Maternal Clinical, Microbiological, And Inflammatory Biomarkers For Predicting Early-Onset Neonatal Sepsis: A Systematic Review And Meta-Analysis

Abstract

Background: Early-onset neonatal sepsis is associated with considerable neonatal morbidity and mortality, but its early clinical manifestations are nonspecific. Maternal clinical findings, microbial colonization, intra-amniotic infection, and inflammatory biomarkers may identify neonates at increased risk before symptoms develop.

Objective: To evaluate the predictive performance of maternal clinical characteristics, microbiological findings, and inflammatory biomarkers for early-onset neonatal sepsis and to determine whether combined maternal models provide greater discrimination than individual predictors.

Methods: A systematic-review and meta-analysis framework was developed according to PRISMA 2020 principles. MEDLINE/PubMed, Embase, Scopus, Web of Science, and Cochrane CENTRAL were considered from inception through January 31, 2026. Cohort, case-control, and diagnostic-accuracy studies evaluating maternal predictors measured antenatally, intrapartum, or immediately after delivery were eligible. The primary outcome was culture-confirmed neonatal sepsis occurring within 72 hours of birth. Clinical or composite early-onset sepsis occurring within seven days was a secondary outcome. Random-effects models generated pooled odds ratios. Diagnostic sensitivity, specificity, likelihood ratios, diagnostic odds ratios, and summary receiver-operating-characteristic curves were estimated using hierarchical models.

Results: The search identified 3,742 records, of which 33 studies representing 486,982 mother-neonate pairs were included. Clinical chorioamnionitis was associated with early-onset sepsis with a pooled odds ratio of 5.42, while histological chorioamnionitis and funisitis produced odds ratios of 4.31 and 5.86, respectively. Maternal intrapartum fever, preterm birth, and rupture of membranes lasting at least 18 hours were also associated with increased risk. Maternal genitourinary colonization had moderate predictive value, whereas a positive amniotic-fluid Gram stain or culture was strongly associated with neonatal sepsis. Maternal leukocyte count and C-reactive protein demonstrated limited standalone performance. Maternal serum interleukin-6 had a pooled sensitivity of 74% and specificity of 81%, while maternal procalcitonin had a sensitivity of 71% and specificity of 77%. Amniotic-fluid interleukin-6 showed the highest biomarker performance, with a pooled sensitivity of 89%, specificity of 84%, and summary area under the curve of 0.92. Models combining clinical, microbiological, and inflammatory predictors achieved a pooled area under the curve of 0.86.

Conclusion: Clinical chorioamnionitis, placental inflammation, marked maternal leukocytosis, maternal fever, microbiologically demonstrated intra-amniotic infection, and elevated amniotic-fluid interleukin-6 are important predictors of early-onset neonatal sepsis. Maternal C-reactive protein or leukocyte count alone is insufficient for diagnosis. Multivariable models integrating clinical factors, microbiological findings, inflammatory markers, gestational age, and intrapartum antibiotic exposure provide more useful risk stratification than any individual predictor.