Reversible Ductus Arteriosus Constriction due to Maternal Indomethacin after Fetal Intervention for Hypoplastic Left Heart Syndrome with Intact/Restrictive Atrial Septum

Department of Cardiology, Children's Hospital Boston, and Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Fetal Diagnosis and Therapy (Impact Factor: 2.94). 12/2009; 27(1):40-5. DOI: 10.1159/000268290
Source: PubMed


Fetal cardiac intervention (FCI) has been performed at our center in selected fetuses with complex congenital heart disease since 2000. Most interventions are performed in fetuses with a ductus arteriosus (DA)-dependent circulation. Indomethacin promotes closure of the DA in newborns and in fetal life, a potentially life threatening complication in fetuses with ductus-dependent congenital heart disease.
We reviewed our experience with FCI with a focus on the frequency, features, and clinical course of ductal constriction. Fetuses undergoing FCI receive comprehensive pre- and postoperative cardiac and cerebral ultrasound evaluation, approximately 24 hours before and after the procedure, including imaging of DA flow and Doppler assessment of the umbilical artery and vein, ductus venosus, and, since 2004, the middle cerebral artery.
Among 113 fetuses that underwent FCI, 24 of which were older than 28 0/7 weeks gestation, 2 were found to have DA constriction due to indomethacin therapy within 24 hours of intervention. Both of these were 30-week fetuses with hypoplastic left heart syndrome and restrictive or intact atrial septum. The DA was stenotic by spectral and color Doppler, and middle cerebral and umbilical artery pulsatility indexes were depressed. After discontinuation of indomethacin, the Doppler indices improved or normalized.
Close echocardiographic monitoring of fetal Doppler flow velocities is very important after fetal intervention and indomethacin treatment, as the consequences of DA constriction in a fetus with hypoplastic left heart syndrome are potentially lethal. Sonographic evaluation should include measurement of cerebral and umbilical arterial flow velocities as well as color and spectral Doppler interrogation of the DA.

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    • "Indomethacin is the drug with prostaglandin inhibiting action most widely reported in the literature. Its inhibitory effect on cyclo-oxygenase is reversible, persisting until the drug is excreted (Gordon and Samuels, 1995; Vogel et al., 2010). The drug passage through the placentary barrier occurs freely during the second half of pregnancy, being minimal in early gestation (Moise et al., 1990). "
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