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Meta-Analysis
. 2018 Feb;218(2):161-180.
doi: 10.1016/j.ajog.2017.11.576. Epub 2017 Nov 17.

Vaginal progesterone for preventing preterm birth and adverse perinatal outcomes in singleton gestations with a short cervix: a meta-analysis of individual patient data

Roberto Romero  1 , Agustin Conde-Agudelo  2 , Eduardo Da Fonseca  3 , John M O'Brien  4 , Elcin Cetingoz  5 , George W Creasy  6 , Sonia S Hassan  2 , Kypros H Nicolaides  7
Affiliations
Meta-Analysis

Vaginal progesterone for preventing preterm birth and adverse perinatal outcomes in singleton gestations with a short cervix: a meta-analysis of individual patient data

Roberto Romero et al. Am J Obstet Gynecol. 2018 Feb.

Abstract

Background: The efficacy of vaginal progesterone for preventing preterm birth and adverse perinatal outcomes in singleton gestations with a short cervix has been questioned after publication of the OPPTIMUM study.

Objective: To determine whether vaginal progesterone prevents preterm birth and improves perinatal outcomes in asymptomatic women with a singleton gestation and a midtrimester sonographic short cervix.

Study design: We searched MEDLINE, EMBASE, LILACS, and CINAHL (from their inception to September 2017); Cochrane databases; bibliographies; and conference proceedings for randomized controlled trials comparing vaginal progesterone vs placebo/no treatment in women with a singleton gestation and a midtrimester sonographic cervical length ≤25 mm. This was a systematic review and meta-analysis of individual patient data. The primary outcome was preterm birth <33 weeks of gestation. Secondary outcomes included adverse perinatal outcomes and neurodevelopmental and health outcomes at 2 years of age. Individual patient data were analyzed using a 2-stage approach. Pooled relative risks with 95% confidence intervals were calculated. Quality of evidence was assessed using the GRADE methodology.

Results: Data were available from 974 women (498 allocated to vaginal progesterone, 476 allocated to placebo) with a cervical length ≤25 mm participating in 5 high-quality trials. Vaginal progesterone was associated with a significant reduction in the risk of preterm birth <33 weeks of gestation (relative risk, 0.62; 95% confidence interval, 0.47-0.81; P = .0006; high-quality evidence). Moreover, vaginal progesterone significantly decreased the risk of preterm birth <36, <35, <34, <32, <30, and <28 weeks of gestation; spontaneous preterm birth <33 and <34 weeks of gestation; respiratory distress syndrome; composite neonatal morbidity and mortality; birthweight <1500 and <2500 g; and admission to the neonatal intensive care unit (relative risks from 0.47-0.82; high-quality evidence for all). There were 7 (1.4%) neonatal deaths in the vaginal progesterone group and 15 (3.2%) in the placebo group (relative risk, 0.44; 95% confidence interval, 0.18-1.07; P = .07; low-quality evidence). Maternal adverse events, congenital anomalies, and adverse neurodevelopmental and health outcomes at 2 years of age did not differ between groups.

Conclusion: Vaginal progesterone decreases the risk of preterm birth and improves perinatal outcomes in singleton gestations with a midtrimester sonographic short cervix, without any demonstrable deleterious effects on childhood neurodevelopment.

Keywords: cervical length; prematurity; preterm delivery; progestins; progestogens; transvaginal ultrasound.

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Conflict of interest statement

Disclosure: RR, AC-A, EDF, EC, SSH, and KHN declare no conflict of interest. JMO’B was involved in studies of progesterone gel treatment for preterm birth prevention sponsored by a maker of progesterone gel. He served on advisory boards and as a consultant for Watson Pharmaceuticals, a company with a financial interest in marketing vaginal progesterone gel for preterm birth prevention; he and others are listed in a patent on the use of progesterone compounds to prevent preterm birth (USA Patent Number 7884093: progesterone for the treatment and prevention of spontaneous preterm birth). He has received no royalty payments. GWC was an Employee of Columbia Laboratories, Inc. when the previous meta-analysis of individual patient data was conducted in 2011.

Professor Jane Norman has no conflict of interest in relation with our meta-analysis of individual patient data.

Figures

Figure 1
Figure 1. Summary of evidence search and selection
CL, cervical length; IPD, individual patient data
Figure 2
Figure 2. Risk of bias in each included study
*Low risk of bias for obstetric and neonatal primary outcomes; high risk of bias for childhood primary outcome
Figure 3
Figure 3. Effect of vaginal progesterone on preterm birth <33 weeks of gestation
Figure 4
Figure 4. Subgroup analyses of the effect of vaginal progesterone on preterm birth <33 weeks of gestation
SPB, spontaneous preterm birth
See this image and copyright information in PMC

Comment in

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