Comparison of a partially hydrolyzed infant formula with two extensively hydrolyzed formulas for allergy prevention: A prospective, randomized study

The aim of this study was to compare the allergy-preventive effect of a par tially hydrolyzed formula with two extensively hydrolyzed formulas, in infa nts 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 Jul y 1995. Five-hundred and ninety-five high-risk infants were identified. Nig h-risk infants were defined as having biparental atopy, or a single atopic first-degree relative combined with cord blood immunoglobulin E (IgE) great er than or equal to 0.3 kU/l, At birth all infants were randomized to one o f three different blinded formulas. All mothers had unrestricted diets duri ng pregnancy and lactation and were encouraged to breast-feed exclusively. If breastfeeding 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 conv entional cow's milk-based formula were given when needed. All infants were followed-up prospectively with interview and physical examination at the ag e of 6, 12, and 18 months, and if any possible atopic symptoms were reporte d. If food allergy was suspected, controlled elimination/challenge procedur es were performed in a hospital setting. Of 550 infants included in the stu dy, 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 ex tensively hydrolyzed whey formula (Profylac), and 85 a partially hydrolyzed whey formula (Nan WA), during the first 4 months of life. These four group s were identical in regard to atopic predisposition, cord blood IgE, birthp lace, and gender. Exclusively breastfed children were exposed less to tobac co smoke and pets at home and belonged to higher social classes, whereas th e three formula groups were identical concerning environmental factors. The frequency of breast-feeding was high; only eight (2%) children were not br east-fed at all. The three formula groups were identical in regard to durat ion of breast-feeding: and age at introduction of formula and solid foods. No significant differences were found in the three groups of infants receiv ing 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 o r 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% tone of 161) i n infants fed extensively hydrolyzed formula (Nutramigen or Profylac), and 4.7% (four of 85) in infants fed partially hydrolyzed formula (Nan HA). Par tially hydrolyzed formula was found to be less effective than extensively h ydrolyzed 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 interpret ed with caution. Compared with other similar studies the frequency of atopi c symptoms was low, even though the dietetic intervention did not include e ither maternal diet during lactation or dietary restrictions to the childre n after the age of 3 months.