A Randomized Placebo-controlled Comparison of 2 Prebiotic/Probiotic Combinations in Preterm Infants: Impact on Weight Gain, Intestinal Microbiota, and Fecal Short-chain Fatty Acids

Randomized, double-blind, placebo-controlled trial in premature infants in a neonatal intensive care unit. Eligible infants had birth weight 750 to 2000 g, gestational age younger than 35 completed weeks, and age younger than 7 days at enrollment. Active intervention arms included Culturelle n=30 and ProBioPlus DDS n=31.

Culturelle (CUL) was administered as 1 mL twice daily by mouth or gavage for up to 28 days or until discharge, providing 5 x 10^8 organisms per dose of Lactobacillus rhamnosus GG with inulin. ProBioPlus DDS (PBP) was given on the same schedule, providing 5 x 10^8 of each organism per dose of Lactobacillus acidophilus, Bifidobacterium longum, Bifidobacterium bifidum, and Bifidobacterium infantis with inulin. Placebo was a 1:30 dilution of Pregestamil elemental formula.

The synbiotic interventions did not improve weight gain, growth, or fecal short-chain fatty acids overall, but ProBioPlus DDS increased bifidobacterial colonization in stool. Regression-adjusted cumulative weight gain versus placebo was not significant at weeks 3, 4, or 5 for ProBioPlus DDS (14.7 g, 22.7 g, 30.7 g; all P>0.50) or Culturelle (3.9 g, 8.2 g, 12.5 g; all P>0.78). By culture, 64% of ProBioPlus DDS infants were colonized with bifidobacteria versus 18% with Culturelle and 27% with placebo (P=0.064), and 16S rDNA qPCR showed higher bifidobacterial stool content with ProBioPlus DDS than with Culturelle or placebo (P=0.011). No adverse reactions were noted, and NEC, infections, length gain, and head circumference gain were not significantly different.

Small single-center NICU trial with only 90 enrolled infants and a short intervention window limited to 28 days or discharge. The primary growth outcome was negative, while microbiota findings were product-specific rather than uniform across both synbiotic regimens. Arm-specific demographic and ethnicity data were not reported, and one infant was excluded from qPCR analysis because of antibiotic exposure.