New Therapeutic Targets in Neonatal Pulmonary Hypertension

Persistent pulmonary hypertension of the newborn (PPHN) is a significant cause of morbidity and mortality in neonates. Despite advances in medical care, mortality remains high. In the United States, inhaled nitric oxide is the gold standard treatment in patients with PPHN. However, while it decreases the need for extracorporeal membrane oxygenation, many patients do not respond to inhaled nitric oxide, and it does not improve overall mortality in those with PPHN. Furthermore, its use is cost-prohibitive in many parts of the world. Thus, there is a critical need to research alternative therapies to improve neonatal outcomes. In this review, we present the animal and human data of some emerging therapeutic targets for pulmonary hypertension, prioritizing pediatric and neonatal data when available. Specifically, we discuss the role of soluble guanylate cyclase stimulators and activators, prostacyclin and analogues, phosphodiesterase 3, 4, and 5 inhibitors, rho-kinase inhibitors, endothelin receptor blockers, PPAR agonists, and antioxidants in the treatment of neonates with PPHN.