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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HD075831-02
Application #
8625804
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Zajicek, Anne
Project Start
2013-04-01
Project End
2018-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
2
Fiscal Year
2014
Total Cost
$137,160
Indirect Cost
$10,160
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Huybrechts, Krista F; Bröms, Gabriella; Christensen, Lotte Brix et al. (2018) Association Between Methylphenidate and Amphetamine Use in Pregnancy and Risk of Congenital Malformations: A Cohort Study From the International Pregnancy Safety Study Consortium. JAMA Psychiatry 75:167-175
Prabhu, Malavika; Dubois, Heloise; James, Kaitlyn et al. (2018) Implementation of a Quality Improvement Initiative to Decrease Opioid Prescribing After Cesarean Delivery. Obstet Gynecol 132:631-636
Gray, Kathryn J; Kovacheva, Vesela P; Mirzakhani, Hooman et al. (2018) Gene-Centric Analysis of Preeclampsia Identifies Maternal Association at PLEKHG1. Hypertension 72:408-416
Huybrechts, Krista F; Hernández-Díaz, Sonia; Straub, Loreen et al. (2018) Association of Maternal First-Trimester Ondansetron Use With Cardiac Malformations and Oral Clefts in Offspring. JAMA 320:2429-2437
Hernandez-Diaz, Sonia; Huybrechts, Krista F; Desai, Rishi J et al. (2018) Topiramate use early in pregnancy and the risk of oral clefts: A pregnancy cohort study. Neurology 90:e342-e351
Rough, Kathryn; Huybrechts, Krista F; Hernandez-Diaz, Sonia et al. (2018) Using prescription claims to detect aberrant behaviors with opioids: comparison and validation of 5 algorithms. Pharmacoepidemiol Drug Saf :
Park, Yoonyoung; Bateman, Brian T; Kim, Dae Hyun et al. (2018) Use of haloperidol versus atypical antipsychotics and risk of in-hospital death in patients with acute myocardial infarction: cohort study. BMJ 360:k1218
Kim, Dae Hyun; Mahesri, Mufaddal; Bateman, Brian T et al. (2018) Longitudinal Trends and Variation in Antipsychotic Use in Older Adults After Cardiac Surgery. J Am Geriatr Soc 66:1491-1498
Park, Yoonyoung; Hernandez-Diaz, Sonia; Bateman, Brian T et al. (2018) Continuation of Atypical Antipsychotic Medication During Early Pregnancy and the Risk of Gestational Diabetes. Am J Psychiatry 175:564-574
Kim, Dae Hyun; Lee, Jung; Kim, Caroline A et al. (2017) Evaluation of algorithms to identify delirium in administrative claims and drug utilization database. Pharmacoepidemiol Drug Saf 26:945-953

Showing the most recent 10 out of 60 publications