Impact of Periconceptional Use of Nitrosatable Drugs on the Risk of Neural Tube Defects.

Abstract

Nitrosatable drugs (NSDs) can, in the presence of nitrosating agents and highly acidic conditions, form N-nitroso compounds that have been found to be teratogenic in animal models. Using data from the Slone Epidemiology Center Birth Defects Study collected from 1998 to 2012, we compared maternal periconceptional NSD use between 334 neural tube defect cases and 7,619 nonmalformed controls. We categorized NSDs according to their functional group (secondary amine, tertiary amine, and amide). With logistic regression models, we estimated adjusted odds ratios and 95% confidence intervals. Neural tube defect risk was associated with maternal periconceptional use of secondary (adjusted odds ratio (aOR) = 1.7, 95% confidence interval (CI): 1.1, 2.4) and tertiary (aOR = 1.7, 95% CI: 1.2, 2.5) amines; an association was observed for amides, but the 95% confidence interval included the null (aOR = 1.4, 95% CI: 0.7, 2.5). Within the secondary amine group, elevated adjusted odds ratios were observed for 3 drugs but were null for the remaining medications. Increases in risk were observed for both strata of folic acid intake (<400 µg/day, ≥400 µg/day), with a slightly higher risk in the ≥400-µg/day stratum. Our findings support previously reported positive associations between neural tube defects and periconceptional exposure to NSDs containing a secondary or tertiary amine or amide.

• Authors: Corey M Benedum, Mahsa M Yazdy, Allen A Mitchell, Martha M Werler
• Journal: American journal of epidemiology (Am J Epidemiol) Vol. 182 Issue 8 Pg. 675-84 (Oct 15 2015) ISSN: 1476-6256 [Electronic] United States
• PMID: 26424074 (Publication Type: Journal Article, Multicenter Study, Research Support, U.S. Gov't, P.H.S.)
• Copyright: © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Amides
• Amines
• Nitroso Compounds

Topics

• Adult
• Amides (administration & dosage, adverse effects)
• Amines (administration & dosage, adverse effects)
• Canada (epidemiology)
• Case-Control Studies
• Evidence-Based Medicine
• Female
• Humans
• Incidence
• Neural Tube Defects (chemically induced, epidemiology)
• Nitroso Compounds (toxicity)
• Pregnancy
• Pregnancy Trimester, First (drug effects)
• Prenatal Exposure Delayed Effects (chemically induced, epidemiology)
• Prevalence
• Risk Assessment
• Risk Factors
• Spinal Dysraphism (chemically induced, epidemiology)
• United States (epidemiology)