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
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Author(s)
Type
Journal Article
Abstract
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); other definitions of NEC yielded similar results. Incidence for late onset sepsis (10.8% versus 11.5%, OR 0.94 (0.90–0.97)) and survival to discharge (96.6% versus 94.2%, OR 1.76 (1.65–1.88)). In infants <28 weeks gestation, severe NEC (8.7% versus 9.8%, OR 0.88 (0.82–0.93) and for ≥28 weeks (1.0% versus 1.7%, OR 0.59 (0.47–0.73).
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.
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); other definitions of NEC yielded similar results. Incidence for late onset sepsis (10.8% versus 11.5%, OR 0.94 (0.90–0.97)) and survival to discharge (96.6% versus 94.2%, OR 1.76 (1.65–1.88)). In infants <28 weeks gestation, severe NEC (8.7% versus 9.8%, OR 0.88 (0.82–0.93) and for ≥28 weeks (1.0% versus 1.7%, OR 0.59 (0.47–0.73).
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.
Date Issued
2026-03-01
Date Acceptance
2025-12-05
Citation
The Lancet Regional Health. Europe, 2026, 62
ISSN
2666-7762
Publisher
Elsevier
Journal / Book Title
The Lancet Regional Health. Europe
Volume
62
Copyright Statement
© 2025 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Publication Status
Published
Article Number
101571
Date Publish Online
2025-12-22