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. Extensively and partially hydrolysed infant formulas for allergy prophylaxis Long-term prevention of allergic diseases by using protein hydrolysate formula in at-risk infants. Safety of casein hydrolysate formula in children with cow milk allergy. Challenge confirmation of late-onset reactions to extensively hydrolyzed formulas in infants with multiple food protein intolerance. Efficacy and safety of hydrolyzed cow milk and amino acid-derived formulas in infants with cow milk allergy. Preventive effect of feeding high-risk infants a casein hydrolysate formula or an ultrafiltrated whey hydrolysate formula. A prospective, randomized, comparative clinical study. An extensively hydrolysed casein-based formula for infants with cows' milk protein allergy: tolerance/hypo-allergenicity and growth catch-up. Nutritional Value of a Rice-Hydrolysate Formula in Infants with Cows' Milk Protein Allergy: A Randomized Pilot Study Effects of a dietary and environmental prevention programme on the incidence of allergic symptoms in high atopic risk infants: three years follow‐up Nutritional evaluation of protein hydrolysate formulas in healthy term infants: plasma amino acids, hematology, and trace elements. Cow's milk IgE and IgG antibody responses to cow's milk formulas The long-term effect of a partial whey hydrolysate formula on the prophylaxis of atopic disease Prospective, controlled, multi-center study on the effect of an amino-acid-based formula in infants with cow's milk allergy/intolerance and atopic dermatitis. 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 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
 Vegetable acceptance by infants: effects of formula flavors. 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. Comparison of a partially hydrolyzed infant formula with two extensively hydrolyzed formulas for allergy prevention: a prospective, randomized study. Plasma amino acid concentrations in term-born infants fed a whey predominant or a whey hydrolysate formula. Breast-feeding and the development of cows' milk protein allergy. 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. Supplementary feeding in maternity hospitals and the risk of cow's milk allergy: A prospective study of 6209 infants.
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 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 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 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 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 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 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 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 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 ABSTRACT A prospect i ve case‐control study is presented to assess an allergy prevention programme in children up to 36 months of age . Infants born at three maternity hospitals were followed from birth : 279 infants with high atopic risk ( intervention group ) were compared with 80 infants with similar atopic risk but no intervention ( non‐intervention group ) . The intervention programme included dietary measures ( exclusive and prolonged milk feeding diet followed by a hypoantigenic weaning diet ) and environmental measures ( avoidance of parental smoking in the presence of the babies , day care > 2 years of life ) . Mothers in this group who had insufficient breast milk were r and omly assigned to one of two coded formulas : either a hydrolysed milk formula ( Nidina HA , Nestlé ) or a conventional adapted formula ( Nan , Nestlé ) . Other environmental measures remained the same as for the breastfeeding mothers . The non‐intervention group were either breastfed or received the usual Italian milk feeding and weaning diet , without environmental advice . The main outcome measures were anthropometric measurements and allergic disease manifestations . Normal anthropometric data were observed both in the intervention group and in the nonintervention group . The incidence of allergic manifestations was much lower in the intervention group than in the nonintervention group at 1 year ( 11.5 versus 54.4 % , respectively ) and at 2 years ( 14.9 versus 65.6 % ) and 3 years ( 20.6 versus 74.1 % ) . Atopic dermatitis and recurrent wheezing were found in both the intervention group and the non‐intervention group from birth up to the second year of life , while urticaria and gastrointestinal disorders were only present in the non‐intervention group in the first year of life . Conjunctivitis and rhinitis were present after the second year in both the intervention group and the non‐intervention group . Relapse of the same allergic symptom was less in the intervention group ( 13.0 % ) than in the non‐intervention group ( 36.9 % ) . In comparison to the non‐intervention group , there were fewer intervention group cases with two or more different allergic symptoms ( 8.7 versus 32.6 % ) , and they were more likely to avoid steroid treatment ( 0 versus 10.8 % ) and hospital admission ( 0 versus 6.5 % ) . Babies in the non‐intervention group fed with adapted formula were more likely to develop allergies than breastfed babies in the same group . In the intervention group the breastfed infants had the lowest incidence of allergic symptoms , followed by the infants fed the hydrolysed formula ( ns ) . Infants in the intervention group fed the adapted formula had significantly more allergies than the breastfed and hydrolysed milk fed infants , although less than their counterparts in the non‐intervention group . Of the affected subjects in the intervention group , 80.4 % were RAST and /or Prick positive to food or inhalant allergens . Total serum IgE values detected at birth in the intervention group were not predictive , but at 1 and 2 years of age , IgE values more than 2 SD above the mean in asymptomatic babies were found to predictive for later allergy . In breastfed babies the total IgE level at 1 and 2 years of age was lower than in the other two feeding groups . Of the various factors tested in the non‐intervention group , the following were the most important in the pathogenesis of allergic symptoms : ( i ) formula implementation begun in the first week of life ; ( ii ) early weaning ( < 4 months ) ; ( iii ) feeding beef ( < 6 months ) ; ( iv ) early introduction of cow 's milk ( < 6 months ) ; and ( v ) parental smoking in the presence of the babies and early day care admission ( < 2 years of life ) . All the preventive measures used in this study ( exclusive breastfeeding and /or hydrolysed milk feeding , delayed and selective introduction of solid foods , and environmental advice ) were effective at the third year of follow‐up , greatly reducing allergic manifestations in high atopic risk babies in comparison with those not receiving these interventions BACKGROUND 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 