Deciphering epigenetic control of Notch signaling in persistent pulmonary hypertension of the newborn

The pulmonary vasculature undergoes a remarkable transition at birth. In utero, gas exchange occurs at the placenta, and the pulmonary vascular bed remains constricted to direct oxygenated blood from the placenta to the fetal brain. Upon taking their first breaths, a newborn’s pulmonary resistance drops, allowing blood to rapidly flow to the lungs for gas exchange. Persistent pulmonary hypertension of the newborn (PPHN) is marked by sustained high pulmonary vascular resistance, often triggered by perinatal stress. 1 PPHN causes deoxygenated blood to bypass the lungs via the patent ductus arteriosus and foramen ovale, leading to severe hypoxia and tissue ischemia. PPHN affects 0.4 to 6.8 per 1000 live births, 1 with mortality rates of 7.6–10.7% and 25% of survivors experience neurodevelopmental impairment. 1 Treatment is primarily supportive, including oxygen, mechanical ventilation, nitric oxide, and extracorporeal membrane oxygenation. 1 Understanding the underlying mechanism of PPHN is key to developing new therapies.