Top

Published in:

Open Access 01-12-2021 | Premature Birth | Protocol

Vaginal progesterone for prevention of preterm birth in asymptomatic high-risk women with a normal cervical length: a systematic review and meta-analysis protocol

Authors: Kimberley P. Williams, Liam McAuliffe, Rosanna Diacci, Anne-Marie Aubin, Ashad Issah, Carol Wang, Jason Phung, Craig E. Pennell

Published in: Systematic Reviews | Issue 1/2021

Abstract

Background

Preterm birth (PTB) is estimated to affect 14.9 million babies globally every year. Global rates of PTB continue to increase from 9.8 to 10.6% over a 15-year period from 2000 to 2014. Vaginal progesterone is commonly used by clinicians as a prevention strategy, with recent evidence affirming the benefit of vaginal (micronised) progesterone to prevent PTB in women with a shortened cervix (< 25 mm). Given the low incidence of a short cervix at mid-gestation in high-risk populations further evidence is required. The objective of this review is to determine if vaginal progesterone reduces spontaneous preterm birth (sPTB) before 37 weeks in asymptomatic high-risk women with a singleton pregnancy with a normal mid-gestation cervical length.

Methods

Studies will be sourced from MEDLINE, Embase and Cochrane Register of Trials (CENTRAL) from their inception onwards with the search terms ‘progesterone’ and ‘preterm birth’. Studies will be screened and included if they assess vaginal progesterone compared to placebo in women with a normal cervical length. The primary outcome will be sPTB < 37 weeks, with secondary outcomes of sPTB < 34 weeks.

Two independent reviewers will conduct study screening at abstract and full text level, data extraction and risk of bias assessment with disagreements resolved by an experienced researcher. The Mantel-Haenszel statistical method and random effects analysis model will be used to produce treatment effect odds ratios and corresponding 95% confidence intervals.

Discussion

This review will assess the current body of evidence and provide clarity regarding the potential benefits and best practice of use of vaginal progesterone in asymptomatic women with high-risk singleton pregnancies and normal cervical length.

Trial registration

PROSPERO CRD42020152051

Available only for authorised users

Blencowe H, Cousens S, Oestergaard MZ, Chou D, Moller A-B, Narwal R, et al. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet. 2012;379(9832):2162–72. https://doi.org/10.1016/S0140-6736(12)60820-4.CrossRefPubMed

Chawanpaiboon S, Vogel JP, Moller A-B, Lumbiganon P, Petzold M, Hogan D, et al. Global, regional, and national estimates of levels of preterm birth in 2014: a systematic review and modelling analysis. Lancet Glob Health. 2019;7(1):e37–46. https://doi.org/10.1016/S2214-109X(18)30451-0.CrossRefPubMed

WHO. recommended definitions terminology format for statistical tables related to the perinatal period use of a new certificate for cause of perinatal deaths. Modifications recommended by FIGO as amended October 14, 1976. Acta Obstet Gynecol Scand. 1977;56:247–53.

Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. The Lancet. 2008;371(9606):75–84. https://doi.org/10.1016/S0140-6736(08)60074-4.CrossRef

Ward RM, Beachy JC. Neonatal complications following preterm birth. Br J Obstet Gynaecol. 2003;110:8–16. https://doi.org/10.1016/S1470-0328(03)00012-0.CrossRef

Malouf R, Redshaw M. Specialist antenatal clinics for women at high risk of preterm birth: a systematic review of qualitative and quantitative research. BMC Pregnancy Childbirth. 2017;17(1):51. https://doi.org/10.1186/s12884-017-1232-9.CrossRefPubMedPubMedCentral

Berghella V, Mackeen AD. Cervical length screening with ultrasound-indicated cerclage compared with history-indicated cerclage for prevention of preterm birth: a meta-analysis. Obstet Gynecol. 2011;118(1):148–55. https://doi.org/10.1097/AOG.0b013e31821fd5b0.CrossRefPubMed

Souza RT, Costa ML, Mayrink J, Feitosa FE, Rocha Filho EA, Leite DF, et al. Clinical and epidemiological factors associated with spontaneous preterm birth: a multicentre cohort of low risk nulliparous women. Sci Rep. 2020;10(1):1–10.CrossRef

Maher MA, Abdelaziz A, Ellaithy M, Bazeed MF. Prevention of preterm birth: a randomized trial of vaginal compared with intramuscular progesterone. Acta Obstet Gynecol Scand. 2013;92(2):215–22. https://doi.org/10.1111/aogs.12017.CrossRefPubMed

10.

Moroz LA, Simhan HN. Rate of sonographic cervical shortening and the risk of spontaneous preterm birth. A J Obstet Gynecol. 2012;206(3):234. e1–5.CrossRef

11.

Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH. Progesterone and the risk of preterm birth among women with a short cervix. N Engl J Med. 2007;357(5):462–9. https://doi.org/10.1056/NEJMoa067815.CrossRefPubMed

12.

Kuusela P, Jacobsson B, Söderlund M, Bejlum C, Almström E, Ladfors L, et al. Transvaginal sonographic evaluation of cervical length in the second trimester of asymptomatic singleton pregnancies, and the risk of preterm delivery. Acta Obstet Gynecol Scand. 2015;94(6):598–607. https://doi.org/10.1111/aogs.12622.CrossRefPubMed

13.

Maerdan M, Shi C, Zhang X, Fan L. The prevalence of short cervix between 20 and 24 weeks of gestation and vaginal progesterone for prolonging of gestation. J Maternal-Fetal Neonatal Med. 2017;30(14):1646–9. https://doi.org/10.1080/14767058.2016.1220528.CrossRef

14.

