Rupsa C. Boelig, MD, MS
Utilization of clinical and translational pharmacology to optimize interventions for preterm birth prevention
Summary
Preterm birth is one of the major causes of neonatal morbidity and mortality. While there are a number of pharmacologic interventions to prevent preterm birth, their use has been based on empiric dosing, generally from studies outside of pregnancy and efficacy determined from observational study or phase III trials without phase I/II study to determine optimal dose/route or fetal effects. Preterm birth is multifactorial, and one size does not fit all. This research portfolio aims to apply pharmacokinetics, pharmacodynamics, and pharmacogenomics to individualize and optimize therapies for preterm birth prevention, with a focus on aspirin, azithromycin, and progesterone. Aspirin is used for prevention of preeclampsia, a major source of preterm birth, and maternal and neonatal morbidity and mortality. The optimal dose of aspirin, balancing safety and efficacy, has not been established, and there is noted to be significant individual variability in response to aspirin therapy. Using a mix of computational methods and clinical and translational studies, pharmacokinetics, pharmacodynamics, and pharmacogenomics of aspirin in preeclampsia prevention will be elucidated so that dosing may be individualized and optimized. Azithromycin is used to delay delivery in the setting of preterm premature rupture of membranes, a high-risk condition that inevitably results in preterm birth. However, azithromycin dosing varies by institution and is not based on pharmacologic studies in pregnancy. By comparing the pharmacokinetics and pharmacodynamics of two common doses of azithromycin in maternal serum and pregnancy specific tissues (placenta, membranes, amniotic fluid, cord blood), the optimal dose/timing may be determined to improve both maternal and neonatal outcomes. Progesterone is one of the oldest and most used medications for preterm birth prevention; however, there are different routes, doses, and formulations used without regard to pregnancy specific pharmacology. Patient level characteristics, including both ultrasound and biologic markers, will be evaluated for association with progesterone therapy and perinatal outcomes.
This PhRMA Foundation award has elevated my career trajectory from being a clinician to becoming a clinician researcher well versed in applying pharmacologic principles to better study and optimize therapies for preterm birth prevention. The research time funded through this award allows me to have dedicated time for training in laboratory techniques and computational methods, conducting novel clinical trials, and generating results that will bolster future research proposals and ultimately improve obstetric care and perinatal outcomes.