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 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 Cow 's milk allergy/intolerance is treated by complete avoidance of cow 's milk proteins . Because cow 's milk is an important food for infants , its avoidance may lead to an increased risk of growth impairment . Whilst there is evidence for the beneficial effects of extensively hydrolyzed cow 's milk formulate ( eHF ) in infants with cow 's milk allergy/intolerance , little is known about the effects of amino-acid-based formulae ( AA ) in such infants . We therefore performed a prospect i ve , controlled , multi-center trial to study the efficacy of AA in comparison with eHF , on the growth and clinical symptoms of 73 infants ( median age 5.7 months ) with cow 's milk allergy/intolerance and atopic dermatitis . Cow 's milk allergy/intolerance was proven in all infants by double-blind , placebo-controlled food-challenge . We observed a significant improvement in the SCORAD index in both groups , from a mean of 24.6 , at entry , to a mean of 10.7 ( p < 0.0001 ) after 6 months . In the AA group there was a significant increase in the length st and ard deviation score ( p < 0.04 ) , whilst there was no difference in the eHF group . The weight-for-length values were stable in both groups . The energy intake during the study was similar in both groups . Both an AA and eHF result ed in a significant clinical improvement in infants with an early onset of symptoms of cow 's milk allergy/intolerance . Feeding an AA result ed in improved growth compared with feeding eHF , despite similar dietary intakes , and may therefore be considered as a beneficial alternative in infants with severe cow 's milk allergy intolerance 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 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 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 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 The aim of this study was to compare the allergy-preventive effect of a partially hydrolyzed formula with two extensively hydrolyzed formulas , in infants with a high risk for development of allergic disease . High-risk infants from four Danish centres were included in the period from June 1994 to July 1995 . Five-hundred and ninety-five high-risk infants were identified . High-risk infants were defined as having biparental atopy , or a single atopic first-degree relative combined with cord blood immunoglobulin E ( IgE ) > or = 0.3 kU/l . At birth all infants were r and omized to one of three different blinded formulas .  All mothers had unrestricted diets during pregnancy and lactation and were encouraged to breast-feed exclusively . If breast-feeding was insufficient , one of the three formulas , according to r and omization , was given during the first 4 months . It was recommended not to introduce cow 's milk , cow 's milk products . and solid foods until the age of 4 months . After the age of 4 months a normal unrestricted diet and conventional cow 's milk-based formula were given when needed . All infants were followed-up prospect ively with interview and physical examination at the age of 6 , 12 , and 18 months , and if any possible atopic symptoms were reported . If food allergy was suspected , controlled elimination/challenge procedures were performed in a hospital setting . Of 550 infants included in the study , 514 were seen at all visits and 36 were excluded owing to noncompliance . Of 478 infants who completed the study , 232 were exclusively breast-fed , 79 received an extensively hydrolyzed casein formula ( Nutramigen ) , 82 an extensively hydrolyzed whey formula ( Profylac ) , and 85 a partially hydrolyzed whey formula ( Nan HA ) , during the first 4 months of life . These four groups were identical in regard to atopic predisposition , cord blood IgE , birthplace , and gender . Exclusively breast-fed children were exposed less to tobacco smoke and pets at home and belonged to higher social classes , whereas the three formula groups were identical concerning environmental factors . The frequency of breast-feeding was high ; only eight ( 2 % ) children were not breast-fed at all . The three formula groups were identical in regard to duration of breast-feeding and age at introduction of formula and solid foods . No significant differences were found in the three groups of infants receiving formula milk regarding the cumulative incidence of atopic dermatitis or respiratory symptoms . The cumulative incidence of parental-reported cow 's milk allergy was significantly higher in children fed partially hydrolyzed formula ( Nan HA ) compared with extensively hydrolyzed formula ( Nutramigen or Profylac ) at 12 and 18 months ( NanHA , 7.1 % ; Nutramigen , 2.5 % ; Profylac , 0 % ; p=0.033 ) . The cumulative incidence of confirmed cow 's milk allergy was 1.3 % ( three of 232 ) in exclusively breast-fed infants , 0.6 % ( one of 161 ) in infants fed extensively hydrolyzed formula ( Nutramigen or Profylac ) , and 4.7%(four of 85 ) in infants fed partially hydrolyzed formula ( Nan HA ) . Partially hydrolyzed formula was found to be less effective than extensively hydrolyzed formula in preventing cow 's milk allergy , 0.6 % vs. 4.7 % ( p=0.05 ) , but because of the small number of cases the results should be interpreted with caution . Compared with other similar studies the frequency ofatopic symptoms was low , even though the dietetic intervention did not include either maternal diet during lactation or dietary restrictions to the children after the age of 4 months BACKGROUND 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 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 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 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
REVIEW ER 'S CONCLUSIONS There is no evidence to support feeding with a hydrolysed formula for the prevention of allergy in preference to exclusive breast feeding .
In high risk infants who are unable to be completely breast fed , there is evidence that prolonged feeding with a hydrolysed compared to a cow 's milk formula reduces infant and childhood allergy and infant CMA .
BACKGROUND Allergies and food reactions are common and may be associated with foods including adapted cow 's milk formulas .
Formulas containing hydrolysed proteins have been used to treat infants with allergy or food intolerance , and have been advocated for prevention of allergy and food intolerance in infants .
OBJECTIVES To determine whether use of hydrolysed formulas for infant feeding prevents allergy and food intolerance .
If hydrolysed formulas are effective , to determine what type of hydrolysed formula is most effective including extensively and partially hydrolysed formulas .
To determine which infants benefit including infants at low or high risk of allergy and infants receiving early , short term or prolonged formula feeding .