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Am J Perinatol 2015; 32(10): 993-1000
DOI: 10.1055/s-0035-1547327
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

Melanie A. van Os
1   Department of Obstetrics and Gynecology, VU University Medical Center, Amsterdam, The Netherlands
,
A. Jeanine van der Ven
2   Department of Obstetrics and Gynecology, Academic Medical Center, Amsterdam, The Netherlands
,
C. Emily Kleinrouweler
2   Department of Obstetrics and Gynecology, Academic Medical Center, Amsterdam, The Netherlands
,
Ewoud Schuit
2   Department of Obstetrics and Gynecology, Academic Medical Center, Amsterdam, The Netherlands
3   Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands
4   Stanford Prevention Research Center, Stanford University, Stanford, California
,
Brenda M. Kazemier
2   Department of Obstetrics and Gynecology, Academic Medical Center, Amsterdam, The Netherlands
,
Corine J. Verhoeven
5   Department of Obstetrics and Gynecology, Máxima Medisch Centrum, Veldhoven, The Netherlands
6   Department of Midwifery Science, AVAG/EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands
,
Esteriek de Miranda
2   Department of Obstetrics and Gynecology, Academic Medical Center, Amsterdam, The Netherlands
,
Aleid G. van Wassenaer-Leemhuis
7   Department of Neonatology, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands
,
J. Marko Sikkema
8   Department of Obstetrics and Gynecology, ZGT, Almelo, The Netherlands
,
Mallory D. Woiski
9   Department of Obstetrics and Gynecology, Radboud University, Nijmegen, The Netherlands
,
Patrick M. Bossuyt
10   Department of Clinical Epidemiology, Academic Medical Center, Amsterdam, The Netherlands
,
Eva Pajkrt
2   Department of Obstetrics and Gynecology, Academic Medical Center, Amsterdam, The Netherlands
,
Christianne J. M. de Groot
1   Department of Obstetrics and Gynecology, VU University Medical Center, Amsterdam, The Netherlands
,
Ben Willem J. Mol
11   The Robinson Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, Australia
,
Monique C. Haak
12   Department of Obstetrics, Leiden University Medical Center, Leiden, The Netherlands
› Author Affiliations
Further Information

Publication History

19 November 2014

23 January 2015

Publication Date:
04 March 2015 (online)

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Abstract

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).

Study Design 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).

Conclusion 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.

Keywords

cervical length - preterm birth - progesterone - neonatal outcome
 

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