Prenatal administration of progesterone for preventing preterm birth.

Background: Preterm birth is the major complication of pregnancy associated with perinatal mortality and morbidity and occurs in up to 6% to 10% of all births. Administration of progesterone for the prevention of preterm labour has been advocated.

Objectives: To assess the benefits and harms of progesterone administration during pregnancy in the prevention of preterm birth.

Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group's Specialised Register of Controlled Trials (March 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2004), MEDLINE (1965 to January 2005), EMBASE (1988 to August 2004), and Current Contents (1997 to August 2004).

Selection Criteria: All published and unpublished randomised controlled trials, in which progesterone was given by any route for preventing preterm birth.

Data Collection and Analysis: Standard methods of the Cochrane Collaboration and the Cochrane Pregnancy and Childbirth Group were used. Evaluation of methodological quality and trial data extraction were undertaken independently by two authors. Results are presented using relative risk with 95% confidence intervals.

Main Results: For all women administered progesterone, there was a reduction in the risk of preterm birth less than 37 weeks (six studies, 988 participants, relative risk (RR) 0.65, 95% confidence interval (CI) 0.54 to 0.79) and preterm birth less than 34 weeks (one study, 142 participants, RR 0.15, 95% CI 0.04 to 0.64). Infants born to mothers administered progesterone were less likely to have birthweight less than 2500 grams (four studies, 763 infants, RR 0.63, 95% CI 0.49 to 0.81) or intraventricular haemorrhage (one study, 458 infants, RR 0.25, 95% CI 0.08 to 0.82). There was no difference in perinatal death between women administered progesterone and those administered placebo (five studies, 921 participants, RR 0.66, 95% CI 0.37 to 1.19). There were no other differences reported for maternal or neonatal outcomes.

Authors' Conclusions: Intramuscular progesterone is associated with a reduction in the risk of preterm birth less than 37 weeks' gestation, and infant birthweight less than 2500 grams. However, other important maternal and infant outcomes have been poorly reported to date, with most outcomes reported from a single trial only (Meis 2003). It is unclear if the prolongation of gestation translates into improved maternal and longer-term infant health outcomes. Similarly, information regarding the potential harms of progesterone therapy to prevent preterm birth is limited. Further information is required about the use of vaginal progesterone in the prevention of preterm birth.