Short- and long-term effects of feeding hydrolyzed protein infant formulas on growth at ≤6 y of age: results from the German Infant Nutritional Intervention Study

Background: The short- and long-term effects of feeding with hydrolyzed formulas on growth are uncertain. Objective: Our aim was to investigate the potential differences in body mass index (BMI) over the first 6 y of life between infants fed with partially hydrolyzed whey (pHF-W), extensively hydrolyzed whey (eHF-W), extensively hydrolyzed casein (eHF-C), or cow-milk formula (CMF) and infants exclusively breastfed for the first 16 wk of life. Design: We established a prospective, randomized, double-blind trial of full-term neonates with atopic heredity in the German birth cohort followed by the German Infant Nutritional Intervention Study through the first 6 y of life. Intention-to-treat and per-protocol analyses of absolute and World Health Organization-standardized BMI trajectories for 1840 infants (pHF-W: n = 253; eHF-W: n 265; eHF-C: n = 250, CMF: n = 276; breastfed: n = 796) were performed. Results: No significant differences in absolute or World Health Organization-standardized BMI trajectories were found among the pHF-W, eHF-W, CMF, and breastfed groups during the 6-y follow-up. However, in the eHF-C group, both intention-to-treat and per-protocol analyses showed a significantly slower sex-adjusted BMI gain through the 8th to 48th week of life (-0.1 to -0.2 lower BMI z score) but not beyond. Analyses of weight and length revealed that this difference is due to a slightly diminished weight gain in the first year of life because growth in length did not differ among study groups for the entire follow-up. Conclusions: To our knowledge, this is the first randomized trial investigating both short-and long-term effects of partially and extensively hydrolyzed formula (pHF-W, eHF-W, eHF-C), CMF, and breastfeeding on growth in one trial. Feeding with eHF-C led to a transient lower weight gain in the first year of life. No long-term consequences of different formulas on BMI were observed. Am J Clin Nutr 2009; 89: 1846-56.