Role of probiotics VSL#3 in prevention of suspected sepsis in low birthweight infants in India: a randomised controlled trial

Randomized, double-blind, placebo-controlled trial in low birthweight newborns in India, conducted at Safdarjung Hospital in New Delhi and the Mahatma Gandhi Institute of Medical Sciences in Wardha, with adjacent community follow-up. Eligible infants were enrolled on days 3-7 of life and followed for 2 months; severe prematurity and certain illnesses were excluded. For the probiotic arm, 668 participants were randomized in a 1:1 allocation ratio.

Infants in the active arm received VSL#3, an oral multi-strain probiotic powder, at 10 billion cfu per day for 30 days. The probiotic was mixed into expressed breast milk and fed orally; the control group received an identical-looking maltodextrin placebo.

VSL#3 did not significantly reduce the primary fieldworker-diagnosed suspected sepsis outcome overall, but results were directionally favorable and a lighter-birthweight subgroup showed a clear benefit. Across all infants, suspected sepsis occurred in 84/668 (12.6%) with probiotic versus 107/672 (15.9%) with placebo, RR 0.79 (95% CI 0.56 to 1.03; p=0.080); incidence was 2.61 vs 3.40 per 1000 days, RR 0.77 (95% CI 0.59 to 0.99; p=0.0493). In infants weighing 1.5-1.99 kg, suspected sepsis was 4/74 (5.4%) versus 14/75 (18.7%), RR 0.29 (95% CI 0.10 to 0.84; p=0.014), with a lower incidence rate as well. Post hoc physician-diagnosed sepsis analyses also favored VSL#3 (38/688 vs 54/672; RR 0.71, p=0.091; incidence-rate RR 0.67, p=0.048), and hospitalizations were fewer and shorter, although these findings were not definitive.

The primary outcome was not statistically significant, and several favorable findings came from subgroup or post hoc analyses, increasing the risk of chance findings. Follow-up was limited to 2 months, and the authors noted limited power, so the trial was not definitive for preventing neonatal sepsis. Generalizability is also limited to low birthweight infants in similar Indian hospital-community settings.