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Am J Perinatol 2012; 29(09): 665-672
DOI: 10.1055/s-0032-1316444
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Safety of Progesterone and 17-Hydroxyprogesterone Caproate Administration for the Prevention of Preterm Birth: An Evidence-Based Assessment

John M. O'Brien
1   Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Kentucky, Lexington, Kentucky
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Publication History

16 December 2011

05 March 2012

Publication Date:
06 July 2012 (online)

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Abstract

The safety of supplemental progestin therapy during pregnancy reflects whether an agent exclusively promotes or potentially inhibits progestational cellular functions and whether treatment incites a metabolic derangement or other pathophysiology to initiate rare untoward events. No safety signal has been identified from intravaginal administration of natural progesterone from phase III clinical trials. The Food and Drug Administration has identified a legitimate safety signal regarding second-trimester miscarriage and stillbirth with exposure to 17-hydroxyprogesterone caproate (17-OHPC). Results from recent phase II and III trials in multiples also demonstrates concern with exposure to this synthetic for fetal loss and increased severe respiratory distress in neonates (one study each), as well as repeated significant associations for shorter duration of pregnancy and poorer fetal growth in others. The biological plausibility for 17-OHPC to be associated with adverse outcomes can be suggested from pharmacogenomic observations, ex vivo experimentation, and clinical observations. Further data are needed interrogating the potential for rare fetal or maternal adverse events/safety outcomes with exposure to progestins. Safety concerns should be incorporated into prescribing decisions.

Keywords

progesterone - 17-hydroxyprogesterone caproate - preterm birth - safety - progestin
 

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