Vaginal progesterone decreases preterm birth and neonatal morbidity and mortality in women with a twin gestation and a short cervix: an updated meta‐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 ≤ 25 mm) in the mid‐trimester.MethodsThis was an updated systematic review and meta‐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 mid‐trimester sonographic cervical length ≤ 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 meta‐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, 0.51–0.93); moderate‐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, 0.35–0.81)), respiratory distress syndrome (RR, 0.70 (95% CI, 0.56–0.89)), composite neonatal morbidity and mortality (RR, 0.61 (95% CI, 0.34–0.98)), use of mechanical ventilation (RR, 0.54 (95% CI, 0.36–0.81)) and birth weight < 1500 g (RR, 0.53 (95% CI, 0.35–0.80)) (all moderate‐quality evidence). There were no significant differences in neurodevelopmental outcomes at 4–5 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 mid‐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. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Plasma progesterone, estradiol, and unconjugated estriol concentrations in twin pregnancies: Relation with cervical length and preterm delivery

“…19 We did not find evidence of an increased plasma hormone concentration Studies suggest that singleton pregnant women who deliver preterm have lower plasma and salivary progesterone concentrations than women who deliver at term. We did not find an association between plasma there may be an effect in twin gestations with a short cervix.…”

“…12,15,16 Several studies have now shown that progesterone treatment during the second and third trimester of pregnancy reduces the risk of preterm delivery in women with a singleton pregnancy and a short cervical length or a history of a previous preterm delivery. 19,20 Few studies have measured hormone concentrations in women treated with prophylactic progesterone during the second trimester. 19,20 Few studies have measured hormone concentrations in women treated with prophylactic progesterone during the second trimester.…”

Vaginal progesterone is as effective as cervical cerclage to prevent preterm birth in women with a singleton gestation, previous spontaneous preterm birth, and a short cervix: updated indirect comparison meta-analysis

“…70,81,127–129 With regard to long-term childhood outcomes, current evidence suggests that in utero exposure to vaginal progesterone, administered in a singleton or twin gestation for the prevention of preterm birth, has no harmful effect on neurodevelopmental outcomes at least until 8 years of age. 91,130–134 No studies have reported on long-term neurodevelopmental outcomes in children whose mothers received a cerclage.…”

Interventions for women with mid‐trimester short cervix: which ones work?

“…The efficacy of vaginal progesterone in women with twins and a short mid‐trimester cervix is reported in this issue by Romero et al . who performed an individual patient data meta‐analysis using data from six randomized controlled trials; it was found that administration of vaginal progesterone to this group of women significantly decreased the risk of PTB < 34 weeks by approximately 30% and, in addition, it decreased neonatal mortality and composite neonatal morbidity/mortality by approximately 50%.…”