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. Palatability of hydrolysates and Other substitution formulas for cow's milk-allergic children: a comparative study of taste, smell, and texture evaluated by healthy volunteers. Comparison of an elemental with a hydrolysed whey formula in intolerance to cows' milk. Hypoallergenicity of an extensively hydrolyzed whey formula. An extensively hydrolysed cow's milk formula improves clinical symptoms of gastroesophageal reflux and reduces the gastric emptying time in infants. 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. Gastric Electrical Activity and Gastric Emptying in Preterm Newborns Fed Standard and Hydrolysate Formulas Use of hypoallergenic formula in the prevention of atopic disease among Asian children. The diagnostic significance of IgG cow's milk protein antibodies re-evaluated Feeding a Formula Supplemented With Long Chain Polyunsaturated Fatty Acids Modifies the “Ex Vivo” Cytokine Responses to Food Proteins in Infants at Low Risk for Allergy Comparisons of a chicken-based formula with soy-based formula in infants with cow milk allergy. Sensitive period in flavor learning: effects of duration of exposure to formula flavors on food likes during infancy. Allergy development and macromolecular absorption in infants with different feeding regimens during the first three days of life. A three‐year prospective follow‐up Cumulative incidence of atopic disorders in high risk infants fed whey hydrolysate, soy, and conventional cow milk formulas. Effect of Feeding a Formula Supplemented With Long-chain Polyunsaturated Fatty Acids for 14 Weeks Improves the Ex Vivo Response to a Mitogen and Reduces the Response to a Soy Protein in Infants at Low Risk for Allergy Importance of the first meal on the development of cow's milk allergy and intolerance. Evaluation of Infant Feeding in Acute Gastroenteritis Resource implications and budget impact of managing cow milk allergy in the UK 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 Safety and efficacy of a new extensively hydrolyzed formula for infants with cow's milk protein allergy. Higher urinary excretion of essential amino acids in preterm infants fed protein hydrolysates Protein hydrolysate formula maintains homeostasis of plasma amino acids in preterm infants. [Effects of feeding intervention on development of eczema in atopy high-risk infants: an 18-month follow-up study]. The effect of feeding four different formulae on stool weights in prolonged dehydrating infantile gastroenteritis. Prebiotic‐supplemented partially hydrolysed cow's milk formula for the prevention of eczema in high‐risk infants: a randomized controlled trial Probiotics: a novel approach in the management of food allergy. Development of atopic disease after early administration of cow milk formula Tolerance of a soy formula by infants and children. Does Early Diet Have an Effect on Subsequent Macromolecular Absorption and Serum IgE? A non-hydrolyzed, fermented milk formula reduces digestive and respiratory events in infants at high risk of allergy Allergy to soy formula and to extensively hydrolyzed whey formula in infants with cow's milk allergy: a prospective, randomized study with a follow-up to the age of 2 years. Partial Protein-Hydrolyzed Infant Formula Decreased Food Sensitization but Not Allergic Diseases in a Prospective Birth Cohort Study Effect of feeding whey hydrolysate, soy and conventional cow milk formulas on incidence of atopic disease in high risk infants. Comparison of Breast, Cow, and Soy Feedings in the Prevention of Onset of Allergic Disease Specific antibodies to cow’s milk proteins in infants: effect of early feeding and diagnosis of cow’s milk allergy Improved general health status in an unselected infant population following an allergen-reduced dietary intervention programme: the ZUFF-STUDY-PROGRAMME
Part II: infant growth and health status to age 6 months Do infants with cystic fibrosis need a protein hydrolysate formula? A prospective, randomized, comparative study. Hydrolyzed infant formula and early β-cell autoimmunity: a randomized clinical trial. Early infant feeding and type 1 diabetes Soy allergy following early soy feeding in neonates. Gastric emptying in healthy newborns fed an intact protein formula, a partially and an extensively hydrolysed formula. Lower Calcium Absorption in Infants Fed Casein Hydrolysate- and Soy Protein-Based Infant Formulas Containing Palm Olein Versus Formulas without Palm Olein Hydrolysed protein accelerates the gastrointestinal transport of formula in preterm infants Early diet of preterm infants and development of allergic or atopic disease: randomised prospective study. Tolerance of a standard intact protein formula versus a partially hydrolyzed formula in healthy, term infants Effectiveness of casein hydrolysate feedings in infants with colic Nutritional evaluation of protein hydrolysate formulas. Maternal compliance with nutritional recommendations in an allergy preventive programme Certain hydrolyzed formulas reduce the incidence of atopic dermatitis but not that of asthma: three-year results of the German Infant Nutritional Intervention Study. Development of immunoglobulin G and immunoglobulin E antibodies to cow's milk proteins and ovalbumin after a temporary neonatal exposure to hydrolyzed and whole cow's milk proteins. The nutritional value of a whey hydrolysate formula compared with a whey-predominant formula in healthy infants. Dietary treatment of infant colic: a double-blind study. Short-term effect of partially hydrolyzed formula on the prevention of development of atopic dermatitis in infants at high risk. The natural history of intolerance to soy and extensively hydrolyzed formula in infants with multiple food protein intolerance. Cost-effectiveness of using an extensively hydrolysed formula compared to an amino acid formula as first-line treatment for cow milk allergy in the UK. Allergen avoidance in infancy and allergy at 4 years of age Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes: The TRIGR Randomized Clinical Trial Nutritional evaluation of various protein hydrolysate formulae in term infants during the first month of life Hypoallergenicity and effects on growth and tolerance of a new amino acid-based formula with docosahexaenoic acid and arachidonic acid. Development of immune response to cow's milk proteins in infants receiving cow's milk or hydrolyzed formula. Soy allergy in infants and children with IgE-associated cow's milk allergy. Role of food protein intolerance in infants with persistent distress attributed to reflux esophagitis. Avoidance of Cow's Milk-Based Formula for At-Risk Infants Does Not Reduce Development of Celiac Disease: A Randomized Controlled Trial. Early exposure to cow's milk protein is protective against IgE-mediated cow's milk protein allergy. The development and prediction of atopy in high-risk children: follow-up at age seven years in a prospective randomized study of combined maternal and infant food allergen avoidance. Dietary manipulation of beta cell autoimmunity in infants at increased risk of type 1 diabetes: a pilot study Effect of combined maternal and infant food-allergen avoidance on development of atopy in early infancy: a randomized study. Effects of brief early exposure to partially hydrolyzed and whole cow milk proteins.
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 BACKGROUND Hydrolyzed formulas used to feed infants with cow 's milk-allergy can be classified as soy based , extensively hydrolyzed ( casein , whey and mixed ) , and amino-acid based . Their unsatisfactory taste is reported by parents and physicians . OBJECTIVE The aim of this study was to ascertain the palatability of these formulas in a double-blind taste test . MATERIAL S AND METHODS Fifty healthy volunteers performed a r and omized-order double-blind test with 12 different milks .  The taste , smell , smell , and texture of each formula were evaluated o n scales ranging from 1 ( worst ) t o 5 ( best ) . The Pearson correlation coefficient between the peptide weight of each formula and the score obtained for each evaluated attribute was calculated . RESULTS The soy formulas and rice formula had the best taste scores , followed by the whey hydrolysates ; the mixed hydrolysates and the casein hydrolysates had the lowest taste scores . Individually the most palatable formula was mixed hydrolysate 1 , by total score . We found a statistically significant correlation between peptide weight , reflecting the degree of hydrolysis of each formula , and the scores obtained for taste , texture , and overall palatability . CONCLUSION The palatability of formulas is determined by the amount of bitter peptides obtained through hydrolysis . Flavorings and sweeteners may also contribute to palatability . Further studies are needed in order to determine how to modify the organoleptic properties of these products with the purpose of improving their palatability In a double blind study , 40 infants with cows ' milk intolerance of various causes were r and omised to receive a nutritionally complete formula in which nitrogen was supplied either as whey hydrolysate or amino acids .  The median age of infants was 10 weeks ( range 36 weeks ' gestation to 108 weeks ' postnatal age ) . After a median follow up period of 25 weeks there was no significant difference in dietary intake between the formulas . Twenty four weeks after entry , weight and weight for length improved equally on both formulas . Plasma albumin improved significantly on the hydrolysed whey formula but not in the amino acid group . Both milks were palatable and normal intakes of formula were maintained . Biochemical and haematological indices remained within normal limits . There was no difference in stool frequency and vomiting between the two formulas . Two infants developed a probable allergic colitis while receiving hydrolysed whey . Amino acid formula may have a role in the management of atopic infants with severe cows ' milk intolerance who have already reacted to whey or casein hydrolysate formula Several different protein hydrolysate-based infant formulas have been promoted as hypoallergenic and considered suitable for the dietary management of cow 's milk allergy ( CMA ) . Accepting that none of the hydrolysate-based products is completely safe , the American Academy of Pediatrics ( AAP ) recommends that these formulas should be tested in a double-blind placebo-controlled setting and tolerated by at least 90 % of children with proven CMA . In principle , this recommendation is also endorsed by the European Society of Paediatric Gastroenterology and Nutrition ( ESPGAN ) and the European Society of Paediatric Allergy and Clinical Immunology ( ESPACI ) . In this two-center study , 32 children with proven CMA were tested with the extensive hydrolysate whey formula Nutrilon Pepti , for comparison with Profylac ( extensive ) and Nan HA ( partial ) whey hydrolysate products .  Skin-prick tests ( SPTs ) were , respectively , positive to the three hydrolysate formulas in 19 % , 15 % , and 32 % of children . After oral challenge it was concluded that 97 % ( 95 % CI : 85 - 100 % ) of the children tolerated  Nutrilon Pepti , 94 % ( 95 % CI : 75 - 100 % ) tolerated Profylac , and 64 % ( 95 % CI : 37 - 81 % ) tolerated Nan HA . This study demonstrates that the extensive hydrolysates Nutrilon Pepti and Profylac are well tolerated in a population of children with proven CMA and that both products can be considered safe for their intended use . This study confirms that a very small number of children react even to extensively hydrolyzed formulas . SPT prior to oral exposure to the hydrolysate-based formulas can indicate whether a child is at risk of showing reactions to the product . Introduction of new products to these children should be carried out under a doctor 's supervision . However , the majority of the SPT-positive children did tolerate the two extensively hydrolyzed whey-based formulas tested BACKGROUND 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 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 Background Because infant formulas containing hydrolyzed cow milk protein are used to reduce feeding intolerance and to improve gastric emptying , the effect on gastrointestinal motility of a hydrolysate formula was compared with that of a st and ard preterm formula . Methods Thirty-six preterm newborns with a gestational age of 32.2 ± 2.3 weeks were assigned r and omly to st and ard formula or hydrolyzed formula .  