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. 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. Safety and efficacy of a new extensively hydrolyzed formula for infants with cow's milk protein allergy. Partial Protein-Hydrolyzed Infant Formula Decreased Food Sensitization but Not Allergic Diseases in a Prospective Birth Cohort Study Effect of a partially hydrolyzed whey infant formula at weaning on risk of allergic disease in high-risk children: a randomized controlled trial. Partially hydrolyzed cow's milk formula has a therapeutic effect on the infants with mild to moderate atopic dermatitis: a randomized, double-blind study. Preventive effect of hydrolyzed infant formulas persists until age 6 years: long-term results from the German Infant Nutritional Intervention Study (GINI). Extensively and partially hydrolysed preterm formulas in the prevention of allergic diseases in preterm infants: a randomized, double‐blind trial Comparison of a partially hydrolyzed infant formula with two extensively hydrolyzed formulas for allergy prevention: a prospective, randomized study. Long-term safety assessment in children who received hydrolyzed protein formulas with Lactobacillus rhamnosus GG: a 5-year follow-up An extensively hydrolysed casein-based formula for infants with cows' milk protein allergy: tolerance/hypo-allergenicity and growth catch-up. Effects of cow milk versus extensive protein hydrolysate formulas on infant cognitive development 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. Extensively and partially hydrolysed infant formulas for allergy prophylaxis Effects of prolonged exposure to partially hydrolyzed milk protein. Efficacy and safety of hydrolyzed cow milk and amino acid-derived formulas in infants with cow milk allergy. Long-term prevention of allergic diseases by using protein hydrolysate formula in at-risk infants.
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 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 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 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 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 OBJECTIVE The allergy-preventing effect of partially hydrolyzed cow 's milk formula ( phCMF ) in infants at high risk of atopic dermatitis ( AD ) has been demonstrated in many studies . However , the therapeutic potential of phCMF in treating the infants with AD has not been reported . We sought to assess such therapeutic efficacy of phCMF in infants with mild to moderate AD . METHODS From 2006 to 2008 , 113 infants < 6 months of age with AD were r and omized to receive either partially hydrolyzed cow 's milk formula ( phCMF ) or conventional cow 's milk formula ( CMF ) in a double-blind clinical trial . Assessment s were made at enrollment and at weeks 4 , 8 , and 12 . The severity of AD was assessed using two scoring systems : St and ard guideline for management ( diagnosis , severity scoring , and therapy ) of AD by the Japanese Dermatological Association Scoring System ( JDASS ) and the SCORing Atopic Dermatitis ( SCORAD ) . Growth status of the infants was evaluated . Allergy profile was assessed by measuring total blood eosinophils ( EOS ) , total/specific IgE , Th1/Th2 cytokine profiles , and the percentage of regulatory T cells . RESULTS After follow-up for 12 wk , 27 infants ( 23.89 % ) dropped off study . Analysis was performed on 86 infants by the end of 12-wk observation . The AD severity scores were significantly reduced in the phCMF group ( n = 56 ) compared with CMF group ( n = 30 ) after 12 wk ( p < 0.05 ) . The severity scores of phCMF group were significantly reduced at weeks 4 , 8 , and 12 compared to enrollment ( p < 0.05 ) . In contrast , no significant improvement was observed for CMF group at any of those time points ( p > 0.05 ) . The number of AD flare-ups was significantly decreased in the phCMF group ( p = 0.002 ) . Th1/Th2 ratio in phCMF was significantly increased compared with CMF group ( p = 0.041 ) . The growth rates did not differ significantly between these feeding groups at any assessed time point ( p > 0.05 ) and were in the normal range . CONCLUSION This study suggests a novel therapeutic effect of phCMF in treating infants with mild to moderate AD during the first 6 months of their life without affecting their nutritional status 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 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 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 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 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 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 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 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 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 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 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
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 .