Hypertensive disorders complicate an estimated 6-8% of all pregnancies and are a significant source of fetal and maternal morbidity and mortality. Approximately 3-4% of all pregnant women will be exposed to antihypertensive medications during pregnancy. The antihypertensive most commonly used in pregnancy in the United States is methyldopa;however, it is an older, often poorly tolerated medication. It may be an inferior therapy with respect to important pregnancy outcomes compared to other classes of agents including alpha-beta blockers, beta blockers, and calcium channel blockers. Yet, for each of these other classes, important fetal safety concerns have been raised. The primary goal of the proposed project is therefore to evaluate the comparative safety and effectiveness of each of these commonly used agents relative to methyldopa. The clinical question this study aims to address is: "If a patient requires an outpatient antihypertensive during pregnancy for pre-existing or gestational hypertension, what is the safest agent for the fetus, and the one most likely to assure a good pregnancy outcome?" We will also examine the safety of first trimester exposure to thiazide diuretics and angiotensin converting enzyme inhibitors, which are the most common types of antihypertensives used in women of reproductive age outside of pregnancy and thus common first trimester exposures. This analysis will address the clinical question: "For a woman in whom pregnancy is planned or possible, which agents can be safely used given the potential for early fetal exposure to the medication?" The study will be performed using a pregnancy cohort obtained from the Medicaid Analytic Extract (MAX), a large population-based claims database. Using this dataset, we have developed a cohort of over 1.1 million pregnancies with longitudinal data that span from the pre-pregnancy to the postpartum periods. This cohort is linked to outpatient pharmacy claims and fetal records making it an exceptionally well-suited data source for the kind of study we propose. I will perform the proposed research within the well developed infrastructure of the Division of Pharmacoepidemiology and Pharmacoeconomics ("The Division") at the Brigham and Women's Hospital. The Division has a long track record of producing outstanding drug safety and effectiveness research using observational data sources. I will work with an interdisciplinary team of mentors and collaborators drawn from across institutions at Harvard University that have deep expertise and national/international reputations in epidemiological and statistical methods, perinatal pharmacoepidemiology, high-risk obstetrics, hypertensive diseases, and drug policy. This research work will be complemented by formal coursework at the Harvard School of Public Health and frequent seminars and lab meetings at the Division. This combination of intensive research, mentoring, and formal education will provide the necessary background for me to become a successful, independent researcher in obstetric pharmacoepidemiology.

Public Health Relevance

About 4% of all pregnant women will take an antihypertensive medication during pregnancy. Much is unknown about the comparative safety and effectiveness of different antihypertensives in pregnancy. The present study aims to define the class of antihypertensive agent that is safest for the fetus and the one most likely to assure a good pregnancy outcome.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Clinical Investigator Award (CIA) (K08)
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Pediatrics Subcommittee (CHHD)
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Zajicek, Anne
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Brigham and Women's Hospital
United States
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Bateman, Brian T; Huybrechts, Krista F; Fischer, Michael A et al. (2015) Chronic hypertension in pregnancy and the risk of congenital malformations: a cohort study. Am J Obstet Gynecol 212:337.e1-14
Cea Soriano, Lucia; Bateman, Brian T; García Rodríguez, Luis A et al. (2014) Prescription of antihypertensive medications during pregnancy in the UK. Pharmacoepidemiol Drug Saf 23:1051-8
Desai, Rishi J; Hernandez-Diaz, Sonia; Bateman, Brian T et al. (2014) Increase in prescription opioid use during pregnancy among Medicaid-enrolled women. Obstet Gynecol 123:997-1002
Bateman, Brian T; Hernandez-Diaz, Sonia; Rathmell, James P et al. (2014) Patterns of opioid utilization in pregnancy in a large cohort of commercial insurance beneficiaries in the United States. Anesthesiology 120:1216-24
Bateman, Brian T; Tsen, Lawrence C; Liu, Jun et al. (2014) Patterns of second-line uterotonic use in a large sample of hospitalizations for childbirth in the United States: 2007-2011. Anesth Analg 119:1344-9
Oberg, Anna Sara; Hernandez-Diaz, Sonia; Palmsten, Kristin et al. (2014) Patterns of recurrence of postpartum hemorrhage in a large population-based cohort. Am J Obstet Gynecol 210:229.e1-8
Oberg, Anna Sara; Hernandéz-Dia?, Sonia; Frisell, Thomas et al. (2014) Genetic contribution to postpartum haemorrhage in Swedish population: cohort study of 466,686 births. BMJ 349:g4984
Patorno, Elisabetta; Neuman, Mark D; Schneeweiss, Sebastian et al. (2014) Comparative safety of anesthetic type for hip fracture surgery in adults: retrospective cohort study. BMJ 348:g4022
Bateman, Brian T; Mhyre, Jill M; Hernandez-Diaz, Sonia et al. (2013) Development of a comorbidity index for use in obstetric patients. Obstet Gynecol 122:957-65
Bateman, B T; Hernandez-Diaz, S; Huybrechts, K F et al. (2013) Outpatient calcium-channel blockers and the risk of postpartum haemorrhage: a cohort study. BJOG 120:1668-76; dicussion 1676-7