The authors found no difference between treatment groups for either coprimary efficacy outcome; PTB < 350/7weeks (17-OHPC 11.0% vs placebo 11.5%; RR = 0.95 [95% CI: 0.71 – 1.26]; P = 0.72) and neonatal composite index (17-OHPC 5.6% vs placebo 5.0%; RR 1.12 [95% CI 0.70 – 1.66]; P = 0.73). After reviewing the individual components of the neonatal composite index, the authors found no differences between the treatment groups for any of the components assessed. Rates of PTB at < 37 and < 32 weeks were not different either.
The fetal/early infant death rates were lower than expected and no different between treatment groups (17-OHPC 1.7 vs placebo 1.9%; RR = 0.87 [95% CI: 0.4-1.81]). Patients receiving 17-OHPC had a lower risk of miscarriage (17 OHPC 0.5% vs 1.6%; RR = 0.28 [95% CI: 0.08 – 0.94]) and there was no statistically significant difference in frequency of stillbirth (17-OHPC 1.1% vs placebo 0.5%; RR 2.07 [95% CI 0.59-7.29]).
Following the results from this study, the American College of Obstetricians and Gynecologists (ACOG) and the Society of Maternal-Fetal Medicine (SMFM) both released statements on the findings. In a Practice Advisory, ACOG stated, “Consideration for offering 17-OHPC to women at risk of recurrent preterm birth should continue to take into account the body of evidence for progesterone supplementation, the values and preferences of the pregnant woman, the resources available, and the setting in which the intervention will be implemented.”
SMFM released a statement calling for a similar approach. The organization, which had supported treatment with 17-OHPC following the original study, reiterated that 17-OHPC “appears to be safe in the short term, with no increase in congenital anomalies or evidence of teratogenic effects.” Furthermore, the statement affirmed the belief that “it is reasonable for providers to use 17-OHPC in women with a profile more representative of the very high-risk population reported on in the Meis trial. For all women at risk of sPTB, the risk/benefit discussion should incorporate a shared decision-making approach, taking into account the lack of short-term safety concerns but uncertainty regarding benefit.”
The authors believe their findings contradict earlier indications that 17-OHPC could decrease recurrent PTB and it was not associated with increased fetal/early infant death. However, they recognize that the PROLONG trial was underpowered and inconclusive regarding assessment of treatment efficacy. Going forward, systematic reviews and/or meta-analyses to differentiate a population with the most optimal benefit/risk ratio could be beneficial.