Introduction Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of infancy, and BPD-associated pulmonary hypertension (PH) is a serious complication that can negatively impact later childhood health. There is growing evidence that lung injury leading to BPD and PH is due to chronic fetal hypoxia-ischemia. The purpose of this study was to investigate whether placental pathologic changes of maternal vascular underperfusion (MVU) are associated with BPD, and further increased with PH. Methods We conducted a 5-year retrospective cohort study of premature infants born ≤28 weeks. BPD was defined as persistent oxygen requirement at 36 weeks corrected gestational age. PH was identified using a standardized algorithm of echocardiogram review. Archived placental slides underwent standardized masked histopathologic review. Logistic regression modeling was performed, taking into account important maternal and infant covariates. Results Among 283 births, 121 had MVU, of which 67 (55%) developed BPD, and 24 (20%) had PH. Among the common neonatal complications of extreme prematurity, BPD was the only outcome that was increased with MVU (P<0.001). After adjustment for birth weight, fetal growth restriction, preeclampsia and other factors, infants with MVU were more likely to develop BPD (adjusted odds ratio=2.6; 95% confidence interval=1.4, 4.8). Certain MVU sublesions (fibrinoid necrosis/acute atherosis and distal villous hypoplasia/small terminal villi) were increased with PH (P<0.001). Discussion Placental MVU may identify BPD infants who were exposed to intrauterine hypoxia-ischemia, which increases their risk for development of PH disease. Conclusions Our findings have important implications for providing earlier and more effective therapies for BPD.

MAP is highly associated with evidence of intraparenchymal placental hemorrhage villous changes of MVU, and a lymphoplasmacytic infiltrate at the implantation site. The contribution of this basal chronic inflammatory infiltrate to MAP requires further investigation.

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