Cutaneous electrogastrography and ultrasound examination of gastric emptying were performed simultaneously to evaluate gastrointestinal motility before and after the test meal . All recording sessions were performed 1 week after infants had reached full enteral feeding . Results No significant difference in gastrointestinal symptoms was noted in the newborns fed the different formulas . In particular , regurgitation and vomiting were observed in 78 % versus 64 % of preterm newborns after st and ard and hydrolyzed formula , respectively ( Fisher exact test , not significant ) . No differences were found in terms of gastric electrical activity and gastric emptying time between the two groups . Conclusions It seems unnecessary to use hydrolysate formulas to improve motility in preterm infants 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 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 Long chain polyunsaturates ( LCP ) status during the early neonatal period is associated with a reduced risk of atopic symptoms and later allergies . In this study , we characterized the immune response of low-risk , term , formula-fed infants r and omized at ≤14 d of age to st and ard term formula ( Formula ) or formula containing LCP ( Formula+LCP ) for 4 wks . Infants exclusively fed human milk  were included for comparison . Peripheral blood was collected at 14 and 42 d of age , and lymphocyte phenotype , proliferation , and cytokine production ( IL-2 , IL-4 , IL-6 , IL-10 , IL-12 , IFN-γ , TNF-α , TGFβ ) were assessed after incubation with β-lactoglobulin ( BLG ) and soy protein ( SOY ) . Lymphocyte proliferation did not differ between groups . Compared with human milk-fed infants at 2 wks , formula-fed infants produced more TNF-α and IFN-γ and had more cells expressing ICAM-1 ( CD54 ) after incubation with BLG and SOY ( p < 0.05 ) . At 6 wks of age , infants fed Formula+LCP  produced more TNF-α with SOY ( 3.2-fold ) and IFN-γ ( 3.3-fold ) with BLG compared with infants fed Formula ( p < 0.05 ) . In conclusion , low-risk term infants fed formula before 14 d of age  produced more TNF-α and IFN-γ in response to food proteins . Feeding Formula+LCP for 4 wks maintained the higher TNF-α and IFN-γ response to these food proteins OBJECTIVE To determine whether chicken-based formula can replace soy-based formula in infants with cow milk allergy . SUBJECTS AND METHODS Thirty-eight infants with cow 's milk allergy , aged between 2 - 24 months of age were r and omized to receive either chicken-based formula or soy-based formula for 14 days . RESULTS In the group of soy-based formula , 12 out of 18 infants had evidence of intolerance and could not continue with the formula . However , only 4 out of 20 infants in the chicken-based formula group had evidence of clinical intolerance . All other 16 infants were fed the chicken-based formula with success . The number of infants who were intolerant to chicken formula  was significantly lower than the number of those fed soy-based formula ( p = 0.009 ) . CONCLUSION Chicken-based formula can be used more effectively than soy-based formula in infants with cow milk allergy BACKGROUND & AIMS Emerging research has revealed the existence of periods in which the developing brain has heightened sensitivity to environmental influences . We discovered a sensitive period , < 4 months of age , when exposure to the flavor of extensively hydrolyzed protein hydrolysate formulas ( ePHF ) determines its hedonic tone . This formula has pronounced bitter , sour , and savory tastes compared to cow-milk-based formulas ( CMF ) . This study aim ed to determine the effects of duration of exposure during the sensitive period on a food containing an exemplar of the savory flavor . METHODS Formula-fed infants were r and omized into four groups at age 0.5 months : one control group fed the CMF for 8 months , and three groups fed ePHF for 1 , 3 , or 8 months and CMF otherwise . When infants were 8.5 months , their acceptance of a savory and plain broth was measured . RESULTS Infants fed hydrolysate formula for 3 or 8 months , but not 1 month , showed greater acceptance of the savory broth relative to the plain broth ( p < 0.01 ) and consumed it at a faster rate ( p = 0.01 ) . CONCLUSIONS The duration of flavor exposure affects infants ' earliest responses to foods : a 3-month exposure to ePHF shifted the hedonic tone for savory flavor A group of 129 infants were r and omly assigned at birth to one of three feeding regimens : human milk ( HM ) , cow 's milk formula ( CMF ) or a casein hydrolysate formula ( CHF ) during the first 3 days of life . Blood sample s were taken on at 4 days and at 2 , 4 , 8 , 12 and 24 months of age . Macromolecular absorption was analysed by measuring the serum concentration of human α‐lactalbumin ( S‐α‐LA ) with a competitive radioimmunoassay ( RIA ) . Total serum IgE was measured by RIA . A family history of allergy correlated to the proportion of infants with allergic symptoms both at 24 and 36 months of age ( p= 0.03 and p= 0.04 respectively ) . In none of the three groups did correlation exist between the duration of breastfeeding and serum α‐LA , serum IgE , family history of allergy , frequency of allergic symptoms and proportion of infants with infections 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 Background and Objective : Feeding long-chain polyunsaturated fatty acids ( LCP ) influences immunity in adults ; however , less is known about their effect during development . The aim of the study was to determine the effect of feeding LCP on immunity in healthy infants during the first 4 months of life . Patients and Methods : Formula-fed infants were r and omized at ≤14 days of age to st and ard term formula ( Formula ) or formula containing LCP ( Formula+LCP ) . Infants exclusively fed human milk ( HM ) were included for comparison . At 16 weeks of age , blood was collected and phenotypes , the ability to proliferate and produce cytokines ( interleukin [IL]-2 , IL-4 , IL-6 , IL-10 , IL-12 , interferon [IFN]-γ , tumor necrosis factor [TNF]-α , TGF-β ) after incubation with phytohemaglutinin ( PHA ) , β-lactoglobulin , or soy protein were measured . Results : Feeding LCP result ed in a higher than and more similar proliferation rate to PHA in HM-fed infants , possibly because of a greater TH1 type cytokine response and a higher percentage of antigen mature ( CD45RO+ ) cells ( P < 0.05 ) . The response to β-lactoglobulin did not differ among groups . After incubation with soy protein Formula+LCP , compared with Formula produced less IL-2 and more TNF-α and had a higher percentage of CD8 + and a lower percentage of CD20 + ( CD20+CD54 + ) cells poststimulation ( P < 0.05 ) . Both formula groups produced less IL-2 after PHA , had a lower percentage of CD80 + cells , and a higher percentage of CD54 + cells after incubation with food proteins ( P < 0.05 ) . Conclusions : Formula-fed infants , at low risk for allergy , respond differently to mitogen and food proteins ex vivo than those fed HM . Feeding LCP altered some of these differences in the direction that is hypothesized to confer immune benefits A cohort of 1749 newborns from the municipality of Odense born during 1985 in the University Hospital of Odense were followed prospect ively for the development of cow 's milk allergy (CMA)/cow 's milk protein intolerance ( CMI ) during their first year . The diagnosis of CMA/CMI was based on elimination/open milk challenge procedures according to generally accepted criteria . Thirty nine infants ( 2.2 % ) developed CMA/CMI .  Infants with CMA/CMI were fed cow 's milk formula daily during the first month of life significantly more often than infants in the study population ( p less than .001 ) . All 39 infants with CMA/CMI had ingested cow 's milk formula ( 40 - 830 mL ) neonatally , whereas none of the 210 neonates without supplements of cow 's milk formula  developed CMA/CMI ( p less than .05 ) . Based on a positive skin-prick test ( 2 + or more ) and /or specific serum IgE antibody to cow 's milk ( AL-RAST class 2 or more ) 16 infants were classified as having CMA . In infants solely breast-fed for greater than 1 month CMA was as frequent ( 1 % [ 14/1414 ] as in cow 's milk formula fed infant ( 0.6 % [ 2/335 ] ) . In infants with CMI , a significant majority ( 3.9 % [ 13/335 ] versus 0.7 % [ 10/1414 ] , p less than .001 ) had been cow 's milk formula fed during the first month . These data indicate an association between early cow 's milk formula feeding and development of reproducible adverse reactions to cow 's milk protein . Early neonatal intake of cow 's milk protein is probably a condition of sensitization and later adverse reactions to cow 's milk protein Sixty-eight bottle-fed babies under 9 months of age with mild acute gastroenteritis were observed to evaluate current feeding regimens following acute gastroenteritis in infancy . All babies were fed for 24 h with a glucose-electrolyte mixture ( GEM ) and then r and omly assigned to either a gradual re introduction to their normal milk , i.e. , slow re grade ; immediate return to full-strength formula ; or a rapid re grade to a hypoallergenic whey hydrolysate formula . All groups were well matched for age , sex , ethnic origin , nutritional state , and degree of hydration . There was no significance difference in stool frequency or reducing substances , vomiting , and duration of hospital stay between the three groups . Many infants ( 6/24 ) refused to take the whey hydrolysate formula , presumably because of unpalatability . Weight gain was more rapid when full-strength milk was given . Clinical relapse developed in 12 ( 17 % ) of patients . An enteric pathogen was detected in eight of this group and cow 's milk protein intolerance in three ( one from each feeding group ) . No infant had clinical ly significant lactose intolerance , in marked contrast to previous experience at Queen Elizabeth Hospital . In this group of previously healthy , well-nourished babies with mild acute gastroenteritis , there was no advantage in regrading slowly to milk or a hypoallergenic formula . An immediate return to normal formula 24 h after GEM feeding was well tolerated and simpler for parents Abstract Aim : To determine current treatment patterns for infants with cow milk allergy ( CMA ) and the associated re source implication s and budget impact , from the perspective of the UK 's National Health Service ( NHS ) . Methods : A computer-based model was constructed depicting current management of newly-diagnosed infants with CMA derived from patients suffering from this allergy in The Health Improvement Network ( THIN ) Data base . The model spanned a period of 12 months following initial presentation to a general practitioner ( GP ) and was used to estimate the 12-monthly healthcare cost ( at 2006/07 prices ) of treating an annual cohort of 18,350 infants from when they initially present to their GP . Results : Patients presenting with a combination of gastrointestinal and atopic symptoms accounted for 59 % of all patients . From the initial GP visit for CMA it took a mean 2.2 months to be put on diet , although treatment varied according to presenting symptoms . A total of 60 % of all infants were initially treated with soy , 18 % with an extensively hydrolysed formula and 3 % with an amino acid formula . A mean 9 % of patients remained symptomatic on soy and 29 % on an extensively hydrolysed formula . The total cost of managing CMA over the first 12 months following initial presentation to a GP was estimated to be £ 1,381 per patient and £ 25.6 million for an annual cohort of 18,350 infants . Limitations : Patients were not r and omised to treatment and re source use was not collected prospect ively . Nevertheless , 1,000 eligible patients have been included in the analysis , which should be a sufficiently large sample to accurately assess treatment patterns and healthcare re source use in actual clinical practice . The diagnosis of CMA may not be secure in all cases . Nevertheless , patients were diagnosed as having CMA by a clinician and have been managed by their GP as if they had CMA . Conclusion : CMA imposes a substantial burden on the NHS . Any strategy that improves healthcare delivery and thereby shortens time to treatment , time to diagnosis and time to symptom resolution should potentially decrease the burden this allergy imposes on the health service and release re sources for alternative use 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 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 Aim : Protein hydrolysates have been introduced in preterm formulae , but it is not clear whether they are needed for the feeding of preterm infants . We design ed a r and omized , controlled trial to test the effects of a preterm formula with hydrolysed cow 's milk proteins on short‐term growth and urinary and plasma amino acids levels . Methods : Infants with a birthweight 1750 g and gestational age 34 wk fed a conventional preterm infant formula ( formula B ) or a hydrolysed formula ( formula A ) .  