Oral supplementation with probiotics in very-low-birth-weight preterm infants: a randomized, double-blind, placebo-controlled trial.

Randomized, double-blind, placebo-controlled trial in very-low-birth-weight preterm infants treated in two French NICUs. Eligible infants had gestational age under 32 weeks, birth weight under 1500 g, and had started enteral feeding before enrollment; 45 infants were randomized to the probiotic arm and the analysis was intention-to-treat.

Very-low-birth-weight preterm infants received an oral probiotic supplement containing Lactobacillus rhamnosus GG and Bifidobacterium longum BB536, delivered enterally as 4 capsules daily. Each unit contained 10^8 lyophilized cells of each strain plus maltodextrin; capsules were opened and mixed with 1 mL sterile water immediately before administration, starting when enteral feeding began and continued until discharge. The active regimen was compared with placebo.

Overall, BB536-LGG did not improve gastrointestinal tolerance to enteral feeding in the full cohort. On the primary endpoint, more than 50% of calories were received enterally on day 14 in 57.8% of the probiotic group versus 57.1% of placebo recipients (P = 0.95), and time to full enteral feeding was not significantly different overall. A prespecified subgroup of infants weighing more than 1000 g showed faster attainment of full enteral feeding with probiotics, with median 16 days versus 19 days in placebo (P = 0.04; pooled analysis P = 0.038). Probiotic strains colonized the gut in treated infants, but there was no clear reduction in sepsis or nosocomial infection and no major short-term safety signal; BB536-LGG was not detected in blood cultures.

The trial was relatively small and likely underpowered for several clinical outcomes, especially subgroup analyses. Follow-up was short, so long-term safety was not assessed. The main benefit was confined to a birth-weight subgroup, limiting confidence in generalizability to the full very-low-birth-weight population.