{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T22:28:43Z","timestamp":1793312923063,"version":"4.5.0"},"reference-count":39,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Probiotics are reported to benefit preterm infants, but population-based clinical evidence is limited. In 2020, the Swedish Neonatal Society issued a national recommendation to supplement very preterm infants (28 weeks 0 days\u2019 to 31 weeks 6 days\u2019 gestation) with probiotics.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To investigate whether probiotic supplementation was associated with risk of death, necrotizing enterocolitis (NEC), and\/or culture-proven sepsis in infants born very preterm.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This population-based cohort study examined data from the Swedish Neonatal Quality Register from January 1, 2017, through December 31, 2024. Live-born, very preterm infants, excluding those who died within the first 3 days of life or due to congenital or chromosomal abnormalities, were included.<\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n \n Daily probiotic supplementation of 1 billion colony-forming units of freeze-dried\n Bifidobacterium infantis<\/jats:italic>\n ,\n Bifidobacterium lactis<\/jats:italic>\n , and\n Streptococcus thermophilus<\/jats:italic>\n initiated following birth and discontinued at postmenstrual week 34.\n <\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n 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 were assessed. Modified Poisson regression, propensity score\u2013matched, and inverse probability of treatment weighting analyses were used for replication analyses. A multivariate bayesian modeling analysis accounting for the association between NEC and mortality was performed to estimate the association between probiotic exposure and mortality.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Among 4695 infants (mean [SD] gestational age, 30.2 [1.1] weeks; 2550 male [54.3%]), probiotic exposure increased from 0% before the national recommendation in 2020 to 16.9% in 2020 and a mean (SD) of 64.8% (4.7%) in 2021 to 2024. Probiotic supplementation vs no supplementation was associated with lower risk of death and\/or NEC (rate, 0.8% vs 3.4%; adjusted relative risk [ARR], 0.28 [95% CI, 0.14-0.56]). When assessed separately, risks of death (rate, 0.3% vs 1.4%; ARR, 0.16 [95% CI, 0.06-0.45]) and NEC (rate, 0.6% vs 2.5%; ARR, 0.25 [95% CI, 0.10-0.61]) were both lower in the probiotic group. Multivariate bayesian modeling suggested that a substantial proportion of the observed mortality reduction was mediated via reduced NEC incidence (42.3% [credible interval, 16.1%-100%]). Probiotic supplementation was not associated with death and\/or culture-proven sepsis (rate, 3.4% vs 4.4%; ARR, 0.86 [95% CI, 0.58-1.26]).<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n This cohort study of very preterm infants found that implementation of a multistrain probiotic was associated with a significant reduction in death and\/or NEC, which may help inform shared decision-making between clinicians and families. These results should not be generalized to extremely preterm infants (&amp;lt;28 weeks\u2019 gestation).<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.35560","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:30:32Z","timestamp":1790177432000},"page":"e2635560","source":"Crossref","is-referenced-by-count":2,"title":["Probiotics and Risk of Death, Necrotizing Enterocolitis, and Sepsis in Very Preterm Infants"],"prefix":"10.1001","volume":"9","author":[{"given":"Ayoub","family":"Mitha","sequence":"first","affiliation":[{"name":"Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden"},{"name":"Department of Neonatal Medicine, Bretonneau Hospital, Fran\u00e7ois Rabelais University, CHU Tours, Tours, France"},{"name":"Universit\u00e9 Paris Cit\u00e9 and Universit\u00e9 Sorbonne Paris Nord, Inserm, INRAE, Center for Research in Epidemiology and Statistics, Obstetric, Perinatal, 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University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn","family":"Brindefalk","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden"},{"name":"Department of Ecology, Environment and Geoscience, Ume\u00e5 Universitet, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Abrahamsson","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences, Link\u00f6ping University and Crown Princess Victoria Children\u2019s Hospital, Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Johansson","sequence":"additional","affiliation":[{"name":"Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden"},{"name":"Department of Neonatology, Karolinska University Hospital, 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T, Ahlsson? F, Diderholm? B, . Probiotika under neonatalperioden nationella riktlinjer. Svenska Neonatalf\u00f6reningen. Svenska Neonatalf\u00f6reningen. 2020. Accessed February 15, 2026. https:\/\/neo.barnlakarforeningen.se\/wp-content\/uploads\/sites\/14\/2020\/02\/Probiotika-neo-va%CC%8Ardprogram-20020205.pdf"},{"key":"zoi260957r27","unstructured":"Pustejovsky? JE. clubSandwich: cluster-robust (sandwich) variance estimators with small-sample corrections. Comprehensive R Network. 2025. Accessed February 15, 2026. https:\/\/CRAN.R-Project.Org\/package=clubSandwich."},{"key":"zoi260957r30","unstructured":"Risk of invasive disease in preterm infants given probiotics formulated to contain live bacteria or yeast. US Food and Drug Administration. Updated September 29, 2023. 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