Weight was measured daily ; length , head circumference , mid‐arm circumference and total skinfold thickness were measured weekly . Blood and urine were analysed for amino acid concentrations at start , 14 and 28 d. Results : Twenty‐one infants met the criteria for r and omization . The daily feeding volumes were : formula A 172.8±5.6 vs formula B 170.1±2.8 ml/kg/d . Infants fed with formula A showed slower weight gain ( 17.4±3.4 vs 20.5±3.3 g/kg/d ; p=0.045 ) and lower mean change in Z‐scores for weight ( −0.18±0.16 vs 0.00±0.09 ; p=0.009 ) and for head circumference ( −0.06±0.13 vs 0.06±0.13 ; p=0.049 ) . After 14 d , infants receiving formula A had statistically significant higher urinary levels of essential amino acids compared to infants receiving formula 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 OBJECTIVE To assess the preventive effects of different dietary regimens on development of eczema and food allergy in infants at high-risk for allergy . METHODS Forty-six infants whose parents were atopic and umbilical cord IgE > 0.35 kU/L were enrolled in the study . The infants were r and omly assigned at birth to one of 2 dietary regimen protocol s : those in intervention group ( 23 cases ) were breast fed till more than 4 months of age , then followed by feeding with partially hydrolyzed formula ( pHF ) , combined solid foods avoidance until 4-month of age , egg , fish , shrimp avoidance until 12-month of age . The other 23 cases in non-intervention group were breast fed for less than 4 months , or bottle fed with cow 's milk-based formula , egg yolk was introduced at 4-month of age , and egg white at 6-month of age , besides , no any other dietary avoidance was applied . All the infants were followed-up for 18 months . The primary end point was the presence of atopic eczema . Food allergy was detected by fresh food prick-to-prick tests or in vitro sIgE or Fx5E . RESULTS At 6 months , 12 months and 18 months , the incidence of eczema in intervention group was 4.3 % ( 1/23 ) , 8.7 % ( 2/23 ) , and 17.4 % ( 4/23 ) , respectively , which was significantly reduced as compared to that of the non-intervention group , which was 26.1 % ( 6/23 ) , 34.8 % ( 8/23 ) , and 39.1 % ( 9/23 ) , respectively . Food allergy was found in 13.0 % ( 3/23 ) of intervention group and 34.8 % ( 9/23 ) of non-intervention group by skin prick tests or sIgE. Egg white was the most common offending food . CONCLUSION Early life dietary interventions which included breastfeeding , delayed solid food introducing , pHF feeding , and high risk food avoidance could reduce the risk of atopic eczema and food allergy development , and was probably an effective primary intervention method for infants at high risk for atopy Prolonged diarrhea following an acute episode of dehydrating gastroenteritis in infants is often treated by the empirical removal of both cow 's milk protein and lactose from the feed , as they both have been implicated in the prolongation of diarrhea . In order to assess the efficacy of this policy and to determine whether there are any advantages in using a lactose-free semi-elemental feed in this situation , infants with prolonged dehydrating gastroenteritis from a developing community in South Africa were studied . Male black children between the ages of 6 weeks and 2 years with prolonged dehydrating gastroenteritis ( requiring intravenous fluids for longer than 72 h to maintain hydration ) were r and omly assigned to receive one of four feeds if the stool weight was greater than 30 g/kg body weight/24 h on the fourth day of admission . The four formula feeds were a partially modified cow 's milk formula ; a lactose-free , casein-containing formula ; a lactose-free , soy-protein-containing formula ; and a lactose-free , whey-hydrolysate-containing formula .  Stool weights were measured for the following 3 days . Seventy-two children were enrolled into the study .  Stool weights were similar in the four groups at the start of the trial , and fell significantly over the trial period in those groups receiving the lactose-free feeds . Mean stool weight in the cow 's milk formula group did not change . Thus , it appears that the continued feeding of a cow 's milk-based lactose-containing formulae to infants with prolonged dehydrating gastroenteritis adversely affects their recovery . ( ABSTRACT TRUNCATED AT 250 WORDS 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 BACKGROUND The gastrointestinal microflora is an important constituent of the gut mucosal defense barrier . We have previously shown that a human intestinal floral strain , Lactobacillus GG ( ATCC 53103 ) , promotes local antigen-specific immune responses ( particularly in the IgA class ) , prevents permeability defects , and confers controlled antigen absorption . OBJECTIVE The aim of this study was to evaluate the clinical and immunologic effects of cow 's milk elimination without ( n = 14 ) and with ( n = 13 ) the addition of Lactobacillus GG ( 5 x 10(8 ) colony-forming units/gm formula ) in an extensively hydrolyzed whey formula in infants with atopic eczema and cow 's milk allergy . The second part of the study involved 10 breast-fed infants who had atopic eczema and cow 's milk allergy . In this group Lactobacillus GG was given to nursing mothers . METHODS The severity of atopic eczema was assessed by clinical scoring . The concentrations of fecal alpha 1- antitrypsin , tumor necrosis factor-alpha , and eosinophil cationic protein were determined as markers of intestinal inflammation before and after dietary intervention . RESULTS The clinical score of atopic dermatitis improved significantly during the 1-month study period in infants treated with the extensively hydrolyzed whey formula fortified with Lactobacillus GG . The concentration of alpha 1-antitrypsin decreased significantly in this group ( p = 0.03 ) but not in the group receiving the whey formula without Lactobacillus GG ( p = 0.68 ) . In parallel , the median ( lower quartile to upper quartile ) concentration of fecal tumor necrosis factor-alpha decreased significantly in this group , from 709 pg/gm ( 91 to 1131 pg/gm ) to 34 pg/gm ( 19 to 103 pg/gm ) ( p = 0.003 ) , but not in those receiving the extensively hydrolyzed whey formula only ( p = 0.38 ) . The concentration of fecal eosinophil cationic protein remained unaltered during therapy . CONCLUSION These results suggest that probiotic bacteria may promote endogenous barrier mechanisms in patients with atopic dermatitis and food allergy , and by alleviating intestinal inflammation , may act as a useful tool in the treatment of food allergy We prospect ively studied the incidence of atopic disease in healthy term infants with a birth weight between ‐1 and ‐2 SD who were fed a cow milk formula during the first few days of life . A total of 216 infants were r and omized to receive either early feeding with formula before normal breastfeeding was started ( n= 112 ) or “ normal feeding ” with breastmilk ( n= 104 ) . Symptoms of allergy developed in 18%% of the infants before 18 months of age in the formula fed group , as compared to 33 % in the breastfed group ( P < 0.05 ) . The difference was confined to the group of infants with a history of allergy in two family members . Thus , 11 % of the formula‐fed infants developed allergy symptoms , as compared to 61 % of the control infants ( P < 0.01 ) . Our study implies that early feeding during the first days of life with a cow milk formula , before the introduction of breastmilk , may reduce the incidence of allergy symptoms before 18 months of age in infants with a family history of allergy For a minimum of one month ( mean , 54 days ) , 287 infants and children less than 8 years of age were fed an isolated soy-protein formula . Prior to entry into the study , a cow 's milk formula was being fed to 71 % , a soy formula to 9 % , and cow 's milk or other formulas to 20 % . Intolerance to cow 's milk was reported in 35 % of the patients , symptoms indicative of cow 's milk intolerance in 23 % , diarrhea or gastroenteritis in 18 % , a family history of allergy in 13 % , and insufficient weight gain , intolerance to other formulas , or constipation in 11 % . The patients showed normal increases in weight and length during the study . A significant decrease in the following symptoms were reported in the patients from before to after treatment : abdominal cramps , bloating or gas , colic , diarrhea , fussiness , rashes or eczema , spitting up , waking up crying at night , wheezing , and vomiting . It is concluded that , while receiving soy formula , infants and children continued to thrive normally and that the formula was well tolerated . After receiving soy formula , the frequency of undesirable feeding-related symptoms was reduced in the majority of infants and children A group of 130 healthy term infants were r and omly assigned at birth to one of three feeding regimens for the first 3 days of life : human milk ( HM ) , cow-milk formula ( CMF ) , or a casein hydrolysate formula ( CHF ) . The formula-fed infants received no human milk during the study days . After day 3 , all infants were exclusively breast-fed . Blood sample s were taken at 4 days and at 2 and 4 months of age during outpatient visits . Macromolecular absorption was analyzed 60 min after a feed of human milk by measuring the serum α-lactalbumin ( S-αLA ) concentrations by a competitive radioimmunoassay . Total serum IgE ( S-lgE ) was assayed by radioimmu-noassay . The median S-IgE value was significantly lower at 2 months of age in the CHF group than in the HM group . The values remained significantly lower , even at 4 months of age , in the CHF group than in either the HM or the CMF group . The median S-αLA concentration at 2 months of age was significantly higher in the CHF group than in either the HM group or the CMF group . No significant differences could be found between the CMF and HM groups at any time . One infant in the HM group and one infant in the CMF group developed infantile colic . Two infants in the CHF group developed symptoms of cow-milk allergy . All other infants were healthy at 4 months of age Background / Objectives : To determine the impact of a not hydrolyzed fermented infant formula containing heat-killed Bifidobacterium breve C50 and Streptococcus thermophilus 065 ( HKBBST ) on the incidence of allergy-like events during the first 2 years of life in children at high risk of atopy . Subjects/ Methods : This multicenter , r and omized , double-blind , controlled study included infants at high risk of atopy . Infants used HKBBST or a st and ard infant formula ( SIF ) since birth until 1 year of age , and were followed at 4 , 12 and 24 months after birth .  