The natural
hormone progesterone and the
progesterone derivative hydroxyprogesterone have been pro- posed 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 evalu- ation 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 pla- cebo 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 pro- gesterone (10% of births versus 26% with placebo), with no impact on perinatal mortality. The results on neo- natal 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 progester- one or intramuscular hydroxyproges- terone reduce the incidence of
preterm birth before 37 weeks.
Progesterone and hydroxyproges- terone 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 hydroxy-
progesterone 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 iden- tified cause.