0.93 - 31.6 ) , lymphocyte CD4+CCR4+/CD4+CXCR3 + ratio ( OR : 2.32 ; 95%CI : 0.78 - 7.53 ) in the both studied groups . Based on the carried out follow-up study we were unable to confirm the usefulness of hydrolyzed formula in prevention of allergy in an unselected cohort of very low birth weight infants Healthy , term infants received extensively hydrolyzed casein formula ( EHF ; control ) , the same formula supplemented with Lactobacillus rhamnosus GG ( EHF-LGG ) , or partially hydrolyzed whey : casein ( 60:40 ) formula supplemented with LGG ( PHF-LGG ) , in this double-blind , r and omized , controlled , parallel , prospect i ve study . Anthropometric measures and 24-hour dietary and tolerance recalls were obtained at 30 , 60 , 90 , 120 , and 150 days of age . Blood collected in a subset of infants was analyzed for fatty acid profiles in plasma and red blood cells and for markers of allergic sensitization . Adverse events were recorded throughout the study . Growth rates were not statistically different between EHF and PHF-LGG and between EHF and EHF-LGG from day 14 to day 30 , 120 , or 150 . No relevant differences in formula tolerance , adverse events , or allergic and immune markers were demonstrated between groups . The extensively and partially hydrolyzed formulas supplemented with LGG support normal growth in healthy , term infants and are well tolerated and safe Oral administration of foreign proteins , e.g. cow 's milk ( CM ) proteins , stimulates the immune system and induces humoral and cellular immune response against these antigens in infants . Up-regulation of adhesion molecules is known to be associated with activation of the immune system . The purpose of the study was to examine whether orally administered CM proteins induce elevation in soluble adhesion molecules , i.e. intercellular adhesion molecule-1 ( ICAM-1 ) and L-selectin , in infants . In a double-blind trial , 10 infants received CM-based formula and 10 infants casein hydrolysate formula until the age of 9 mo . The infants of mothers with insulin-dependent diabetes mellitus ( IDDM ) were recruited into a pilot study of a trial for primary prevention of IDDM by elimination of CM proteins from the diet during early infancy . A cord blood sample and peripheral blood sample s were taken at the ages of 3 , 6 , 9 , and 12 mo of age . The levels of soluble ICAM-1 and L-selectin were measured by ELISA . The levels of soluble ICAM-1 were higher at the ages of 3 , 6 , 9 , and 12 mo in infants who received CM-based formula than in infants who received hydrolyzed formula ( p = 0.05 ) . Instead , no difference was found in the the levels of soluble L-selectin . The levels of soluble ICAM-1 and L-selectin were higher in all infants when compared with the levels reported in adults or to the levels seen in cord blood . Orally fed CM proteins induce an elevation in soluble ICAM-1 in infants . This may reflect the generation of an immune response against these proteins , because ICAM-1 has an important costimulatory role in lymphocyte activation Background : Colic , regurgitation and constipation are common feeding problems in formula‐fed infants that might benefit from dietary treatment . A formula containing fructo‐ and galacto‐oligosaccharides , partially hydrolysed proteins , low levels of lactose and palmitic acid in the β position and higher density has been tested to reduce the occurrence of these symptoms . The aim of this prospect i ve study was to describe the effects of such a formula in infants with minor gastrointestinal disorders . Methods : An observational prospect i ve trial involving practising Italian paediatricians was performed .  Formula fed‐infants up to 90 d of age with minor gastrointestinal problems such as infantile colics and /or regurgitation and /or constipation were enrolled in the study from January 2001 to May 2001 . The study was completed within 14 d of treatment . On days 1 , 7 and 14 the infants were visited by the paediatricians . Parents were given a structured diary to record daily episodes of colic , regurgitation and type and number of stools . Results : Of the 932 infants enrolled , 604 completed the study . Of the 214 infants with colic , 169 ( 79 % ) demonstrated a reduction in frequency of colic from 4.1 ± 2.0 per day at the beginning of the study to 2.0 ± 1.8 at the end of the study ( I.C. 95 % : 1.72–2.39 ; p < 0.005 ) . A reduction in the number of episodes of colic of 1.8 per day at the beginning of the study ( I.C. 95 % : 1.49–2.11 ; p < 0.05 ) was recorded between day 1 and day 7 , and of 0.26 ( I.C. 95 % : 0.15–0.37 ; p < 0.05 ) between day 7 and day 14 . Of the 201 infants with regurgitation problems , 141 ( 70 % ) demonstrated a reduction of frequency of the symptoms from 4.2 ± 2.0 per day at the beginningof the study to 2.1 ± 2.2 at the end of the study ( I.C. 95 % : 1.75–2.35 ; p < 0.005 ) . A reduction of 1.87 in the number of regurgitation episodes was reported between day 1 and day 7 ( I.C. 95 % : 1.57–2.16 ; p < 0.05 ) and of 0.18 ( I.C. 95 % : 0.06–0.31 ; p < 0.05 ) between day 7 and day 14 . Of the 232 infants with constipation , 147 ( 63 % ) demonstrated an increase in the daily number of stools of 0.42 ( I.C. 95 % : 0.5–0.3 ; p < 0.005 ) . An increase in stool frequency of 0.41 ( I.C. 95 % : 0.51–0.23 ; p < 0.05 ) was reported between day 1 and day 7 , and of 0.04 ( I.C. 95 % : 0.22–0.14 ; p= ns ) between day 7 and day 14 . Parents’evaluation of the formula was 7.9 ± 1.8 ( score 0–10 ) ; 550 parents ( 91 % ) gave a positive judgement ( score > 6 ) . The evaluation by the paediatricians of the improvement in symptoms after the treatment was 8.2 ± 1.5 ; 574 ( 95 % ) a positive effect ( score > 6 ) 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 Objectives : To come even closer to the functional composition of human milk , acidic oligosaccharides ( AOS ) from pectin were added to well known neutral prebiotics ( galacto-oligosaccharides ( GOS ) and long-chain fructo-oligosaccharides ( FOS ) ) . The effect of AOS and GOS/FOS/AOS on intestinal flora , stool characteristics as well as acceptance and tolerance was investigated . Methods : Human milk contains 75 % to 85 % neutral and 15 % to 25 % acidic oligosaccharides . In this prospect i ve , r and omized , double blind study , a mixture of 80 % neutral oligosaccharides ( from long-chain galacto- and long-chain fructo-oligosaccharides ) with 20 % acidic oligosaccharides derived from pectin hydrolysis was investigated . Forty-six term infants were fed a st and ard formula supplemented with either maltodextrin as control ( n = 15 ) , or with 0.2 g acidic oligosaccharides ( n = 16 ) , or with the latter plus 0.6 g neutral oligosaccharides ( mixture of galacto- and fructo-oligosaccharides ; n = 15 ) . Fecal flora using plating technique and pH were measured . Stool characteristics and possible side effects ( crying , vomiting , and regurgitation ) were recorded . Results : There was no difference in the bifidobacteria counts between the control and the group supplemented with acidic oligosaccharides alone ( 8.75 ± 0.50 vs. 8.58 ± 0.94 log colony forming units [CFU]/g stool ) . In infants fed the combination of acidic and neutral oligosaccharides , bifidobacteria were increased ( 9.61 ± 0.70 log CFU/g stool ; P < 0.01 ) . The same pattern was observed with lactobacilli . Stool consistency was softest in infants fed the complete oligosaccharide mixture , but also in those fed formula supplemented with acidic oligosaccharides alone , the stool consistency was significantly softer compared with the control group . Fecal pH increased in the controls , remained constant in acidic oligosaccharides alone , and decreased in the complete mixture of oligosaccharides group . Conclusion : There was no difference in growth , crying , vomiting , and regurgitation patterns between the groups . In summary , acidic oligosaccharides from pectin hydrolysate are well tolerated as ingredient in infant formulae but do not affect intestinal microecology Objective : To evaluate growth , tolerance and plasma biochemistries in infants fed an experimental rice protein-based infant formula .  