Skin prick tests ( SPTs ) for six foods and six aeroallergens were systematic ally performed and adverse events ( AEs ) were recorded . In case of potentially allergic AE ( PAAE ) , allergy could be further tested by SPT , patch tests and quantification of specific IgEs . If cow 's milk allergy ( CMA ) was suspected , an oral challenge could also be performed . Results : The study included 129 children , 63 were r and omized to SIF , 66 to HKBBST . The use of HKBBST milk did not alter the proportion of CMA but decreased the proportion of positive SPT to cow 's milk ( 1.7 vs 12.5 % , P=0.03 ) , and the incidence of digestive ( 39 vs 63 % , P=0.01 ) and respiratory potentially allergic AEs ( 7 vs 21 % , P=0.03 ) at 12 months , and that of respiratory PAAEs at 24 months ( 13 vs 35 % , P=0.01 ) . Conclusions : HKBBST decreased the incidence of PAAEs in children with family history of atopy , during the first months of life and after the formula was stopped . Oral tolerance to cow 's milk in infants at high risk of atopy may therefore be improved using not hydrolyzed fermented formulae OBJECTIVES We conducted a prospect i ve , r and omized study to evaluate the cumulative incidence of allergy or other adverse reactions to soy formula and to extensively hydrolyzed formula up to the age of 2 years in infants with confirmed cow 's milk allergy . STUDY DESIGN Infants ( n = 170 ) with documented cow 's milk allergy were r and omly assigned to receive either a soy formula or an extensively hydrolyzed formula . If it was suspected that the formula caused symptoms , a double-blind , placebo-controlled challenge ( DBPCFC ) with the formula was performed . The children were followed to the age of 2 years , and soy-specific immunoglobulin E antibodies were measured at the time of diagnosis and at the ages of 1 and 2 years . RESULTS An adverse reaction to the formula was confirmed by challenge in 8 patients ( 10 % ; 95 % confidence interval , 4.4%-18.8 % ) r and omly assigned to soy formula and in 2 patients ( 2.2 % ; 95 % confidence interval , 0.3 % to 7.8 % ) r and omly assigned to extensively hydrolyzed formula .  Adverse reactions to soy were similar in IgE-associated and non-IgE-associated cow 's milk allergy ( 11 % and 9 % , respectively ) . IgE to soy was detected in only 2 infants with an adverse reaction to soy . Adverse reactions to soy formula  were more common in younger ( < 6 months ) than in older ( 6 to 12 months ) infants ( 5 of 20 vs 3 of 60 , respectively , P = .01 ) . CONCLUSIONS Soy formula was well tolerated by most infants with IgE-associated and non-IgE-associated cow 's milk allergy . Development of IgE-associated allergy to soy was rare . Soy formula can be recommended as a first-choice alternative for infants > or=6 months of age with cow 's milk allergy Background : 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 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 It has been reported that the feeding of cow 's milk may enhance the development of atopy in predisposed infants . A prospect i ve study following children from birth through 15 years of age in a private pediatric practice was design ed to determine if the food ingested during the first months of life is related to the development of atopy in the offspring of allergic families . Each of 328 children with a positive family history of allergy was assigned to one of three groups . according to the feeding preference of the parents : 48 were fed breast milk ; 79 , soy-based formula ; and 201 , cow 's milk formula . All groups had egg , citrus , tomato , and wheat restrictions as well as inhalant allergen avoidance . These were compared to a control group of 580 children with no family history of allergy . Breast fed infants were found to have approximately one-half the incidence of atopy of cow 's milk or soy formula fed infants from atopic families when followed for up to 15 years . Soy feeding produced no advantage over cow 's milk in the prophylaxis of allergic disease . There was a threefold increase in clinical ly apparent atopic disease in offspring of allergic families when compared to controls but only a two-fold increase if the infant was breast fed . These results support the hypothesis that breast feeding and delay of exposure to known allergens may reduce the frequency of clinical allergic disease in the offspring of allergic families Purpose To investigate whether specific IgA , IgG , IgG1 and IgG4 responses to cow ’s milk proteins differ between infants with cow ’s milk allergy and infants with cow ’s milk related symptoms ( control subjects ) , and whether early feeding affects these responses as well as specific IgE. Methods A cohort of 6,209 healthy , full-term infants in a double-blind r and omized trial received , as supplementary feeding at maternity hospitals ( mean duration 4 days ) , either cow ’s milk formula , extensively hydrolyzed whey formula or donor breast milk .  Infants who developed cow ’s milk associated symptoms ( n = 223 ) underwent an open oral cow ’s milk challenge ( mean age 7 months ) , which confirmed cow ’s milk allergy in 111 and was negative in 112 . We measured in sera cow ’s milk specific IgE levels with UniCAP ( Phadia , Uppsala , Sweden ) , and β-lactoglobulin and α-casein specific IgA , IgG1 , IgG4 and IgG levels with enzyme-linked immunosorbent assay . Results Infants with IgE-mediated cow ’s milk allergy had lower β-lactoglobulin and α-casein specific IgG1 , IgG4 and IgG levels ( p < 0.05 ) than infants with non-IgE-mediated cow ’s milk allergy or control subjects . Within the group of infants with cow ’s milk allergy , exposure to cow ’s milk during the first few days after birth led to higher β-lactoglobulin and α-casein specific IgG4 levels ( p < 0.005 ) compared to infants fed with either breast milk or extensively hydrolyzed formula . Conclusions Subdued IgG class responses to cow ’s milk proteins characterized IgE-mediated cow ’s milk allergy . In infants who developed cow ’s milk allergy early exposure to cow ’s milk result ed in a heightened specific IgG4 response Summary Aim of the study . An allergen-reduced dietary intervention programme with strict dietary requirements was implemented over the first four months of life in an unselected population -based infant cohort and compared to a non-intervention cohort ( the ZUFF study ) . Recommendations for the dietary programme in the intervention cohort were extended , but not strictly implemented , until the end of month six . The intervention was based on breastfeeding , a moderate whey hydrolysate formula ( pHF ) , and delayed introduction of weaning foods with a high allergenicity . This study was a prospect i ve , controlled , and unblinded study , the first to assess the effects of an allergen-reduced , pHF-based early nutritional programme in a broad unselected infant population . Because overall healthy development of the infant is a major objective of any nutritional programme , the study evaluated the effects of the dietary intervention on infant growth and general health status rather than specific allergic manifestations . Part I of this paper gave results for nutritional behaviour only , and Part II gives results for growth and general health status during the intervention period through the sixth month of life . Methods . Assignment of study infants was to demographically comparable intervention ( Z ) or control ( FF ) cohorts according to place of birth . In the intervention cohort ( Z=564 ) , the recommended dietary regimen was breastfeeding and – if exclusive breastfeeding was not possible – supplementation with a moderately hydrolysed , allergen-reduced infant formula ( pHF ) . Weaning foods were delayed until four months of age or later in case of weaning foods with high allergenicity . In the control cohort ( FF=566 ) , there was no specific intervention . Imbalances between cohorts in confounding ( adjuvant ) factors that could influence health related outcomes were integrated as covariates into the logistic regression of the main analyses . Growth parameters included weight , length , head circumference , BMI , and Z scores ( SDS ) . General health status was assessed by clinical ly significant findings in gastrointestinal , respiratory , or skin symptoms . Results . Growth at 6 weeks and at 3 and 6 months was similar for Z and FF . Significantly fewer Z than FF infants had clinical ly noteworthy health findings at 3 months ( Z=27 % versus FF=37 % , odds ratio=0.63 , CI=0.48–0.82 ) and 6 months ( Z=33 % versus FF=49 % , odds ratio=0.51 , CI=0.40–0.66 ) . This corresponds to a 30 % reduction in overall health concerns at 6 months for the intervention cohort . At 3 and 6 months , differences between cohorts in most measures of general health status were strongly influenced by a lower incidence of skin symptoms in the Z cohort . Within FF , there were fewer exclusively breastfed ( eBF ) infants with health problems at 3 months compared with those who were partially ( pBF ) or non-breastfed ( nBF ) ( eBF=31 % , pBF=40 % , nBF=39 % , p<0.05 ) . In contrast , in the Z intervention cohort , the number of infants with health concerns was similar for exclusively breastfed infants and for those in whom mother 's milk was supplemented or replaced by pHF ( eBF=29 % , pBF=25 % , nBF=26 % , ns ) . In a sub analysis of overall health findings in infants without a family risk of allergies , there were again significantly fewer Z than FF infants with any health or any skin problem . Conclusion .An allergen-reduced dietary recommendation that includes a moderate whey hydrolysate infant formula ( pHF ) has no negative effects on growth parameters up to 6 months of life in an infant population unselected for atopic risk . The dietary intervention produced improvements in general health status when compared with a control cohort that received infant formula with unhydrolysed proteins ( IF ) , and high allergenic weaning foods at an earlier age . The difference between cohorts was principally due to fewer adverse skin findings . In infants following our allergen-reduced feeding recommendation , 3-month general health status was comparable between those who were exclusively breastfed and those in whom breastfeeding was supplemented or replaced by pHF . Our results demonstrate that a pHF feeding recommendation during the first 4 to 6 months of life – when exclusive breestfeeding is not possible – is a safe and feasible regimen not only in high-allergic risk population s but in general unselected infant population . The general use of pHF formula in non- or partly breastfed infants could therefore be considered an important contribution to optimised infant nutrition OBJECTIVES We compared the nutritional benefits of a protein hydrolysate and a conventional infant formula in infants newly diagnosed with cystic fibrosis ( CF ) . STUDY DESIGN Twenty-three infants with CF ( < 6 months of age ) and pancreatic insufficiency were r and omized to receive a hydrolysate formula ( Alimentum ) or a cow 's milk-based formula ( Similac ) . Each patient was monitored at 1 month and then every 3 months for 1 year . RESULTS Eighteen patients ( 8 Alimentum , 10 Similac ) completed the study . At entry , the age distribution and clinical characteristics of each group were comparable . Energy intake with each formula was the same at 1 and 3 months , but at 6 and 12 months the hydrolysate-fed infants had higher age-adjusted energy intake . There were no differences in fecal energy or fecal fat at entry or throughout the study . Although the hydrolysate-fed infants were slightly more malnourished at diagnosis , growth velocity and nutritional status of infants with CF in each group were the same throughout the study . CONCLUSIONS The results of this r and omized study fail to support the use of a hydrolyzed formula for the routine care of infants newly diagnosed with CF IMPORTANCE The disease process leading to clinical type 1 diabetes often starts during the first years of life . Early exposure to complex dietary proteins may increase the risk of β-cell autoimmunity in children at genetic risk for type 1 diabetes .  