To determine the prevalence of probiotic administration in infants born preterm over time, as well as the association between probiotic administration and select adverse outcomes.

We performed a multicenter cohort study of infants 23-29 weeks of gestational age admitted to 289 neonatal intensive care units from 1997 to 2016. We evaluated the type of probiotics given and prevalence of exposure to probiotics over time and by site. We matched infants exposed to probiotics by several factors to unexposed infants receiving enteral feeds on the same postnatal day. We performed conditional logistic regression to evaluate the association between probiotics exposure and adverse outcomes, including necrotizing enterocolitis (NEC), bloodstream infections, meningitis, and death.

Of 78 076 infants, 3626 (4.6%) received probiotics. Probiotic use increased over the study period and varied among neonatal intensive care units. We matched 2178 infants exposed to probiotics to 33 807 without exposure. Probiotic administration was associated with a decrease in NEC (OR 0.62, 95% CI 0.48-0.80) and death (OR 0.52, 95% CI 0.39-0.70), an increase in Candida infection (OR 2.23, 95% CI 1.29-3.85), but no increase in bloodstream infection (OR 0.86, 95% CI 0.70-1.05) or meningitis (OR 1.18, 95% CI 0.40-3.46).

Probiotic use increased over time and was associated with decreased odds of NEC and death. Prospective, randomized-controlled studies of specific probiotic products are needed to further investigate the safety and efficacy of probiotics in preterm infants.