Sfakianaki AK, Norwitz ER. Mechanisms of progesterone action in inhibiting prematurity. J Maternal-Fetal Neonatal Med. 2006;19(12):763–72. https://doi.org/10.1080/14767050600949829.CrossRef

15.

Kuon R-J, Voß P, Rath W. Progesterone for the prevention of preterm birth–an update of evidence-based indications. Geburtshilfe Frauenheilkd. 2019;79(8):844–53. https://doi.org/10.1055/a-0854-6472.CrossRefPubMedPubMedCentral

16.

Da Fonseca E, Bittar R, Carvalho MH, Zugaib M. Prophylactic administration of progester-one by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at in-creased risk: a randomized placebo-controlled double-blind study. Am J Obstet Gynecol. 2003;188(2):419–24. https://doi.org/10.1067/mob.2003.41.CrossRefPubMed

17.

Dodd JM, Flenady VJ, Cincotta R, Crowther CA. Progesterone for the prevention of preterm birth: a systematic review. Obstet sGynecol. 2008;112(1):127–34. https://doi.org/10.1097/AOG.0b013e31817d0262.CrossRef

18.

Romero R, Stanczyk FZ. Progesterone is not the same as 17α-hydroxyprogesterone caproate: implications for obstetrical practice. Am J Obstet Gynecol. 2013;208(6):421–6. https://doi.org/10.1016/j.ajog.2013.04.027.CrossRefPubMed

19.

Romero R, Conde-Agudelo A, Da Fonseca E, O’Brien JM, Cetingoz E, Creasy GW, et al. Vaginal progesterone for preventing preterm birth and adverse perinatal outcomes in singleton gestations with a short cervix: a meta-analysis of individual patient data. Am J Obstet Gynecol. 2018;218(2):161–80. https://doi.org/10.1016/j.ajog.2017.11.576.CrossRefPubMed

20.

Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH, et al. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med. 2003;348(24):2379–85. https://doi.org/10.1056/NEJMoa035140.CrossRefPubMed

21.

Saccone G, Khalifeh A, Elimian A, Bahrami E, Chaman-Ara K, Bahrami M, et al. Vaginal progesterone vs intramuscular 17α-hydroxyprogesterone caproate for prevention of recurrent spontaneous preterm birth in singleton gestations: systematic review and meta-analysis of randomized controlled trials. Ultrasound Obstet Gynecol. 2017;49(3):315–21. https://doi.org/10.1002/uog.17245.CrossRefPubMed

22.

Shirodkar V. A new method of operative treatment for habitual abortions in the second trimester of pregnancy. Antiseptic. 1955;52:299–300.

23.

de Lignieres B, Dennerstein L, Backstrom T. Influence of route of administration on progesterone metabolism. Maturitas. 1995;21(3):251–7. https://doi.org/10.1016/0378-5122(94)00882-8.CrossRefPubMed

24.

Endnote X9. Clarivate analytics. Philadelphia: Thomson Reuters; 2019.

25.

Review Manager (RevMan). [Computer program]. Copenhagen The Nordic Cochrane Centre: The Cochrane Collaboration; 2014.

26.

Tufanaru CMZ, Aromataris E, Campbell J, Hopp L. Chapter 3: Systematic reviews of effectiveness. In: MZ AE, editor. Joanna Briggs Institute Reviewer's Manual: The Joanna Briggs Institute; 2017.

27.

Schünemann H BJ, Guyatt G, Oxman A. Handbook for grading the quality of evidence and the strength of recommendations using the GRADE approach (updated October 2013) GRADE Working Group, 2013. [Available from: guidelinedevelopment.org/app/handbook/handbook.html].

28.

Higgins JPT, Thomas J, Chandler J, Cumpston MLT, Page MJ, Welch VA. Chapter 10: Analysing data and undertaking meta-analyses. In: In: Cochrane Handbook for Systematic Reviews of Interventions version 60 (updated July 2019) [Internet]. Cochrane. Available from: www.training.cochrane.org/handbook; 2019. https://doi.org/10.1002/9781119536604.CrossRef

Title: Vaginal progesterone for prevention of preterm birth in asymptomatic high-risk women with a normal cervical length: a systematic review and meta-analysis protocol
Authors: Kimberley P. Williams
Liam McAuliffe
Rosanna Diacci
Anne-Marie Aubin
Ashad Issah
Carol Wang
Jason Phung
Craig E. Pennell
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Premature Birth
Progesterone
Published in: Systematic Reviews / Issue 1/2021
Electronic ISSN: 2046-4053
DOI: https://doi.org/10.1186/s13643-021-01702-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Vaginal progesterone for prevention of preterm birth in asymptomatic high-risk women with a normal cervical length: a systematic review and meta-analysis protocol

Abstract

Background

Methods

Discussion

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Discussion

Trial registration

Please log in to get access to this content

Other articles of this Issue 1/2021

Process evaluation of complex interventions in chronic and neglected tropical diseases in low- and middle-income countries—a scoping review protocol

Sputum colour as a marker for bacteria in acute exacerbations of COPD: protocol for a systematic review and meta-analysis

Massage therapy in infants and children under 5 years of age: protocol for an overview of systematic reviews

Racial and ethnic disparities in viral acute respiratory infections in the United States: protocol of a systematic review

Tricyclic antidepressants versus ‘active placebo’, placebo or no intervention for adults with major depressive disorder: a protocol for a systematic review with meta-analysis and Trial Sequential Analysis

Protocol for a systematic review and meta-analysis of observational studies examining the impact of COVID-19 safety measures on physical activity patterns in adults