Allergic manifestation 15 years after early intervention with hydrolyzed formulas--the GINI Study

Allergy. 2016 Feb;71(2):210-9. doi: 10.1111/all.12790. Epub 2015 Nov 23.


Background: Data on the long-term impact of hydrolyzed formulas on allergies are scarce.

Objective: To assess the association between early intervention with hydrolyzed formulas in high-risk children and allergic outcomes in adolescence.

Methods: GINI trial participants (n = 2252) received one of four formulas in the first four months of life as breastmilk substitute if necessary: partial or extensive whey hydrolyzate (pHF-W, eHF-W), extensive casein hydrolyzate (eHF-C) or standard cow's milk formula (CMF) as reference. Associations between these formulas and the cumulative incidence and prevalence of parent-reported physician-diagnosed asthma, allergic rhinitis (AR) and eczema, as well as spirometric indices and sensitization, were examined using generalized linear models.

Results: Between 11 and 15 years, the prevalence of asthma was reduced in the eHF-C group compared to CMF (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.26-0.89), which is consistent with the spirometric results. The cumulative incidence of AR was lower in eHF-C (risk ratio (RR) 0.77, 95% CI 0.59-0.99]) and the AR prevalence in pHF-W (OR 0.67, 95% CI 0.47-0.95) and eHF-C (OR 0.59, 95% CI 0.41-0.84). The cumulative incidence of eczema was reduced in pHF-W (RR 0.75, 95% CI 0.59-0.96) and eHF-C (RR 0.60, 95% CI 0.46-0.77), as was the eczema prevalence between 11 and 15 years in eHF-C (OR 0.42, 95% CI 0.23-0.79). No significant effects were found in the eHF-W group on any manifestation,nor was there an effect on sensitization with any formula.

Conclusion: In high-risk children, early intervention using different hydrolyzed formulas has variable preventative effects on asthma, allergic rhinitis and eczema up to adolescence.

Keywords: 15-year follow-up from birth; allergy prevention; double-blind; hydrolyzed infant formulas; nutritional intervention; randomized trial.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Animals
  • Cattle
  • Child
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • Humans
  • Hypersensitivity / diagnosis
  • Hypersensitivity / epidemiology*
  • Hypersensitivity / etiology
  • Hypersensitivity / prevention & control*
  • Incidence
  • Infant
  • Infant Formula*
  • Infant, Newborn
  • Male
  • Milk
  • Milk Proteins
  • Odds Ratio
  • Patient Outcome Assessment
  • Prevalence
  • Spirometry


  • Milk Proteins