Design : R and omized , blinded , 16 week parallel feeding trial of 65 healthy infants fed either an experimental partially hydrolyzed rice protein-based infant formula fortified with lysine and threonine ( RPF , n = 32 ) , or a st and ard intact cow ’s milk protein-based formula ( CMF , n = 33 ) as a control . Assessment s occurred at enrollment ( average 2 days ) , 2 , 4 , 8 , and 16 weeks of age . Results : Growth as indicated by weight , length , and head circumference was not different between the 2 formula groups . All plasma biochemistries for both groups were within reference normal range . However , RPF group had lower phosphorus and urea nitrogen , lower essential amino acids except threonine , which was higher , and lower ratio of essential ( including semi-essential ) to non-essential amino acids . Differences in the concentrations and ratios of amino acids became less as feeding progressed with age . Plasma total protein , albumin , prealbumin , calcium , magnesium , and alkaline phosphatase were not different between groups . Conclusion : Healthy infants fed an experimental partially hydrolyzed rice protein-based formula  had normal growth , tolerance , and plasma biochemistry comparable to those of infants fed a st and ard intact milk protein-based formula , despite some differences in amino acid profiles OBJECTIVE In study 1 , to compare the effect on growth in healthy infants of a new amino acid-based formula ( AAF )  and a control extensively hydrolyzed formula ( EHF ) , with both docosahexaenoic acid ( DHA ) and arachidonic acid ( ARA ) at levels similar to those in human milk worldwide . In study 2 , to evaluate the hypoallergenicity of this new AAF in infants and children with confirmed cow 's milk allergy ( CMA ) . STUDY DESIGN In study 1 , a total of 165 healthy , full-term , formula-fed infants r and omly received the  new AAF or control formula .  Anthropometric measurements , tolerance , and adverse events were recorded throughout the study . Plasma amino acid profiles were evaluated in a subset of the infants . In study 2 , the hypoallergenicity of the new AAF was evaluated in 32 infants and children using a double-blind , placebo-controlled food challenge ; an open challenge ; and a 7-day feeding . RESULTS In study 1 , overall growth , tolerance , and safety outcomes were similar in both groups . In study 2 , 29 of the 32 subjects completed both challenges ; no allergic reaction was seen in any of the 32 subjects . CONCLUSIONS The new AAF with DHA and ARA at levels similar to those in human milk worldwide is hypoallergenic . It also is safe and supports growth in healthy , term infants Background Parents who perceive common infant behaviors as formula intolerance-related often switch formulas without consulting a health professional . Up to one-half of formula-fed infants experience a formula change during the first six months of life . Methods The objective of this study was to assess discontinuance due to study physician-assessed formula intolerance in healthy , term infants . Infants ( 335 ) were r and omized to receive either a st and ard intact cow milk protein formula ( INTACT ) or a partially hydrolyzed cow milk protein formula ( PH ) in a 60 day non-inferiority trial . Discontinuance due to study physician-assessed formula intolerance was the primary outcome . Secondary outcomes included number of infants who discontinued for any reason , including parent-assessed . Results Formula intolerance between groups ( INTACT , 12.3 % vs. PH , 13.7 % ) was similar for infants who completed the study or discontinued due to study physician-assessed formula intolerance . Overall study discontinuance based on parent- vs. study physician-assessed intolerance for all infants ( 14.4 vs.11.1 % ) was significantly different ( P = 0.001 ) . Conclusion This study demonstrated no difference in infant tolerance of intact vs. partially hydrolyzed cow milk protein formulas for healthy , term infants over a 60-day feeding trial , suggesting nonst and ard partially hydrolyzed formulas are not necessary as a first-choice for healthy infants . Parents frequently perceived infant behavior as formula intolerance , paralleling previous reports of unnecessary formula changes . Trial Registration clinical trials.gov : In a previously published prospect i ve study , we followed the development of allergic symptoms in term infants with a slightly reduced birthweight ( − 1 SD to − 2 SD ) . These children received , according to local routing early feeding with cow milk formula in order to diminish such neonatal problems as hypoglycemia and hyperbilirubinemia . Of 216 infants 207 were observed for allergic symptoms up to 18 months of age . One group ( F ) received cow milk formula during the first days of life before the mother 's breastmilk production started and was then breastfed ; the other ( B ) was not given any formula before normal breastfeeding started . Unexpectedly , we found fewer allergic symptoms , in particular allergic skin problems , in the group fed cow milk , the difference being concentrated to children with a family fistory of allergic symptoms . At 5 Years of age 183 of the 207 children have been reinvestigated . Mild symptoms of allergy ( suspected and obvious ) were found in 22 % ( F ) and 27 % ( B ) respectively(NS ) . Moderate and severe symptoms of allergy ( obvious ) were found in 4.2 % ( F ) and 4.5 % ( B ) . In the subgroup with a double family history of allergic symptoms , 28 % ( 7/25 , F ) and 59 % ( 10/17 , B ) had symptoms of allergy ( p<0.05 ) . This difference was even more pronounced when laboratory tests in favour of atopic diagnosis were included , 1.4 % ( F ) and 53%(B ) respectively ( p < 0.05 ) . Thus at 5 years we still find a significantly lower frequency of allergic symptoms in the subgroup fed cow milk formula early with a family history of allergic symptoms . This difference was mainly caused by a reduced incidence of mild symptoms , some of which might not be true allergic symptoms . The incidence of moderate to severe disease was not affected , which can possibly be due to the relatively small number of children , expecially in the high risk group . Thus feeding with a high allergenic load during the first days of life seems , in the long run , to be ineffective in inhibiting the development of Significant ( moderate and severe ) atopic disease The objective of this study was to determine whether the growth and bone mineral status of discharged preterm infants fed human milk  differed from those of infants fed one of three different formulas varying in calcium content ( 545 mg/L , 660 mg/L , or 1290 mg/L ) . A r and omized , blinded study was conducted for 16 weeks after discharge in 16 human milk-fed and 43 formula-fed infants . All formula-fed infants received one of the three study formulas from discharge to 8 weeks afterward , and the st and ard formula , which contained 545 mg/L calcium , from 8 to 16 weeks . The human milk-fed infants gained weight more slowly than the formula-fed infants . The human milk-fed infants also had lower gains in length and higher serum alkaline phosphatase values than the formula-fed infants . The infants who received the formula containing the highest calcium concentration ( 1290 mg/L ) had greater bone mineral density during the first 8 weeks of the study . We conclude that preterm infants recently discharged from the hospital may benefit from higher calcium intake than is provided by either human milk or st and ard term formula Summary The role of delayed gastric emptying ( GE ) in the pathogenesis of gastroesophageal reflux ( GER ) in infants is controversial at present . GE has been shown to be altered by the composition and osmolality of the feedings . This prospect i ve study was undertaken to assess the changes in the GE and the percentage of time GER was detected by scintigraphy using three different formulas on consecutive days in infants with GER . Twenty-eight infants under 1 year of age diagnosed to have GER by extended intraesophageal pH monitoring ( pH being < 4.0 for > 5 % of the duration of the test ) , underwent scintigraphy on three consecutive days using the same volume per single feeding of a casein-predominant , soy , or a wheyhydrolysate formula in a r and omized order . The formulas were isocaloric . Gastric emptying and percentage of GER into the esophagus were estimated for 60 min following these feedings . Mean GER percent during the study was 20.39 , 17.68 , and 16.34 on casein-predominant , soy , and whey-hydrolysate formulas , respectively , and was not significantly different . Mean values of GE were 39.7 % , 44.6 % , and 48.5 % on casein , soy , and whey formula , respectively . No significant difference in GE was also observed between casein-predominant and soy formula . However , a significant difference was observed ( p < 0.05 ) on GE between casein-predominant and whey-hydrolysate