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. Extensively and partially hydrolysed infant formulas for allergy prophylaxis. Efficacy and safety of hydrolyzed cow milk and amino acid-derived formulas in infants with cow milk allergy. Supplementary feeding in maternity hospitals and the risk of cow's milk allergy: A prospective study of 6209 infants. Immunogenicity and antigenicity of a partially hydrolyzed cow's milk infant formula. Long-term prevention of allergic diseases by using protein hydrolysate formula in at-risk infants. Effect of a whey hydrolysate prophylaxis of atopic disease. Oral immunotherapy for cow's milk allergy with a weekly up-dosing regimen: a randomized single-blind controlled study.
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 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. 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. To determine the antigenicity, nutritional adequacy, and growth-promoting efficacy of protein hydrolysate or amino acid-derived formulas in infants with cow milk allergy.
                Several protein hydrolysate or amino acid-derived formulas were graded for beta-lactoglobulin content and skin reactivity in 74 atopic children with cow milk allergy proved by a double-blind, placebo-controlled challenge. A randomized, prospective 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).
                Both formulas were clinically 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.
                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. 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. 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. 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. 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. Cow's milk allergy (CMA) in children is a important problem in medical practice. Oral desensitization has been proposed as a therapeutic approach, but current protocols are time-consuming and impractical.
                To establish a patient-friendly desensitization regimen with weekly up-dosing and to evaluate it in a randomized controlled trial.
                Thirty children with IgE-mediated CMA confirmed by double-blind placebo-controlled food challenge were equally randomized to desensitization with CM or soy milk as control. The weekly up-dosing lasted 18 weeks. The occurrence and severity of reactions after each dose was evaluated, and the desensitization was stopped if severe reactions occurred. Specific IgE and IgG4 levels to CM were measured at baseline, after 8 weeks, and at the end of the study. The double-blind food challenge was repeated once the desensitization was completed or after premature discontinuation.
                Two active and 1 control patient dropped out. Full tolerance to CM (200 mL) was achieved in 10 active patients and partial tolerance in 1. Two active patients discontinued the desensitization after experiencing severe reactions, whereas no reactions occurred in controls, whose sensitivity to CM remained unchanged. A significant increase in specific IgG4 levels was found only in the active group.
                This weekly up-dosing desensitization protocol for CMA performed under medical supervision was effective and reasonably safe and induced consistent immunologic changes.
                Copyright © 2010 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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.