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?
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
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 .