The structural basis of persistent pulmonary hypertension of the newborn infant

Six neonates of 35 to 42 weeks' gestation had findings of persistent pulmonary hypertension and died between one and 6 days of age despite intensive medical therapy. Each patient had pulmonary artery pressure near or above systemic level, with a right-to-left shunt via the foramen ovale and/or ductus arteriosus. At postmortem, morphometric analysis of the peripheral pulmonary vascular bed revealed extension of muscle into small arteries, which was severe in five of six patients; all alveolar duct and wall arteries (less than 30 micrometers external diameter), normally nonmuscular, were fully muscularized. In these five patients medial wall thickness of the normally muscular intra-acinar arteries was doubled; arterial size and number, however, were normal in all. This striking structural maldevelopment of the peripheral pulmonary arterial bed occurred or was initiated in utero and does not merely represent a failure of the fetal pattern to regress. We suggest that this particular group of patients remained refractory to all current modes of therapy because of these severe structural pulmonary vascular changes.