Extensively hydrolyzed formulas do not contain intact proteins . OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of diabetes-associated autoantibodies in young children . DESIGN , SETTING , AND PARTICIPANTS A double-blind r and omized clinical trial of 2159 infants with HLA-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries ; 1078 were r and omized to be weaned to the extensively hydrolyzed casein formula and 1081 were r and omized to be weaned to a conventional cows ' milk-based formula .  The participants were observed to April 16 , 2013 . INTERVENTIONS The participants received either a casein hydrolysate or a conventional cows ' milk formula supplemented with 20 % of the casein hydrolysate . MAIN OUTCOMES AND MEASURES : Primary outcome was positivity for at least 2 diabetes-associated autoantibodies out of 4 analyzed . Autoantibodies to insulin , glutamic acid decarboxylase , and the insulinoma-associated-2 ( IA-2 ) molecule were analyzed using radiobinding assays and islet cell antibodies with immunofluorescence during a median observation period of 7.0 years ( mean , 6.3 years ) . RESULTS The absolute risk of positivity for 2 or more islet autoantibodies was 13.4 % among those r and omized to the casein hydrolysate formula ( n = 139 ) vs 11.4 % among those r and omized to the conventional formula ( n = 117 ) . The unadjusted hazard ratio for positivity for 2 or more autoantibodies among those r and omized to be weaned to the casein hydrolysate was 1.21 ( 95 % CI , 0.94 - 1.54 ) , compared with those r and omized to the conventional formula , while the hazard ratio adjusted for HLA risk , duration of breastfeeding , vitamin D use , study formula duration and consumption , and region was 1.23 ( 95 % CI , 0.96 - 1.58 ) . There were no clinical ly significant differences in the rate of reported adverse events between the 2 groups . CONCLUSIONS AND RELEVANCE Among infants at risk for type 1 diabetes , the use of a hydrolyzed formula , when compared with a conventional formula , did not reduce the incidence of diabetes-associated autoantibodies after 7 years . These findings do not support a benefit from hydrolyzed formula . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00179777 Background Infant feeding practice s , particularly the type of milk feeding , have been associated with the development of type 1 diabetes . Aim of the study We studied the relationship between early infant feeding ( during the first year of life ) and diabetes in a large population -based cohort . Methods In 1994–1995 , 6,209 healthy full-term newborns participated in a study examining the effect of supplementary feeding , on development of allergy to cow ’s milk , in maternity hospitals . All supplements in the maternity hospitals were known . Mothers recorded the feeding of infants prospect ively at home . In August 2006 , from a nationwide diabetes registry , 45 children from our cohort were listed as having type 1 diabetes . Results The distribution of cases was similar in the r and omized feeding groups : 9/1,789 in the group that received adapted cow ’s milk-based formula ; 12/1,737 in those who received extensively hydrolyzed formula ; 16/1,859 in those who received banked human milk ; and 8 among those 824 exclusively breast-fed in the hospital . When children who had received cow ’s milk-based formula in the maternity hospital were compared with those without such exposure , less number of children in the former group had diabetes by age 8 ( P = 0.026 ) , but by the end of the follow-up ( 11.5 years ) the difference disappeared ( P = 0.16 ) . Length of breast-feeding and introduction of cereals and other solid foods were similar among those developing type 1 diabetes and those remaining healthy , while early regular daily feeding with cow ’s milk-based formula tended to associate with lower risk for type 1 diabetes ( OR 0.66 ; 95 % confidence interval 0.38–1.13 ; P = 0.08 ) . Conclusions In an extended , secondary analysis of a population -based cohort , very early exposure to cow ’s milk is not a risk factor for type 1 diabetes ; it may in fact diminish its appearance before age 8 UNLABELLED B ACKGROUND : Feeding neonates with humanized milk formula in maternity hospitals may increase the prevalence of  milk allergy in infants . However , prospect i ve studies of the possible allergenic effect of very early soy-based formula feeding are lacking . OBJECTIVES To assess the prevalence of soy allergy in infants fed soy-based formula in the first 3 days of life . METHODS The study group included 982 healthy full-term infants born within a 7 month period at a hospital that routinely uses soy-based formula to supplement breastfeeding .  In-hospital feeding was recorded and the parents were interviewed once monthly over the next 6 months regarding feeding practice s and clinical symptoms suggesting soy allergy in the infant . RESULTS Ninety-nine percent of the infants received soy-based formula supplement in hospital , and 33%-42 % at home . No cases of immediate allergic reaction to soy or soy-induced enterocolitis were reported . CONCLUSIONS The use of soy-based formula in the early neonatal period does not apparently increase the prevalence of soy allergy in infants followed for the next 6 months 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 Objective : Quantitative balance studies were performed to compare fat and calcium absorption in healthy , full term infants fed casein hydrolysate-based ( CHF ) and soy protein-based ( SPF ) infant formulas with or without palm olein ( PO ) .  Previous studies have reported that PO significantly reduced absorption of both fat and calcium in cow ’s milk-based formulas in which most of the calcium is inherent in the milk protein . In both SPF and CHF virtually all calcium is added as calcium salts . Methods : Two r and omized , blinded , crossover balance studies were conducted in normal term infants using a three-day home balance method . One study evaluated 10 infants fed commercially available CHF with or without PO , and the other study evaluated 12 infants fed commercially available SPF with or without PO .  Fat and calcium absorption were determined based on the weight of formula intake , weight of stools , and measured calcium and fat in formula and stools . Results : Fat and calcium intake did not differ between the groups fed CHF . However , infant ’s calcium and fat absorption was less , 41 ± 6 % ( Mean ± SEM ) and 92.0 ± 0.8 % , respectively , when fed CHF with PO compared to 66 ± 5 % and 96.6 ± 1.1 % , respectively , when fed CHF without PO , ( p < 0.01 ) . For infants fed SPF , fat and calcium intake did not differ between the feeding groups . Mean calcium absorption was also significantly less when infants were fed SPF with PO , 22 ± 3 % , than when fed SPF with no PO , 37 ± 4 % ( p < 0.05 ) . Fat absorption did not differ between the two SPFs . Conclusion : This study demonstrates that PO , as the predominant fat , is associated with significantly lower absorption of calcium from infant formulas in which calcium salts are the source of calcium . These findings corroborate previous reports of this negative effect of PO in cow milk-based infant formulas in which most of the calcium is a component of the cow milk protein source Vomiting , large gastric residuals and abdominal distension are common in very immature infants on formula feeding . The present trial investigated whether a protein hydrolysate formula reduces the gastrointestinal transit time in preterm infants . Fifteen preterm infants ( median gestational age 29 ( 24–32 ) wk , birthweight 1241 ( 660–1900 ) g , postnatal age 18 ( 5–54 ) d ) on full enteral feeds ( > 150 ml/kg*d ) were enrolled . It was hypothesized that the gastrointestinal transit time is at least 2 h shorter when protein hydrolysate formula is fed compared with st and ard preterm formula . In a r and omized cross‐over design study , each formula was fed for 5 d. On days 4 and 9 the gastrointestinal transit time was estimated using carmine red . The protein hydrolysate formula had a markedly shorter gastrointestinal transit time ( 9.8 h ) than the st and ard formula ( 19 h ) ( p= 0.0022 , two‐sided Mann‐Whitney U test ) OBJECTIVE --To study the effect of early diet on the development of allergic reactions in infants born preterm . DESIGN --Two r and omised prospect i ve trails . In trail A infants were r and omly allocated banked donor milk or preterm formula as their sole diet or ( separately r and omised ) as a supplement to their mother 's expressed breast milk . In trial B infants were allocated term or preterm formula . A blind follow up examination was done 18 months after the expected date of birth . SETTING --Neonatal units of hospitals in Cambridge , Ipswich , King 's Lynn , Norwich , and Sheffield . Outpatient follow up . PARTICIPANTS --777 Infants with a birth weight less than 1850 g born during 1982 to 1984 . MAIN OUTCOME MEASURES --Development of eczema , allergic reactions to food or drugs , and asthma or wheezing by nine and 18 months after term . Whenever possible the observations were confirmed by rechallenge or clinical examination . RESULTS --At 18 months after term there was no difference in the incidence of allergic reactions between dietary groups in either trial . In the subgroup of infants with a family history of atopy , however , those in trial A who received preterm formula rather than human milk had a significantly greater risk of developing one or more allergic reactions ( notably eczema ) by 18 months ( odds ratio 3.6 ; 95 % confidence interval 1.4 to 9.1 ) . CONCLUSIONS --Feeding neonates on formulas based on cows ' milk , including those with a high protein content , did not increase the overall risk of allergy . Nevertheless , in the subgroup with a family history of atopy early exposure to cows ' milk increased the risk of a wide range of allergic reactions , especially eczema Background Parents who perceive common infant behaviors as formula intolerance-related often switch formulas without consulting a health professional . Up to one-half of formula-fed infants experience a formula change during the first six months of life . Methods The objective of this study was to assess discontinuance due to study physician-assessed formula intolerance in healthy , term infants . Infants ( 335 ) were r and omized to receive either a st and ard intact cow milk protein formula ( INTACT ) or a partially hydrolyzed cow milk protein formula ( PH ) in a 60 day non-inferiority trial . Discontinuance due to study physician-assessed formula intolerance was the primary outcome . Secondary outcomes included number of infants who discontinued for any reason , including parent-assessed . Results Formula intolerance between groups ( INTACT , 12.3 % vs. PH , 13.7 % ) was similar for infants who completed the study or discontinued due to study physician-assessed formula intolerance . Overall study discontinuance based on parent- vs. study physician-assessed intolerance for all infants ( 14.4 vs.11.1 % ) was significantly different ( P = 0.001 ) . Conclusion This study demonstrated no difference in infant tolerance of intact vs. partially hydrolyzed cow milk protein formulas for healthy , term infants over a 60-day feeding trial , suggesting nonst and ard partially hydrolyzed formulas are not necessary as a first-choice for healthy infants . Parents frequently perceived infant behavior as formula intolerance , paralleling previous reports of unnecessary formula changes . Trial Registration clinical trials.gov : This study found that two casein hydrolysate formulas varying in composition were equally effective in managing  colicky symptoms associated with protein sensitivity . Both hydrolysate formulas were associated with a significant , comparable reduction in crying duration and intensity from baseline in 15 of 22 infants with complete data . Subsequent challenge data suggest that the population studied were infants experiencing colicky symptoms due to protein sensitivity . A greater proportion of infants showed a positive reaction ( ≥1.5h of crying/d ) to the protein challenges than the placebo challenge , and crying was rated as more intense during whey and milk protein challenges Growth parameters , biochemical indice of protein metabolism and plasma Amino acid ( AA ) concentrations were investigated during the first month of life in term infants ( n = 61 ) fed various protein hydrolysate formulas ( whey ( WHF , n = 3 ) , soy collagen ( SCHF , n = 1 ) and whey-casein hydrolysate formulas ( WCHF , n = 1 ) ) . In addition , metabolic balance studies were performed in 10 infants fed WHF and in 5 fed WCHF . Comparatively to breast fed infants , growth reduction and decrease in plasma protein concentrations were observed with the use of one of the WHF and in a lesser extent with the SCHF and the WCHF . Plasma amino acid pattern reflected the AA content of the formulas . Whey hydrolysate formulas induced mainly an increase in threonine and a decrease in tyrosine concentrations .  