Relationship Between Plasma Concentration of Hydroxyprogesterone Caproate (17-OHPC) and Preterm Birth

The study will determine the association between plasma concentrations of 17-OHPC
(hydroxyprogesterone caproate) and the rate of preterm birth and will evaluate the impact of
several potential covariates on plasma concentrations of 17-OHPC and its efficacy. 17-OHPC
(hydroxyprogesterone caproate) administration has proven effective in reducing preterm births
in high risk groups but the current dose of 250mg administered IM is thought to be an
inadequate for a substantial portion of women receiving the therapy. The potential benefit of
identifying a therapeutic concentration range and of optimizing the dosage of 17-OHPC are
substantial.

Pregnant subjects with a history of a prior spontaneous preterm birth with be randomized to
either the 250mg or 500mg weekly intramuscular injections. All subjects will have trough
blood samples collected immediately prior to their second injection of the 17-OHPC, at 26-30
weeks (but only after a minimum of 7 injections have been administered) , 6-9 weeks later and
at the time of delivery. Another tube of maternal blood will be collected during one of the
scheduled blood samples for genotyping. A cord blood specimen will also be collected and with
consent, a cord blood specimen will be collected for genetic studies of the infant. We will
also collect a small sample of the placenta after delivery.

Inclusion Criteria:

- pregnant with a prior preterm birth 16 0/7-35 6/7 weeks from spontaneous labor or
PPROM,

- current gestational age <22 weeks,

- pregnant with one baby

- age between 18-45 years

- able to give consent and undergo study procedures

Exclusion Criteria:

- plans for cerclage at enrollment, plan for progesterone treatment other than study
medications at enrollment

- known fetal anomaly or chromosomal anomaly that could affect gestational age at
delivery

- malformation of the uterus or known cervical length <2.5cm

- participation in another trial that may affect gestational age at delivery

- planned delivery where outcome data cannot be collected

- medical or obstetrical complication that may affect gestational age at delivery, such
as active ulcerative colitis, liver tumors, liver disease/failure, renal
disease/failure, undiagnosed vaginal bleeding unrelated to pregnancy, or hypertension
requiring 2 or more agents

- Current or history of thrombosis or thromboembolic disorders

- known or suspected breast cancer, other hormone-sensitive cancer, or a history of
these conditions

- moderately severe depression (PHQ-9 score ≥ 15 or suicidal ideation)