Risk of taking nitrosatable drugs during pregnancy

(COLLEGE STATION, TX) — Women who take drugs that are secondary or tertiary amines in early pregnancy may be at increased risk of having babies with neural tube defects, especially if the mothers also have higher intakes of dietary nitrites, notes a team of investigators that includes the Texas A&M Health Science Center (TAMHSC) School of Rural Public Health.

Jean Brender, Ph.D., RN, associate dean of research at the TAMHSC-School of Rural Public Health, is principal investigator on the project and lead author on the study published as an advance access article Nov. 1 in the journal American Journal of Epidemiology. The paper is part of a project funded by the National Institute of Environmental Sciences on “Nitrates, nitrites, nitrosatable drugs, and risk of selected birth defects.”  Other study contributors include the Boston University Slone Epidemiology Unit, University of Iowa College of Public Health and Texas Department of State Health Services.

“These findings underscore the importance of women taking a daily multivitamin supplement during their childbearing years and checking with their health care provider before taking medications while pregnant,” Dr. Brender states.
Using data from the U.S. Centers for Disease Control and Prevention National Birth Defects Prevention Study, the investigators classified drugs taken by the study population located in 10 states around conception according to their nitrosatability (a drug’s ability to react with nitrite in the stomach to form nitrosamines and nitrosamides). They also estimated daily intake of dietary nitrate and nitrite from a food frequency questionnaire.

The strongest associations between drugs classified as tertiary amines and anencephaly in offspring were observed in women with the highest estimated dietary intake of total nitrite. Risk for anencephaly associated with this type of drug exposure appeared lessened if the women also took daily a supplement with vitamin C during the first month of pregnancy.
Another study published from this project earlier this year in Birth Defects Research Part A: Clinical and Molecular Teratology indicated five of the 10 most commonly taken nitrosatable drugs in this study population were available over the counter.

Co-authors on the paper included Martha Werler, Ph.D., and Katherine Kelley (Boston University); Ann Vuong, Mayura Shinde, Qi Zheng, Ph.D., John Huber Jr., Ph.D., Joseph Sharkey, Ph.D., John S. Griesenbeck, Dr.P.H. (Texas A&M Health Science Center); Paul Romitti, Ph.D. (University of Iowa); and Peter Langlois, Ph.D., Lucina Suarez, Ph.D., and Mark Canfield, Ph.D. (Texas Department of State Health Services).