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

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.

Key words: Birth cohort, long-term allergy prevention, hydrolysates, double-blind randomized trial

Abbreviations used: AM, Allergic manifestation, AD, Atopic dermatitis used synonymously to eczema according to the new nomenclature for reasons of continuity with previous articles by the GINI, CMF, Cow's milk formula, eHF-C, Extensively hydrolyzed casein formula, eHF-W, Extensively hydrolyzed whey formula, GINI, German Infant Nutritional Intervention, ITT, Intent-to-treat, pHF-W, Partially hydrolyzed whey formula, PP, Per-protocol