Effects of Infant Formula With Human Milk Oligosaccharides on Growth and Morbidity: A Randomized Multicenter Trial

Randomized multicenter trial in healthy term infants who were exclusively formula-fed at enrollment, conducted at two European centers in Belgium and Italy. For the active intervention arm, 88 infants were randomized, 88 were included in the ITT analysis, and 71 were included in the per-protocol analysis.

The active formula contained human milk oligosaccharides 2'FL and LNnT at 1.0 g/L and 0.5 g/L, respectively, in reconstituted cow's milk-based infant formula. Infants received the test formula orally from enrollment until 6 months of age, compared with standard formula.

The supplemented formula supported normal, age-appropriate growth and was safe and well-tolerated, but it did not improve the primary growth endpoint versus standard formula. In the per-protocol analysis, weight gain from 0 to 4 months was 29.84 vs 30.15 g/day, with a difference of -0.30 (-1.94, 1.34) g/day; the ITT analysis was similarly null at -0.13 (-1.63, 1.37) g/day. Anthropometrics and z-scores were not significantly different at any visit. Secondary findings favored the supplemented formula for some tolerance and morbidity outcomes, including lower bronchitis rates (for example, 0 to 12 months: 10.2% vs 27.6%) and reduced antibiotic and antipyretic use, although these findings should be confirmed in future studies.

The primary growth outcome was neutral, and the morbidity and tolerance findings were secondary and should be interpreted cautiously. The per-protocol sample was smaller than the randomized active arm, the study population was limited to healthy term exclusively formula-fed infants at two European centers, and multiple secondary comparisons increase the risk of chance findings.