Background Persistent pulmonary hypertension of the newborn (PPHN) is a cause of neonatal hypoxic respiratory failure due to the failed transition of the pulmonary vasculature after birth. Mechanisms of disease are unknown, but we hypothesize they are directly related to insults in the intrauterine environment. The objective was to describe and compare placentas of PPHN infants to understand significant preceding factors from the maternal-fetal environment.

Methods We conducted a case-control study of mother–infant dyads ≥35 weeks gestation who delivered at a tertiary care center between 2020–2025. Cases were infants diagnosed with PPHN and treated with inhaled nitric oxide; controls were infants without congenital anomalies. Placentas underwent blinded histopathologic review using standardized criteria.

Results 106 placentas were analyzed (53 PPHN, 53 controls). Placental lesions were significantly more common in PPHN, including maternal vascular malperfusion (30.2% vs 9.4%, p<0.01), fetal vascular malperfusion (34.0% vs 17.0%, p=0.05), placental inflammation (66.0% vs 37.7%, p<0.01), meconium (43.4% vs 15.2%, p<0.01), and chorangiosis (7.6% vs 0%, p=0.04).

Conclusion PPHN placentas demonstrate lesions of malperfusion, inflammation, and chronic meconium exposure, suggesting a complex interplay between intrauterine hypoxia and inflammation as a mechanism for the abnormal pulmonary vascular reactivity see in PPHN.

The authors have declared no competing interest.

This study was funded by T32HL160508-01A1 [SMT]

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IRB of University of California, San Francisco gave ethical approval for this work.

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