Cow's milk-specific cellular and humoral immune responses and atopy skin symptoms in infants from atopic families fed a partially (pHF) or extensively (eHF) hydrolyzed infant formula. The effect of hypoallergenic formula on the occurrence of allergic diseases in high risk infants. Comparison of a partially hydrolyzed infant formula with two extensively hydrolyzed formulas for allergy prevention: a prospective, randomized study. Immunogenicity and antigenicity of a partially hydrolyzed cow's milk infant formula. Effects of a dietary and environmental prevention programme on the incidence of allergic symptoms in high atopic risk infants: three years' follow-up. Higher urinary excretion of essential amino acids in preterm infants fed protein hydrolysates. [The prevention of allergic diseases with a hypoallergenic formula: a follow-up at 24 months. The preliminary results]. Extensive and partial protein hydrolysate preterm formulas: the effect on growth rate, protein metabolism indices, and plasma amino acid concentrations. Long-term prevention of allergic diseases by using protein hydrolysate formula in at-risk infants. Influence of hypoallergenic milk formula on the incidence of early allergic manifestations in infants predisposed to atopic diseases. The effect of hydrolyzed cow's milk formula for allergy prevention in the first year of life: the German Infant Nutritional Intervention Study, a randomized double-blind trial. Extensively and partially hydrolysed infant formulas for allergy prophylaxis. Allergy development and macromolecular absorption in infants with different feeding regimens during the first three days of life. A three-year prospective follow-up. Nutritional efficacy of preterm formula with a partially hydrolyzed protein source: a randomized pilot study. The nutritional value of a whey hydrolysate formula compared with a whey-predominant formula in healthy infants. Effect of a whey hydrolysate prophylaxis of atopic disease. Supplementary feeding in maternity hospitals and the risk of cow's milk allergy: A prospective study of 6209 infants.
Hydrolyzed milk formulas are recommended to feed infants at high risk of atopy if breast-feeding is not possible. We studied the specific cellular and humoral immune response to cow's milk proteins and occurrence of atopic dermatitis under different feeding regimens: two hydrolyzed infant milk formulas (partially [pHF] and extensively hydrolyzed [eHF]) and under exclusive breast-feeding (BF).
                Seventy-two infants from families with atopic symptoms were randomized in the pHF and eHF groups, respectively. At 6 and 12 months of age, peripheral blood mononuclear cell proliferation along with specific IgG and IgE to cow's milk proteins was determined in infants fed pHF or eHF, respectively, and those who had not yet received any formula at 6 months of age (BF). Cases of atopic dermatitis were recorded throughout the first 12 months of life, and their severity was evaluated with SCORAD points.
                A significantly decreased proliferation to cow's milk caseins was found in the pHF group compared to the exclusively breast-fed group. Medians of stimulation indexes for CAS at 6 months were as follows: pHF 1.18; n=24; BF 1.70; n=24 (P=0.033, Mann-Whitney U-test). Higher levels of plasma IgG antibodies to BCAS were found in infants fed pHF than in those fed eHF at 12 months. Optical density (OD): (25th percentile; median; 75th percentile): pHF: 0.00; 0.14; 0.38; n=30; eHF: 0.00; 0.03; 0.14; n=28; P=0,089, Mann-Whitney U-test. Cow's milk-specific IgE was detected at 6 months as follows: BF: 3 of 24; eHF: 2 of 21; pHF: 0 of 23. The number of cases of atopic dermatitis and their severity did not differ among the groups during the first 12 months.
