Predictive value of maternal serum occludin for neonatal respiratory distress syndrome in spontaneous preterm birth

Abstract Objective This study investigates maternal serum occludin and human leukocyte antigen G (HLA‐G) profiles across preterm birth subtypes and their predictive value for neonatal respiratory distress syndrome (NRDS). Methods This retrospective analysis was conducted at Tianjin Central Hospital of Gynecology Obstetrics in Tianjin, China. The study utilized a prospectively collected cohort of 133 singleton preterm births, including iatrogenic preterm birth (iPB, n = 22), spontaneous preterm labor with intact membranes (sPTL, n = 61), and preterm premature rupture of membranes (pPROM, n = 50). Maternal serum levels of occludin and HLA‐G were measured via ELISA assays. Subtype‐specific predictive performance for NRDS was assessed using receiver operating characteristic curve analysis based on logistic regression analysis. Results Maternal serum occludin concentrations exhibited distinct subtype‐specific distributions: the highest levels in the iPB group, intermediate levels in the pPROM group, and lowest levels in the sPTL group (overall P < 0.001), which remained significant after adjusting for gestational age at delivery. HLA‐G levels were markedly lower in the pPROM and sPTL groups compared to the iPB group ( P < 0.01). Notably, within the sPTL cohort, pregnancies complicated by NRDS exhibited not only a reduced gestational age ( P < 0.001) but also a paradoxical elevation in maternal occludin levels ( P = 0.019). A combined model incorporating occludin and gestational age at delivery demonstrated excellent discriminatory power for predicting NRDS specifically within the sPTL subtype (area under the curve = 0.829, 95% confidence interval: 0.714–0.943). Conclusion Preterm birth subtypes manifest substantial pathophysiological heterogeneity along the “barrier‐immune” axis. Specifically in sPTL, the combination of maternal occludin levels with gestational age might serve as a potential noninvasive adjunctive biomarker for NRDS risk stratification, although its predictive value requires further validation in larger prospective cohorts.