679: 17-hydroxy progesterone caproate levels and risk for preterm birth

Weekly injections of 17-hydroxyprogesterone caproate (17OHPC), a synthetic progesterone, is recommended for the prevention of recurrent preterm birth (PTB). There are conflicting data on the relationship between maternal serum levels of 17OHPC and its efficacy. We tested the hypothesis that lower levels of maternal blood 17OHC is associated with an increased risk of recurrent PTB. We performed a nested case control within a prospective cohort study of patients with singleton pregnancies receiving 17OHPC (Makena) for PTB prevention. 17OHPC injections were used according to standard of care (150 mg, weekly dosing beginning at 16 weeks or as soon as the patient presented for care). Maternal blood samples were obtained serially antepartum and at delivery. Liquid chromatography-mass spectroscopy was used to assess maternal blood plasma levels of 17OHPC. 10 cases of PTB (delivery at <37 weeks) were compared with 10 term birth controls. Maternal 17OHPC levels at 22-24 weeks were compared between women with preterm and term births using Wilcoxon Signed Rank Test. We chose 22-24 weeks of gestation because patients will have received sufficient injections to reach steady state and it is a clinically relevant gestational age for risk stratification for possible additional interventions. Low 17OHPC was defined as levels below the <25th percentile at 22-24 weeks. A total of 20 maternal and fetal dyads were included. Median maternal plasma 17OHPC level at 22-24 weeks was not significantly different in preterm versus term birth (median[IQR]: 7.2 [4.7, 8.5] versus 8.1 [6.7, 9.0] ng/ml, p=0.2. However, patients with PTB were markedly more likely to have low 17OHPC levels compared to women with term birth (40% versus 0%, p=0.09). Remarkably no patients who delivered at term had low 17OHPC at 22 - 24 weeks. The number of injections of 17OHPC received, and time elapsed since last injection were similar in the two groups. Low levels of maternal plasma 17OHPC at 22-24 weeks appear to associate with failure in preventing recurrent PTB. If confirmed, assessment of maternal 17OHPC at 22-24 weeks may help identify patients at risk for failure who may benefit from additional interventions.