Safety and efficacy of a probiotic-containing infant formula supplemented with 2’-fucosyllactose: a double-blind randomized controlled trial

Double-blind, multicenter randomized controlled trial in healthy term infants enrolled within 2 weeks of birth in Belgium and Italy, with a non-randomized breastfed reference group. The active formula group was randomized n = 144, with 108 in the full analysis set and 99 in the per-protocol set.

Healthy term infants received an oral starter formula containing Limosilactobacillus reuteri DSM 17938 at 1 × 10^7 CFU/g plus 2'-fucosyllactose (2'FL) 1 g/L, compared with the same formula without 2'FL. The formula was given for approximately 180 days, with exclusive formula feeding until at least 4 months of age.

Adding 2'FL to the L. reuteri-containing infant formula supported age-appropriate growth and was well tolerated, with no evidence of harm. Weight gain was non-inferior and essentially identical between groups: 29.15 (0.65) g/day vs 28.89 (0.71) g/day, with a between-group difference of 0.26 (-1.26; 1.79) g/day; p = 0.736. Gastrointestinal tolerance and adverse events were similar, including stool consistency (p = 0.278), stool frequency (p = 0.978), and adverse events in 65.7% versus 73.4% of infants. The 2'FL formula also produced subtle microbiota effects, including lower C. difficile counts at 1 month (16.0 ± 5.3 × 10^4 copies/mg vs 29.2 ± 8.3 × 10^4 copies/mg; p = 0.047), suggesting a shift toward a more breastfed-like gut microbial pattern.

The analyzed sample was smaller than the randomized sample because of attrition between randomization, full analysis, and per-protocol populations. The population was highly selected and mostly Caucasian healthy term infants, which limits generalizability. Follow-up was relatively short, and the microbiota changes were subtle with uncertain clinical significance; the breastfed reference group was non-randomized.