Vaginal progesterone decreases preterm birth and neonatal morbidity and mortality in women with a twin gestation and a short cervix: an updated metaâ analysis of individual patient data

Abstract

ObjectiveTo assess the efficacy of vaginal progesterone for the prevention of preterm birth and neonatal morbidity and mortality in asymptomatic women with a twin gestation and a sonographic short cervix (cervical length â ¤ 25 mm) in the midâ trimester.MethodsThis was an updated systematic review and metaâ analysis of individual patient data (IPD) from randomized controlled trials comparing vaginal progesterone with placebo/no treatment in women with a twin gestation and a midâ trimester sonographic cervical length â ¤ 25 mm. MEDLINE, EMBASE, POPLINE, CINAHL and LILACS (all from inception to 31 December 2016), the Cochrane Central Register of Controlled Trials, Research Registers of ongoing trials, Google Scholar, conference proceedings and reference lists of identified studies were searched. The primary outcome measure was preterm birth < 33 weeks’ gestation. Two reviewers independently selected studies, assessed the risk of bias and extracted the data. Pooled relative risks (RRs) with 95% confidence intervals (CI) were calculated.ResultsIPD were available for 303 women (159 assigned to vaginal progesterone and 144 assigned to placebo/no treatment) and their 606 fetuses/infants from six randomized controlled trials. One study, which included women with a cervical length between 20 and 25 mm, provided 74% of the total sample size of the IPD metaâ analysis. Vaginal progesterone, compared with placebo/no treatment, was associated with a statistically significant reduction in the risk of preterm birth < 33 weeks’ gestation (31.4% vs 43.1%; RR, 0.69 (95% CI, 0.51â 0.93); moderateâ quality evidence). Moreover, vaginal progesterone administration was associated with a significant decrease in the risk of preterm birth < 35, < 34, < 32 and < 30 weeks’ gestation (RRs ranging from 0.47 to 0.83), neonatal death (RR, 0.53 (95% CI, 0.35â 0.81)), respiratory distress syndrome (RR, 0.70 (95% CI, 0.56â 0.89)), composite neonatal morbidity and mortality (RR, 0.61 (95% CI, 0.34â 0.98)), use of mechanical ventilation (RR, 0.54 (95% CI, 0.36â 0.81)) and birth weight < 1500 g (RR, 0.53 (95% CI, 0.35â 0.80)) (all moderateâ quality evidence). There were no significant differences in neurodevelopmental outcomes at 4â 5 years of age between the vaginal progesterone and placebo groups.ConclusionAdministration of vaginal progesterone to asymptomatic women with a twin gestation and a sonographic short cervix in the midâ trimester reduces the risk of preterm birth occurring at < 30 to < 35 gestational weeks, neonatal mortality and some measures of neonatal morbidity, without any demonstrable deleterious effects on childhood neurodevelopment. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.