Effectiveness of progesterone, cerclage and pessary for preventing preterm birth in singleton pregnancies: a systematic review and network meta‐analysis

Abstract

Background Preterm birth (PTB) is the leading cause of infant death, but it is unclear which intervention is best to prevent it.Objectives To compare progesterone, cerclage and pessary, determine their relative effects and rank them.Search strategy We searched Medline, EMBASE, CINAHL, Cochrane CENTRAL and Web of Science (to April 2016), without restrictions, and screened references of previous reviews.Selection criteria We included randomised trials of progesterone, cerclage or pessary for preventing PTB in women with singleton pregnancies at risk as defined by each study.Data collection and analysis We extracted data by duplicate using a piloted form and performed Bayesian random-effects network meta-analyses and pairwise meta-analyses. We rated evidence quality using GRADE, ranked interventions using SUCRA and calculated numbers needed to treat (NNT).Main results We included 36 trials (9425 women; 25 low risk of bias trials). Progesterone ranked first or second for most outcomes, reducing PTB < 34 weeks [odds ratio (OR) 0.44; 95% credible interval (CrI) 0.22-0.79; NNT 9; low quality], <37 weeks (OR 0.58; 95% CrI 0.41-0.79; NNT 9; moderate quality), and neonatal death (OR 0.50; 95% CrI 0.28-0.85; NNT 35; high quality), compared with control, in women overall at risk. We found similar results in the subgroup with previous PTB, but only a reduction of PTB < 34 weeks in women with a short cervix. Pessary showed inconsistent benefit and cerclage did not reduce PTB < 37 or <34 weeks.Conclusions Progesterone was the best intervention for preventing PTB in singleton pregnancies at risk, reducing PTB < 34 weeks, <37 weeks, neonatal demise and other sequelae.Keywords Cervical cerclage, cervical pessary, network metaanalysis, preterm birth, progesterone, systematic review.Tweetable abstract Progesterone was better than cerclage and pessary to prevent preterm birth, neonatal death and more in network meta-analysis.Please cite this paper as: Jarde A, Lutsiv O, Park CK, Beyene J, Dodd JM, Barrett J, Shah PS, Cook JL, Saito S, Biringer AB, Sabatino L, Giglia L, Han Z, Staub K, Mundle W, Chamberlain J, McDonald SD. Effectiveness of progesterone, cerclage and pessary for preventing preterm birth in singleton pregnancies: a systematic review and network meta-analysis.

Bitter taste receptors as targets for tocolytics in preterm labor therapy

“…These results highlight an attractive characteristic of bitter tastants as tocolytics because the cause of PTB is multifactorial and often unknown, and therefore a tocolytic with a broad spectrum of applicability could provide better protection from PTB than those with a narrow spectrum effect. Currently, progesterone is the only pharmacologic reagent approved by FDA for preventing PTB (41, 42). According to the U.S. Institutes of Medicine Committee on Understanding Premature Birth and Assuring Healthy Outcomes (26), 3 possibilities may account for the effectiveness of progesterone: 1 ) progesterone inhibits a pathway shared by diverse causes of PTB, 2 ) progesterone exerts diverse effects that act on several different pathways, or 3 ) progesterone is very effective against one highly prevalent pathway or cause.…”

Recent advances in the prevention of preterm birth

“…This is consistent with a recent patient-level meta-analysis, which concluded that cervical cerclage lacked demonstrable efficacy in women with a shortened cervix (<25 mm) 30 , although this may depend on previous PTB status. On the other hand, progesterone therapy was found to significantly decrease rates of PTB at <34 weeks (OR 0.44) and <37 weeks (OR 0.58) and neonatal death (OR 0.50) 29 . Romero et al had earlier come to similar conclusions following their own re-analysis of published trials, supporting previous analyses of benefits and risks 31 .…”

“…Despite the controversy over the effectiveness of these interventions in recent years, some clarity is emerging. Jarde et al , in a recently published network meta-analysis, concluded that progesterone was more effective than cerclage for primary prevention of PTB in high-risk women with a singleton pregnancy 29 . This is consistent with a recent patient-level meta-analysis, which concluded that cervical cerclage lacked demonstrable efficacy in women with a shortened cervix (<25 mm) 30 , although this may depend on previous PTB status.…”

Contemporary Issues in Women's Health

“…Interventions such as the use of vaginal progesterone, insertion of a cervical cerclage, or a vaginal pessary are practiced widely to attempt to reduce PTB. Two recently published systematic reviews have looked at the comparative effectiveness of progesterone, pessary, and cervical cerclage in preventing PTB in singleton pregnancies and in twin pregnancies, respectively.…”

“…In the first systematic review of 36 randomized trials and 9425 singleton pregnancies, progesterone ranked best in preventing PTB compared with cerclage or pessary. Reduced odds of PTB before 34 weeks of pregnancy (odds ratio 0.44, credible interval 0.22–0.79; number needed to treat 9) and neonatal death (odds ratio 0.50, credible interval 0.28–0.85; number needed to treat 35) were observed with progesterone treatment compared with a control group.…”