Abstract Depression and anxiety during pregnancy affect over 10% of women with 6-8% of pregnant women receiving a prescription for a selective serotonin reuptake inhibitor (SSRI) antidepressant. Sertraline is the most commonly prescribed SSRI in women of reproductive years. However, there remains limited information for optimizing its treatment during pregnancy. Sertraline shows large inter-individual variability although studies generally suffer from small sample sizes and inconsistent observations. Physiological changes accompanying pregnancy can alter drug pharmacokinetics (e.g., clearance) which can significantly affect steady-state concentrations of medications, supporting the need for dose adjustments in order to maintain pre-pregnancy drug exposure. Our objective is to quantify the contribution of sertraline pharmacokinetic exposure to maternal health and obstetrical/neonatal outcomes. The Women’s Mental Health Program database contains prospectively collected data from more than 2,500 individuals with neuropsychiatric illnesses across more than 15,000 unique visits during the perinatal and postpartum periods. Sertraline and metabolite concentrations along with maternal symptoms and obstetrical/neonatal outcome information will be analyzed via pharmacokinetic/pharmacodynamic modeling enabling characterization of the relationships between changes in sertraline exposure with maternal symptoms of depression and neonatal outcomes during pregnancy and postpartum. Results from this project will support refinement of dosing strategies and evidence-based personalized treatment planning for the use of sertraline during pregnancy. The application of pharmacokinetic- guided dosing will result in enhanced prevention of disease-related symptoms and improved maternal and child health. This project will provide the foundation for investigation of other antidepressants and psychotropic medications used during pregnancy.