feedings . Our data suggest that formula selection may be important in the treatment of conditions associated with delayed gastric emptying BACKGROUND Early exposure to complex dietary proteins may increase the risk of beta-cell autoimmunity and  type 1 diabetes in children with genetic susceptibility . We tested the hypothesis that supplementing breast milk with highly hydrolyzed milk formula would decrease the cumulative incidence of diabetes-associated autoantibodies in such children . METHODS In this double-blind , r and omized trial , we assigned 230 infants with HLA-conferred susceptibility to type 1 diabetes and at least one family member with type 1 diabetes to receive either a casein hydrolysate formula or a conventional , cow's-milk-based formula ( control ) whenever breast milk was not available during the first 6 to 8 months of life . Autoantibodies to insulin , glutamic acid decarboxylase ( GAD ) , the insulinoma-associated 2 molecule ( IA-2 ) , and zinc transporter 8 were analyzed with the use of radiobinding assays , and islet-cell antibodies were analyzed with the use of immunofluorescence , during a median observation period of 10 years ( mean , 7.5 ) . The children were monitored for incident type 1 diabetes until they were 10 years of age . RESULTS The unadjusted hazard ratio for positivity for one or more autoantibodies in the casein hydrolysate group , as compared with the control group , was 0.54 ( 95 % confidence interval [ CI ] , 0.29 to 0.95 ) , and the hazard ratio adjusted for an observed difference in the duration of exposure to the study formula was 0.51 ( 95 % CI , 0.28 to 0.91 ) . The unadjusted hazard ratio for positivity for two or more autoantibodies was 0.52 ( 95 % CI , 0.21 to 1.17 ) , and the adjusted hazard ratio was 0.47 ( 95 % CI , 0.19 to 1.07 ) . The rate of reported adverse events was similar in the two groups . CONCLUSIONS Dietary intervention during infancy appears to have a long-lasting effect on markers of beta-cell autoimmunity -- markers that may reflect an autoimmune process leading to type 1 diabetes . ( Clinical Trials.gov number , NCT00570102 . ) 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 Objective . Perceived intolerance to infant formula is a frequently reported reason for formula switching . Formula intolerance may be related to perceived symptoms of constipation , fussiness , abdominal cramps , and excessive spit-up or vomit . Commercially available formulas differ from each other in processing and in sources and levels of protein , lipids , and micronutrients . These differences may affect tolerance . The objective of this article was to compare the tolerance of two commercially available powder infant formulas that differ in composition . Measures of tolerance in exclusively breastfed infants weaned to an infant formula and exclusively formula-fed infants were evaluated . Methods . Two clinical studies were conducted . In study 1 , 82 healthy , full-term infants who were exclusively breastfed at the time of enrollment were  r and omized at weaning to formula A ( commercially available Similac With Iron Powder ) or formula B ( previously available Enfamil With Iron Powder ) . Parents completed daily records of tolerance during exclusive breast milk feeding , during the weaning period , and for a 2-week exclusive formula-feeding period . In study 2 , 87 healthy , full-term infants who were exclusively formula-fed at the time of study enrollment ( by 2 weeks of age ) were fed a st and ard cow milk-based formula ( previously commercially available Similac With Iron Powder ) and then r and omized to receive formula A or B for a 2-week period . Parents completed daily records of tolerance throughout the study . Formula A was a cow milk-based formula with a whey : casein ratio of 48:52 and a fat blend of 42 % high-oleic safflower , 30 % coconut , and 28 % soy oils . Formula B was a cow milk-based formula with a whey : casein ratio of 60:40 and a fat blend of 45 % palm olein , 20 % soy , 20 % coconut , and 15 % high-oleic sunflower oils . Both formulas had lactose as the source of carbohydrate and contained 12 mg of iron per liter . Only formula A contained nucleotides at the time of the study . Measures of tolerance included volume of each formula feeding , occurrences of spit-up and /or vomit , and the color ( yellow , green , brown , or black ) and consistency ( water , loose/mushy , soft , formed , or hard ) of each stool . Results . In both studies , volume of formula intake , weight gain , and incidence of spit-up or vomit did not differ between feeding groups . In study 1 , stool frequency decreased significantly from the exclusive breast milk period to weaning . Stools also became firmer as infants moved from breast milk to weaning and to exclusive formula feeding . When formula was introduced into the diet , stools became less yellow and more green . Infants weaned to formula B had less frequent stools , fewer brown stools , and more yellow stools than did infants fed formula A. In both studies , infants fed formula B experienced significantly firmer stools than did those fed formula A. Conclusions . The present clinical studies indicate that the composition and /or processing of milk-based powder iron-fortified infant formulas affect stool characteristics experienced by infants . The inclusion of palm olein oil in formula B may be the reason for the observed differences in stool characteristics . Palm olein is used in infant formulas to provide palmitic acid at a level similar to that found in breast milk . However , palmitic acid from palm olein is arranged differently from that in breast milk triglyceride and is poorly absorbed . Unabsorbed palmitic acid tends to react with calcium to form insoluble soaps , and the level of these soaps is correlated with stool hardness . The pattern of softer stools and greater frequency of stooling associated with formula A is similar to the stool pattern in the exclusively breastfed infant . Thus , the use of formula A may ease the transition from breast milk to formula feeding and ameliorate parents ' perception that constipation is associated with iron-fortified formula Formulas containing proteins with reduced potential to sensitize might be effective in reducing the risk of atopic disease , but such products should be nutritionally adequate . We design ed a r and omized , double-blind study to evaluate nutritional adequacy and sensitization potential of a formula containing partially hydrolyzed whey-predominant milk proteins .  Subjects were term infants enrolled at birth . Infants in group A were fed human milk , and group B received the partially hydrolyzed formula ; group C , fed a formula containing intact whey-predominant milk proteins , served as control subjects . We recorded anthropometric measurements and symptoms of formula intolerance at monthly intervals for 4 months in 205 infants .  Milk IgE and IgG antibodies were measured until 8 months of age in 63 infants .  Daily weight gain was not significantly different among the groups . Gastrointestinal symptoms attributed to feeding intolerance were also comparable . Increases in serum IgG antibodies were significantly greater in group C throughout the study . There were no significant differences in IgE antibodies . Thus a formula containing partially hydrolyzed whey-predominant milk protein promoted adequate growth and induced a lesser priming effect for IgG antibody response than did an intact whey-predominant formula BACKGROUND : Eczema is the most common inflammatory skin disease of childhood , characterized by an itchy red rash that usually involves the face and skin folds . There is currently no curative treatment for eczema , so the reduction of eczema incidence through disease prevention is a desirable goal . Potential interventions for preventing eczema include exclusive breastfeeding , hydrolysed protein formulas and soy formulas when bottle feeding , maternal antigen avoidance , omega oil supplementation , prebiotics and probiotics . OBJECTIVES : This overview of review s aims to present the current body of data from Cochrane and non-Cochrane review s to provide the most up-to- date evidence on the efficacy and safety of interventions to prevent eczema in infants and children at different risk levels for developing allergic disease . METHODS : Our pool of Cochrane and non-Cochrane review s came from the 2010 United Kingdom National Health Service ( NHS ) Evidence Skin Disorders Annual Evidence Up date s Mapping Exercise on Atopic Eczema . This group used a comprehensive search strategy last conducted in August 2010 to identify all systematic review s on eczema prevention . We identified all review s that met our pre-specified inclusion criteria , and data were extracted , analysed , compiled into tables and synthesized using quantitative and qualitative methods . MAIN RESULTS : Seven systematic review s containing 39 relevant trials with 11 897 participants were included in this overview . Overall , there was no clear evidence that any of the main interventions review ed reduced eczema incidence . In subgroup analyses of infants at high risk of allergic disease , an observational study found that exclusive breastfeeding for at least six months compared with introduction of solids at three to six months decreased the incidence of eczema by 60 % ( risk ratio ( RR ) : 0.40 ; 95 % confidence interval ( CI ) : 0.21 , 0.78 ) , and a r and omized controlled trial found that prebiotics compared with no prebiotics  decreased incidence by 58 % ( RR : 0.42 ; 95 % CI : 0.21 , 0.84 ) . However , each of these findings was based on the results of a single small trial , and no intervention reduced eczema incidence beyond the first two years of life . Although we pre-specified incidence of atopic eczema ( i.e. eczema associated with immunoglobulin E ( IgE ) sensitization ) as a primary outcome , data on whether participants diagnosed with eczema were truly atopic were largely lacking from systematic review s. Similarly , data on atopy , measured using skin prick tests or specific IgE tests to allergens , were not reported in many review s. No interventions were found to decrease atopy when reported . Adverse events data were generally lacking , but data from a trial of probiotics versus no probiotics showed significantly more spitting up in the first one ( RR : 1.88 ; 95 % CI : 1.03 , 3.45 ) and two ( RR : 1.69 ; 95 % CI : 1.02 , 2.80 ) months of life , but no overall increase in risk of gastrointestinal symptoms in the first year . AUTHORS # ENTITYSTARTX02019 ; CONCLUSIONS : Although there is currently no clear evidence showing that any of the interventions examined in this overview prevent eczema in participants not selected for risk of allergic disease , there is some evidence that exclusive breastfeeding for at least six months and prebiotics might reduce eczema incidence in high-risk participants . However , these conclusions are based on limited evidence with method ological shortcomings . Future research on prevention of eczema is needed and should examine different types of hydrolysed formulas , prebiotics and probiotics , as well as enhancement of the skin barrier and other novel approaches in infants at different risk levels for developing allergic disease Abstract Aim : To determine current treatment patterns for infants with cow milk allergy ( CMA ) and the associated re source implication s and budget impact , from the perspective of the UK 's National Health Service ( NHS ) . Methods : A computer-based model was constructed depicting current management of newly-diagnosed infants with CMA derived from patients suffering from this allergy in The Health Improvement Network ( THIN ) Data base . The model spanned a period of 12 months following initial presentation to a general practitioner ( GP ) and was used to estimate the 12-monthly healthcare cost ( at 2006/07 prices ) of treating an annual cohort of 18,350 infants from when they initially present to their GP . Results : Patients presenting with a combination of gastrointestinal and atopic symptoms accounted for 59 % of all patients . From the initial GP visit for CMA it took a mean 2.2 months to be put on diet , although treatment varied according to presenting symptoms . A total of 60 % of all infants were initially treated with soy , 18 % with an extensively hydrolysed formula and 3 % with an amino acid formula . A mean 9 % of patients remained symptomatic on soy and 29 % on an extensively hydrolysed formula . The total cost of managing CMA over the first 12 months following initial presentation to a GP was estimated to be £ 1,381 per patient and £ 25.6 million for an annual cohort of 18,350 infants . Limitations : Patients were not r and omised to treatment and re source use was not collected prospect ively . Nevertheless , 1,000 eligible patients have been included in the analysis , which should be a sufficiently large sample to accurately assess treatment patterns and healthcare re source use in actual clinical practice . The diagnosis of CMA may not be secure in all cases . Nevertheless , patients were diagnosed as having CMA by a clinician and have been managed by their GP as if they had CMA . Conclusion : CMA imposes a substantial burden on the NHS . Any strategy that improves healthcare delivery and thereby shortens time to treatment , time to diagnosis and time to symptom resolution should potentially decrease the burden this allergy imposes on the health service and release re sources for alternative use OBJECTIVE To compare three low-lactose milk formulas differing in osmolality and degree of protein hydrolysis in the treatment of diarrhoea and malnutrition in subjects with high rates of lactose intolerance , osmotic diarrhoea and a tropical/environmental enteropathy . METHODS A r and omized double-blind trial of 180 Aboriginal children under 3 years of age admitted with acute diarrhoea and /or malnutrition was carried out . The intervention milk formulas were : ( i ) De-Lact , a low-osmolality lactose-free formula ; ( ii ) O-Lac , a lactose-free formula ; and ( iii ) Alfaré , a partially hydrolysed formula . Outcome measures were diarrhoeal severity , weight gain , formula palatability and changes in intestinal permeability ( L/R ratios ) . RESULTS The duration of diarrhoea in days ( mean ; 95 % confidence interval ) was significantly longer on Alfaré ( 8.5 ; 7.0 - 10.0 ) compared to De-Lact ( 6.1 ; 5.0 - 7.2 ) and O-Lac ( 6.9 ; 5.6 - 8.1 ; P = 0.04 ) . There were no differences in mean intake between formulas , but palatability of Alfaré was significantly worse ( P < 0.01 ) than the other formulas . Over the trial 5 days , improvement in L/R ratios was significantly greater ( P = 0.05 ) for De-Lact ( 18.6 ; 10.6 - 26.6 ) than for Alfaré ( 8.5 ; 2.1 - 14.9 ) . Weight gain was not significantly different between the three formulas , except in a malnourished subgroup who had better weight gain on De-Lact ( P = 0.05 ) . CONCLUSIONS In these Aboriginal children with diarrhoea and growth failure , a low osmolality milk was associated with better outcomes and a partially hydrolysed formula with less improvement in mucosal recovery , suggesting that cow 's milk protein intolerance is not contributing to greater diarrhoeal severity or enteropathy in Aboriginal children Very fussy or extremely fussy infants were r and omized to receive :  soy-based formula ( Soy : n = 82 ) or a partially hydrolyzed cow 's milk protein ( CMP ) , low-lactose formula ( PHF : n = 77 ) in a multicenter , double-blind , r and omized , parallel , prospect i ve 28-day feeding trial . Body weight and infant formula tolerance were reported . Adverse events were recorded throughout the study . A significant reduction in mean scores of fussiness , gas , spit-up , and crying compared with baseline measures was observed in infants who received either Soy or PHF within 1 day of formula intake ; improvement in symptoms was sustained by study end . Stool consistency remained constant through day 28 in the PHF group , whereas stools in the Soy group became more firm by day 2 and did not return to pre study consistency . PHF , with a protein profile patterned more closely on human breast milk , improved symptoms of formula intolerance as well as soy-based formula Background / Objectives : To determine the impact of a not hydrolyzed fermented infant formula containing heat-killed Bifidobacterium breve C50 and Streptococcus thermophilus 065 ( HKBBST ) on the incidence of allergy-like events during the first 2 years of life in children at high risk of atopy . Subjects/ Methods : This multicenter , r and omized , double-blind , controlled study included infants at high risk of atopy . Infants used HKBBST or a st and ard infant formula ( SIF ) since birth until 1 year of age , and were followed at 4 , 12 and 24 months after birth .  