Intra-Amniotic Infection Is Associated with Severe Histological Fetal Inflammatory Response in Preterm Delivery

Background and Objectives: This study aimed to evaluate whether intra-amniotic infection is associated with severe histological fetal inflammatory response in pregnant women with spontaneous preterm delivery. Materials and Methods: This retrospective study included patients diagnosed with preterm labor, cervical insufficiency, or preterm pre-labor rupture of membranes between 20 and 33 weeks of gestation. Patients underwent amniotic fluid tests via transabdominal amniocentesis to detect intra-amniotic infection (positive amniotic fluid culture in combination with a high IL-6 level and/or a low glucose level and/or a high white blood cell count) between April 2014 and March 2022. Severe histological fetal inflammatory response (≥stage 2 and/or grade 2) was assessed via placental pathology. Multivariate regression analysis was performed to identify risk factors for severe histological fetal inflammatory response. Results: Of the 155 patients, 14.8% (23/155) were diagnosed with intra-amniotic infection. The incidence of severe histological fetal inflammatory response was significantly higher in the intra-amniotic infection group than in the non-intra-amniotic infection group (52.2% vs. 9.1%, p < 0.001). Univariate analysis has revealed that IAI (OR 10.9, 95% CI, 3.97–30), fever (OR 5, 95% CI, 1.25–20.4), and CRP ≥1.24 mg/dL (OR 3.5, 95% CI, 1.4–8.6) were significantly associated with severe histological fetal inflammatory response. Multivariate logistic regression revealed that intra-amniotic infection remained significantly associated with severe fetal inflammatory response even after adjustment for fever and elevated CRP (OR 9.1, 95% CI 2.4–34.2). Conclusions: Intra-amniotic infection in pregnant women with threatened spontaneous preterm delivery was identified as a significant risk factor for severe fetal inflammatory response, which may contribute to adverse neonatal outcomes in preterm infants. Amniotic fluid testing for intra-amniotic infection may aid in predicting fetal inflammatory response antenatally.