                Feeding pHF appears to suppress cow's milk-specific cellular responses and stimulate specific IgG production. Specific IgE sensitization can occur also with breast-feeding. To study the influence of hypoallergenic milk on the occurrence of allergic diseases, thirty-three high risk, normal full-term newborns were divided into two groups with comparable family allergy score (FAS) and cord serum IgE. Group A consisted of 18 babies fed since birth with regular formula, while group B included 15 babies fed breast milk and/or NAN H.A. (Hypoallergenic infant formula) for the first 6 months of life. Close clinical observations for the appearance of atopic dermatitis, allergic rhinitis and wheezing as well as serial examination of total serum IgE and milk-specific IgE antibodies were done during the first year of life. The results showed: 1) Infants fed regular formula had a higher incidence of moderate to severe atopic dermatitis (AD) and allergic rhinitis (AR) than those fed NAN H.A. (39% vs 13% for AD; and 33% vs 13% for AR), but the difference was not significant. There was no difference in the incidence of wheezing between these two groups; 2) There was no relationship between cord blood IgE and FAS; 3) Neither the cord blood IgE nor FAS influenced the occurrence of allergic diseases and total serum IgE at one year of age; 4) Hypoallergenic milk (NAN H.A.) could support normal growth and development. In conclusion, a higher incidence of moderate to severe AD and AR was found in high risk infants fed regular formula than in those fed hypoallergenic milk. However, a study with a larger number of babies and a longer period of follow-up is needed to obtain a solid conclusion. 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 randomized 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 randomization, 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 prospectively 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. We evaluated the immunogenicity and antigenicity of a formula based on partially hydrolyzed cow's milk whey protein in infants at risk of atopy and in controls. Total IgE and specific IgE, IgG, and IgG4 subclass antibodies against egg albumin and cow's milk alpha-lactalbumin, casein, and beta-lactoglobulin were measured by radioimmunoassay of cord blood and of peripheral blood at 5 days and 6 months of life in five groups of infants: 16 breast-fed infants at risk of atopy (group 1), 21 partially hydrolyzed whey formula-fed infants at risk of atopy (group 2), 14 formula-fed infants at risk of atopy (group 3), 10 breast-fed control infants (group 4), and 13 formula-fed control infants (group 5). Total IgE concentration was significantly lower in group 2 at 6 months than in groups 3 and 5 infants and similar to that observed in groups 1 and 4 infants. The concentration of specific antiegg and anti-cow's milk protein IgG and of specific anti-cow's milk alpha-lactalbumin and beta-lactoglobulin IgG4 subclass antibodies was significantly reduced in group 2 as compared to group 3 infants and similar to that found in breast-fed infants. In conclusion, the partially hydrolyzed formula was less immunogenic and antigenic than a traditional formula and was as immunogenic and antigenic as breast milk. A prospective 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 randomly 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 non-intervention group. The incidence of allergic manifestations was much lower in the intervention group than in the non-intervention 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 Protein hydrolysates have been introduced in preterm formulae, but it is not clear whether they are needed for the feeding of preterm infants. We designed a randomized, 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.
                Infants with a birthweight < or = 1750 g and gestational age < or = 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.
                Twenty-one infants met the criteria for randomization. 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 B.
                Our results support the hypothesis of less nutritional value of hydrolysed versus conventional preterm formulae. Higher renal excretion of essential amino acids may be one of the mechanisms involved. These findings must be confirmed by further studies with larger sample sizes and protein hydrolysates with different degrees of hydrolysis. One hundred-eight infants from atopic families were admitted to the study. Each had at least one first-degree relative affected by asthma or rhinitis, conjunctivitis, eczema, cow's milk protein intolerance. All infants not breast fed were hypoallergenic formula. 46 infants were breast fed, 39 were bottle fed by the ordinary formula and 23 received the hypoallergenic one. No other food was introduced up to 6 months. Cow's milk proteins, egg, poultry and fish were introduced after 6 months. All infants were followed up to 24 months. Incidence of allergic diseases up to 24 months was not significantly different among the 3 groups. The use of protein hydrolysate preterm formulas is restricted because data on their nutritional adequacy are scarce. The authors evaluated the rate of growth and indices of protein metabolism in low-birth weight infants fed extensive and partial protein hydrolysate preterm formula followed for 12 weeks.
                A total of 61 low-birth weight infants were assigned randomly to receive extensive protein hydrolysate preterm formula (EH: n = 16), partial protein hydrolysate preterm formula (PH: n = 15), and standard preterm formula (SF; n = 15), or were fed their own mother's fortified breast milk (FBM; n = 15). The infants were investigated at study entry, and at 4, 8, and 12 weeks after study entry.
                There were no differences with respect to growth rate (weight gain, increments in length and head circumference), urea, albumin, prealbumin, transferrin, and plasma amino acid concentrations (except for tyrosine on a single occasion) according to the degree of hydrolysis. There were also no differences between groups fed hydrolyzed formulas and SF. However, several differences were found when EH and PH were compared with FBM. Weight gain from the entry to 12 weeks, serum urea at 12 weeks, and total plasma essential amino acids at 8 weeks were significantly higher in groups fed EH and PH than in those fed FBM. In addition, valine was significantly higher in groups fed PH (P < 0.05) than in the group fed FBM at 8 and 12 weeks, tyrosine was higher in EH and PH in comparison with FBM at 4 weeks, and in PH versus FBM at 12 weeks after study entry.
                This study suggests that experimental EH and PH are at least nutritionally equivalent to SFs. This prospective, long-term study assessed the effects of a protein hydrolysate formula on allergy prevention in infants with a family history of allergy. Infants were randomly 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. One hundred twenty-two infants at risk of atopy on the basis of IgE screening at birth and family history of atopy were studied. The occurrence of atopic manifestations was analyzed in relation to their diets during the first 3 months of age. Only the infants receiving hypoallergenic milk were protected effectively; all other regimens (humanized cow milk, hypoallergenic milk or humanized cow milk + supplements) increased the frequency of allergic symptoms (P < .07). After a 1-year follow-up, the infants fed strictly on hypoallergenic milk during their 3 first months presented allergic symptoms less frequently than other infants (P < .007). The potential of extensively or partially hydrolyzed formulas to reduce the risks for allergies is controversial.
