Clinical Review

Managing preterm birth in those at risk: Expert strategies

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Screen cervical length early, and use cerclage or vaginal progesterone as appropriate

Michael G. Ross, MD, MPH

In patients with a history of a previous preterm birth, if 17P is no longer an option, I would revert to screening for short cervix with transvaginal ultrasound.

Screen all high-risk patients at the first prenatal visit, so as not to miss a short cervix before 16 weeks' gestation. Then, beginning at 16 weeks, screen every 2 weeks until approximately 24 weeks.

If the cervix shortens to 25 mm or less, offer cerclage or vaginal progesterone. If the cervix shortens to 20 mm or less, I would strongly support cerclage or vaginal progesterone.

Use of 17P is still an option, for now

Errol R. Norwitz, MD, PhD, MBA

The way in which 17P was handled by the FDA is exactly the way the system is designed to work; this should be seen as a success, not a failure.

Given the urgent need for an intervention to prevent preterm birth, the lack of any alternative, and a single, well-designed randomized controlled trial that confirmed safety and suggested some benefit, the FDA approved 17P supplementation in February 2011 for a limited indication only—one or more prior unexplained sPTD—using the expedited review mechanism.2 Under this mechanism, a follow-up clinical trial is required to confirm efficacy. This was the PROLONG trial, which failed to show any significant benefit of 17P supplementation in terms of either preterm birth prevention or neonatal outcome.1

In October 2019, an FDA advisory committee met again to review these and other data. After presentations from a range of stakeholders and a robust discussion, the advisory committee voted to pursue approval withdrawal of 17P due to the lack of consistent evidence of benefit (it is important to note that this was not because of safety concerns). This is exactly the way the process is designed to work.

Where does this leave physicians and patients? It is clear that progesterone supplementation is not a panacea for preterm birth prevention and is not indicated for all women at high risk, even those with one or more prior unexplained sPTDs. Given that preterm birth is a syndrome and not a single diagnosis, it is still possible that there is a subgroup of women who may benefit from this intervention. For this reason—and because there is no clear alternative and no known downside to the administration of this drug (other than cost)—physicians still may choose to discuss this option with their patients and, after counseling, patients still may choose to accept it. If in doubt, engage the "shared decision-making model"; talk to your patients.

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