Evaluating the effect of probiotics on severe necrotising enterocolitis in preterm infants born before 32 weeks gestation in England and Wales: a propensity-matched population study.

Background: Necrotising enterocolitis (NEC) remains an important cause of morbidity and mortality in preterm infants. This study aimed to examine whether probiotics reduce the risk of severe NEC and other key neonatal morbidities including late onset sepsis and mortality. Methods: Retrospective study using the United Kingdom National Neonatal Research Database. Infants <32 weeks gestation in England and Wales (01/01/2016-31/12/2022) were included if alive on day four, without major congenital anomaly. A propensity score matched approach was applied matching for gestational age cohorts, birth year epochs and 17 further items. Comparators were infants who were exposed or not to probiotics within 14 days. Primary outcome was severe NEC (confirmed at laparotomy or postmortem or listed primary cause of death). Parent focus groups and former NICU patients supported this study but did not contribute to design or writing. Findings: 48,048 infants (45.2% (21,695/48,048) female), median gestational age 29.4 weeks (IQR 27.4-30.9) were included; 25.3% (12,161/48,048) were exposed to at least one of five available probiotics. 3.6% (1728/48,048) had severe NEC. Of 16,586 infants (8293 exposed and 8293 unexposed) in the propensity-matched analysis, incidence and odds ratios (OR) (95% CI) for exposed versus unexposed for severe NEC was 3.3% versus 4.2%, OR 0.80 (0.72-0.89); Interpretation: Probiotics were associated with a reduction in severe NEC including in those <28 weeks gestation. We currently recommend neonatal units not already using probiotics, to consider the introduction of products meeting appropriate recommendations, in the context of their local morbidity rates. Funding: NIHR Advanced Fellowship (CB reference: NIHR300617), Imperial College PhD studentship (AA), NIHR RfPB grant (NIHR203590, SO), Imperial NIHR Biomedical Research Centre.