This population-based cohort study (Sweden, 2017–2024; n=4,695) examined whether daily multistrain probiotic supplementation (1 billion CFU of *Bifidobacterium infantis*, *B. lactis*, and *Streptococcus thermophilus*) in very preterm infants (28–31 weeks' gestation) was associated with reduced risk of death, NEC (Bell stage 2–3), and culture-proven late-onset sepsis, following a 2020 Swedish national recommendation.
Probiotic supplementation was associated with a large reduction in death and/or NEC (0.8% vs 3.4%; ARR 0.28, 95% CI 0.14–0.56), including lower risks of death alone (0.3% vs 1.4%; ARR 0.16) and NEC alone (0.6% vs 2.5%; ARR 0.25); Bayesian mediation analysis estimated ~42% of the mortality reduction was mediated through reduced NEC incidence. No association was found with death and/or culture-proven sepsis (3.4% vs 4.4%; ARR 0.86, 95% CI 0.58–1.26).
Observational, unblinded design with potential residual confounding and information bias; NEC diagnoses may be overestimated in the registry (prior validation suggests ~28% overcounting), though surgical NEC analyses yielded consistent results; findings cannot be generalized to extremely preterm infants (<28 weeks' gestation).
For very preterm infants (28–31 weeks' gestation), daily supplementation with this multistrain probiotic (ProPrems) appears to substantially reduce NEC and mortality and should be considered as standard of care. Clinicians should not extend these findings to infants under 28 weeks, and ongoing local safety surveillance for probiotic-associated sepsis remains important.
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