Relationship between 17-alpha hydroxyprogesterone caproate concentration and spontaneous preterm birth

Abstract

Objective 17-alpha hydroxyprogesterone caproate (17-OHPC) 250 mg weekly reduces recurrent spontaneous preterm birth (SPTB) in women with a prior SPTB by 33%. The dose is not based on pharmacological considerations. A therapeutic concentration has not been determined hampering any attempt to optimize treatment. This study evaluated the relationship between 17-OHPC plasma concentrations and the rate of SPTB in women with singleton gestation. Study Design A single blood sample was obtained between 25 and 28 weeks gestation from 315 women with a SPTB who participated in a placebo-controlled, prospective, randomized clinical trial evaluating the benefit of omega-3 supplementation in reducing preterm birth. All women in the parent study received 17-OHPC and 434 received omega-3 supplementation and 418 received a placebo. Plasma from 315 consenting women was analyzed for 17-OHPC concentration. Results There were no differences between placebo and omega-3 supplemented groups in demographic variables, outcomes or in mean 17-OHPC concentration. Plasma concentrations of 17-OHPC ranged from 3.7- 56 ng/ml. Women with plasma concentrations of 17-OHPC in the lowest quartile had a significantly higher risk of spontaneous preterm birth (p= 0.03) and delivered at significantly earlier gestational ages (p = 0.002) than did women in the 2nd to 4th quartiles. The lowest preterm birth rates were seen when median 17-OHPC concentrations exceeded 6.4 ng/ml. Conclusions Low plasma 17-OHPC concentration is associated with an increased risk of SPTB. This finding validates efficacy of this treatment but suggests that additional studies are needed to determine the optimal dosage.

Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention

“…3,[18][19][20][21] Some studies have shown that protease inhibitors reduce progesterone production in the trophoblast in vitro and that low progesterone levels are associated with preterm delivery. [22][23][24][25] However, other studies have shown that nevirapine-based ART is also associated with a higher rate of preterm delivery than zidovudine plus single-dose nevirapine. 5,6 The PROMISE trial was not designed to compare protease inhibitor-based ART with NNRTI-based ART, and we cannot comment on whether the current WHO-recommended ART regimen of tenofovir, emtricitabine, and efavirenz would be associated with a lower risk of low birth weight or preterm delivery than the ART regimens in the PROMISE trial.…”

Progesterone inhibits in vitro fetal membrane weakening

“…55 Studies with primary human chorion cells, and in a mouse inflammatory-mediated parturition model, suggest that MPA may be more promising than HP for prevention of preterm birth. [56][57][58][59] However, the only randomized clinical trial to use MPA to prevent prematurity in at-risk pregnancies failed to demonstrate benefit.…”

Prevention of preterm delivery with 17-hydroxyprogesterone caproate: Pharmacologic considerations

“…In 315 women with a singleton gestation receiving 17-OHPC weekly, the concentrations ranged between 3.7–56ng/mL between 25 and 28 weeks of gestation 53 . Women with 17-OHPC plasma concentrations in the lowest quintile had a higher risk of recurrent spontaneous preterm birth compared to women in the third to fifth quintiles (36.5% vs. 25%, Figure 3).…”