Progesterone, cerclage, pessary, or acetylsalicylic acid for prevention of preterm birth in singleton and multifetal pregnancies – A systematic review and meta-analyses

Abstract

BackgroundPreterm birth is the leading cause of childhood mortality and morbidity. We aimed to provide a comprehensive systematic review on randomized controlled trials (RCTs) on progesterone, cerclage, pessary, and acetylsalicylic acid (ASA) to prevent preterm birth in asymptomatic women with singleton pregnancies defined as risk of preterm birth and multifetal pregnancies.MethodsSix databases (including PubMed, Embase, Medline, the Cochrane Library) were searched up to February 2022. RCTs published in English or Scandinavian languages were included through a consensus process. Abstracts and duplicates were excluded. The trials were critically appraised by pairs of reviewers. The Cochrane risk-of-bias tool was used for risk of bias assessment. Predefined outcomes including preterm birth, perinatal/neonatal/maternal mortality and morbidity, were pooled in meta-analyses using RevMan 5.4, stratified for high and low risk of bias trials. The certainty of evidence was assessed using the GRADE approach. The systematic review followed the PRISMA guideline.ResultsThe search identified 2,309 articles, of which 87 were included in the assessment: 71 original RCTs and 16 secondary publications with 23,886 women and 32,893 offspring. Conclusions were based solely on trials with low risk of bias (n = 50).Singleton pregnancies: Progesterone compared with placebo, reduced the risk of preterm birth <37 gestational weeks: 26.8% vs. 30.2% (Risk Ratio [RR] 0.82 [95% Confidence Interval [CI] 0.71 to 0.95]) (high certainty of evidence, 14 trials) thereby reducing neonatal mortality and respiratory distress syndrome. Cerclage probably reduced the risk of preterm birth <37 gestational weeks: 29.0% vs. 37.6% (RR 0.78 [95% CI 0.69 to 0.88]) (moderate certainty of evidence, four open trials). In addition, perinatal mortality may be reduced by cerclage. Pessary did not demonstrate any overall effect. ASA did not affect any outcome, but evidence was based on one underpowered study.Multifetal pregnancies: The effect of progesterone, cerclage, or pessary was minimal, if any. No study supported improved long-term outcome of the children.ConclusionProgesterone and probably also cerclage have a protective effect against preterm birth in asymptomatic women with a singleton pregnancy at risk of preterm birth. Further trials of ASA are needed. Prevention of preterm birth requires screening programs to identify women at risk of preterm birth.Systematic Review Registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021234946].

Cervical Length and Perinatal Outcome

“…Some of the studies used in this analysis included a variety of risk factors for preterm birth, such as maternal age and smoking. These risk factors did not appear to have the same predictive value as other risk factors, such as history of previous preterm birth and presence of abnormalities in the uterus, so a subsequent statistical analysis was performed in this study and found that the results of the analysis were still the same even after exclusion of Watson's study that included smoking in older women in risk factors [24][25][26][27][28].…”

“…The cervical threshold under which the cervix was considered to be short was set at 25 mm, predicting with high sensitivity the risk of premature birth below 35 weeks of gestation, while women with a prior history of preterm labor and cervical surgery were identified as high risk for preterm labor. It was also found that the likelihood of preterm birth below 35 weeks is less in cases where cervical length < 25 mm is measured at 20-24 weeks of gestation, than the likelihood of preterm labor in cases where cervical length < 25 mm is measured at a gestational age less than 20 weeks or more than 24 weeks [20][21][22][23][24].…”

Desafios na prevenção do parto pré-termo associado à insuficiência cervical

“…Para gestantes com gestação única e de alto risco de parto pré--termo (seja por história de parto pré-termo espontâneo anterior e/ ou colo curto ao US), deve ser oferecido o uso da progesterona para prevenção da prematuridade 1,48,49 . O benefício do uso da progesterona é mais significativo nas gestantes com história prévia de parto pré--termo espontâneo e colo curto.…”