Probiotic Supplementation Associated With Lower NEC and Mortality Risk in Very Preterm Infants

Multistrain probiotic supplementation was associated with a lower risk of death or necrotizing enterocolitis (NEC) among very preterm infants in Sweden, according to a population-based cohort study published in JAMA Network Open. The study did not find an association with the composite of death or culture-proven late-onset sepsis.

Investigators analyzed Swedish Neonatal Quality Register data for 4,695 infants born at 28 weeks 0 days to 31 weeks 6 days of gestation from 2017 through 2024. After a 2020 recommendation, 1,571 infants received a daily preparation containing Bifidobacterium infantis, Bifidobacterium lactis, and Streptococcus thermophilus; 3,124 did not. The study assessed death or NEC, death or surgical NEC, and death or culture-proven late-onset sepsis. Infants who died within the first 3 days of life were excluded.

Death or NEC occurred in 0.8% of supplemented infants and 3.4% of those who did not receive probiotics (adjusted relative risk [RR], 0.28; 95% CI, 0.14-0.56). Considered separately, death occurred in 0.3% versus 1.4%, and NEC in 0.6% versus 2.5%, respectively. The composite outcome associations were similar in propensity score–matched and inverse probability–weighted analyses.

The death or late-onset sepsis composite occurred in 3.4% of supplemented infants and 4.4% of unsupplemented infants (adjusted RR, 0.86; 95% CI, 0.58-1.26). Sepsis alone occurred in 3.2% and 3.1%. The registry did not capture whether sepsis was caused by probiotic organisms, although a survey of Swedish neonatal units reported no cases of probiotic-associated sepsis.

The authors noted that the retrospective, unblinded observational design leaves room for residual confounding, selection bias, and possible misclassification of NEC. They cautioned against extending these findings to infants born before 28 weeks of gestation, who were outside the study population.

Source: Mitha A, Söderquist Kruth S, Sinervo E, et al. Probiotics and risk of death, necrotizing enterocolitis, and sepsis in very preterm infants. JAMA Netw Open. 2026;9(9):e2635560. doi:10.1001/jamanetworkopen.2026.35560