Cyclo-oxygenase (COX) inhibitors for treating preterm labour

Abstract

Background: Preterm birth is a major cause of perinatal mortality and morbidity. Cyclo-oxygenase (COX) inhibitors inhibit uterine contractions, are easily administered and have fewer maternal side-effects compared to conventional tocolytics. However, adverse effects have been reported on the fetus and newborn as a result of exposure to COX inhibitors.

Objectives: To assess the effects on maternal, fetal and neonatal outcomes of COX inhibitors administered as a tocolytic agent to women in preterm labour when compared with (i) placebo or no intervention and (ii) other tocolytics. In addition, to compare the effects of non-selective COX inhibitors with COX-2 selective inhibitors.

Search strategy: We searched the Cochrane Pregnancy and Childbirth Group's trials register (August 2004). We also contacted recognised experts and cross referenced relevant material.

Selection criteria: All published and unpublished randomised trials in which COX inhibitors were used for tocolysis for women in labour between 20 and 36 completed weeks' gestation.

Data collection and analysis: Three authors independently evaluated methodological quality and extracted data. We sought additional information from trial authors.

Main results: This review includes outcome data from 13 trials with a total of 713 women. The non-selective COX inhibitor, indomethacin was used in 10 trials. When compared with placebo, COX inhibition (indomethacin only) resulted in a reduction in birth before 37 weeks' gestation (relative risk (RR) 0.21; one trial, 36 women), an increase in gestational age (weighted mean difference (WMD) 3.53 weeks) and birthweight (WMD 716.34 gm; two trials, 67 women). Compared to any other tocolytic, COX inhibition resulted in a reduction in birth before 37 weeks' gestation (RR 0.53; three trials, 168 women) and a reduction in maternal drug reaction requiring cessation of treatment (RR 0.07; five trials and 355 women). A comparison of non-selective COX inhibitors versus any COX-2 inhibitor (two trials, 54 women) did not demonstrate any differences in maternal or neonatal outcomes. Due to small numbers, all estimates of effect are imprecise and need to be interpreted with caution. Potential adverse effects of COX inhibition on the fetus, newborn or mother could not be adequately assessed due to insufficient data.

Authors' conclusions: There is insufficient information on which to base decisions about the role of COX inhibition for women in preterm labour. Further well designed trials are needed.