You are here

Article Text

Article menu

Download PDFPDF

XML
Obstetrics and gynaecology
Protocol
Metformin in Pregnancy Study (MiPS): protocol for a systematic review with individual patient data meta-analysis
  1. Aya Mousa1,
  2. Tone Løvvik2,
  3. Ijäs Hilkka3,
  4. Sven M Carlsen2,4,
  5. Laure Morin-Papunen3,
  6. Kristiina Tertti5,6,
  7. Tapani Rönnemaa6,7,
  8. Argyro Syngelaki8,
  9. Kypros Nicolaides8,
  10. Hassan Shehata9,
  11. Christy Burden10,
  12. Jane E Norman10,
  13. Janet Rowan11,12,
  14. Jodie M Dodd13,14,
  15. William Hague13,14,
  16. Eszter Vanky2,
  17. Helena J Teede1
  1. 1Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Clayton, Victoria, Australia
  2. 2Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
  3. 3Department of Obstetrics and Gynaecology, University of Oulu and Oulu University Hospital, Medical Research Centre, PEDEGO Research Unit, Oulu, Finland
  4. 4Department of Endocrinology, St Olavs Hospital, Trondheim, Norway
  5. 5Department of Obstetrics and Gynecology, University of Turku, Turku, Finland
  6. 6Department of Obstetrics and Gynecology, Turku University Hospital, Turku, Finland
  7. 7Department of Medicine, University of Turku, Turku, Finland
  8. 8Fetal Medicine Research Unit, King's College London, London, UK
  9. 9Department of Maternal Medicine, Epsom Hospital, Epsom and St Helier University Hospitals NHS Trust, Epsom, Surrey, UK
  10. 10Faculty of Health Sciences, University of Bristol, Bristol, UK
  11. 11Auckland District Health Board, Auckland, New Zealand
  12. 12School of Medicine, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
  13. 13Robinson Research Institute, The University of Adelaide Discipline of Obstetrics and Gynaecology, Adelaide, South Australia, Australia
  14. 14Women's and Babies Division, Women's and Children's Hospital, Adelaide, North Adelaide, South Australia, Australia
  1. Correspondence to Dr Aya Mousa; aya.mousa{at}monash.edu

Abstract

Introduction Gestational diabetes mellitus (GDM) is a common disorder of pregnancy and contributes to adverse pregnancy outcomes. Metformin is often used for the prevention and management of GDM; however, its use in pregnancy continues to be debated. The Metformin in Pregnancy Study aims to use individual patient data (IPD) meta-analysis to clarify the efficacy and safety of metformin use in pregnancy and to identify relevant knowledge gaps.

Methods and analysis MEDLINE, EMBASE and all Evidence-Based Medicine will be systematically searched for randomised controlled trials (RCT) testing the efficacy of metformin compared with placebo, usual care or other interventions in pregnant women. Two independent reviewers will assess eligibility using prespecified criteria and will conduct data extraction and quality appraisal of eligible studies. Authors of included trials will be contacted and asked to contribute IPD. Primary outcomes include maternal glycaemic parameters and GDM, as well as neonatal hypoglycaemia, anthropometry and gestational age at delivery. Other adverse maternal, birth and neonatal outcomes will be assessed as secondary outcomes. IPD from these RCTs will be harmonised and a two-step meta-analytic approach will be used to determine the efficacy and safety of metformin in pregnancy, with a priori adjustment for covariates and subgroups to examine effect moderators of treatment outcomes. Sensitivity analyses will assess heterogeneity, risk of bias and the impact of trials which have not provided IPD.

Ethics and dissemination All IPD will be deidentified and studies contributing IPD will have ethical approval from their respective local ethics committees. This study will provide robust evidence regarding the efficacy and safety of metformin use in pregnancy, and may identify subgroups of patients who may benefit most from this treatment modality. Findings will be published in peer-reviewed journals and disseminated at scientific meetings, providing much needed evidence to inform clinical and public health actions in this area.

  • diabetes in pregnancy
  • obstetrics
  • preventive medicine
  • reproductive medicine
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjopen-2020-036981

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    View Full Text

    Footnotes

    • Contributors AM is the project lead, conceptualised and designed the protocol, wrote the first draft of the manuscript and will coordinate the MiPS project. TL, IH, SMC, LMP, KT, TR, AS, KN, HS, CB, JEN, JR, JMD and WH are key collaborators on the project and members of the MiPS steering committee, contributed to writing and editing the manuscript and will contribute IPD for the meta-analysis. EV and HJT are chair and deputy chair of the MiPS steering committee, respectively, and codesigned the protocol, contributed to writing and editing the manuscript and will colead the project with AM. HJT is the study guarantor and will oversee data collection, analysis and interpretation. All authors meet ICMJE criteria for authorship and have approved the final version for publication.

    • Funding AM is supported by a Peter Doherty Biomedical Research Fellowship provided by the National Health and Medical Research Council (NHMRC) of Australia. HJT is supported by a Senior Research Fellowship from the NHMRC.

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.