Skin prick tests ( SPTs ) for six foods and six aeroallergens were systematic ally performed and adverse events ( AEs ) were recorded . In case of potentially allergic AE ( PAAE ) , allergy could be further tested by SPT , patch tests and quantification of specific IgEs . If cow 's milk allergy ( CMA ) was suspected , an oral challenge could also be performed . Results : The study included 129 children , 63 were r and omized to SIF , 66 to HKBBST . The use of HKBBST milk did not alter the proportion of CMA but decreased the proportion of positive SPT to cow 's milk ( 1.7 vs 12.5 % , P=0.03 ) , and the incidence of digestive ( 39 vs 63 % , P=0.01 ) and respiratory potentially allergic AEs ( 7 vs 21 % , P=0.03 ) at 12 months , and that of respiratory PAAEs at 24 months ( 13 vs 35 % , P=0.01 ) . Conclusions : HKBBST decreased the incidence of PAAEs in children with family history of atopy , during the first months of life and after the formula was stopped . Oral tolerance to cow 's milk in infants at high risk of atopy may therefore be improved using not hydrolyzed fermented formulae OBJECTIVE To assess whether the maternal consumption of milk and milk products affects development of cow 's milk ( CM ) antibodies in infants . DESIGN A r and omized pilot trial using food frequency question naires ( mothers ) and food records ( infants ) . SETTING Families with a newborn infant with increased HLA-DQB1-conferred risk of type 1 diabetes and at least one first-degree relative affected by type 1 diabetes from 16 hospitals in Finl and between April 1995 and November 1997 . SUBJECTS AND INTERVENTION Infants r and omized to receive a hydrolysed formula when breast milk was not available during their first 6 - 8 mo ( n=112 ) . Of these , 13 dropped out by the age of 3 mo and two were excluded due to incomplete CM antibody data . RESULTS Maternal milk protein intake from cheese during pregnancy was inversely related to IgA-class antibody titres to beta-lactoglobulin ( BLG ) and casein ( CAS ) at 3 mo , and to IgA antibody titres to BLG at 6 mo . Maternal consumption of raw milk products during lactation was positively related to the development of IgA antibody titres to CAS at 6 mo , and inversely correlated to IgG antibody titres to bovine serum albumin ( BSA ) and IgA antibody titres to CAS at 2 y. Maternal cheese consumption was inversely related to the IgG antibody titres to CM formula and CAS and to the IgA antibody titres to CAS in early infancy . CONCLUSIONS Few associations were established between maternal CM protein intake and CM protein antibody levels in the infants . The milk and milk products taken by the mother differed in their impact on the emerging CM antibody response in the offspring BACKGROUND The isoflavones genistein , daidzein , and their glycosides , found in high concentrations in soybeans and soy-protein foods , may have beneficial effects in the prevention or treatment of many hormone-dependent diseases . Because these bioactive phyto-oestrogens possess a wide range of hormonal and non-hormonal activities , it has been suggested that adverse effects may occur in infants fed soy-based formulas . METHODS To evaluate the extent of infant exposure to phyto-oestrogens from  soy formula  , the isoflavone composition of 25 r and omly selected sample s from five major br and s of commercially available soy-based infant formulas were analysed , and the plasma concentrations of genistein and daidzein , and the intestinally derived metabolite , equol , were compared in 4-month-old infants fed exclusively soy-based infant formula ( n = 7 ) , cow-milk formula ( n = 7 ) , or human breast-milk ( n = 7 ) . FINDINGS All of the soy formulas contained mainly glycosides of genistein and daidzein , and the total isoflavone content was similar among the five formulas analysed and was related to the proportion of soy isolate used in their manufacture . From the concentrations of isoflavones in these formulas ( means 32 - 47 micrograms/mL ) , the typical daily volume of milk consumed , and average bodyweight , a 4-month-old infant fed soy formula would be exposed to 28 - 47 per day , or about 4.5 - 8.0 mg/kg bodyweight per day , of total isoflavones . Mean ( SD ) plasma concentrations of genistein and daidzein in the seven infants fed soy-based formulas were 684 ( 443 ) ng/mL and 295 ( 60 ) ng/mL , respectively , which was significantly greater ( p < 0.05 ) than in the infants fed either cow-milk formulas ( 3.2 [ 0.7 ] and 2.1 [ 0.3 ] ng/mL ) , or human breast-milk ( 2.8 [ 0.7 ] and 1.4 [ 0.1 ] ng/mL ) , and an order of magnitude higher per bodyweight than typical plasma concentrations of adults consuming soy foods . INTERPRETATION The daily exposure of infants to isoflavones in soy infant-formulas is 6 - 11 fold higher on a bodyweight basis than the dose that has hormonal effects in adults consuming soy foods . Circulating concentrations of isoflavones in the seven infants fed soy-based formula were 13000 - 22000 times higher than plasma oestradiol concentrations in early life , and may be sufficient to exert biological effects , whereas the contribution of isoflavones from breast-milk and cow-milk is negligible In a prospect i ve r and omized study we investigated in 28 mainly bottle-fed infants younger than 60 days whether in acute gastroenteritis a hypoallergenic formula could prevent the development of cow 's milk protein intolerance . Group 1 ( 14 infants ) was fed with a formula adapted to human milk , Group 2 ( 14 infants ) got a semi-elementary formula ( Alfaré ) . After 3 months group II was exposed to cow 's milk protein with a st and ardized challenge and the incidence of CMPI in both groups was calculated . All cases with the acute form of CMPI occurred in group II ( 5/12 ) whereas in group I only one infant suffered from the protracted mild form of the disease . Inspite of the relatively small number of prob and s we conclude from our results that in infants who are not totally breast-fed in the post-enteritic period feeding with a formula adapted to human milk is preferable to hypoallergenic semi-elementary preparations . An allergen free period of 3 months seems to induce symptoms of cow 's milk intolerance , probably as a booster-effect to early sensibilisation Background and Objectives : Postdischarge formulas with extra energy and protein improve short-term growth but may also influence long-term body composition in an unwanted manner . Energy- and protein-enriched formulas with an increased protein-to-energy ratio improves gain of lean mass . The objective of the study was to investigate whether feeding a nutrient-enriched formula without extra energy after term , usually 3 to 4 weeks after discharge , would influence growth and body composition in infancy . Methods : In this r and omized controlled trial preterm infants were fed fortified human milk or preterm formula until term . At term , 102 infants were r and omized to a nutrient-enriched formula without extra energy or st and ard formula until 6 months corrected age . Twenty-six infants received unfortified human milk after term . At term and 6 months corrected age , anthropometry and a dual-energy x-ray absorptiometry ( DEXA ) scan were performed . Lean and fat mass ( FM ) were corrected for height . Results : There were no differences in growth or body size between the feeding groups . Infants fed the enriched formula gained less FM and had lower FM corrected for body size at 6 months corrected age than infants fed st and ard formula . Infants fed human milk had lower lean mass and higher FM corrected for body size at 6 months corrected age than formula-fed infants . Conclusions : Feeding nutrient-enriched formula without extra energy after term does not change quantity of growth but does influence type of weight gain and body composition of preterm infants . Infants fed the nutrient-enriched formula had lower FM corrected for body size at 6 months corrected age than infants fed st and ard formula or human milk Background Immunologic development of soy-fed infants has not been extensively studied . Early studies of soy flour – based formulas showed decreased immunoglobulin production when soy protein intake was limited . However , there were no significant differences in rotavirus vaccine responses between breast-fed and soy protein isolate – based formula-fed infants .  