Preterm birth represents a significant cause of morbidity and mortality with the highest risks for infants born prior to 28 weeks, but with risks still present up to term. Risks to infants born very premature include cerebral palsy, blindness, deafness, profound neurologic impairment while infants born in the late preterm and early term window are at risk for behavioral issues such as ADHD, learning disabilities, developmental delay and SIDS.
In patients with a history of a spontaneous preterm birth (either due to preterm labor or PPROM), progesterone therapy is recommended, to be started between 16-20 weeks. Cervical length screening is also recommended typically between 16-24 weeks. Traditionally 17 OHPC has been used for risk reduction based on a trial performed by Meis et al and published in 2003. That trial showed a 30% reduction in risk of recurrent preterm birth. Based on that study, 17 OHPC was widely used as the preferred form of progesterone. Subsequent studies have not been able to replicate the initial success rates found in the Meis trial for 17OHPC and a more recent study, the PROLONG trial found that 17 OHPC was not effective at all in prevention of preterm birth. The patient populations in the two trials are different with the Meis trial having a higher risk population (differences in number of preterm births, socioeconomic factors, race, among others) compared to the PROLONG trial which was a more broad representation of the population. The lack of findings of effect in the PROLONG trial called into question the efficacy of 17 OHPC in prevention of preterm birth.
The FDA advisory panel recently has revisited 17 OHPC and made a recommendation that it should no longer be FDA approved for the indication of prevention of preterm birth. They made this recommendation previously, just prior to the COVID pandemic and the FDA did not make any changes at that time. ACOG and SMFM still state that 17 OHPC is an acceptable medication for use for risk reduction.
There have been other studies using alternate forms of progesterone including vaginal progesterone in pill or capsule form (Prometrium) and gel form (Crinone) which have also shown some success in risk reduction. However, vaginal progesterone therapy is most effective for the treatment of cervical shortening. The published literature is mixed as is it pertains to efficacy in risk reduction for preterm birth. ACOG and SMFM both continued their recommendation for progesterone supplementation
Some insurance companies are not covering 17 OHPC (which started after the original advisory panel recommendations several years ago) and only cover vaginal Prometrium. In other cases a prior authorization is needed for the medication, but it can still be obtained. We no longer have access to a compounding pharmacy locally that will make the medication and in most cases, will need to be ordered from the patient’s specialty pharmacy. In the event that it is not covered or prohibitively expensive, vaginal Prometrium is an appropriate alternative.
After review of the available evidence and national recommendations, NWP is adjusting its traditional approach to management of pregnancy with a history of preterm birth. Our clinicians remain available to discuss the risks/benefits/alternatives with your patients. Our team is continuing to monitor decisions being made on a national advisory level. We are also reviewing our local cervical length screening practice in response to data we have discovered during our review.
Our current recommendations are for patients that are progesterone naïve, vaginal progesterone should be the preferred treatment modality, combined with cervical length screening to evaluate for shortening that may indicate the need for additional interventions such as cervical cerclage. Based on medication cost and insurance coverage, Prometrium 200mg per vagina is the recommended formulation. In patients that have previously used 17 OHPC, an informed discussion about the published data, concerns about efficacy of the medication, uncertainty about its status with the FDA, and discussion of the alternate forms of therapy she be conducted. If the patient, after an informed discussion, opts for 17 OHPC, that is still considered an acceptable option until such time as the FDA makes an alternate decision about drug approval.