Preventing Preterm Birth with Progesterone in Women with a Short Cervical Length from a Low-Risk Population: A Multicenter Double-Blind Placebo-Controlled Randomized Trial.
OBJECTIVE
The objective of this study was to evaluate the effectiveness of vaginal progesterone in reducing adverse neonatal outcome due to preterm birth (PTB) in low-risk pregnant women with a short cervical length (CL).


METHODS
Women with a singleton pregnancy without a history of PTB underwent CL measurement at 18 to 22 weeks. Women with a CL ≤ 30 mm received vaginal progesterone or placebo. Primary outcome was adverse neonatal outcome, defined as a composite of respiratory distress syndrome, bronchopulmonary dysplasia, intracerebral hemorrhage > grade II, necrotizing enterocolitis > stage 1, proven sepsis, or death before discharge. Secondary outcomes included time to delivery, PTB before 32, 34, and 37 weeks of gestation. Analysis was by intention to treat.


RESULTS
Between 2009 and 2013, 20,234 women were screened. A CL of 30 mm or less was seen in 375 women (1.8%). In 151 women, a CL ≤ 30 mm was confirmed with a second measurement and 80 of these women agreed to participate in the trial. We randomly allocated 41 women to progesterone and 39 to placebo. Adverse neonatal outcomes occurred in two (5.0%) women in the progesterone and in four (11%) women in the control group (relative risk [RR], 0.47; 95% confidence interval [CI], 0.09-2.4). The use of progesterone resulted in a nonsignificant reduction of PTB < 32 weeks (2.0 vs. 8.0%; RR, 0.33; 95% CI, 0.04-3.0) and < 34 weeks (7.0 vs. 10%; RR, 0.73; 95% CI, 0.18-3.1) but not on PTB < 37 weeks (15 vs. 13%; RR, 1.2; 95% CI, 0.39-3.5).


CONCLUSIONS
In women with a short cervix, who are otherwise low risk, we could not show a significant benefit of progesterone in reducing adverse neonatal outcome and PTB.
Department of Obstetrics and Gynecology, VU University Medical Center, Amsterdam, The Netherlands.
Melanie A
MA
van Os
Department of Obstetrics and Gynecology, Academic Medical Center, Amsterdam, The Netherlands.
A Jeanine
AJ
van der Ven
Department of Obstetrics and Gynecology, Academic Medical Center, Amsterdam, The Netherlands.
C Emily
CE
Kleinrouweler
Department of Obstetrics and Gynecology, Academic Medical Center, Amsterdam, The Netherlands.
Ewoud
E
Schuit
Department of Obstetrics and Gynecology, Academic Medical Center, Amsterdam, The Netherlands.
Brenda M
BM
Kazemier
Department of Obstetrics and Gynecology, Máxima Medisch Centrum, Veldhoven, The Netherlands.
Corine J
CJ
Verhoeven
Department of Obstetrics and Gynecology, Academic Medical Center, Amsterdam, The Netherlands.
Esteriek
E
de Miranda
Department of Neonatology, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands.
Aleid G
AG
van Wassenaer-Leemhuis
Department of Obstetrics and Gynecology, ZGT, Almelo, The Netherlands.
J Marko
JM
Sikkema
Department of Obstetrics and Gynecology, Radboud University, Nijmegen, The Netherlands.
Mallory D
MD
Woiski
Department of Clinical Epidemiology, Academic Medical Center, Amsterdam, The Netherlands.
Patrick M
PM
Bossuyt
Department of Obstetrics and Gynecology, Academic Medical Center, Amsterdam, The Netherlands.
Eva
E
Pajkrt
Department of Obstetrics and Gynecology, VU University Medical Center, Amsterdam, The Netherlands.
Christianne J M
CJ
de Groot
The Robinson Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, Australia.
Ben Willem J
BW
Mol
Department of Obstetrics, Leiden University Medical Center, Leiden, The Netherlands.
Monique C
MC
Haak
D000282:Administration, Intravaginal; D000328:Adult; D001997:Bronchopulmonary Dysplasia / Q000453:epidemiology; D002543:Cerebral Hemorrhage / Q000453:epidemiology; D054791:Cervical Length Measurement; D002584:Cervix Uteri / Q000000981:diagnostic imaging*; D004311:Double-Blind Method; D020345:Enterocolitis, Necrotizing / Q000453:epidemiology; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D011247:Pregnancy; D047928:Premature Birth / Q000517:prevention & control*; D011374:Progesterone / Q000627:therapeutic use*; D011372:Progestins / Q000627:therapeutic use*; D012127:Respiratory Distress Syndrome, Newborn / Q000453:epidemiology; D018805:Sepsis / Q000453:epidemiology; D013997:Time Factors; D016896:Treatment Outcome
D011372:Progestins; D011374:Progesterone