Ewoud Schuit, University Medical Centre Utrecht, Utrecht, Netherlands
Sarah Stock, University of Edinburgh, Edinburgh, Scotland
Rolf H.H. Groenwold, University Medical Centre Utrecht, Utrecht, Netherlands
Kimberly Maurel, Obstetrix Medical Group, Fountain Valley, CA
C. Andrew Combs, Obstetrix Medical Group
Thomas Garite, Obstetrix Medical Group, Steamboat Springs, CO
Catherine Y. Spong, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD
Elizabeth A. Thom, George Washington UniversityFollow
Dwight J. Rouse, University of Alabama - Birmingham
Steve N. Caritis, University of Pittsburgh
George Saade, University of Texas
Julia M. Zachary, George Washington University
Jane E. Norman, Medical University of Vienna, Vienna, Austria
Line Rode, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Katharina Klein, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Ann Tabor, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Elcin Cetingoz, Zeynep Kamil Women and Children Diseases Education, Research Hospital, Uskudar, Istanbul, Turkey
John C. Morrison, University of Mississippi Medical Centre
Everett F. Magann, University of Arkansas for Medical Sciences
Christian M. Briery, Willis Knighton Medical Centre, Shreveport, LA
Vicente Serra, University of Valencia, Valencia, Spain
Alfredo Perales, University Hospital La Fe, Valencia, Spain
Juan Meseguer, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain
Anwar Nassar, American University of Beirut
Arianne C. Lim, Academic Medical Centre, Amsterdam, Netherlands
Karel G.M. Moons, University Medical Centre Utrecht, Utrecht, Netherlands
Anneke Kwee, University Medical Centre Utrecht, Utrecht, Netherlands
Ben W.J. Mol, Academic Medical Centre, Amsterdam, Netherlands

Document Type

Journal Article

Publication Date



BMC Pregnancy and Childbirth


Volume 12, Article number 13

Inclusive Pages



Pregnancy Complications--prevention & control; Pregnancy Outcome; Pregnancy; Twin--drug effects; Premature Birth--prevention & control; Progestins--therapeutic use



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.


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.


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.


Reproduced with permission of BioMed Central Pregnancy and Childbirth

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.

Peer Reviewed


Open Access