Effect of Bifidobacterium breve M-16V Supplementation on Fecal Bifidobacteria in Preterm Neonates - A Randomised Double Blind Placebo Controlled Trial

Randomized, double-blind, placebo-controlled trial in 159 preterm very-low-birth-weight neonates admitted to a tertiary neonatal intensive care unit in Perth, Western Australia, who were up to 32 weeks 6 days' gestation and ready to commence or already receiving enteral feeds for up to 12 hours. The probiotic arm was randomized 79 and 77 were analyzed; the placebo arm was randomized 80 and 76 were analyzed.

Bifidobacterium breve M-16V was given daily by orogastric feeding tube from birth until corrected age 37 weeks. The regimen was 3 x 10^9 cfu/day as a single dose; in infants younger than 27 weeks' gestation, the daily dose was 1.5 x 10^9 cfu/day until milk feeds reached 50 mL/kg/day, then increased to 3 x 10^9 cfu/day. The placebo was an equal volume of dextrin.

Bifidobacterium breve M-16V increased fecal B. breve colonization in preterm neonates and was well tolerated, with no probiotic sepsis or supplement-related adverse effects observed. In stool sample 2, colonization was 67/74 (91%) with probiotic versus 25/66 (38%) with placebo, and the between-sample change in log10 counts was higher with probiotic, 3.1 (4.3-4.9) versus 0 (3.2-5.0), p<0.001. In stool sample 1, colonization was 29/74 (39%) versus 2/66 (3%). Clinical outcomes such as time to full enteral feeds, length of hospital stay, discharge weight, and sepsis outcomes were not significantly different between groups.

This was a single-center neonatal trial with a modest sample size and smaller subsets for microbiologic analyses than the randomized groups. Most clinical outcomes were secondary and event rates were low, limiting power to detect differences beyond fecal colonization. Follow-up was limited to the hospitalization period and corrected age 37 weeks, so longer-term clinical effects are unknown.