Multistrain Probiotics Associated With Lower Death and Necrotizing Enterocolitis in Very Preterm Infants: JAMA
Sweden: In a cohort study of very preterm infants, implementation of a multistrain probiotic was associated with a significant reduction in death and/or necrotizing enterocolitis (NEC). The findings may inform clinician–family decision-making, but should not be generalized to extremely preterm infants born before 28 weeks’ gestation.
The findings, published in JAMA Network Open, were reported by Ayoub Mitha, MD, PhD, Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden, and colleagues.
Probiotics have been investigated as a strategy to improve gastrointestinal outcomes in premature infants, although population-level evidence remains limited. In 2020, the Swedish Neonatal Society recommended probiotic supplementation for very preterm infants born between 28 weeks 0 days and 31 weeks 6 days of gestation.
The researchers conducted a population-based cohort study using data from the Swedish Neonatal Quality Register covering January 2017 through December 2024. The analysis included live-born very preterm infants after excluding those who died within the first three days or had congenital or chromosomal abnormalities.
A total of 4695 infants were included, with a mean gestational age of 30.2 weeks. Of these, 2550 (54.3%) were male. The probiotic regimen consisted of 1 billion colony-forming units daily of freeze-dried Bifidobacterium infantis, Bifidobacterium lactis, and Streptococcus thermophilus. Supplementation was initiated after birth and continued until postmenstrual week 34.
Researchers evaluated composite outcomes involving death and NEC, death and surgical NEC, and death and culture-confirmed sepsis. Multiple statistical approaches were used to assess the robustness of the findings.
Key findings:
- Probiotic supplementation was associated with a lower risk of death and/or NEC, occurring in 0.8% of supplemented infants versus 3.4% of those who did not receive probiotics.
- The adjusted relative risk for death and/or NEC was 0.28 (95% CI, 0.14–0.56).
- Death occurred in 0.3% of infants receiving probiotics compared with 1.4% without supplementation.
- NEC occurred in 0.6% of the probiotic group versus 2.5% of the nonsupplemented group.
- Bayesian analysis suggested that about 42.3% of the observed reduction in mortality could be mediated through a lower incidence of NEC.
- Probiotic exposure was not significantly associated with death and/or culture-proven sepsis, which occurred in 3.4% versus 4.4% of infants, respectively.
The researchers noted several limitations. The retrospective observational design and lack of blinding may have resulted in residual confounding or information bias, while NEC misclassification and selection or indication bias could not be excluded. Although the findings remained consistent after adjustment for birth year and other analyses, the study lacked information on ethnicity and social characteristics that could influence outcomes.
Overall, multistrain probiotic supplementation was associated with lower risks of death and NEC among very preterm infants. The findings may support shared decision-making between clinicians and families, but the authors emphasized that the results should not be extrapolated to extremely preterm infants born before 28 weeks’ gestation, who have substantially different baseline risks.
Reference:
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
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