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
Open accessAbstract
Background An indirect comparison meta-analysis published in 2013 reported that both vaginal progesterone and cerclage are equally efficacious for preventing preterm birth and adverse perinatal outcomes in women with a singleton gestation, previous spontaneous preterm birth, and a sonographic short cervix. The efficacy of vaginal progesterone has been challenged after publication of the OPPTIMUM study. However, this has been resolved by an individual patient-data meta-analysis (Am J Obstet Gynecol. 2018;218:161-180).Objective To compare the efficacy of vaginal progesterone and cerclage in preventing preterm birth and adverse perinatal outcomes in women with a singleton gestation, previous spontaneous preterm birth, and a midtrimester sonographic short cervix.Data sources MEDLINE, EMBASE, LILACS, and CINAHL (from their inception to March 2018); Cochrane databases, bibliographies, and conference proceedings.Study eligibility criteria Randomized controlled trials comparing vaginal progesterone to placebo/no treatment or cerclage to no cerclage in women with a singleton gestation, previous spontaneous preterm birth, and a sonographic cervical length <25 mm.Study appraisal and synthesis methods Updated systematic review and adjusted indirect comparison meta-analysis of vaginal progesterone vs cerclage using placebo/no cerclage as the common comparator. The primary outcomes were preterm birth <35 weeks of gestation and perinatal mortality. Pooled relative risks (RRs) with 95% confidence intervals were calculated.Results Five trials comparing vaginal progesterone vs placebo (265 women) and 5 comparing cerclage vs no cerclage (504 women) were included. Vaginal progesterone, compared to placebo, significantly reduced the risk of preterm birth <35 and <32 weeks of gestation, composite perinatal morbidity/mortality, neonatal sepsis, composite neonatal morbidity, and admission to the neonatal intensive care unit (RRs from 0.29 to 0.68). Cerclage, compared to no cerclage, significantly decreased the risk of preterm birth <37, <35, <32, and <28 weeks of gestation, composite perinatal morbidity/mortality, and birthweight <1500 g (RRs from 0.64 to 0.70). Adjusted indirect comparison meta-analyses did not show statistically significant differences between vaginal progesterone and cerclage in the reduction of preterm birth or adverse perinatal outcomes.Conclusion Vaginal progesterone and cerclage are equally effective for preventing preterm birth and improving perinatal outcomes in women with a singleton gestation, previous spontaneous preterm birth, and a midtrimester sonographic short cervix. The choice of treatment will depend on adverse events and cost-effectiveness of interventions and patient/physician's preferences.
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Meta-analyses of randomized controlled trials of women with singleton gestation, no prior spontaneous preterm birth and transvaginal sonographic CL <25mm before 24 weeks have shown that administration of vaginal progesterone significantly decreases the risk of preterm birth and neonatal morbidity.
“Meta-analyses of randomized controlled trials of women with singleton gestation, no prior spontaneous preterm birth and transvaginal sonographic CL < 25mm before 24weeks have shown that administration of vaginal progesterone significantly decreases the risk of preterm birth and neonatal morbidity 99-101 .”
From <scp>ISUOG</scp> Practice Guidelines (updated): performance of the routine mid‐trimester fetal ultrasound scan (2022) · cites this paper as [99]
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References 159 · Cited by 168
Research works printed but not linked: 3
- [4]Institute of Medicine, US Committee on Understanding Premature Birth and Assuring Healthy Outcomes. In: Behrman RE, Butler AS, eds. Preterm birth: causes, consequences, and prevention. Washington, DC: National Academies Press; 2007. 20669423
- [75]National Institute for Health and Care Excellence. Preterm labor and birth. NICE guideline 25. 2015 Available at: https://www.nice.org.uk/guidance/ng25/evidence/full-guideline2176838029. Accessed Jan. 30, 2018. 37184164
- [102]Higgins J, Altman D, Sterne J. Chapter 8: Assessing risk of bias in included studies. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 (updated March 2011). The Cochrane Collaboration; 2011.
- Authors
- Conde-Agudelo, A., Romero, R., Da Fonseca, E., O’Brien, J. M., Cetingoz, E., Creasy, G. W., Hassan, S. S., Erez, O., Pacora, P., & Nicolaides, K. H.
- Affiliations
- National Institutes of Health (US)
- University of Kentucky (US)
- Population Council (US)
- Ben-Gurion University of the Negev (IL)
- Harris Birthright Research Centre for Fetal Medicine (GB)
- Corresponding author
- Romero, Roberto
- ORCID
- Venue
- American Journal of Obstetrics and Gynecology
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 219
- Issue
- 1
- Pages
- 10-25
- ISSN
- 0002-9378 (ISSN-L)
- PMC
- PMC6449041
- OpenAlex
- W2796022765
- Cited by
- 168
- References
- 159
- Citations by year
- 2026: 12 · 2025: 13 · 2024: 15 · 2023: 27 · 2022: 32 · 2021: 25 · 2020: 23 · 2019: 14 · 2018: 6 · 2017: 1
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Obstetrics and Gynecology (acceptedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute for Health and Care Research (09/800/27)
- National Institutes of Health
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (ZIAHD002401)
- Topics
- Health Sciences › Medicine › Epidemiology › Preterm Birth and Chorioamnionitis
- Health Sciences › Medicine › Obstetrics and Gynecology › Maternal and Perinatal Health Interventions
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Health and Contraception
- Keywords
- vaginal progesterone, cervical cerclage, preterm birth prevention, short cervix, singleton pregnancy, perinatal mortality, perinatal morbidity, neonatal sepsis, neonatal intensive care admission, cervical length, perinatal complications, gestational age
- MeSH terms
- Neonatal Sepsis, Administration, Intravaginal, Female, Humans, Infant, Newborn, Infant, Premature, Intensive Care Units, Neonatal, Pregnancy, Pregnancy Trimester, Second, Pregnancy Trimester, Third, Progestins, Progesterone, Infant, Very Low Birth Weight, Cerclage, Cervical, Premature Birth, Perinatal Mortality, Cervical Length Measurement, Secondary Prevention, Infant, Extremely Premature
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