Cyclo-oxygenase (COX) inhibitors for preventing labour before full-term pregnancy

Labour before full term in pregnancy can lead to preterm birth of the baby. Preterm labour describes frequent uterine contractions (at least four in 20 minutes or eight in 60 minutes) and progressive changes in the cervix. If preterm labour is not managed properly, active labour can occur and result in preterm birth, before 37 completed weeks' gestation. Preterm birth is the leading cause of low birthweight, illness and death for newborn babies. Substances called prostaglandins play an important role in the contraction of the muscle of the womb and are important during labour and birth. They are produced by cyclo-oxygenase (COX), which is an enzyme that increases the level of prostaglandins. Giving COX inhibitors to pregnant women at risk of preterm labour might stop contraction of the womb and allow them to reach full term. We included one small randomised trial (involving 98 women) that involved the drug rofecoxib, which is one type of COX inhibitor. The included study did not report any information about prevention of labour before full-term pregnancy. However, use of this COX inhibitor was associated with an increased risk of the baby being born before full term. We found insufficient data to make any recommendation about using COX inhibitors for preventing preterm labour. Future research should include the follow-up of babies to examine the short- and longer-term effects associated with using COX inhibitors during pregnancy.

Authors' conclusions: 

There was very little evidence about using COX inhibitors for preventing preterm labour. There are inadequate data to make any recommendation about using COX inhibitor in practice to prevent preterm labour. Future research should include follow-up of the babies to examine the short-term and long-term effects of COX inhibitors.

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Background: 

Preventing preterm labour is the most important step in preventing preterm birth. Prostaglandins play an important role in labour and birth. Prostaglandin production can be obstructed by inhibition of the cyclo-oxygenase (COX) enzyme and this may arrest uterine contraction. A Cochrane review on COX inhibitors for the treatment of preterm labour found insufficient data to draw conclusions about its effectiveness.

Objectives: 

To assess the effectiveness and safety of COX inhibitors for preventing preterm labour in high-risk women.

Search strategy: 

We searched the Cochrane Pregnancy and Childbirth Group's Trial Register (30 June 2012).

Selection criteria: 

All published and unpublished randomised trials evaluating administration of any COX inhibitor for prevention of preterm labour in pregnant women at gestational age less than 36 weeks at risk of, but not experiencing, preterm labour. Cluster-randomised trials were eligible for inclusion. Quasi-randomised trials and studies with cross-over designs were excluded.

Data collection and analysis: 

Two review authors (T Khanprakob and U Sangkomkamhang) independently assessed all potential studies for inclusion. Disagreement was resolved by discussion and, where necessary, by consultation with a third review author. Two review authors independently assessed trial quality and extracted data. Data were checked for accuracy.

Main results: 

We included one randomised trial (involving 98 women) that evaluated the effectiveness of one type of COX inhibitor (rofecoxib) for preventing preterm birth. The included study did not report any data for one of our primary outcomes: preterm labour. Rofecoxib use was associated with an increased risk for preterm birth and preterm premature rupture of membranes (PPROM). Rofecoxib was associated with a higher risk of oligohydramnios and low fetal urine production but the effects were reversible after stopping treatment. There were no differences in the number of women who discontinued treatment before 32 weeks of gestation. There was no difference in neonatal morbidities and admission to neonatal intensive care unit. There were no maternal adverse effects or perinatal mortalities in either group.

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