Use of progesterone for treating preterm labour

Premature birth is associated with various medical problems for the newborn including death and long-term health problems. The parents of premature babies can experience emotional turmoil and the economic costs are high for healthcare systems. Various medications have been used to delay the onset of labour and prevent premature deliveries but with limited success. Some of the drugs have side-effects. Progesterone is a hormone that is known to suppress uterine activity and keep the uterus quiescent until term. Medications that mimic this hormone (progestational agents) were first tried in the late 1950s but interest waned. Recently, new trials studying the use of progestational agents both for prevention as well as treatment of preterm labour have been published. This review of the literature found eight randomised controlled trials involving 563 women, but data from only seven studies from a total of 538 women with threatened or established preterm labour with intact membranes contributed data to this updated review. Four trials compared the use of progestational agents versus placebo in women concurrently treated with another drug to reduce uterine contractions (tocolytic agent). Progesterone was used independently in the other four trials compared with another tocolytic agent or placebo. Limited evidence suggests that the use of a progesterone, as a co-treatment, may reduce preterm deliveries at less than 37 weeks' gestation and increase birthweight. There is insufficient evidence from the seven small studies with contributing data to advocate progestational agents as a tocolytic agent for women presenting with preterm labour.

Authors' conclusions: 

There is insufficient evidence to advocate progestational agents as a tocolytic for women presenting with preterm labour.

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Background: 

Prematurity is not only the leading cause of perinatal morbidity and mortality but is associated with long-term impairment. Studies of various tocolytic agents have shown mixed results with little effect in improving pregnancy duration and insufficient data to confirm a definite beneficial effect on neonatal morbidity or mortality. Progesterone is known to have an inhibitory effect on uterine contractility and is thought to play a key role in the maintenance of pregnancy until term.

Objectives: 

To determine if the use of progestational agents is effective as a form of treatment or co-treatment for women with threatened or established preterm labour with intact membranes.

Search strategy: 

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2013), CENTRAL (The Cochrane Library 2013, Issue 10), MEDLINE (1966 to August 31 2013) and Embase (1974 to 31 August 2013). We checked the reference lists of all included studies to identify any additional studies and communicated with authors and the pharmaceutical industry.

Selection criteria: 

Randomised controlled trials that compared progestational agents, given either alone or in combination with other tocolytics, with a control group receiving another tocolytic, placebo or no treatment, for the treatment of preterm labour.

Data collection and analysis: 

Two review authors independently extracted data and assessed trial quality.

Main results: 

Eight studies were included in this review, involving 563 women, but only seven studies, involving 538 women, contributed data for analyses. There are some data suggesting that the use of progestational agents results in a reduction of preterm deliveries at less than 37 weeks of gestation and an increase in birthweight. The use of a progestational agent may also reduce the frequency of uterine contractions, prolong pregnancy and attenuate the shortening of cervical length. However, the analysis was limited by the relatively small number of available studies. The power of the meta-analysis was also limited by the varying types, dosages and routes of administration of progesterone.