Effects of Prostaglandins and Inhibitors of Prostaglandin Synthesis in the Fetus and Newborn Infant
Journal of Perinatal Medicine
Fetal tissues, including the placenta, have been shown to contain significant amounts of prostaglandins (PG) and also to have the capacity to synthesize PG. Furthermore, PGE 2 and F2 have been demonstrated in fetal blood, but circulating levels drop rapidly after birth. PGEi infusion into fetal lambs produced a marked increase in blood flow to the lungs, myocardium, adrenal gland, and musculo-skeletal System. However, the studies do not indicate the role of PCs in normal regulation of
... y function in the fetal lamb in utero. Administration of drugs that inhibit synthesis of PCs provides the opportunity to assess their role. Inhibition of PG synthesis in fetal lambs in utero produced a small increase in conibined ventricular Output ,and in umbilical-placental blood flow, a marked increase in myocardial and adrenal flows, and a small rise in pulmonary flow. Blood flow to the peripheral and gastrointestinal circulations were reduced. PCs thus do not have a significant role in regulating blood flow to the placenta or the lungs in the normal fetus but may exert a mild peripheral vasodilator effect. Evidence is increasing that PCs have an important role in maintaining dilatation of the ductus arteriosus during fetal life. PGEi and PGE 2 produced striking relaxation of isolated Strips of ductus arteriosus obtained from fetal lambs. We found that acetylsalicylic acid, indomethacin, or naproxen resulted in constriction of the ductus, with a rise in pulmonary arterial pressure in fetal lambs in utero (2) . It is not known whether the ductus is influenced by locally-produced PCs alone or also by circulating PCs. The ductus arteriosus produces PGE2 and PGF 2a in small amounts, but the main PG found was 6-keto-PGFia, a metabolic product of the more active precursor, prostacyclin or PGI 2 . However, PGE 2 has a much greater dilator action on the lamb ductus arteriosus than does PGI 2 , on a molar concentration basis (1). The relative roles of oxygen and of removal of the PG relaxation effect, in constriction of the ductus arteriosus after birth, have not been resolved. Since circulating PG levels fall rapidly after birth, removal of their effect on the ductus may be important in postnatal ductus closure. The dilator effect of PGEi and E 2 on the ductus arteriosus has been used to treat infants with congenital heart disease in whom the ductus is important in maintaining pulmonary or systemic blood flow. In infants with lesions that obstruct right ventricular out flow, pulmonary blood flow after birth is dependent on flow from the aorta through the ductus arteriosus. In infants with pulmonary atresia, while the ductus is open, pulmonary flow is adequate and there is mild hypoxia. Constriction of the ductus decreases pulmonary flow and results in severe hypoxia. PGEi has been infused at rates of 0.05 -0.1 micrograms/kg per minute in these infants with dramatic improvement in P0 2 (3). Infants with Interruption of the aortic arch are dependent on the ductus arteriosus to provide blood flow from the pulmonary artery to the descending aorta. When the ductus constricts, blood flow and arterial pressure in the descending aorta decrease. Infusion of PGEi may result in a marked increase in descending aortic pressure and decrease of the pressure gradient across the ductus arteriosus in these infants.