The inhibition of premature labor with indomethacin.

We administered indomethacin orally for the treatment of premature labor in a prospective, randomized, double-blind fashion, and all infants were followed up. Indomethacin was significantly more effective than placebo in inhibition of premature labor during a 24-hour course of therapy, with treatment failure during therapy occurring in only one of 15 indomethacin-treated patients compared to nine of 15 placebo-treated patients (p less than 0.01). Mean plasma concentrations of indomethacin were approximately 0.8 micrograms/ml at both 4 and 12 hours after administration. Mean plasma levels of 15-oxo-13,14-dihydroprostaglandin F2 alpha (PGFM) were similar in the two groups before treatment, decreased markedly in the indomethacin group by 4 hours, and were not detected at 12 hours in all but the one indomethacin-treated patient who was delivered within 24 hours. Patients in the placebo group who were delivered prematurely had higher pretreatment PGFM levels (mean +/- SE, 83 +/- 18 pg/ml, n = 9) than the patients who responded to placebo (25 +/- 6 pg/ml, n = 6) (p less than 0.05). There was no difference between the indomethacin and placebo groups with respect to gestational age at delivery, birth weight, and neonatal morbidity and deaths. In particular, we found no evidence of premature closure of the ductus arteriosus, pulmonary hypertension, or increase in bleeding problems among the infants exposed to indomethacin in utero. Although no difference in neonatal outcome was observed in this small number of patients, it would seem prudent still to consider indomethacin as an experimental therapy.