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Review
. 2024 Jan 22:16:119-130.
doi: 10.2147/IJWH.S394305. eCollection 2024.

Challenges in Using Progestin to Prevent Singleton Preterm Births: Current Knowledge and Clinical Advice

David B Nelson  1 , Yevgenia Y Fomina  1
Affiliations
Review

Challenges in Using Progestin to Prevent Singleton Preterm Births: Current Knowledge and Clinical Advice

David B Nelson et al. Int J Womens Health. .

Abstract

Preterm birth is the leading cause of infant morbidity and mortality in children younger than 5 years old and accounts for approximately 35% of newborn deaths worldwide. The use of progestogen therapy for prevention of preterm birth has been one of the most controversial topics in modern obstetrics. Progestogens can be classified as natural or synthetic. Progesterone is a natural progestogen while progestins such as 17-alpha-hydroxyprogesterone caproate (17OHP-C) are synthetic steroid hormones. Evidence supporting the use of progestogens varies by formulation and populations studied. After more than a decade, the US Food and Drug Administration has withdrawn accelerated approval of 17OHP-C for the prevention of recurrent preterm birth in pregnant individuals with a singleton gestation. With this decision, there is no current FDA-approved treatment for prevention of spontaneous preterm birth. In this review, we provide a historical context behind the rise and fall of 17OHP-C clinical application, highlight the challenges behind the data supporting progestogen use, and offer suggestions on how to make an impact on preterm birth moving forward.

Keywords: 17-alpha-hydroxyprogesterone caproate; FDA; Makena®; National Institute of Health; accelerated approval; anxiety; healthcare costs; neonatal morbidity and mortality; pregnancy; preterm birth; progesterone; progestin; progestogen; spontaneous preterm birth.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Preterm birth rate in the United States over time. Adapted from March of Dimes full report card; 2022. Available from: https://www.marchofdimes.org/peristats/data?top=3&lev=1&stop=60®=99&obj=1&slev=1.
Figure 2
Figure 2
OE- and LMP- based measures of gestational age for selected weeks: United States, 2013.
Figure 3
Figure 3
Proposed mechanisms of disease implicated in spontaneous preterm labor. Created with BioRender.com.
Figure 4
Figure 4
Clinical timeline of 17OHP-C trials and FDA decisions.
Figure 5
Figure 5
The PROLONG trial examining 5 demographic and baseline characteristics. Data from Nyugen CP.
Figure 6
Figure 6
NIH funding allocation in 2022.
See this image and copyright information in PMC

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