Mechanisms of Allergy
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,☆☆,

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Abstract

Background: The potential of extensively or partially hydrolyzed formulas to reduce the risks for allergies is controversial. Objective: We sought to assess the preventive effect of differently hydrolyzed formulas compared with cow's milk formula (CMF) in high-risk infants. Methods: 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. Results: 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. Conclusions: 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. (J Allergy Clin Immunol 2003;111:533-40.)

Section snippets

Methods

This study is a prospective, randomized, double-blind intervention trial to assess the allergy-preventive effect of differently hydrolyzed formulas compared with CMF in infants at risk for atopy. Infants were recruited between September 1995 and June 1998 in obstetric units throughout 2 areas of Germany (Wesel, North Rhine Westphalia, and Munich, Bavaria).

Baseline characteristics

A total of 2252 infants were included in the study and randomized to the study formula (Fig 1).

. Trial profile.

Within the first 4 weeks, 114 (5%) of 2252 children left the study without physical examination and information on feeding modalities. A total of 889 (42%) of 2138 mothers exclusively breast-fed their infants during the first 4 months; all but 24 (3%) of 889 could be followed-up during the entire study period. Study formula was given to 1249 infants, but 166 (13%) of 1249 dropped out

Discussion

Our results confirm that allergy prevention in the first year of life in infants with a familial risk for atopy is possible by feeding hydrolyzed formulas instead of CMF as a supplement or substitute for breast milk. AM was significantly prevented by eHF-C, whereas AD as the predominant allergic disease during infancy was prevented by eHF-C and pHF-W but not by eHF-W. For the first time, we could demonstrate that the preventive potential of the different formulas depends on the family history

Acknowledgements

We thank the families for participation in the study; the obstetric units for allowing the recruitment procedure; the GINI Study team for excellent work, especially Angela Schoetzau; and the advisory board (Ulrich Wahn, Stephan Strobel, Max Kjellman, and Willi Heine [until 1997]) for scientific support. We also thank Torsten Bauer for helping to prepare the manuscript.

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    *A list of contributors and members of the GINI Study team are listed in the Appendix.

    ☆☆

    Supported by the Federal Ministry for Education, Science, Research, and Technology (grant no. 01 EE 9401-4) and the Child Health Foundation, Munich, Germany. Nestlé, Hipp, Milupa, Numico, and Mead Johnson provided the study formulas, and SHS provided the formula for the elimination diet.

    Reprint requests: Andrea von Berg, MD, Research Institute for Prevention of Allergies and Airway Diseases, Children's Department Marien-Hospital, Pastor-Janßen-Str. 8-38, 46483 Wesel, Germany.

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