We thank Drs Usta, Usta, and Nassar for their questions and comments. The method that was used to assay 17-hydroxyprogesterone caproate (HPLC-MS/MS) distinguishes progesterone from 17-hydroxyprogesterone and 17-hydroxyprogesterone caproate. We are confident therefore that the measurements reflect concentrations of 17-hydroxyprogesterone caproate and not other gestational hormones. We found a relationship between C-reactive protein and 17-hydroxyprogesterone caproate and agree that it would have been useful to have corticotropin-releasing hormone concentrations at baseline; however, we did not have a pretreatment blood sample, so such analysis could not be done. In this study, blood was obtained only once during 2 epochs of time. The samples were obtained before the next injection and therefore represent trough concentrations. Unlike previous studies in which we obtained daily blood samples for 7 days, we could measure only trough concentrations in this cohort of subjects.

The possibility that higher doses of 17-hydroxyprogesterone caproate could have improved efficacy in twin pregnancies has been considered. We have demonstrated in twin pregnancies that women with higher concentrations had a shorter gestational length than did women with lower concentrations of 17-hydroxyprogesterone caproate. Thus, in twin pregnancies, we do not think that the lack of efficacy was due to an inadequate blood level of 17-hydroxyprogesterone caproate. In singleton pregnancies, however, efficacy may be improved by higher concentrations of 17-hydroxyprogesterone caproate. Clearly, additional studies are needed to determine the optimal plasma concentration of 17-hydroxyprogesterone caproate.

The suggestion that combined weight of the uterine contents might be a good predictor of gestational length was not considered in our analysis because evidence that would support this as a determinant of gestational age is limited.

The determination of intrapartum concentrations of 17-hydroxyprogesterone caproate at the time of delivery does reflect the plasma concentration at that time. However, this measurement may not be as useful as it might appear because women who deliver preterm are likely to have lower concentrations than women who deliver at term because the plasma concentration of 17-hydroxyprogesterone caproate continues to increase with continued injections.