Supplementary file 1_Association between maternal preeclampsia and the risk of neonatal sepsis: a systematic review and meta-analysis.docx

BackgroundBackground: Preeclampsia is a common hypertensive disorder of pregnancy associated with adverse maternal and neonatal outcomes, while neonatal sepsis remains a leading cause of neonatal morbidity and mortality worldwide. However, the association between maternal preeclampsia and neonatal sepsis remains uncertain, with inconsistent findings across studies. We conducted a systematic review and meta-analysis to evaluate this relationship.
MethodsPubMed, Embase, and Web of Science were searched from inception to January 05, 2026, including full-text articles published in English. Observational studies including neonates (≤28 days) born to women with and without preeclampsia, with gestational age (GA) at delivery matched or adjusted, were eligible. Risk ratios (RRs) were pooled using random-effects models accounting for between-study heterogeneity. The certainty of evidence for the outcome was assessed using the GRADE framework.
ResultsEleven cohort studies comprising 1,513,008 neonates (65,848 exposed to preeclampsia) and 24,925 cases of neonatal sepsis were included. Overall, preeclampsia was associated with a modestly increased risk of neonatal sepsis (RR: 1.27, 95% CI: 1.02–1.56; p = 0.03), although substantial heterogeneity was present (I2 = 88%). Sensitivity analyses showed broadly consistent estimates (RR range: 1.18–1.32). Excluding the largest study reduced heterogeneity (I2 = 34%) while the association remained statistically significant (RR: 1.18, 95% CI: 1.05–1.32). Subgroup analyses did not demonstrate statistically significant differences across study design, sample size, GA at delivery, exposure or outcome definitions (all p for subgroup difference >0.05). Stronger associations were observed in studies with lower NOS scores (7–8 vs. 9; p = 0.04). Meta-regression suggested that sample size and study quality may partially explain between-study heterogeneity. The overall certainty of evidence for this association was rated as low according to the GRADE framework.
ConclusionsMaternal preeclampsia may be associated with a modest increase in the risk of neonatal sepsis. These findings suggest that neonates born to mothers with preeclampsia may warrant closer clinical surveillance for early signs of infection. However, substantial heterogeneity and the low certainty of evidence warrant cautious interpretation, and further well-designed studies are needed to clarify the clinical significance and underlying mechanisms of this association.
Systematic Review Registrationidentifier CRD420261320994.