Lack of effect of antenatal indomethacin on fetal cerebral blood flow

OBJECTIVE: Our purpose was to investigate fetal cerebral blood flow and the incidence of intraventricular hemorrhage in patients undergoing tocolysis with either indomethacin or magnesium sulfate at <30 weeks' gestation. STUDY DESIGN: Consenting patients at <30 weeks' gestation with preterm labor were randomized to receive indomethacin or magnesium sulfate tocolysis. Magnesium sulfate was administered intravenously with an 8 gm loading dose given over the first hour, 4 gm over the second hour, and then a maintenance infusion of 2.5 gm per hour. The infusion was continued for approximately 12 hours after the cessation of uterine contractions. Patients randomized to receive indomethacin were given an initial dose of 50 to 100 mg orally or per rectum, followed by 25 to 50 mg orally every 4 to 6 hours for 24 to 48 hours. Oral tocolytic agents were not used after successful tocolysis. Betamethasone was administered to all patients. Patients underwent fetal cerebral Doppler studies during tocolytic therapy and at least 24 hours after completion of the treatment. RESULTS: Twelve patients were randomized to receive indomethacin and twelve patients were randomized to receive magnesium sulfate. Twenty-one fetuses underwent cerebral Doppler studies in triplicate during and after therapy. The mean gestational age at tocolysis was 27.5 ± 1.9 weeks for the indomethacin group and 26.4 ± 1.6 weeks for the magnesium sulfate group (p = 0.14). The middle cerebral artery resistance index for fetuses during indomethacin treatment was 0.73 ± 0.09, whereas the resistance index after therapy was 0.75 ± 0.05 (p = 0.49). The resistance index during magnesium sulfate tocolysis was 0.79 ± 0.04 and after therapy it was 0.76 ± 0.04 (p = 0.18). There was no significant difference in the resistance index between the groups on or off therapy. In addition, the incidence of intraventricular hemorrhage was similar in both groups. CONCLUSION: These results suggest that indomethacin does not significantly affect fetal cerebral blood flow. If antenatal indomethacin in the preterm fetus increases the risk of intraventricular hemorrhage, it would appear to be by another mechanism.