Acetaminophen, aspirin, ibuprofen, and amoxicillin are among the most commonly used drugs during pregnancy, but the safety of these medications with respect to birth defects is not established. Given the wide use of these drugs, even a small increase in the risk of birth defects may have considerable clinical and public health implications. We propose to evaluate the association between these drugs and 1) specific malformations previously hypothesized to be associated with each of them, and 2) specific malformations that occur most commonly in the general population. In addition, we propose to evaluate other commonly used medications by systematically screening each exposure in relation to the risk of specific malformations. These goals can be achieved at relatively modest cost by taking advantage of a large existing ongoing multicenter case-control surveillance program of birth defects in North America, the Slone Epidemiology Center Birth Defects Study (BDS). The BDS involves approximately 95 institutions in four metropolitan areas (Boston, Philadelphia, Toronto, and San Diego), and for over 25 years has interviewed over 20,000 mothers of malformed infants and over 4,000 mothers of non-malformed infants. The BDS identifies infants with a wide range of malformations within 5 months after birth at tertiary and birth hospitals, and within 6 months of delivery, study nurses interview mothers about demographic, reproductive, and medical factors; medication and vitamin use; cigarette smoking and alcohol consumption; and dietary intake. The study has discovered likely teratogenic effects that have subsequently been confirmed by others (e.g., salycilates in relation to gastroschisis). In the proposed analyses, we will estimate odds ratios and 95% confidence intervals using logistic regression, and results will be adjusted for potential confounders. Findings will test hypotheses about some drugs and provide leads for further research for others; both objectives seek to improve our understanding of risks associated with drugs commonly used by pregnant women.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
Project #
Application #
Study Section
Epidemiology of Chronic Diseases Study Section (ECD)
Program Officer
Hewitt, Tyl
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Boston University
Public Health & Prev Medicine
Schools of Medicine
United States
Zip Code
Louik, Carol; Kerr, Stephen; Kelley, Katherine E et al. (2015) Increasing use of ADHD medications in pregnancy. Pharmacoepidemiol Drug Saf 24:218-20
Yazdy, Mahsa M; Mitchell, Allen A; Werler, Martha M (2014) Maternal genitourinary infections and the risk of gastroschisis. Am J Epidemiol 180:518-25
Ahrens, Katherine A; Louik, Carol; Kerr, Stephen et al. (2014) Seasonal influenza vaccination during pregnancy and the risks of preterm delivery and small for gestational age birth. Paediatr Perinat Epidemiol 28:498-509
Yau, Wai-Ping; Mitchell, Allen A; Lin, Kueiyu Joshua et al. (2013) Use of decongestants during pregnancy and the risk of birth defects. Am J Epidemiol 178:198-208
Li, Qian; Mitchell, Allen A; Werler, Martha M et al. (2013) Assessment of antihistamine use in early pregnancy and birth defects. J Allergy Clin Immunol Pract 1:666-74.e1
Thorpe, Phoebe G; Gilboa, Suzanne M; Hernandez-Diaz, Sonia et al. (2013) Medications in the first trimester of pregnancy: most common exposures and critical gaps in understanding fetal risk. Pharmacoepidemiol Drug Saf 22:1013-8
Lin, Kueiyu Joshua; Mitchell, Allen A; Yau, Wai-Ping et al. (2013) Safety of macrolides during pregnancy. Am J Obstet Gynecol 208:221.e1-8
Ahrens, Katherine; Lash, Timothy L; Louik, Carol et al. (2012) Correcting for exposure misclassification using survival analysis with a time-varying exposure. Ann Epidemiol 22:799-806
Lin, Kueiyu Joshua; Mitchell, Allen A; Yau, Wai-Ping et al. (2012) Maternal exposure to amoxicillin and the risk of oral clefts. Epidemiology 23:699-705
Margulis, Andrea V; Mitchell, Allen A; Gilboa, Suzanne M et al. (2012) Use of topiramate in pregnancy and risk of oral clefts. Am J Obstet Gynecol 207:405.e1-7

Showing the most recent 10 out of 19 publications