Stephanie M. Tsoi, Cynthia Gasper, Emin Maltepe, Megan A. Chidboy, Nida Ozarslan, Christine A. Blauvelt, Sirirak Buarpung, Shannon Cheung, Martina Steurer, Roberta L. Keller, Jeffrey R. Fineman, Stephanie L. Gaw
University of California San Francisco.
United States
Placenta
Placenta 2026; 182: 341-347
DOI: 10.1016/j.placenta.2026.06.024
Abstract
Objectives: The primary objective was to elucidate whether placental histopathology representative of intrauterine insults during pulmonary vascular development are associated with a diagnosis of persistent pulmonary hypertension of the newborn (PPHN). The secondary objective was to compare placental histopathologic lesions across PPHN etiologies.
Study design: We conducted a case-control study of mother-infant dyads ≥35 weeks gestation who delivered at a tertiary care center between 2020 and 2025. Cases were infants diagnosed with PPHN and treated with inhaled nitric oxide; unaffected controls were infants without congenital anomalies. Placentas underwent blinded histopathologic review using standardized criteria. Multivariate logistic regression modeling was used to control for confounding maternal and infant factors.
Results: 106 placentas were analyzed (53 PPHN, 53 controls). Placental lesions were significantly more common in PPHN placentas, including fetal vascular malperfusion (30.2% vs 9.4%, p < 0.01), placental inflammation (66.0% vs 37.7%, p < 0.01), chronic presence of meconium (43.4% vs 15.2%, p < 0.01), and chorangiosis (7.6% vs 0%, p = 0.04). In adjusted analyses compared to controls, among 41 placentas with fetal development etiologies (e.g. congenital anomalies) of PPHN, fetal vascular malperfusion, placental inflammation and fetal inflammatory response were more common. Among 12 placentas with typical causes of PPHN (e.g. meconium aspiration syndrome), placental inflammation, maternal and fetal inflammatory responses, and meconium were more common.
Conclusions: PPHN placentas demonstrate lesions of malperfusion, inflammation, and chronic meconium, suggesting a complex interplay between intrauterine hypoxia and inflammation as a potential mechanism for the abnormal pulmonary vascular development and function seen in PPHN.
Category
Class I. Persistent Pulmonary Hypertension of the Newborn
Acquired Patient Factors Associated with Pulmonary Vascular Disease
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes