Open Access Study protocol

Progestogens to prevent preterm birth in twin pregnancies: an individual participant data meta-analysis of randomized trials

Ewoud Schuit1*, Sarah Stock2, Rolf HH Groenwold1, Kimberly Maurel3, C Andrew Combs4, Thomas Garite5, Cathy Y Spong6, Elizabeth A Thom7, Dwight J Rouse8, Steve N Caritis9, George R Saade10, Julia M Zachary7, Jane E Norman2, Line Rode11, Katharina Klein12, Ann Tabor11, Elçin Çetingöz13, John C Morrison14, Everett F Magann15, Christian M Briery16, Vicente Serra17, Alfredo Perales18, Juan Meseguer19, Anwar H Nassar20, Arianne C Lim21, Karel GM Moons1, Anneke Kwee22 and Ben Willem J Mol21

Author Affiliations

1 Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, the Netherlands

2 MC Centre for Reproductive Health, University of Edinburgh, Edinburgh, Scotland, USA

3 The Centre for Research, Education & Quality (CREQ), Obstetrix Medical Group, Fountain Valley, California, USA

4 Obstetrix Medical Group, San Jose, California, USA

5 The Centre for Research, Education & Quality (CREQ), Obstetrix Medical Group, Steamboat Springs, Colorado, USA

6 National Institute of Child Health and Human Development, Bethesda, Maryland, USA

7 The Biostatistics Centre, George Washington University, Rockville, MD, USA

8 Department of Obstetrics and Gynecology, Brown University, Providence, Rhode Island and Providence Plantations, USA

9 Department of Obstetrics and Gynecology, Magee Womens Hospital, University of Pittsburgh, Pittsburgh, USA

10 Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, USA

11 Department of Fetal Medicine 4002, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

12 Department of Obstetrics and Feto maternal Medicine, Medical University of Vienna, Vienna, Austria

13 Department of Obstetrics and Gynecology, Zeynep Kamil Women and Children Diseases Education and Research Hospital, Uskudar, Istanbul, Turkey

14 Department of Obstetrics and Gynecology, University of Mississippi Medical Centre, Jackson, USA

15 Department of Obstetrics and Gynecology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

16 Department of Obstetrics and Gynecology, Willis Knighton Medical Centre, Shreveport, Louisiana, USA

17 Maternal-Fetal Medicine Unit, Instituto Valenciano de Infertilidad, University of Valencia, Valencia, Spain

18 Department of Obstetrics and Gynecology, University Hospital La Fe, Valencia, Spain

19 Departamento de Obstetricia y Ginecología, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain

20 Department of Obstetrics and Gynecology, American University of Beirut, Beirut, Lebanon

21 Department of Obstetrics and Gynecology, Academic Medical Centre, Amsterdam, the Netherlands

22 Department of Obstetrics, and Gynecology, University Medical Centre Utrecht, Utrecht, the Netherlands

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BMC Pregnancy and Childbirth 2012, 12:13  doi:10.1186/1471-2393-12-13

Published: 15 March 2012

Abstract

Background

Preterm birth is the principal factor contributing to adverse outcomes in multiple pregnancies. Randomized controlled trials of progestogens to prevent preterm birth in twin pregnancies have shown no clear benefits. However, individual studies have not had sufficient power to evaluate potential benefits in women at particular high risk of early delivery (for example, women with a previous preterm birth or short cervix) or to determine adverse effects for rare outcomes such as intrauterine death.

Methods/design

We propose an individual participant data meta-analysis of high quality randomized, double-blind, placebo-controlled trials of progestogen treatment in women with a twin pregnancy. The primary outcome will be adverse perinatal outcome (a composite measure of perinatal mortality and significant neonatal morbidity). Missing data will be imputed within each original study, before data of the individual studies are pooled. The effects of 17-hydroxyprogesterone caproate or vaginal progesterone treatment in women with twin pregnancies will be estimated by means of a random effects log-binomial model. Analyses will be adjusted for variables used in stratified randomization as appropriate. Pre-specified subgroup analysis will be performed to explore the effect of progestogen treatment in high-risk groups.

Discussion

Combining individual patient data from different randomized trials has potential to provide valuable, clinically useful information regarding the benefits and potential harms of progestogens in women with twin pregnancy overall and in relevant subgroups.