Abstract

• The natural hormone progesterone and the progesterone derivative hydroxyprogesterone have been proposed for the prevention of preterm birth in pregnant women considered at high risk due to a history of prior preterm birth or a short cervix on ultrasound examination.
   
• What are the results of the evaluation of these progestogens in the prevention of preterm birth in women at high risk? And what are the adverse effects on the mother and the unborn child? We identified a Cochrane systematic review and searched the literature for more recent data.
   
• Four randomised trials evaluated the administration of intramuscular hydroxyprogesterone, beginning in the second trimester of pregnancy, in about 650 women with a history of preterm birth. The data on perinatal mortality and on the incidence of preterm birth were uninterpretable due to heterogeneity between the placebo groups.
   
• Seven randomised placebo-controlled trials evaluated oral or vaginal progesterone in about 1300 women with a history of preterm birth. Delivery before 34 weeks’ gestation was less frequent with progesterone (10% of births versus 26% with placebo), with no impact on perinatal mortality. The results on neonatal health outcomes are undermined by reporting bias.
   
• In five randomised trials in women found to have a short cervix midway through pregnancy, there was no firm evidence that either vaginal progesterone or intramuscular hydroxyprogesterone reduce the incidence of preterm birth before 37 weeks.
   
• Progesterone and hydroxyprogesterone were evaluated in 16 randomised trials in women with a multiple pregnancy, with no evidence of a reduction in the risk of preterm birth.
   
• At the doses evaluated, the adverse effects of these progestogens are moderate for the mother, although women at risk for deep vein thrombosis were excluded from several trials. Exposure to progesterone or hydroxyprogesterone after the first trimester of pregnancy does not appear to increase the risk of congenital defects in the newborn. The long-term effects of these progestogens are unknown.
   
• In practice, the efficacy of progesterone and hydroxyprogesterone administered from the second trimester of pregnancy for the prevention of preterm birth is highly uncertain. As of early 2016, the evaluation results are not sufficiently convincing to justify progestogen exposure as soon as the risk of preterm birth appears high. They do, however, justify continued evaluation of progesterone in clinical trials for women with a history of recurrent preterm birth with no identified cause.

©Prescrire 1 July 2016

"Progestogens and prevention of preterm birth in women at risk" Prescrire Int 2016; 25 (173): 185-188. (Pdf, subscribers only)