Persistent Pulmonary Hypertension of the Newborn

ABSTRACT

Persistent pulmonary hypertension of the newborn (PPHN) is defined as a failure of normal pulmonary vascular relaxation at or shortly after birth, resulting in impedance to pulmonary blood flow which exceeds systemic vascular resistance, such that unoxygenated blood is shunted to the systemic circulation. Perinatal stressors including hypoxia, hypoglycemia, cold stress, sepsis, and direct lung injury alter the course of transition. The initial clinical picture of PPHN is one of dynamic pulmonary vasospasm, with labile flow through the pulmonary circuit and right-to-left shunting of blood across the ductus arteriosus and foramen ovale. The normal postnatal decline in pulmonary vascular tone is absent following exposure to chronic hypoxia. The pathophysiology of neonatal pulmonary hypertension can involve multiple pathways of injury, from altered circulating agonist balance, to endothelial dysfunction, to smooth muscle dysfunction and phenotypic change. The treatment for PPHN has evolved over the past 10 to 15 years but reported mortality remains at 10% to 20% in newborns with PPHN. Extracorporeal membrane oxygenation (ECMO) has been proven of value for this condition, and several "alternative" therapies such as high-frequency ventilation (HFV), surfactant, and inhaled NO (iNO) have been used in a rescue mode.