Soy-collagen hydrolysate formula led to an increase of non-essential amino acids , such as glycine and hydroxyproline and a decrease in plasma lysine and cystine .  Whey-casein hydrolysate formula induced a plasma amino acid pattern close to the profile observed in breast fed infant . Metabolic balance studies showed a relative reduction in nitrogen absorption and utilisation in the infants fed the WHF and the WCHF . In addition a drastic reduction in fat , calcium and phosphorus absorption was also observed with the use of the WCHF . In preterm infants ( n = 19 ) fed whey predominant hydrolysed preterm formulas ( n = 3 ) , metabolic balance studies an plasma AA concentration were evaluated at the end of the first month of life at 34 weeks of gestation age . Comparatively to similar preterm infants fed conventional preterm formulas , a relative reduction in nitrogen absorption ( 83 % vs 90 % ) and retention ( 64 vs 70 % ) as well as in phosphorus absorption ( 78 vs 89 % ) was observed . Calcium retention was similar ( 48 vs 45 mg/kg/d ) but calcium intake was significantly higher in infants fed hydrolysate formulas 120 vs 91 mg/kg/d . Plasma amino acid concentrations were related to amino acid composition of the formulas . Compared with the st and ard preterm formulas , all three protein hydrolysate formulas led to a significant increase in plasma threonine and a decrease in tyrosine and phenylalanine concentrations . In addition , there was a reduction in plasma histidine , valine , leucine , cystine , methionine and /or tryptophane with some of the hydrolysate formulas used . In conclusion , these studies provide evidence that protein hydrolysed formulas are not equivalent to whole protein formulas in terms of nutritional efficiency for preterm and term infants . Therefore further extensive nutritional studies on growth , biochemical indices of protein metabolism and metabolic balance , including minerals and trace elements , appear to be necessary before maintaining and promoting the use of such formulas for teh potential benefits on atopic disease in preterm and in full-term newborn infants Aims : To assess maternal compliance with nutritional recommendations in an allergy preventive programme , and identify factors influencing compliance behaviour . Methods : R and omised double-blind intervention study on the effect of infant formulas with reduced allergenicity in healthy , term newborns at risk of atopy . Maternal compliance with dietary recommendations concerning milk and solid food feeding was categorised . Results : A total of 2252 newborns were r and omised to one of four study formulas . The drop out rate during the first year of life was 13.5 % ( n = 304 ) . The rates of high , medium , and low compliance to milk feeding during weeks 1–16 were 83.4 % , 4.0 % , and 7.5 % ; the corresponding rates to solid food feeding during weeks 1–24 were 60.0 % , 12.1 % , and 22.9 % . In 5.1 % of subjects no nutritional information was available . Low compliance was more frequent among non-German parents , parents with a low level of education , young mothers , smoking mothers , and those who weaned their infant before the age of 2 months . Conclusions : Evaluation of allergy preventive programmes should take into account non-compliance for assessing the preventive effectiveness on study outcome BACKGROUND Recommendations for primary prevention of allergic diseases in high-risk children include feeding with hydrolyzed formulas if breast-feeding is insufficient . OBJECTIVE The primary objective of the German Infant Nutritional Intervention study was to investigate the allergy preventive effect of 3 hydrolyzed formulas compared with cow 's milk formula in the first 3 years of life in a r and omized , double-blind trial . METHODS Between 1995 and 1998 , 2252 newborns with atopic heredity were allocated to a group receiving cow 's milk formula , partially or extensively hydrolyzed whey formula , or extensively hydrolyzed casein formula as a milk substitute for the first 4 months if breast-feeding was insufficient . Main outcome parameters were allergic manifestations , atopic dermatitis ( AD ) , and asthma . RESULTS After 3 years , 396 of 2252 children ( 17.6 % ) had dropped out . Breast-fed infants without formula feeding during the intervention ( n = 889 ) were considered separately . A significant reduction of the incidence of AD was achieved with the extensively hydrolyzed casein formula in the intention-to-treat ( ITT ; n = 1363 ) and per protocol ( PP ; n = 904 ) analyses ( ITT : population odds ratio [ 95 % CI ] , 0.67 [ 0.45 - 0.99 ] ; PP : adjusted odds ratio [ OR(adj ) ] , 0.53 [ 0.32 - 0.88 ] ) , and with the partially hydrolyzed whey formula in the PP analysis ( ITT : population odds ratio , 0.76 [ 0.52 - 1.11 ] ; PP : OR(adj ) , 0.60 [ 0.37 - 0.97 ] ) . None of the formulas reduced the incidence of asthma . CONCLUSION The risk for AD , but not for asthma , can be reduced with certain cow 's milk hydrolyzates in high-risk infants when breast-feeding is insufficient . CLINICAL IMPLICATION S Early nutritional intervention in high-risk children has significant influence on the incidence of AD , but not of asthma The ingestion of food antigens usually results in the induction of oral tolerance , but the clinical and immunologic consequences of brief exposure to cow 's milk proteins during the neonatal period are not well-documented . The aim of this work was to study immunoglobulin (Ig)E and IgG responses to cow 's milk proteins and ovalbumin after exposure during the first three days of life in infants who were otherwise exclusively breast-fed . A group of 129 infants was r and omly assigned at birth to one of three feeding regimens : human milk ( HM ) , cow 's milk formula ( CMF ) , or a casein hydrolysate formula ( CHF ) , during the first three days of life . They were then all exclusively breast-fed for a varying period of time and followed for two years . Serum IgG and IgE antibodies to cow 's milk proteins and ovalbumin ( OVA ) were analyzed in blood sample s obtained at birth , at 4 days and at 2 , 4 , 8 , 12 and 24 months of age . The levels of IgG antibodies to beta-lactoglobulin ( IgG-BLG ) and bovine serum albumin ( IgG-BSA ) were higher in the CMF and the HM groups than in the CHF group for up to two years . This was particularly obvious for IgG-BLG in infants who started weaning before two months . The levels of IgG antibodies to casein ( IgG-CAS ) were higher in the CMF group , as compared with the CHF group at 8 and 12 months . The levels of IgG antibodies to OVA were similar in all three feeding groups . The levels of IgE antibodies to CAS or OVA were similar in the three feeding groups . Exposure to cow 's milk during the first three days of life stimulated IgG antibody production to cow 's milk proteins and this was still obvious at 2 years of age , while feeding with a casein hydrolysate during the first three days of life was associated with low levels of IgG antibodies to cow 's milk proteins Forty-five healthy infants were included in a double-blind r and omized prospect i ve study comparing the nutritional value of two formulas . One group received a whey-predominant formula ( n = 20 ) ; the other group received a whey hydrolysate formula ( n = 25 ) . Four infants of the whey hydrolysate group were dropped because they refused the formula . Although the mean daily volume intake was smaller with the whey hydrolysate formula compared with the whey-predominant formula ( p < 0.001 ) , the weight gain in the two groups after 13 weeks was identical ( 27.2 g/day in both groups ; the mean difference in weight gain between the groups after 13 weeks was only 8 g ) . Length gain at 13 weeks was 10.4 cm in the whey-predominant formula group and 10.8 cm in the whey hydrolysate formula group ( p = NS ) . After 13 weeks , blood was sample d for hemoglobin , hematocrit , red blood cell count , white blood cell count , lymphocytes , glycemia , proteins , albumin , prealbumin , calcium , phosphorus , urea , creatinine , iron , iron-binding capacity , zinc , and vitamins A and E. Except for the iron-binding capacity , zinc , urea ( in plasma as well as in urine ) ( all three were higher in the whey hydrolysate group ) , no significant differences were found . According to these results , exclusive feeding of the whey hydrolysate formula from birth to 3 months of age to healthy infants appears to result in an adequate nutritional status , as assessed at 3 months of age The possible role of cows milk intolerance in the aetiology of infant colic was evaluated in 19 babies presenting to their health visitor or general practitioner in one town . Over a three week period a st and ard modified cows milk formula was compared with a soya milk formula on a double blind basis . The duration of colic symptoms was significantly reduced during the week on soya milk ( P less than 0.01 ) , with 11 out of 19 babies fulfilling the diagnostic criteria for cows milk intolerance . Four babies whose symptoms failed to improve either spontaneously or with soya milk were given a hydrolysed protein milk with a positive response in two , confirmed by challenge testing . Thus in 13 out of 19 babies ( 68 % ) the symptoms of infant colic resolved almost completely with dietary change This short-term , prospect i ve study was aim ed to assess the effects of partially hydrolyzed formula ( PHF ) on the prevention of the development of  atopic dermatitis in infants at high risk . The infants of parents with allergy symptoms and serum total IgE over 200 kU/L were divided into 3 groups by their feeding patterns :  PHF group ( n=15 ) ,  st and ard formula ( SF ) group ( n=32 ) , and  breast milk ( BM ) group ( n=22 ) . No allergenic food was given during the study period of 6 months , and breastfeeding mothers avoided egg ingestion . Their atopic symptoms were monitored every 2 months . The cumulative incidence and prevalence of atopic dermatitis at the age of 6 months were significantly less in the PHF group than in the SF group ( 47 % vs. 78 % , p<0.05 ; 20 % vs. 59 % , p<0.05 ) . Those rates of the PHF group were also less than those of the BM group , but they were not statistically significant . There was no difference in the onset age and disease severity . These results suggest that early feeding of PHF to infants at high risk has a short-term preventive effect on the development of atopic dermatitis during the first 6 months of life . Long-term preventive effects should be evaluated Infants ( n = 18 ) with intolerance to extensively hydrolyzed formulas and soy who responded to an L-amino acid-based elemental formula ( AAF ) were studied until 3 years of age . By 2 years of age most tolerated non-formula foods , and by 3 years only 3 required AAF .  