Persistent pulmonary hypertension in the newborn

When first described in cyanotic newborns presenting as congenital heart disease, persistent pulmonary hypertension in the newborn (PPHN) was considered to be an idiopathic failure by the pulmonary circulation to relax its high fetal resistance.' The expression was soon extended to cover severe hypoxic illness in term babies shortly after birth, and acquired substantial literature as a syndrome with poorly defined limits and pathological correlations. Thus aspects of causation or clinical features received differing emphasis from one publication to another. Spontaneous recovery in oxygen was not unknown but respiratory failure often dictated ventilator support. A prevailing rationale in management, stemming from the original notion of persistent fetal circulation, aims to promote vessel relaxation by oxygenation, correction of acidosis and vasodilator drugs. Mortality, however, has remained high in many reports. A prenatal origin, suggested by the frequency of pregnancy complications,2 might cast the condition in a different light. Some experimental and human observations seemed to point in the same direction. Medial thickening of small arteries in newborn rats after chronic maternal hypoxia was described soon after the first account and also an apparent human example has been rep~r ted .~ Similar changes followed pulmonary hypertension produced in fetal lambs by elevation of systemic pressure (from renal artery or umbilical cord con~triction)~ or by closure of the fetal ductus by a prostaglandin synthetase inhibitor; the latter association was also observed in two babies who died from PPHN.5 Constriction of the umbilical cord caused fetal hypoxaemia and, after birth, pulmonary hyperlension but no right to left shunt or hypoxaemia; fetal pulmonary and systemic pressures were not measured and postnatal histology was not reported.6 Although not developed systematically, the implication of these reports is to be found in classifications of disorders leading to elevated pulmonary vascular resistance (PVR) which include 'pulmonary vasoconstriction with or without increased smooth muscle' and 'increased pulmonary vascular smooth muscle from chronic hypoxia or prenatal pulmonary hyperten~ion'.'.~ However, none of the histological observations cited met the critical test of landmarking a vessel by the companion airway, which required that when muscle mass appears to be increased, vessels of the same level should be compared in order to distinguish hypertrophy or hyperplasia from mere contra~tion.~ Pursuing the possibility of antenatal pathogenesis, Reid et a/. exposed guinea-pig mothers to chronic hypoxia but found