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

TY - JOUR

T1 - Progestogens to prevent preterm birth in twin pregnancies

T2 - an individual participant data meta-analysis of randomized trials

AU - Schuit, Ewoud

AU - Stock, Sarah

AU - Groenwold, Rolf H H

AU - Maurel, Kimberly

AU - Combs, C Andrew

AU - Garite, Thomas

AU - Spong, Cathy Y

AU - Thom, Elizabeth A

AU - Rouse, Dwight J

AU - Caritis, Steve N

AU - Saade, George R

AU - Zachary, Julia M

AU - Norman, Jane E

AU - Rode, Line

AU - Klein, Katharina

AU - Tabor, Ann

AU - Cetingöz, Elçin

AU - Morrison, John C

AU - Magann, Everett F

AU - Briery, Christian M

AU - Serra, Vicente

AU - Perales, Alfredo

AU - Meseguer, Juan

AU - Nassar, Anwar H

AU - Lim, Arianne C

AU - Moons, Karel G M

AU - Kwee, Anneke

AU - Mol, Ben Willem J

PY - 2012/3/15

Y1 - 2012/3/15

N2 - 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.

AB - 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.

KW - Adult

KW - Clinical Protocols

KW - Female

KW - Humans

KW - Infant, Newborn

KW - Models, Statistical

KW - Pregnancy

KW - Pregnancy Complications

KW - Pregnancy Outcome

KW - Pregnancy, Twin

KW - Premature Birth

KW - Progestins

KW - Randomized Controlled Trials as Topic

U2 - 10.1186/1471-2393-12-13

DO - 10.1186/1471-2393-12-13

M3 - Journal article

C2 - 22420582

SN - 1471-2393

VL - 12

SP - 13

JO - B M C Pregnancy and Childbirth

JF - B M C Pregnancy and Childbirth

ER -