Progress toward personalized prevention of preterm birth: When progesterone works and when it does not

DETROIT – The most effective intervention to prevent preterm birth is the administration of a natural hormone, progesterone, in patients at risk for premature delivery. Two categories of patients have been eligible for this treatment: those with a short cervix and those with a previous preterm birth.

But research published this week in the American Journal of Obstetrics and Gynecology by researchers of the Perinatology Research Branch at the Wayne State University School of Medicine indicates that progesterone is not effective in reducing the rate of preterm birth in women with a history of such birth.

In the article, “Does vaginal progesterone prevent recurrent preterm birth in women with a singleton gestation and a history of spontaneous preterm birth? Evidence from a systematic review and meta-analysis,” the researchers call for revision of American College of Obstetricians and Gynecologists, and Society for Maternal-Fetal Medicine guidelines that recommend the use of progesterone in women with a history of spontaneous pre-term birth.

“We have advocated that vaginal progesterone reduces the rate of preterm birth in women with a short cervix. This evidence is solid and derived from multiple studies including randomized clinical trials, meta-analyses and implementation research,” said Roberto Romero, M.D., DMedSci, chief of the Eunice Kennedy Shriver National Institute of Child Health and Human Development’s Perinatology Research Branch and Professor of Molecular Obstetrics and Genetics at the Wayne State University School of Medicine. “Some people believe that vaginal progesterone is effective not only in women with a short cervix but also in patients with a prior history of preterm birth. We have completed a systematic review and meta-analysis that shows that this is not the case.”

The effective use of vaginal progesterone in women identified with a short cervix via sonograph to prevent pre-term birth was identified and developed by the PRB in 2010. But extrapolating these findings to patients with a prior history of preterm birth is not correct, the latest findings show.

Women with a history of spontaneous preterm birth have a 2.5- to four-fold increased risk of subsequent such issues compared to women with no history of pre-term birth. The American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine recommend the use of vaginal progesterone or 17α-hydroxyprogesterone caproate for all pregnant women with a history of pre-term birth.

“We believe it is important to understand the limitations of a successful strategy to avoid overtreatment. We advocate for universal screening of cervical length and the identification of patients who may benefit from a specific intervention. In other words, individualized medicine and not one size fits all,” said Dr. Romero, who published the findings with Agustin Conde-Agudelo, M.D., M.P.H., Ph.D., adjunct professor of Obstetrics and Gynecology, and head of the Unit of Perinatal Epidemiology, Systematic Reviews and Meta-analyses.

The team reviewed findings from 10 randomized controlled trials that compared vaginal progesterone to placebo or no treatment in asymptomatic women with a singleton gestation and a history of spontaneous preterm birth. They found no convincing evidence that the use of progesterone prevented pre-term birth in these women.

Preterm labor, Dr. Romero explained, is a syndrome associated with multiple mechanisms of disease, including infection and/or inflammation, decidual hemorrhage and vascular disease, uterine overdistention, cervical disease, disruption of maternal-fetal tolerance, maternal stress and decline in progesterone action. The syndromic nature of preterm labor explains why a single method of intervention does not prevent all or even predict most cases of preterm birth, he said.

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About Wayne State University

Wayne State University is one of the nation’s pre-eminent public research universities in an urban setting. Through its multidisciplinary approach to research and education, and its ongoing collaboration with government, industry and other institutions, the university seeks to enhance economic growth and improve the quality of life in the city of Detroit, state of Michigan and throughout the world. For more information about research at Wayne State University, visit research.wayne.edu.