Nucleotides added to milk-based formula benefit infant immune status , but reports of the immunologic effects of adding nucleotides to soy-based formula are not available . This study evaluated immune status and morbidity of infants fed soy protein isolate formulas with and without added nucleotides for 1 year . Methods Newborn , term infants enrolled in a masked 12-month feeding trial were assigned r and omly to groups fed soy formula with or without added nucleotides ( n = 94 , n = 92 ) . A nonr and omized human milk/formula cohort ( n = 81 ) was concurrently enrolled . Recommended immunizations were administered at 2 , 4 , and 6 months . Immune status was determined from antibody responses to Haemophilus influenzae type b , tetanus , diphtheria , and poliovirus vaccines at 6 , 7 , and 12 months . Parents and physicians reported morbidity data . Results All vaccine responses were within normal ranges . No response differences were observed between infants fed soy formula and those fed nucleotide-supplemented soy . However , antibody to H. influenzae type b at 7 and 12 months was higher in infants fed nucleotide-supplemented soy than in infants fed human milk/formula ( P = 0.007 , P = 0.008 , respectively ) . Human milk/formula-fed infants had higher poliovirus neutralizing antibody at 12 months than did soy-fed infants ( P = 0.016 ) . Morbidity analyses showed that only physician-reported diarrhea was different among groups ( groups fed human milk/formula had less diarrhea than did soy groups , P = 0.011 ) . Conclusions Term infants fed soy protein isolate – based formulas  have normal immune development as measured by antibody responses to childhood immunizations Background Protein quality of breast milk is superior to that of formula proteins . To ensure that the protein intake is sufficient , starter formulas with conventional protein composition provide a protein/energy ratio of 2.2–2.5 g per 100 kcal to infants , which is much higher than that supplied with breast milk . Several studies have shown that formula-fed infants have higher plasma or serum urea concentrations than breast-fed infants do . We tested if feeding formulas with improved protein quality and a protein content corresponding to the minimum level that is consistent with international recommendations ( 1.8 g/100 kcal ) allows patients to achieve normal growth and plasma urea concentrations . Methods Healthy term infants were enrolled into the study and were either breast-fed or r and omly assigned to three formula-fed groups . Formula-fed infants received either a st and ard formula with a protein/energy ratio of 2.2 g/100 kcal , whereas the two other groups received formulas with a protein/energy ratio of 1.8g/100 kcal differing mainly by their source of protein . Subjects received breast milk or these formulas ad libitum as the sole source of energy from birth to four months of age in a controlled blind design ( except for the breast-fed group ) . Anthropometric measurements ( body weight and length ) were obtained at birth , at 30 , 60 , 90 , and 120 days . Energy and protein intakes were calculated from three-day dietary records . Blood was collected for biochemical measurements at 30 , 60 , and 120 days . Results No differences were found between the four feeding groups for weight- and length-gains or for body mass indices ( BMI ) . No differences in energy intakes between the formula-fed groups could be found , whereas protein intakes were less in infants fed the 1.8 g/100 kcal formulas . Plasma urea levels of the infants fed the 1.8 g/100 kcal formulas were closer to those found in the breast-fed infants . Conclusion Improvement of the amino acid profile permits a whey predominant starter formula with 1.8 g protein per 100 kcal to meet the needs of normal term infants during the first four months of life Abstract . The optimum level and ratios of protein to be used in cow 's milk formula has recently been under discussion . Healthy term infants were fed from birth exclusively human milk or a formula that varied in protein level or whey : casein ratio : ( A ) 1.4 g/dl ; 55:45 , ( B ) 1.5 g/dl ; 55:45 , ( C ) 1.3 g/dl ; 55:45 , ( D ) 1.4 g/dl ; 60:40 , ( E ) 1.4 g/dl ; 20:80 . Infants were followed for 12 weeks and blood sample s were taken at 2 , 4 , 8 and 12 weeks . Anthropometric indices did not show any significant differences among groups . Plasma amino acid and BUN levels of the C group were closest to the breast‐fed group , while the formula with the highest protein level ( B ) result ed in high values for some amino acids . When comparing the formulas with 1.4 g protein/dl , the high casein group had the lowest plasma tryptophan levels . Taurine was added to all formulas at a level similar to that of breast milk ; plasma taurine levels were similar for all groups . All formulas contained 0.7 mg iron and 0.7 mg zinc/dl ; no differences were found among the groups in hematological indices or serum trace elements . These data show that feeding a formula with 1.3 g protein/dl and 55:45 whey : casein ratio from birth will result in growth and metabolic indices similar to those of breast‐fed infants , although some plasma amino acid levels are not identical , 1990 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 The growth , behavior , and protein status of 59 healthy preterm ( mean gestational age 30 wk ) infants fed either human milk or one of three infant formulas were studied post-discharge from the hospital . Formula-fed infants received either a st and ard term formula , a st and ard preterm formula , or an experimental preterm formula from discharge to 8 wk of age . From 8 to 16 wk , all formula-fed infants received the st and ard term formula . At 2 , 8 , and 16 wk , anthropometric , dietary intake , blood biochemistry , amino acid , and Brazelton Neonatal Behavioral Assessment measurements were evaluated . Weights , lengths , and head circumferences were similar for all feeding groups at discharge . After discharge all formula-fed infants were heavier than human milk-fed infants . Length and head circumference values and plasma urea nitrogen and retinol-binding protein concentrations were not different among dietary groups . Formula-fed infants had higher plasma concentrations of numerous amino acids compared with those of human milk-fed infants during the first 8 wk but not at 16 wk . There were no differences among the feeding groups in the Brazelton assessment . This study found little effect on the growth or behavioral or protein status of preterm infants discharged from the hospital who were fed either human milk or formulas design ed for term or preterm infants Long chain polyunsaturates ( LCP ) status during the early neonatal period is associated with a reduced risk of atopic symptoms and later allergies . In this study , we characterized the immune response of low-risk , term , formula-fed infants r and omized at ≤14 d of age to st and ard term formula ( Formula ) or formula containing LCP ( Formula+LCP ) for 4 wks . Infants exclusively fed human milk  were included for comparison . Peripheral blood was collected at 14 and 42 d of age , and lymphocyte phenotype , proliferation , and cytokine production ( IL-2 , IL-4 , IL-6 , IL-10 , IL-12 , IFN-γ , TNF-α , TGFβ ) were assessed after incubation with β-lactoglobulin ( BLG ) and soy protein ( SOY ) . Lymphocyte proliferation did not differ between groups . Compared with human milk-fed infants at 2 wks , formula-fed infants produced more TNF-α and IFN-γ and had more cells expressing ICAM-1 ( CD54 ) after incubation with BLG and SOY ( p < 0.05 ) . At 6 wks of age , infants fed Formula+LCP  produced more TNF-α with SOY ( 3.2-fold ) and IFN-γ ( 3.3-fold ) with BLG compared with infants fed Formula ( p < 0.05 ) . In conclusion , low-risk term infants fed formula before 14 d of age  produced more TNF-α and IFN-γ in response to food proteins . Feeding Formula+LCP for 4 wks maintained the higher TNF-α and IFN-γ response to these food proteins Background : Recent data have outlined a relationship between the composition of the intestinal microflora and  allergic inflammation  , and demonstrated the competence of probiotics in downregulation of such inflammation . Aims : Our aims were to characterise the relationship between gut microbes and the extent of allergic sensitisation and to assess whether the efficacy of bifidobacterial supplementation in the treatment of allergy could relate to modulation of the intestinal microbiota . Methods : This r and omised study included 21 infants with early onset atopic eczema of whom eight were intolerant ( highly sensitised group ( HSG ) ) and 13 tolerant ( sensitised group ( SG ) ) to extensively hydrolysed whey formula ( EHF ) .  