Histologic Chorioamnionitis and Neonatal Outcomes in Preterm Infants: A Gestational Age- and Birth Weight-Matched Cohort Study

Abstract Background Histologic chorioamnionitis (HCA) is frequently implicated in adverse neonatal outcomes, but most evidence derives from unmatched comparisons in which gestational age (GA) — the dominant determinant of prematurity-related morbidity — acts as a powerful confounder. We evaluated neonatal outcomes of HCA-exposed preterm infants in a cohort matched for GA and birth weight (BW). Methods In this single-center retrospective matched cohort study (January 2018–December 2024), 83 preterm infants with histologically confirmed HCA were compared with 88 non-HCA controls matched for GA and BW. Short-term outcomes (intraventricular hemorrhage [IVH], bronchopulmonary dysplasia [BPD], respiratory distress syndrome [RDS], clinical sepsis, necrotizing enterocolitis [NEC], retinopathy of prematurity [ROP], and mortality), respiratory support trajectories, and serial maternal and neonatal inflammatory markers were compared. Adjusted odds ratios (aORs) were estimated by logistic regression controlling for GA and BW. Results Groups were well matched (GA 32.6 ± 2.7 vs 32.5 ± 2.6 weeks, P = 0.708; BW 1847 ± 660 vs 1805 ± 623 g, P = 0.714). The HCA group had higher rates of premature rupture of membranes (59.0% vs 20.5%, P < 0.001), vaginal delivery (45.8% vs 13.6%, P < 0.001), and antenatal antibiotic exposure (42.2% vs 22.7%, P = 0.009), confirming exposure validity. After adjustment, HCA was not associated with clinical sepsis, RDS, NEC, ROP, BPD of any grade or moderate-to-severe BPD, pulmonary surfactant use, duration of respiratory support, length of stay, or mortality. Unexpectedly, HCA was inversely associated with IVH of any grade (23.0% vs 42.1%; aOR 0.38, 95% CI 0.17–0.83, P = 0.015); the association strengthened in an extended model additionally adjusting for delivery mode, antenatal corticosteroids, and fetal distress (aOR 0.28, 95% CI 0.11–0.71, P = 0.007), and was confined to infants born at ≥ 32 weeks (6.7% vs 31.8%; OR 0.15, 95% CI 0.04–0.58, P = 0.003). All IVH in the HCA group was grade I–II. Maternal pre-delivery leukocytosis and neutrophilia, and neonatal day-0 leukocyte and neutrophil responses, were significantly more pronounced in the HCA group, whereas C-reactive protein did not differ at any time point. Conclusions In a GA- and BW-matched preterm cohort, HCA exposure produced a measurable maternal–neonatal inflammatory response without worsening conventional short-term outcomes, and was associated with a substantially lower risk of IVH, particularly among infants born at ≥ 32 weeks. The relationship between intrauterine inflammation and neonatal brain injury warrants re-examination in prospective cohorts with histologic staging.