                We sought to assess the preventive effect of differently hydrolyzed formulas compared with cow's milk formula (CMF) in high-risk infants.
                Between 1995 and 1998, 2252 infants with a hereditary risk for atopy were enrolled in the German Infant Nutritional Intervention Study and randomly 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.
                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.
                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 clinically evaluated. 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 randomised 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. A group of 129 infants were randomly 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 samples 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 alpha-lactalbumin (S-alpha-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 alpha-LA, serum IgE, family history of allergy, frequency of allergic symptoms and proportion of infants with infections. Decreased nitrogen levels, calcium intestinal absorption rates, and plasma amino acid imbalances were reported for preterm infants who were fed partially hydrolyzed preterm formulas. In this pilot study, we evaluated a new formula with modified nitrogen and calcium sources.
                During their second week of life, 16 preterm infants were randomly assigned to one of two groups: 9 were fed the new partially hydrolyzed formula and 7 were fed a conventional formula. Nutrient balance was performed at the end of the first month of life. Amino acid concentrations and anthropometric parameters were measured at theoretical term.
                Birth weight and gestational age (mean +/- SD) were similar in the two groups (28.9 +/- 7.0 weeks and 1183 +/- 242 g vs. 27.7 +/- 1.0 weeks and 1139 +/- 162 g). Median nitrogen absorption rates (85% vs. 89%; P = 0.03) and biological values (59% vs. 69%; P = 0.13) were lower for infants who were fed the new formula than for those fed the conventional formula. After correction for difference in nitrogen intake, there was no significant difference in nitrogen retained between the two groups (P = 0.11). Plasma amino acid concentrations were also similar in the two groups. Median calcium absorption tended to be higher in the new-formula group than in the conventional-formula group (54% vs. 45%, P = 0.19). At theoretical term, infants fed the conventional formula were heavier than infants fed the new formula (3559 +/- 362 g vs. 3193 +/- 384 g, P = 0.04).
                Because nitrogen content is 10% higher in hydrolyzed-protein formula than in entire-protein formula, appropriate nitrogen retention, plasma amino acid profile, and mineral use can be achieved with the new partially hydrolyzed formula. Further studies with larger groups are needed to evaluate the effect on growth. Forty-five healthy infants were included in a double-blind randomized prospective 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 sampled 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 incidence of atopic manifestations was analyzed in infants "at risk" because of histories of atopy in first degree relatives. The incidence of atopic manifestations was significantly reduced (P = .0011) during the first 6 months of life when only the whey hydrolysate was administered (2/32 infants, 6.3%) compared with the incidence when an adapted formula was given (14/35 infants, 40%). This beneficial effect continued during the 6 to 12-month period, after diversification of the diet at 6 months. At the age of 1 year, 7/32 (21.8%) of the infants in the whey hydrolysate group had presented with manifestations of probable atopic disease compared with 17/35 (48.6%) infants in the adapted formula group (P = .021). The incidence of cow milk protein sensitivity was evaluated at 5/32 (15.6%) in the hydrolysate group and 15/35 (42.8%) in the adapted formula group (P = .014). Other foods such as egg and fish may be responsible for manifestations in three infants in hydrolysate group and in five infants of the adapted group (9.4% and 14.3%, respectively NS). These preliminary data show that the administration of a whey hydrolysate during the first 6 months of life to babies "at risk" decreased the incidence of atopic disease up to the age of 12 months. The incidence of cow milk protein sensitivity appeared to be decreased, whereas the incidence of sensitivities to other food proteins was comparable in both groups. Early feeding with cow's milk (CM) may increase the risk of cow's milk allergy (CMA).
                We sought to examine prospectively whether supplementary feeding of CM at the maternity hospital would increase the risk when compared with feeding with pasteurized human milk or hydrolyzed formula.
                We studied 6209 unselected healthy, full-term infants, of whom 5385 (87%) required supplementary milk while in the hospital. The infants were randomly 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.
                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.
                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.
There is no evidence to support feeding with a hydrolysed formula for the prevention of allergy compared to exclusive breast feeding. In high risk infants who are unable to be completely breast fed, there is limited evidence that prolonged feeding with a hydrolysed formula compared to a cow's milk formula reduces infant and childhood allergy and infant CMA. In view of methodological concerns and inconsistency of findings, further large, well designed trials comparing formulas containing partially hydrolysed whey, or extensively hydrolysed casein to cow's milk formulas are needed.