title: Progestogens to prevent preterm birth in twin pregnancies: an individual participant data meta-analysis of randomized trials.
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
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, the Netherlands. e.schuit@umcutrecht.nl
authors.forename: Ewoud
authors.initials: E
authors.lastname: Schuit
authors.forename: Sarah
authors.initials: S
authors.lastname: Stock
authors.forename: Rolf H H
authors.initials: RH
authors.lastname: Groenwold
authors.forename: Kimberly
authors.initials: K
authors.lastname: Maurel
authors.forename: C Andrew
authors.initials: CA
authors.lastname: Combs
authors.forename: Thomas
authors.initials: T
authors.lastname: Garite
authors.forename: Cathy Y
authors.initials: CY
authors.lastname: Spong
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Thom
authors.forename: Dwight J
authors.initials: DJ
authors.lastname: Rouse
authors.forename: Steve N
authors.initials: SN
authors.lastname: Caritis
authors.forename: George R
authors.initials: GR
authors.lastname: Saade
authors.forename: Julia M
authors.initials: JM
authors.lastname: Zachary
authors.forename: Jane E
authors.initials: JE
authors.lastname: Norman
authors.forename: Line
authors.initials: L
authors.lastname: Rode
authors.forename: Katharina
authors.initials: K
authors.lastname: Klein
authors.forename: Ann
authors.initials: A
authors.lastname: Tabor
authors.forename: Elçin
authors.initials: E
authors.lastname: Cetingöz
authors.forename: John C
authors.initials: JC
authors.lastname: Morrison
authors.forename: Everett F
authors.initials: EF
authors.lastname: Magann
authors.forename: Christian M
authors.initials: CM
authors.lastname: Briery
authors.forename: Vicente
authors.initials: V
authors.lastname: Serra
authors.forename: Alfredo
authors.initials: A
authors.lastname: Perales
authors.forename: Juan
authors.initials: J
authors.lastname: Meseguer
authors.forename: Anwar H
authors.initials: AH
authors.lastname: Nassar
authors.forename: Arianne C
authors.initials: AC
authors.lastname: Lim
authors.forename: Karel G M
authors.initials: KG
authors.lastname: Moons
authors.forename: Anneke
authors.initials: A
authors.lastname: Kwee
authors.forename: Ben Willem J
authors.initials: BW
authors.lastname: Mol
mesh_terms: D000328:Adult; D002985:Clinical Protocols; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D015233:Models, Statistical; D011247:Pregnancy; D011248:Pregnancy Complications / Q000517:prevention & control*; D011256:Pregnancy Outcome; D059285:Pregnancy, Twin / Q000187:drug effects*; D047928:Premature Birth / Q000517:prevention & control*; D011372:Progestins / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
chemical_list: D011372:Progestins