Persistent pulmonary hypertension of the newborn (PPHN) results from disrupted fetal–neonatal circulatory transition, characterized by elevated pulmonary vascular resistance (PVR), right-to-left shunting, and refractory hypoxemia. Despite improved perinatal care, PPHN remains a major source of neonatal morbidity and mortality. This review details PPHN phenotypes, pathophysiology, etiology, diagnostics including echocardiography and biomarkers like B-type Natriuretic Peptide (BNP) or N-terminal pro-B-type Natriuretic Peptide (NT-proBNP), and current therapeutic modalities, from lung recruitment and surfactant to targeted vasodilator therapy (iNO, sildenafil, milrinone, bosentan) and extracorporeal membrane oxygenation (ECMO). We emphasize the role of endothelial and molecular mechanisms in precision therapy and outline guidelines for clinical decision-making in diverse care settings.

Bronchopulmonary dysplasia (BPD) remains a major long-term morbidity among preterm infants. As lung-protective strategies advance and survival of extremely premature neonates improves, BPD has evolved from a ventilator-induced inflammatory and fibrotic process to a disease marked by arrested pulmonary vascular and alveolar development—pulmonary vascular disease. Within this evolving phenotype, pulmonary hypertension (PH) has emerged as a critical yet underrecognized complication. BPD-associated pulmonary hypertension (BPD-PH) is increasingly linked to higher mortality and worse clinical outcomes, but its pathophysiology, screening strategies to detect early changes, and optimal management remain incompletely understood. This review delineates the pathophysiology of BPD-PH, linking impaired pulmonary vascular development with subsequent maladaptation influenced by genetic, prenatal, and postnatal factors. The phenotypic and hemodynamic spectrum of BPD-PH is further subclassified using echocardiographic markers to support a physiology-based approach to diagnosis and management. We also propose a pragmatic algorithm for screening, evaluation, and longitudinal follow-up. Collectively, this review highlights the need for physiology-driven strategies and clinical studies to improve outcomes in these neonates.