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, A Jeanine van der Ven, C Emily Kleinrouweler, Ewoud Schuit, Brenda M Kazemier, Corine J Verhoeven, Esteriek de Miranda, Aleid G van Wassenaer-Leemhuis, J Marko Sikkema, Mallory D Woiski, Patrick M Bossuyt, Eva Pajkrt, Christianne J M de Groot, Ben Willem J Mol, Monique C Haak

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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.

Original languageEnglish
Pages (from-to)993-1000
Number of pages8
JournalAmerican Journal of Perinatology
Volume32
Issue number10
DOIs
Publication statusPublished - Aug 2015

Keywords

  • cervical length
  • preterm birth
  • progesterone
  • neonatal outcome

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