Vaginal progesterone may not be effective for preventing preterm births

Vaginal progesterone, a hormone treatment considered the standard of care for preventing preterm birth in at-risk pregnant women, may not be effective, according to UT Southwestern Medical Center researchers.

Anyone who has held the fragile body of a preterm baby – born between 20 and 37 weeks – knows every extra day and week in the womb is vital to the newborn's health. Previous early deliveries are one of the biggest risk factors for preterm birth. Doctors usually recommend progesterone for women in this group.

The new study, involving more than 1,600 pregnant women with a history of early delivery, found vaginal progesterone had no effect on preterm birth. The findings, reported in the journal JAMA Network Open, add to growing evidence suggesting that progesterone may not be worth prescribing for some women.

Our hope is that this information will help practitioners guide conversations with their patients. Certainly in different populations there may be different outcomes. But among our patients, we did not find benefit of vaginal progesterone when given for an indication of prior preterm birth."

David Nelson, M.D., Study Leader, Associate Professor of Obstetrics and Gynecology and Division Chief of Maternal-Fetal Medicine

.Despite decades of advances in neonatal care, babies born prematurely face short- and long-term health complications. Preterm birth affects about 10% of all live births in the United States and is the leading cause of death in children under age 5. For pregnant women with previous preterm births, the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine recommend progesterone therapy.

In 2017, a study by Dr. Nelson and UTSW colleagues concluded that injectable progesterone was ineffective at preventing preterm births in at-risk women. However, the use of vaginal progesterone had not been analyzed in a large study among similar patient populations.

"Because of the controversy around injectable progesterone, professional organizations pivoted and began to recommend vaginal progesterone," said Dr. Nelson. "Everybody hoped this was the answer to reduce preterm births and there's been enthusiasm that it may show a benefit."

Women in the new study all had a history of preterm birth and were treated at Parkland Health, an urban safety net health system served by UT Southwestern physicians. Between 2017 and 2019, 417 study patients received vaginal progesterone. The research team then compared the rate of preterm births in this group with the historical rate among 1,251 similar patients seen at Parkland.

Of women who took vaginal progesterone during the study period, 24% gave birth at or before 35 weeks' gestation, compared to 16.8% in the historical control. Dr. Nelson, a Dedman Family Scholar in Clinical Care at UTSW, said thus progesterone therapy did not reduce preterm births. Moreover, the team found no association between preterm births and how well patients adhered to the medication schedule, or between preterm births and patients' blood levels of progesterone.

Additional studies are likely needed before clinicians eliminate vaginal progesterone as a treatment option, Dr. Nelson said. He and his colleagues hope their results help spur not only new research into progesterone but other potential treatment for preterm birth.

"As we begin to better understand the diverse underlying causes of preterm birth, our hope is that we can develop treatments that are more targeted and effective to patients," said Catherine Spong, M.D., Chair of Obstetrics and Gynecology at UTSW and an author of the study.

Other UTSW researchers who contributed to this study include Ashlyn Lafferty, Chinmayee Venkatraman, Jeffrey McDonald, Kaitlyn Eckert, and Donald McIntire. Ms. Eckert is also currently employed by SCIEX.

Dr. Spong holds the Paul C. MacDonald Distinguished Chair in Obstetrics and Gynecology.