Growth normalized during AAF feeding in 4 infants with failure to thrive OBJECTIVE To estimate the cost-effectiveness of using an extensively hydrolysed formula ( eHF ; Nutramigen ) compared with an amino acid formula ( AAF ; Neocate ) as first-line treatment for cow milk allergy ( CMA ) in the UK , from the perspective of the National Health Service ( NHS ) . METHOD A decision model was constructed depicting the treatment paths and associated re source use attributable to first-line management of CMA with the two formulae . The model was based on the case records of 145 AAF-treated infants and 150 matched eHF-treated patients from The Health Improvement Network ( THIN ) data base [ a nationally representative data base of patients registered with general practitioners ( GPs ) in the UK ] . The model estimated the costs and consequences of patient management over 12 months following their initial GP visit for CMA . RESULTS Patients presenting with a combination of gastrointestinal symptoms and eczema accounted for 44 % of all patients in both groups . Those with gastrointestinal symptoms alone and eczema alone accounted for up to a further 39 % and 13 % , respectively . Those with  urticaria  and faltering growth  accounted for < 5 % and ≤6 % of all patients , respectively . Patients ' age and weight at presentation was a mean 2.6 - 2.8 months and 4.4 kg , respectively . It took a mean 2.2 months to start a formula after initially seeing a GP . Time to symptom resolution following the start of treatment was 1.2 months in both groups ; hence , the mean number of symptom-free months during the 12 months following the initial GP visit was estimated to be 8.6 months in both groups . Patients treated with an eHF had a mean 13.1 GP visits over the 12 months compared to 17.5 visits made by AAF-treated patients ( p < 0.001 ) . The NHS cost of managing a CMA infant over the first 12 months following initial presentation to a GP was estimated to be £ 1853 and £ 3161 for an eHF-treated and AAF-treated patient , respectively . CONCLUSION Starting treatment for CMA with an eHF was the cost-effective option , as there were no significant differences in clinical outcomes between the two groups . A prospect i ve , r and omized controlled trial would allow a definitive confirmation of these findings In an attempt to prevent or reduce the manifestations of atopic disease , a group of infants considered to be genetically at high risk of atopy was entered in a prenatally r and omized , controlled study . A prophylactic group ( n= 58 ) was either breast‐fed with their mothers excluding foods regarded as highly antigenic from their diets , or given an extensively hydrolysed formula . In addition , strenuous efforts were made to reduce exposure to the house‐dust mite by application of acaricide to the bedroom and living room carpets and upholstered furniture . A control group ( n= 62 )  was fed conventionally by breast or on formula , and no specific environmental measures were taken . The results ( previously reported ) after 1 year showed significantly less total allergy , asthma , and eczema in the prophylactic group . Similar results were obtained at 2 years although the reduction in asthma no longer achieved statistical significance . However , there was significantly less sensitization , as shown by a battery of skin prick tests ( SPTs ) , to both dietary allergens and aeroallergens in the prophylactic group . A11 the children have now been review ed at the age of 4 years , and SPTs to a wide range of dietary allergens and aeroallergens have been performed . The control group continues to show more total allergy ( odds ratio [ OR ] 2.73 , 95 % confidence interval [ CI ] 1.21–6.13 , P<0.02 ) , definite allergy ( allergic symptoms plus positive SPT ) ( OR 5.6 , CI 1.8–17.9 , P<0.005 ) , and eczema ( OR 3.4 , CI 1.2–10.1 , P<0.05 ) . More control children have positive SPTs ( OR 3.7 , CI 1.3–10.0 , P<0.02 ) . A dual approach to the prevention of allergic disease , avoiding as far as possible sensitization to food and aeroallergens , significantly reduces the risk of atopic disease . This should be reserved for infants considered at very high risk of atopy , and close medical and dietetic supervision must be available Importance Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility . There are no intact proteins in extensively hydrolyzed formulas . Objective To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children . Design , Setting , and Participants An international double-blind r and omized clinical trial of 2159 infants with human leukocyte antigen – conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries ; 1081 were r and omized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula .  The follow-up of the participants ended on February 28 , 2017 . Interventions The participants received either a casein hydrolysate or a conventional adapted cow ’s milk formula supplemented with 20 % of the casein hydrolysate . The minimum duration of study formula exposure was 60 days by 6 to 8 months of age . Main Outcomes and Measures Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria . Secondary outcomes included age at diabetes diagnosis and safety ( adverse events ) . Results Among 2159 newborn infants ( 1021 female [ 47.3 % ] ) who were r and omized , 1744 ( 80.8 % ) completed the trial . The participants were observed for a median of 11.5 years ( quartile [ Q ] 1-Q3 , 10.2 - 12.8 ) . The absolute risk of type 1 diabetes was 8.4 % among those r and omized to the casein hydrolysate ( n = 91 ) vs 7.6 % among those r and omized to the conventional formula ( n = 82 ) ( difference , 0.8 % [ 95 % CI , −1.6 % to 3.2 % ] ) . The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group , duration of breastfeeding , duration of study formula consumption , sex , and region while treating study center as a r and om effect was 1.1 ( 95 % CI , 0.8 to 1.5 ; P = .46 ) . The median age at diagnosis of type 1 diabetes was similar in the 2 groups ( 6.0 years [ Q1-Q3 , 3.1 - 8.9 ] vs 5.8 years [ Q1-Q3 , 2.6 - 9.1 ] ; difference , 0.2 years [ 95 % CI , −0.9 to 1.2 ] ) . Upper respiratory infections were the most common adverse event reported ( frequency , 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group ) . Conclusions and Relevance Among infants at risk for type 1 diabetes , weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years . These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes . Trial Registration clinical trials.gov Identifier : The aim of the study was to compare , during the first month of life , growth parameters , biochemical indices of protein metabolism and plasma amino acid concentrations in newborn infants fed either human milk ( n = 23 ) , three different whey hydrolysate formulae ( WHF 1 , n = 13 ; WHF 2 , n = 10 ; WHF 3 , n = 13 ) , a soy-collagen hydrolysate formula ( SCHF n = 18 ) or a whey-casein hydrolysate formula ( WCHF , n = 20 ) .  Growth parameters and the various protein concentrations determined in the infants fed WHF 1 and WHF 2 were similar to the values observed with human milk . With WHF 3 , growth in weight , length and head circumference and serum total protein concentrations were reduced significantly whereas blood urea nitrogen was increased . With SCHF , growth in weight and length as well as serum total protein and transferrin concentration were decreased significantly , whereas serum IgG concentration was increased . With WCHF growth in length and serum transferrin concentration were decreased compared to the human milk group . In the various groups , the plasma amino acid pattern reflected the amino acid content of the formula . Whey hydrolysate formula induced mainly an increase in threonine and a decrease in tyrosine concentrations .  Soy-collagen hydrolysate formula led to an increase of non-essential amino acids , such as glycine and hydroxyproline , and a decrease in plasma lysine and cystine .  Whey-casein hydrolysate formula induced a plasma amino acid pattern close to the profile observed with human milk . Nevertheless , the plasma concentrations of most of the various amino acids were higher . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE In study 1 , to compare the effect on growth in healthy infants of a new amino acid-based formula ( AAF )  and a control extensively hydrolyzed formula ( EHF ) , with both docosahexaenoic acid ( DHA ) and arachidonic acid ( ARA ) at levels similar to those in human milk worldwide . In study 2 , to evaluate the hypoallergenicity of this new AAF in infants and children with confirmed cow 's milk allergy ( CMA ) . STUDY DESIGN In study 1 , a total of 165 healthy , full-term , formula-fed infants r and omly received the  new AAF or control formula .  Anthropometric measurements , tolerance , and adverse events were recorded throughout the study . Plasma amino acid profiles were evaluated in a subset of the infants . In study 2 , the hypoallergenicity of the new AAF was evaluated in 32 infants and children using a double-blind , placebo-controlled food challenge ; an open challenge ; and a 7-day feeding . RESULTS In study 1 , overall growth , tolerance , and safety outcomes were similar in both groups . In study 2 , 29 of the 32 subjects completed both challenges ; no allergic reaction was seen in any of the 32 subjects . CONCLUSIONS The new AAF with DHA and ARA at levels similar to those in human milk worldwide is hypoallergenic . It also is safe and supports growth in healthy , term infants BACKGROUND Development of humoral and cellular immune responses to orally administered antigens in human beings is poorly understood , although antigen administration has been suggested as a treatment for hypersensitivity disorders and autoimmune diseases . OBJECTIVE The purpose of the study was to investigate the development of systemic immune response in infants fed with formula containing whole cow 's milk proteins or hydrolyzed formula containing casein peptides .  METHODS In a double-blind trial , 10 infants received cow 's milk-based formula , and 10 infants received a casein hydrolysate formula until the age of 9 months . Blood sample s were taken at the ages of 6 , 9 , and 12 months . Cellular responses were assessed by proliferation assay of peripheral blood mononuclear cells to cow 's milk proteins ( beta-lactoglobulin , bovine serum albumin , and alpha-casein ) . Humoral responses to the same proteins were measured by ELISA for IgG antibodies . RESULTS Feeding infants with cow 's milk-based formula induced systemic humoral and cellular responses to cow 's milk proteins . T-cell response later declined , supporting the concept of oral tolerization . Exposure to cow 's milk proteins after the age of 9 months result ed in depressed cellular and humoral responsiveness to these proteins . CONCLUSION Our results support the view that induction of oral tolerance in human beings is an age-dependent phenomenon OBJECTIVES To determine the prevalence of soy allergy in IgE-associated cow 's milk allergy ( CMA ) . STUDY DESIGN Children < 3.5 years with documented IgE-associated CMA ( n = 93 ) were evaluated for soy allergy by double-blind , placebo-controlled food challenge , open challenge , or convincing previous history of an anaphylactic reaction to soy .  Children tolerant to soy at entry received soy formula and were followed up for 1 year . RESULTS Of this IgE-associated CMA cohort ( ages 3 to 41 months ) , 14 % ( 95 % CI = 7 . 7%-22.7 % ) were determined to have soy allergy , 12 definitely at entry and 1 possibly after 1 year of soy ingestion . The latter child experienced severe failure to thrive at enrollment and exhibited improved growth while receiving soy during follow-up but was diagnosed with eosinophilic esophagitis at study completion . Improved growth ( P < .05 ) occurred in the non-soy-allergic cohort ingesting soy formula ( 579 31 mL/d ) during the year of follow-up . CONCLUSIONS Soy allergy occurs in only a small minority of young children with IgE-associated CMA . As such , soy formula may provide a safe and growth-promoting alternative for the majority of children with IgE-associated CMA shown to be soy tolerant at the time of introduction of soy formula BACKGROUND Distressed behavior is common in infants and is often attributed to gastroesophageal reflux ( GER ) or food protein intolerance . OBJECTIVE To examine the effect of a hypoallergenic amino acid-based infant formula ( AAF ) on distressed behavior and GER symptoms in infants who failed to respond to extensively hydrolyzed formula and antireflux medications . STUDY DESIGN Nineteen distressed infants ( 9 boys and 10 girls ; median age , 5.0 months ) with presumed GER underwent gastroscopy ( n = 17 ) and esophageal 24-hour pH monitoring ( n = 14 ) . Double-blind placebo-controlled ( DBPC ) formula challenges of AAF versus previously besttolerated formula were conducted . RESULTS Nine infants had histologic evidence of esophagitis , and 9 had inflammatory changes in the stomach and /or duodenum . Symptoms remitted in all infants within 2 weeks of the start of feeding with AAF . On DBPC challenge after a median period of 3 months of receiving AAF , 12 infants were intolerant to active formula ( distress score , 287 vs 580 min/wk , P = . 