Atopic dermatitis and skin disease
Preventive effect of hydrolyzed infant formulas persists until age 6 years: Long-term results from the German Infant Nutritional Intervention Study (GINI)

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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 randomized, double-blind trial.

Methods

Between 1995 and 1998, 2252 newborns with atopic heredity were randomly 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 questionnaires. 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.

Section snippets

Subjects

Between September 1995 and July 1998, healthy term newborns were recruited at birth in 2 regions of Germany (rural Wesel and urban Munich) for the GINI study birth cohort. The infants were enrolled before any formula supplementation had occurred and at the latest at 14 days of age. Detailed description of screening and recruitment has been provided elsewhere.22, 23 High-risk infants, defined as having at least 1 parent or sibling with a history of allergic diseases, were selected for the GINI

Study population and participation

The present analysis is based on the 2252 children primarily randomized to one of the 4 study formulas. The pattern concerning the beginning and duration of feeding with the study formula was equally distributed between the study formula groups. Only 139 (6%) infants were fed exclusively with study formula, whereas 889 (39.4%) of 2252 were exclusively breast-fed. During the strict intervention period (birth to 4 months of age), 988 children were compliant with the milk-feeding recommendation,

Discussion

The results of the GINI study with a follow-up until 6 years of age revealed the important finding that nutritional intervention with hydrolyzed infant formulas in the first 4 months of life has a long-lasting preventive effect on atopic eczema in high-risk children. The preventive effect of pHF-W and eHF-C on AM and AD found in the 2 previous analyses at age 1 year and until 3 years21, 22 could now be confirmed up to age 6 years in both the ITT and the PP analyses. Although we previously

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  • Cited by (0)

    The German Infant Nutritional Intervention study was supported for the first 3 years by grants of the Federal Ministry for Education, Science, Research and Technology (Grant No. 01 EE 9401-4). The 6-year follow-up was partly funded by the Federal Ministry for Environment (IUF, FKZ 20462296) and by the GSF National Research Center for the Environment and Health.

    Disclosure of potential conflict of interest: A. von Berg has served on the speakers' bureau for MSD, Nestlé, Novartis, and Aerocrine; has served as the principal investigator for Nestlé, Mead Johnson, GlaxoSmithKline, Aerocrine, Nycomed, MSD, Allergopharma, and ALK-Abelló; and has served as an expert witness for Aerocrine and Novartis. U. Krämer has received research support from the Deutsche gesetzliche Unfallversicherung and the Federal Ministry for Environment. E. Link has received research support from the Federal Ministry for Environment. S. Koletzko has received honoraria from Nestlé, Nutricia, and Hipp and has served as an investigator for Nestlé. D. Berdel has served on the speakers' bureau for MSD, Nestlé, and Wyeth. The rest of the authors have declared that they have no conflict of interest.

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