Probiotic supplementation is associated with reduced risk of death and necrotizing enterocolitis among preterm infants
1. Probiotic supplementation was associated with a lower risk of death and/or necrotizing enterocolitis in very preterm infants.
Evidence Rating Level: 2 (Good)
Specific probiotics have been shown to reduce the incidence of necrotizing enterocolitis (NEC) and all-cause mortality in preterm infants; however, population-based clinical evidence is limited. In 2020, a national recommendation in Sweden was issued to provide probiotics to very preterm infants in neonatal intensive care units. This study examined the association between probiotic supplementation and risk of death, NEC, and/or culture-proven sepsis in very preterm infants. This cohort study included very preterm infants (28 weeks 0 days’ to 31 weeks 6 days’ gestation) live born in Sweden from January 1, 2017, through December 31, 2024. The daily probiotic supplementation included 1 billion colony-forming units of freeze-dried Bifidobacterium infantis, Bifidobacterium lactis, and Streptococcus thermophilus given after birth to postmenstrual week 34. The primary outcomes were composites of death and/or NEC (Bell stage 2-3), death and/or surgical NEC (Bell stage 3), and death and/or culture-proven sepsis. Among 4695 infants analyzed (mean [SD] gestational age, 30.2 [1.1] weeks; 2145 female [45.7%]), 1571 (33.5%) were in the probiotics group and 3124 infants (66.5%) were in the no probiotics group. Following the national probiotic supplementation guideline in 2020, probiotic uptake increased from 0% before 2020 to 16.9% in 2020 and to a mean (SD) of 64.8% (4.7%) in 2021 to 2024. The probiotic group had a 72% lower risk of death and/or NEC (adjusted relative risk [aRR], 0.28 [95% CI, 0.14-0.56]) compared to no probiotic supplementation. When analyzed separately, the probiotic group had an 84% lower risk of death (aRR, 0.16 [95% CI, 0.06-0.45]) and 75% lower risk of NEC (aRR, 0.25 [95% CI, 0.10-0.61]) compared to the no-probiotic group. About 42.3% (credible interval, 16.1%-100%) of the observed mortality reduction was mediated via reduced NEC incidence. Risk of culture-proven sepsis was similar in both groups (ARR, 1.22 [95% CI, 0.78-1.90]). Overall, this study found that probiotic supplementation was associated with a lower risk of death and/or NEC in very preterm infants. These findings support the use of probiotic supplementation in very preterm infants in Sweden.
Click here to read this study in JAMA Network Open
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Citation: Mitha A, Söderquist Kruth S, Sinervo E, Domellöf M, Brindefalk B, Abrahamsson T, et al. Probiotics and Risk of Death, Necrotizing Enterocolitis, and Sepsis in Very Preterm Infants. JAMA Netw Open. 2026 Sep 1;9(9):e2635560. doi: 10.1001/jamanetworkopen.2026.35560. PMID: 42776528; PMCID: PMC13602013.
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