In the SG , six were weaned to EHF without ( placebo group ( PG ) ) and seven to EHF with Bifidobacterium lactis Bb-12 supplementation ( bifidobacteria treated group ( BbG ) ) . The faecal microflora of infants in the HSG was analysed only before weaning whereas in the SG the faecal microflora was analysed both before and after weaning . Results : Infants in the HSG had greater numbers of lactobacilli/enterococci than those in the SG . Serum total IgE concentration correlated directly with Escherichia coli counts in all infants and with bacteroides counts in the HSG , indicating that the presence of these bacteria is associated with the extent of atopic sensitisation . The effect of supplementation was characterised as a decrease in the numbers of Escherichia coli and protection against an increase in bacteroides numbers during weaning . Conclusions : These data indicate that bifidobacterial supplementation appears to modify the gut microbiota in a manner that may alleviate allergic inflammation . Further studies are needed to confirm this conclusion UNLABELLED B ACKGROUND : Feeding neonates with humanized milk formula in maternity hospitals may increase the prevalence of  milk allergy in infants . However , prospect i ve studies of the possible allergenic effect of very early soy-based formula feeding are lacking . OBJECTIVES To assess the prevalence of soy allergy in infants fed soy-based formula in the first 3 days of life . METHODS The study group included 982 healthy full-term infants born within a 7 month period at a hospital that routinely uses soy-based formula to supplement breastfeeding .  In-hospital feeding was recorded and the parents were interviewed once monthly over the next 6 months regarding feeding practice s and clinical symptoms suggesting soy allergy in the infant . RESULTS Ninety-nine percent of the infants received soy-based formula supplement in hospital , and 33%-42 % at home . No cases of immediate allergic reaction to soy or soy-induced enterocolitis were reported . CONCLUSIONS The use of soy-based formula in the early neonatal period does not apparently increase the prevalence of soy allergy in infants followed for the next 6 months 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 This short-term , prospect i ve study was aim ed to assess the effects of partially hydrolyzed formula ( PHF ) on the prevention of the development of  atopic dermatitis in infants at high risk . The infants of parents with allergy symptoms and serum total IgE over 200 kU/L were divided into 3 groups by their feeding patterns :  PHF group ( n=15 ) ,  st and ard formula ( SF ) group ( n=32 ) , and  breast milk ( BM ) group ( n=22 ) . No allergenic food was given during the study period of 6 months , and breastfeeding mothers avoided egg ingestion . Their atopic symptoms were monitored every 2 months . The cumulative incidence and prevalence of atopic dermatitis at the age of 6 months were significantly less in the PHF group than in the SF group ( 47 % vs. 78 % , p<0.05 ; 20 % vs. 59 % , p<0.05 ) . Those rates of the PHF group were also less than those of the BM group , but they were not statistically significant . There was no difference in the onset age and disease severity . These results suggest that early feeding of PHF to infants at high risk has a short-term preventive effect on the development of atopic dermatitis during the first 6 months of life . Long-term preventive effects should be evaluated Whether breast milk influences later neurodevelopment  has been explored in non-r and omised studies , potentially confounded by social and demographic differences between feed groups . Here in a strictly r and omised prospect i ve multicentre trial , Bayley psychomotor and mental development indices ( PDI and MDI ) were assessed at 18 months postterm in survivors of 502 preterm infants assigned to receive , during their early weeks , mature donor breast milk or a preterm formula .  These diets were compared as sole enteral feeds or as supplements to the mother 's expressed breast milk . No differences in outcome at 18 months were seen between the two diet groups despite the low nutrient content of donor milk in relation to the preterm formula and to the estimated needs of preterm infants . These results contrast with those reported from our parallel two centre study that compared infants r and omly assigned a st and ard term formula or the preterm formula during their early weeks ; those fed st and ard formula , now regarded as nutritionally insufficient for preterm infants , were substantially disadvantaged in PDI and MDI at 18 months post-term . It is shown here that infants from that study fed solely on st and ard formula had significantly lower developmental scores at 18 months than those fed on donor breast milk in the present study ; yet the st and ard formula had a higher nutrient content than the donor milk . Thus , donor milk feeding was associated with advantages for later development that may have offset any potentially deleterious effects of its low nutrient content for preterm infants . As these outcome advantages were not confounded by the social and educational biases usually associated with mothers ' choice to breast feed , our data add significant support to the view that breast milk promotes neurodevelopment Abstract When term infants are fed st and ard formula that does not contain long-chain polyunsaturated fatty acids ( LC-PUFA ) , they still show lower levels of docosahexaenoic acid ( DHA ) in red blood cell ( RBC ) phospholipids by several weeks or months postnatally . This study was design ed in order to evaluate a potential alternative for supplementing term infant formulas with DHA by adding a high-DHA/low-eicosapentanoic acid fish oil to levels similar to that in human milk ( 0.3 % ) . A total of 37 term infants were included in the study at 3 days of life .  DHA concentrations remained stable between inclusion and 4 months of life at around 8 % of the RBC phospholipids in the LC-PUFA enriched formula-fed group whereas it decreased significantly in the st and ard formula-fed group . In the human milk-fed group , RBC DHA concentrations at 4 months of age were significantly lower than that at birth and were significantly correlated with the duration of breast feeding ( r = 0.85 ; P = 0.0002 ) . A significant decrease of arachidonic acid between inclusion and 4 months of age was observed in the enriched formula-fed group and reached a mean value at 4 months , which was significantly lower than that observed in the human milk or st and ard formula-fed groups ( P < 0.0001 ) . Conclusion Supplementing term formulas with a high-docosahexaenoic acid/low-eicosapentanoic acid fish oil up to 4 months of age is efficient in improving docosahexaenoic acid status , however it increases the risk of impaired n-6 fatty acid status OBJECTIVE Compare milk-based , iron-fortified formulas containing 7.4 and 12.7 mg/L iron and breast-feeding during the first year of life . DESIGN Partially r and omized , double-blind trial : non-breast-fed infants r and omly assigned to receive one of two coded formulas , identical except for iron content ; infants discontinuing breast-feeding between 1 and 8 weeks of age r and omly assigned to a formula late-start group . SETTING Five general community pediatric practice s in Missouri , Indiana , Illinois , and Pennsylvania . PARTICIPANTS Sample of 347 healthy , term infants , enrolled within 1 week after birth ; 172 included in statistical analyses . OUTCOME MEASURES Length , weight , and indicators of formula intolerance recorded at clinic visits ; formula consumption , bowel movements , stool consistency , and other tolerance indicators recorded by parents on daily and weekly report forms ; hemoglobin , hematocrit , and serum ferritin , iron zinc , and copper measured at 6 and 12 months . RESULTS No significant differences between formula-fed groups in growth , attrition , formula consumption , bowel movements , hematocrit , hemoglobin level , and serum iron , zinc , and copper levels ( P > .05 ) ; first 6-month weight and length changes of the breast-fed group significantly less than in both formula-fed groups ( P < .008 ) ; serum ferritin level of the formula-fed , high-iron group significantly higher than that of the low-iron and breast-fed groups ( P < .008 ) , although all groups ' values were normal ; no apparent differences between formula groups in formula tolerance and stool characteristics but data were not analyzed statistically . CONCLUSIONS Milk-based formulas containing either 7.4 or 12.7 mg/L iron support normal growth and iron status of healthy , term , normally fed infants during the first year and both are well tolerated and accepted