The effects of nonsteroidal antiinflammatory compounds on fetal circulation and pulmonary function

Nonsteroidal antiinflammatory compounds that act by inhibiting synthesis of prostaglandins from arachidonic acid have been shown to have various and sometimes profound effects on fetal and neonatal circulation. Agents such as acetylsalicylic acid, indomethacin, and naproxen pass readily across the placenta and have been shown to cause severe constriction and, in some cases, closure of the ductus arteriosus, resulting in an increase in pulmonary blood pressure and a significant pressure gradient between the pulmonary artery and the aorta of the fetus. Inhibitors of prostaglandin synthesis produce only a mild increase in systemic vascular resistance under normal conditions, but have been observed to potentiate vasoconstriction under conditions of hypoxia. Umbilical-placental and myocardial blood flow was increased by these agents. Although single doses of these agents do not appear to affect fetal pulmonary vessels, prolonged pulmonary arterial hypertension resulting from chronic administration may stimulate an increased development of medial smooth muscle in fetal precapillary vessels, resulting in persistent pulmonary hypertension in the newborn. Inhibitors of prostaglandin synthesis have also been shown to produce a marked increase in fetal respiration, resulting in an increased oxygen requirement.