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

Abstract

Background: Placental infections, particularly chorioamnionitis, villitis, and intervillositis, are strongly associated with adverse neonatal outcomes. Histopathological evaluation of placentae offers important insights into the pathophysiological mechanisms underlying neonatal morbidity. However, data remain fragmented across different studies.

Objective: To systematically review and synthesize available evidence on histopathological patterns of placental infections and their correlation with neonatal morbidity.

Methods: We systematically searched PubMed, Scopus, Web of Science, and Embase from inception to July 2025. Eligible studies included observational, case-control, and cohort studies that reported histopathological placental findings in infectious conditions (bacterial, viral, parasitic, or fungal) and neonatal outcomes. Risk of bias was assessed using the Newcastle-Ottawa Scale. A meta-analysis using a random-effects model was performed, and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for associations between specific histopathological lesions and neonatal morbidity.

Results: A total of 42 studies (n=12,874 placentae) met inclusion criteria. The most frequent histopathological lesions were acute chorioamnionitis (48%), villitis of unknown etiology (23%), chronic intervillositis (11%), and funisitis (8%). Acute chorioamnionitis was significantly associated with preterm birth (OR 3.21; 95% CI 2.45–4.12), early-onset sepsis (OR 4.08; 95% CI 3.12–5.34), and neonatal respiratory distress syndrome (OR 2.67; 95% CI 1.89–3.76). Chronic villitis correlated with intrauterine growth restriction (IUGR) (OR 2.94; 95% CI 2.01–4.10) and stillbirth (OR 3.55; 95% CI 2.27–5.56). Intervillositis was linked with recurrent pregnancy loss and neonatal intensive care unit (NICU) admission (OR 2.11; 95% CI 1.32–3.16).

Conclusion: Placental histopathology provides vital prognostic information. Acute inflammatory lesions correlate strongly with preterm-related complications, whereas chronic lesions are more associated with growth restriction and stillbirth. Routine histopathological evaluation of placentae in infectious settings should be considered for risk stratification and guiding neonatal surveillance.