01 ; symptom score , 23.1 vs 36.1 , P = .03 ) . Seven infants did not relapse and were considered tolerant ( distress score , 470 vs 581 , P = .77 ; symptom score , 29.5 vs 20.2 ; P = .89 ) . CONCLUSION Treatment with AAF may reduce distressed behavior and symptoms of GER in infants with food protein intolerance BACKGROUND & AIMS Feeding during the first months of life might affect risk for celiac disease .  Individuals with celiac disease or type 1 diabetes have been reported to have high titers of antibodies against cow 's milk proteins . Avoidance of cow 's milk-based formula for infants with genetic susceptibility for type 1 diabetes reduced the cumulative incidence of diabetes-associated autoantibodies . We performed a r and omized controlled trial in the same population to study whether weaning to an extensively hydrolyzed formula reduced the risk of celiac disease autoimmunity or celiac disease . METHODS We performed a double-blind controlled trial of 230 infants with HLA-defined predisposition to type 1 diabetes and at least 1 family member with type 1 diabetes . The infants were r and omly assigned to groups fed a casein hydrolysate formula ( n = 113 ) or a conventional formula ( control , n = 117 ) whenever breast milk was not available during the first 6 - 8 months of life . Serum sample s were collected over a median time period of 10 years and analyzed for antibodies to tissue transglutaminase ( anti-TG2A ) using a radiobinding assay , to endomysium using an immunofluorescence assay , and antibodies to a deami date d gliadine peptide using an immunofluorometry assay . Duodenal biopsies were collected if levels of anti-TG2A exceeded 20 relative units . Cow 's milk antibodies were measured during the first 2 years of life . RESULTS Of the 189 participants analyzed for anti-TG2A , 25 ( 13.2 % ) tested positive . Of the 230 study participants observed , 10 ( 4.3 % ) were diagnosed with celiac disease . We did not find any significant differences at the cumulative incidence of anti-TG2A positivity ( hazard ratio , 1.14 ; 95 % confidence interval , 0.51 - 2.54 ) or celiac disease ( hazard ratio , 4.13 ; 95 % confidence interval , 0.81 - 21.02 ) between the casein hydrolysate and cow 's milk groups . Children who developed celiac disease had increased titers of cow 's milk antibodies before the appearance of anti-TG2A or celiac disease . CONCLUSIONS In a r and omized controlled trial of 230 infants with genetic risk factors for celiac disease , we did not find evidence that weaning to a diet of extensively hydrolyzed formula compared with  cow 's milk-based formula would decrease the risk for celiac disease later in life . Increased titers of cow 's milk antibody before anti-TG2A and celiac disease indicates that subjects with celiac disease might have increased intestinal permeability in early life . Clinical Trials.gov Number : NCT00570102 BACKGROUND The diversity in the perceived prevalence , recovery , and risk factors for cow 's milk allergy ( CMA ) necessitated a large-scale , population -based prospect i ve study . OBJECTIVE We sought to determine the prevalence , cross-reactivity with soy allergy , and risk factors for the development of CMA . METHODS In a prospect i ve study the feeding history of 13,019 infants was obtained by means of telephone interview ( 95.8 % ) or question naire ( 4.2 % ) . Infants with probable adverse reactions to milk were examined , skin prick tested , and challenged orally . RESULTS Ninety-eight percent of the cohort participated in the study . The cumulative incidence for IgE-mediated CMA was 0.5 % ( 66/13,019 patients ) . The mean age of cow 's milk protein ( CMP ) introduction was significantly different ( P < .001 ) between the healthy infants ( 61.6 + /- 92.5 days ) and those with IgE-mediated CMA ( 116.1 + /- 64.9 days ) . Only 0.05 % of the infants who were started on regular CMP formula within the first 14 days versus 1.75 % who were started on formula between the ages of 105 and 194 days had IgE-mediated CMA ( P < .001 ) . The odds ratio was 19.3 ( 95 % CI , 6.0 - 62.1 ) for development of IgE-mediated CMA among infants with exposure to CMP at the age of 15 days or more ( P < .001 ) . Sixty-four patients with IgE-mediated CMA tolerated soy , and none had a proved allergy to soy . CONCLUSIONS IgE-mediated CMA is much less common than generally reported . Early exposure to CMP as a supplement to breast-feeding might promote tolerance . Finally , soy is a reasonable feeding alternative in patients with IgE-mediated CMA BACKGROUND The natural history of allergic disease and its potential for prevention merit close examination because of the explosive worldwide increase in the prevalence and morbidity of atopic disorders . This study examines the development of atopy at age 7 years in 165 children in a high-risk cohort , previously reported from birth to age 4 years . METHODS In this prospect i ve , r and omized , controlled study of food allergen avoidance in infancy , the prophylactic-treated group consisted of infants whose mothers avoided cow 's milk , egg , and peanut during the last trimester of pregnancy and lactation and who , themselves ,  avoided cow 's milk until age 1 year ( casein hydrolysate supplementation before age 1 ) , egg until age 2 years , and peanut and fish until age 3 years . The control group consisted of maternal/infant pairs who followed st and ard feeding practice s. RESULTS Despite a significant reduction in food allergy and milk sensitization before age 2 years , none of the following differed between the groups at age 7 years : food allergy , atopic dermatitis , allergic rhinitis , asthma , any atopic disease , lung function , food or aeroallergen sensitization , serum IgE level , or presence of nasal eosinophils or nasal basophilic cells .  Children with food allergy by 4 years evidence d higher 7-year ( current ) prevalences of allergic rhinitis and asthma ( p < 0.01 ) . Atopic diseases/parameters at age 7 years were shown , by multivariate analysis ( p < 0.05 ) , to be associated with several genetic and environmental risk factors ( male gender , maternal nonwhite ethnicity and asthma , and household smoking ) , as well as predictive atopic markers during infancy ( elevated serum IgE level ; egg , cow 's milk , and peanut sensitization ; and nasal eosinophils and nasal basophilic cells ) . CONCLUSIONS These findings help to : ( 1 ) eluci date the natural history of atopic disease in high-risk children ; ( 2 ) document the progression of allergy from atopic dermatitis , food allergy , and food sensitization to respiratory allergy and aeroallergen sensitization despite food allergy prevention in infancy ; ( 3 ) identify allergy predictive markers ; and ( 4 ) exp and our appreciation of the interactions of genetic and environmental factors in the development of atopy Aims /hypothesisWe aim ed to assess the feasibility of a dietary intervention trial with weaning to hydrolysed formula in infants at increased risk of type 1 diabetes and to study the effect of the intervention on the emergence of diabetes-associated autoantibodies in early childhood . Methods We studied 242 newborn infants who had a first-degree relative with type 1 diabetes and carried risk-associated HLA-DQB1 alleles . After exclusive breastfeeding , the infants underwent a double-blind , r and omised pilot trial of either casein hydrolysate ( Nutramigen ; Mead Johnson ) or conventional cow ’s milk-based formula  until the age of 6–8 months . During a mean observation period of 4.7 years , autoantibodies to insulin , anti-glutamic acid decarboxylase and insulinoma-associated antigen-2 were measured by radiobinding assays , and islet cell antibodies ( ICA ) by immunofluorescence . Results The feasibility of screening and identifying a cohort of first-degree relatives with HLA-conferred disease susceptibility , enrolling them in a dietary intervention trial and following them for seroconversion to autoantibody positivity is established . The cumulative incidence of autoantibodies was somewhat smaller in the casein hydrolysate vs control formula group , suggesting the need for a larger well-powered study . After adjustment for duration of study formula feeding , life-table analysis showed a significant protection by the intervention from positivity for ICA ( p=0.02 ) and at least one autoantibody ( p=0.03 ) . Conclusions /interpretationThe present study provides the first evidence ever in man , despite its limited power , that it may be possible to manipulate spontaneous beta cell autoimmunity by dietary intervention in infancy The effect of maternal and infant avoidance of allergenic foods on food allergy was examined in a prenatally r and omized , controlled trial of infants of atopic parents . The diet of the prophylactic-treated group ( N = 103 ) included ( 1 ) maternal avoidance of cow 's milk , egg , and peanut during the third trimester of pregnancy and lactation and ( 2 ) infant use of casein hydrolysate ( Nutramigen ) for supplementation or weaning , and avoidance of solid foods for 6 months ; cow 's milk , corn , soy , citrus , and wheat , for 12 months ; and egg , peanut , and fish , for 24 months . In the control group ( N = 185 ) , mothers had unrestricted diets , and infants followed American Academy of Pediatrics feeding guidelines . The cumulative prevalence of atopy was lower at 12 months in the prophylactic-treated ( 16.2 % ) compared to the control ( 27.1 % ) group ( p = 0.039 ) , result ing from reduced food-associated atopic dermatitis , urticaria and /or gastrointestinal disease by 12 months ( 5.1 % versus 16.4 % ; p = 0.007 ) , and any positive food skin test by 24 months ( 16.5 % versus 29.4 % ; p = 0.019 ) , caused primarily by fewer positive milk skin tests ( 1 % versus 12.4 % ; p = 0.001 ) . The prevalences of allergic rhinitis , asthma , and inhalant skin tests were unaffected . Serum IgE levels in the prophylactic-treated group were marginally lower only at 4 months . Thus , reduced exposure of infants to allergenic foods appeared to reduce food sensitization and allergy primarily during the first year of life Clinical experience ( " the dangerous bottle " ) and experimental evidence indicate that the early life of an infant is particularly important for the development of the immune responses to food antigens . However , the clinical and immunologic consequences of a brief exposure to , or avoidance of , food antigens during the neonatal period in human infants are poorly understood and documented . We present the preliminary results of a prospect i ve controlled study of 256 normal breast-fed infants r and omly assigned to receive ( blind ) either an adapted formula ( Nidina ) or a partially hydrolyzed formula ( Nidal HA ) as a supplement to breast-feeding for a few days when necessary , and to be examined at days 5 , 90 , 150 , and 365 . The results indicated that ( 1 ) the prevalence of clinical symptoms and of total and specific IgE responses was not statistically different in the two groups of infants and ( 2 ) infants fed a hydrolyzed formula had median titers of specific IgG lower than those fed an adapted formula ; the difference was significant for alpha-lactalbumin at day 90 ( p < 0.005 ) and for alpha-lactalbumin ( p < 0.05 ) , casein ( p < 0.05 ) , and hydrolyzed formula ( p < 0.01 ) at day 150 . Humoral immune responses of breast-fed infants to food antigens thus appear to be modulated by early , short-term exposure to them
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 .