Preterm birth prevention in twin pregnancies with progesterone, pessary, or cerclage: a systematic review and meta-analysis.
BACKGROUND
About half of twin pregnancies deliver preterm, and it is unclear whether any intervention reduces this risk.


OBJECTIVE
To assess the evidence for the effectiveness of progesterone, cerclage, and pessary in twin pregnancies.


METHODS
We searched Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and ISI Web of Science, without language restrictions, up to 25 January 2016.


METHODS
Randomised controlled trials of progesterone, cerclage, or pessary for preventing preterm birth in women with twin pregnancies, without symptoms of threatened preterm labour.


METHODS
Two independent reviewers extracted data using a piloted form. Study quality was appraised with the Cochrane Risk of Bias tool. We performed pairwise inverse variance random-effects meta-analyses.


RESULTS
We included 23 trials (all but three were considered to have a low risk of bias) comprising 6626 women with twin pregnancies. None of the interventions significantly reduced the risk of preterm birth overall at <34 or <37 weeks of gestation, or neonatal death, our primary outcomes, compared to a control group. In women receiving vaginal progesterone, the relative risk (RR) of preterm birth <34 weeks of gestation was 0.82 (95% CI 0.64-1.05, seven studies, I236%), with a significant reduction in some key secondary outcomes, including very low birthweight (<1500 g, RR 0.71, 95% CI 0.52-0.98, four studies, I246%) and mechanical ventilation (RR 0.61, 95% CI 0.45-0.82, four studies, I222%).


CONCLUSIONS
In twin gestations, although no overarching intervention was beneficial for the prevention of preterm birth and its sequelae, vaginal progesterone improved some important secondary outcomes.


CONCLUSIONS
Vaginal progesterone may be beneficial in twin pregnancies, but not 17-OHPC, cerclage, or pessary.
Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON, Canada.
A
A
Jarde
Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON, Canada.
O
O
Lutsiv
Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
C K
CK
Park
Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
J
J
Barrett
Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
J
J
Beyene
Department of Obstetrics and Gynecology, University of Toyama, Toyama, Japan.
S
S
Saito
Department of Obstetrics and Gynecology, University of Adelaide, Adelaide, Australia.
J M
JM
Dodd
Department of Paediatrics, University of Toronto, Toronto, ON, Canada.
P S
PS
Shah
The Society of Obstetricians and Gynaecologists of Canada, Ottawa, ON, Canada.
J L
JL
Cook
Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada.
A B
AB
Biringer
Department of Pediatrics, McMaster University, Hamilton, ON, Canada.
L
L
Giglia
The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
Z
Z
Han
Canadian Premature Babies Foundation, Sherwood Park, AB, Canada.
K
K
Staub
Maternal Fetal Medicine Clinic, Windsor Regional Hospital, Windsor, ON, Canada.
W
W
Mundle
Division of Obstetrics and Gynecology, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
C
C
Vera
Midwifery Education Program, McMaster University, Hamilton, ON, Canada.
L
L
Sabatino
Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON, Canada.
S K
SK
Liyanage
Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON, Canada.
S D
SD
McDonald
D000282:Administration, Intravaginal; D023802:Cerclage, Cervical / Q000706:statistics & numerical data*; D005260:Female; D005865:Gestational Age; D006801:Humans; D010570:Pessaries / Q000706:statistics & numerical data*; D011247:Pregnancy; D059285:Pregnancy, Twin; D047928:Premature Birth / Q000453:epidemiology / Q000517:prevention & control*; D011374:Progesterone / Q000008:administration & dosage*; D011372:Progestins / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D016896:Treatment Outcome
D011372:Progestins; D011374:Progesterone
Cerclage; pessary; preterm birth; progesterone; randomised controlled trials; twin