The Antenatal and Postnatal Consequences of Antenatal Exposure to Prolonged Low Dose Indomethacin

Despite its many clinical applications, indomethacin is seldom used in pregnancy, principally because of concerns regarding the potential for constriction of the arterial duct. The aim of this study was to document adverse antenatal effects and postnatal outcomes after in utero exposure to low-dose indomethacin. We studied a retrospective cohort of pregnancies between 2005 and 2016 at the John Radcliffe Hospital, Oxford, UK, in which mothers at extremely high risk of preterm birth were treated as prophylaxis with indomethacin 25 mg, 12 hourly, before 29 weeks. Antenatal effects on the arterial duct and postnatal outcomes were analysed. Overall, 198 fetuses had in utero follow-up, and 13 (6.6%) had ductal constriction, all within 9 days of starting treatment. No ductal constriction was seen in pregnancies when therapy was started before 20 weeks, and all effects were reversed after cessation of therapy. An analysis of postnatal complications was possible in 181 neonates. There were eight (4.4%) neonatal deaths, all but one associated with extreme preterm birth. Seven (5%) patent ductus arteriosus cases occurred in the 140 neonates delivered after 28 weeks who were alive at discharge. Postnatal complications were not more common in neonates in whom antenatal ductal constriction had been demonstrated. In conclusion, fetuses exposed to prolonged low dose indomethacin have a low incidence of in utero complications; these complications can be diagnosed with ultrasound and are reversible. Adverse postnatal events are related to gestation at birth and do not appear more common.