Supplemental progesterone to prevent preterm birth

Abstract

In this issue, da Fonseca et al report the results of a randomized, placebo-controlled trial of supplemental progesterone to prevent preterm birth in women with risk factors for preterm birth.1da Fonseca EB Bittar RE Carvalho MHB Zugaib M Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study.Am J Obstet Gynecol. 2003; 188: 419-424Abstract Full Text Full Text PDF PubMed Scopus (628) Google Scholar Vaginal suppositories containing 100 mg of progesterone or placebo were administered once daily at bedtime from 24 through 34 weeks' gestation in 142 women. The incidence of preterm birth was significantly reduced in women who received progesterone, from 28.5% to 13.8% for births before 37 weeks and, remarkably, from 18.6% to 2.8% for births before 34 weeks in the placebo versus progesterone groups, respectively. The study is founded on the progesterone withdrawal hypothesis of initiation of parturition advanced by Csapo2Csapo AI The see-saw theory of parturition.in: The fetus and birth. Elsevier, New York1977: 159-210Google Scholar in which the high ratio of progesterone to estrogen that allows the uterus to expand during pregnancy is reversed as labor approaches, thus allowing cervical ripening and uterine contractility to increase and labor to occur. This pathway has been explored in animal species3Saito Y Sakimoto H MacKusky NJ Naftolin F Gap- junctions and myometrial steroid hormone receptors in pregnant and post-partum rats: a possible cellular basis for the progesterone withdrawal hypothesis.Am J Obstet Gynecol. 1985; 151: 805-812Abstract Full Text PDF PubMed Google Scholar but has been difficult to adopt directly to explain term and preterm labor in primates. Clinical studies in humans have been reported, with variable results.4Johnson JWC Austin KL Jones GS Davis GH King TM Efficacy of 17 alpha hydroxyprogesterone caproate in the prevention of premature labor.N Engl J Med. 1975; 292: 675-680Crossref PubMed Scopus (188) Google Scholar, 5Hartikainen-Sorri A-L Kauppila A Tuimala R Inefficacy of 17α-hydroxyprogesterone caproate in the prevention of prematurity in twin pregnancy.Obstet Gynecol. 1980; 56: 692-695PubMed Google Scholar, 6Hauth JC Gilstrap LC Brekken AL Hauth JM The effect of 17α-hydroxyprogesterone caproate on pregnancy outcome in an active-duty military population.Am J Obstet Gynecol. 1983; 146: 187-190Abstract Full Text PDF PubMed Scopus (86) Google Scholar A meta-analysis of prophylactic administration of prophylactic treatment with 17α-hydroxyprogesterone caproate, a metabolite of progesterone, showed favorable odds ratios for reduction of preterm labor: 0.43 (95% CI 0.20-0.89), preterm birth: 0.50 (0.30-0.85), and low birth weight (||2500 g): 0.50 (0.27-0.80) but no change in perinatal morbidity or mortality.7Keirse MJNC Progesterone administration in pregnancy may prevent pre-term delivery.Br J Obstet Gynaecol. 1990; 97: 149-154Crossref PubMed Scopus (218) Google Scholar The data reported by da Fonseca et al similarly report improvements in intermediate end points for prematurity reduction, but the sample size is insufficient to address the question of whether progesterone supplementation can reduce perinatal morbidity. This report, together with similarly encouraging data from a larger trial presented in abstract form at the 2003 meeting of the Society for Maternal Fetal Medicine,8Meis PJ National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network 17α-Hydroxyprogesterone acetate to prevent recurrent preterm birth [abstract].Am J Obstet Gynecol. 2002; 187: S54PubMed Google Scholar should serve to re-energize both basic and clinical research in this area. Although it is not yet time to treat all women at risk for preterm birth with supplemental progesterone, it is not too soon to hope that these early reports will be followed by larger series showing not only a decline in preterm birth but a reduction in perinatal morbidity and mortality as well.