Correlation of Placental Histopathological Patterns in Infections with Neonatal Morbidity: A Systematic Review and Meta-Analysis

Abstract

Background: Placental histopathology provides insights into intrauterine infection and inflammation. The relationship between specific placental lesions and neonatal morbidity, however, remains variably reported.

Objective: To systematically review and quantitatively synthesize the association between histopathological patterns of infectious placental inflammation and neonatal morbidity outcomes.

Data sources: MEDLINE, Embase, Web of Science, Scopus, Cochrane CENTRAL, and Google Scholar (first 200 results), from inception to March 2025.

Eligibility criteria: Observational studies and trials reporting infectious placental histopathology and at least one neonatal outcome.

Review methods: Independent screening, extraction, and risk of bias assessment by two reviewers. Random-effects meta-analyses with Hartung–Knapp adjustment. Certainty of evidence assessed with GRADE.

Results: Twenty-eight studies comprising 18,452 neonates were included. Funisitis/fetal inflammatory response (FIR) was significantly associated with early-onset sepsis (EOS) (OR 2.15, 95% CI 1.72–2.69; I² = 38%). Histologic chorioamnionitis (maternal inflammatory response, MIR) showed a weaker, non-significant association with composite morbidity (OR 1.12, 95% CI 0.94–1.34; I² = 41%). FIR was linked to higher odds of respiratory support ≥24 h (OR 1.86, 95% CI 1.42–2.44; I² = 29%) and intraventricular hemorrhage grade ≥III (OR 1.59, 95% CI 1.11–2.27). Mortality was also increased with necrotizing funisitis (OR 2.41, 95% CI 1.54–3.78). Funnel plots showed minimal asymmetry, suggesting limited publication bias.

Conclusions: Infectious placental inflammation, particularly FIR/funisitis, correlates strongly with neonatal morbidity. Standardized pathology reporting and well-designed prospective studies are needed.