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.