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Review
. 2023 Feb 28:10:1111315.
doi: 10.3389/fmed.2023.1111315. eCollection 2023.

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

Ulla-Britt Wennerholm  1   2 , Lina Bergman  1   2   3   4 , Pihla Kuusela  2   5 , Elin Ljungström  1 , Anna C Möller  1 , Cecilie Hongslo Vala  6 , Ann-Catrin Ekelund  7 , Ann Liljegren  8 , Max Petzold  9 , Petteri Sjögren  6 , Mikael Svensson  10 , Annika Strandell  1   2   6 , Bo Jacobsson  1   2   11
Affiliations
Review

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

Ulla-Britt Wennerholm et al. Front Med (Lausanne). .

Erratum in

Abstract

Background: Preterm 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.

Methods: Six 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.

Results: The 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.

Conclusion: Progesterone 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].

Keywords: acetylsalicylic acid; cerclage; perinatal morbidity and mortality; pessary; preterm birth; progesterone; systematic review.

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Conflict of interest statement

LB board member and responsible for the biobank in the IMPACT study where PlGF reagents have been donated by Roche, Perkin Elmer, and Thermo Fischer. Course leader for the course in Preeclampsia in Sweden with sponsorship by Thermo Fischer and Roche. Obtained reimbursement for lecture by iLab Medical and reimbursement as expert opinion from Homburg and Partner. Board member in intervention trials where the trial drug is donated by Merck. Associate member in FIGO for the working group of maternal longterm health. Chair of the Swedish Preeclampsia Working Group. Board member in CoLab. Author of the chapter about preeclampsia in “Obstetrik” and about pulmonary hypertension in “Internetmedicin.” Research grants from the Swedish Research Council, STINT, Märta Lundqvist stiftelse, Swedish Society of Medicine, Gothenburg Society of Medicine, SSMF, Jane and Dan Olssons Stiftelse, Swedish Brain fund, Jeanssons stiftelse and Wallenberg Center for Molecular and Translational Medicine. BJ Research grants from Swedish Research Council, Norwegian Research Council, March of Dimes, Burroughs Wellcome Fund and the US National Institute of Health. During the last years performed clinical diagnostic trials on NIPT with Ariosa (completed), Natera (ongoing), Vanadis (completed), and Hologic (ongoing) with expenditures reimbursed per patient. Also performed clinical probiotic studies with the probiotic product provided by FukoPharma (ongoing, no funding) and BioGaia (ongoing; also provided a research grant for the specific study). Previously (2018–2020) a collaborator in IMPACT study where Roche, Perkin Elmer and Thermo Fisher provided reagents to PLGF analyses. No lectures, presentations, travel or personal reimbursement has been financed by any company. Division Director of Maternal and Neonatal Health of the International Federation of Gynecology and Obstetrics (FIGO), Board member of the European Association of Perinatal Medicine and chair the EAPM special interest group of preterm delivery. Steering group member of Genomic Medicine Sweden and is in charge of the Genomic Medicine Sweden complex diseases group. Swedish representative in Nordic Society of Precision Medicine. U-BW, BJ, and PK declare being co-investigators in the OPPTIMUM trial, an included trial in this review. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram presenting the selection process after the literature search (all interventions).
Figure 2
Figure 2
Summary graph of pooled estimates from meta-analyses comparing progesterone and placebo in women with a singleton pregnancy and any type of risk factor for preterm birth, from trials with low risk of bias regarding (A) preterm birth, (B) neonatal, and (C) maternal outcomes.
Figure 3
Figure 3
Summary graph of pooled estimates from meta-analyses comparing cerclage versus no cerclage in women with a singleton pregnancy and any type of risk factor for preterm birth, from trials with low risk of bias regarding (A) preterm birth, (B) neonatal, and (C) maternal outcomes.
Figure 4
Figure 4
Summary graph of pooled estimates from meta-analyses comparing pessary versus pessary in women with a singleton pregnancy and short cervical length, from trials with low risk of bias regarding (A) preterm birth, (B) neonatal, and (C) maternal outcomes.
Figure 5
Figure 5
Summary graph of pooled estimates from meta-analyses comparing progesterone and placebo in women with a multifetal pregnancy with or without additional risk factor(s) for preterm birth, from trials with low risk of bias regarding (A) preterm birth, (B) neonatal, and (C) maternal outcomes.
Figure 6
Figure 6
Summary graph of pooled estimates from meta-analyses comparing cerclage versus no cerclage in women with a multifetal pregnancy with or without additional risk factor(s) for preterm birth from trials with low risk of bias regarding (A) preterm birth, (B) neonatal, and (C) maternal outcomes.
Figure 7
Figure 7
Summary graph of pooled estimates from meta-analyses comparing pessary versus no pessary in women with a multifetal pregnancy with or without additional risk factor(s) for preterm birth from trials with low risk of bias regarding (A) preterm birth, (B) neonatal, and (C) maternal outcomes.
See this image and copyright information in PMC

Comment in

References

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