Summary : Very low birthweight ( VLBW ) infants weighing < 1,600 g at birth were fed their own mother 's milk ( OMM ) or r and omly assigned to receive one of three formulas : a “ humanized ” formula ( SF ) , a partially modified casein-predominant cow 's milk formula ( CF ) , or a premature formula ( PF ) . All infants were fed at 120 kcal/kg/day where possible , PF infants had significantly greater weight increments ( 28.0 g/day ) than those on OMM ( 19.4 g/day ) , SF ( 18.9 g/day ) , and CF ( 18.2 g/day ) . Those on PF also had greater increments of length , head circumference , and skinfold thickness than those on the other two formulas and greater length increments than those on OMM . Dynamic skinfold measurements suggested that no infants accumulated excessive amounts of interstitial fluid . Infants on the two st and ard formulas had significantly greater base deficits , whereas those on CF also had higher urea values . Those on OMM had lower phosphate and higher alkaline phosphatase values than the other groups . Thus VLBW infants fed a premature formula had better growth and fewer biochemical problems than those on st and ard formulas , whereas supplementation of OMM may be necessary to ensure optimal growth and bone mineralization In an attempt to prevent or reduce the manifestations of atopic disease , a group of infants considered to be genetically at high risk of atopy was entered in a prenatally r and omized , controlled study . A prophylactic group ( n= 58 ) was either breast‐fed with their mothers excluding foods regarded as highly antigenic from their diets , or given an extensively hydrolysed formula . In addition , strenuous efforts were made to reduce exposure to the house‐dust mite by application of acaricide to the bedroom and living room carpets and upholstered furniture . A control group ( n= 62 )  was fed conventionally by breast or on formula , and no specific environmental measures were taken . The results ( previously reported ) after 1 year showed significantly less total allergy , asthma , and eczema in the prophylactic group . Similar results were obtained at 2 years although the reduction in asthma no longer achieved statistical significance . However , there was significantly less sensitization , as shown by a battery of skin prick tests ( SPTs ) , to both dietary allergens and aeroallergens in the prophylactic group . A11 the children have now been review ed at the age of 4 years , and SPTs to a wide range of dietary allergens and aeroallergens have been performed . The control group continues to show more total allergy ( odds ratio [ OR ] 2.73 , 95 % confidence interval [ CI ] 1.21–6.13 , P<0.02 ) , definite allergy ( allergic symptoms plus positive SPT ) ( OR 5.6 , CI 1.8–17.9 , P<0.005 ) , and eczema ( OR 3.4 , CI 1.2–10.1 , P<0.05 ) . More control children have positive SPTs ( OR 3.7 , CI 1.3–10.0 , P<0.02 ) . A dual approach to the prevention of allergic disease , avoiding as far as possible sensitization to food and aeroallergens , significantly reduces the risk of atopic disease . This should be reserved for infants considered at very high risk of atopy , and close medical and dietetic supervision must be available Aims /hypothesisThe Trial to Reduce  IDDM  in the Genetically at Risk ( TRIGR ) study was design ed to establish whether weaning to a highly hydrolysed formula in infancy subsequently reduces the risk of type 1 diabetes . Methods The study population comprises newborn infants who have first-degree relatives with type 1 diabetes and meet the increased risk HLA inclusion , but not exclusion criteria . The study is being performed in 15 countries in three continents . First-degree relatives of patients with type 1 diabetes were identified from diabetes clinics , diabetes registries , and from other endocrinology or obstetrics offices and websites . HLA typing was performed at birth from cord or heel stick blood , and the results sent to the study ’s Data Management Unit within 2 weeks for communication of eligibility to the clinical study centre . All mothers recruited were encouraged to breastfeed . The intervention lasted for 6 to 8 months , and weaning formulas based on hydrolysed casein and st and ard cow ’s milk were compared . Results TRIGR recruited 5,606 infants , of whom 2,160 were enrolled as eligible participants , 6 % more than the target of 2,032 . Of those enrolled , 80 % were exposed to the study formula . The overall retention rate over the first 5 years is 87 % , with protocol compliance at 94 % . The r and omisation code will be opened when the last recruited child turns 10 years of age , i.e. in 2017 . Conclusions /interpretationThe TRIGR experience demonstrates the feasibility and successful implementation of an international dietary intervention study . TRIGR is the first ever primary prevention trial for type 1 diabetes and , if completed successfully , will provide a definite answer to the research question .Trial registration Clinical Trials.gov NCT00179777 Funding The study was funded by the National Institute of Child Health and Development ( NICHD ) and National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK ) , National Institutes of Health ( NIH ) ( grant numbers HD040364 , HD042444 and HD051997 ) , Canadian Institutes of Health Research , the Juvenile Diabetes Research Foundation International and the Commission of the European Communities ( specific RTD programme ‘ Quality of Life and Management of Living Re sources ’ , contract number QLK1 - 2002 - 00372 ‘ Diabetes Prevention ’ . Other funding came from the EFSD/JDRF/Novo Nordisk Focused Research Grant , Academy of Finl and , Dutch Diabetes Research Foundation and Finnish Diabetes Research Foundation ) BACKGROUND Results on growth and nutrient intake in infants in the second half of infancy fed human milk or formulas with varying protein concentrations in combination with supplementary foods  have not previously been reported . METHODS Seventy-one healthy infants were studied from 3 to 12 months of age . They were exclusively breast-fed until 3 months and were then r and omly assigned to one of three feeding groups , F13 , F15 , or F18 , indicating formulas with 13 , 15 or 18 g/l of protein , respectively . Formula was gradually introduced when breast-feeding was terminated . Infants fed  breast milk only were included in the breast-fed group , and those with breast milk and formula were included in the mixed-fed group . The same supplementary foods were provided to all infants . RESULTS There were no differences in growth between the feeding groups . Total protein intake exceeded minimum recommendations in all groups at all ages and was higher at 6 months in F18 than in F13 ( 2.3 vs. 1.9 g/kg per day ; p < 0.01 ) , whereas formula protein intake was higher at all ages in F18 compared with F13 . Intake of protein from supplementary foods increased , but that from formula decreased between 6 and 12 months in all groups . CONCLUSIONS Intake of breast milk or infant formula with 13 g/l of protein along with high-protein supplementary foods provided enough protein with no adverse effect on growth . Infants fed formulas with higher protein concentrations had similar growth , despite higher intakes of formula protein
We found no evidence to support short-term or prolonged feeding with a hydrolysed formula compared with exclusive breast feeding for prevention of allergic disease .
Very low- quality evidence indicates that short-term use of an EHF compared with a CMF may prevent infant CMA .
Further trials are recommended before implementation of this practice .We found no evidence to support prolonged feeding with a hydrolysed formula compared with a CMF for prevention of allergic disease in infants unable to be exclusively breast fed
BACKGROUND Infant formulas containing hydrolysed proteins have been widely advocated for preventing allergic disease in infants , in place of st and ard cow 's milk formula ( CMF ) .
However , it is unclear whether the clinical trial evidence supports this .
OBJECTIVES To compare effects on allergic disease when infants are fed a hydrolysed formula versus CMF or human breast milk .
If hydrolysed formulas are effective , to determine what type of hydrolysed formula is most effective , including extensively or partially hydrolysed formula ( EHF/PHF ) .
To determine whether infants at low or high risk of allergic disease , and whether infants receiving early short-term ( first few days after birth ) or prolonged formula feeding benefit from hydrolysed formulas .