Prenatal exposure to nitrosatable drugs, vitamin C, and risk of selected birth defects

Mayura U Shinde; Ann M Vuong; Jean D Brender; Martha M Werler; Katherine E Kelley; John C Huber Jr; Joseph R Sharkey; Qi Zheng; Lucina Suarez; Peter H Langlois; Mark A Canfield; Paul A Romitti; Sadia Malik; National Birth Defects Prevention Study

doi:10.1002/bdra.23137

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Prenatal exposure to nitrosatable drugs, vitamin C, and risk of selected birth defects

Journal article

Peer reviewed

Prenatal exposure to nitrosatable drugs, vitamin C, and risk of selected birth defects

Mayura U Shinde, Ann M Vuong, Jean D Brender, Martha M Werler, Katherine E Kelley, John C Huber Jr, Joseph R Sharkey, Qi Zheng, Lucina Suarez, Peter H Langlois, …

Birth defects research. A Clinical and molecular teratology, Vol.97(8), pp.515-531

08/2013

DOI: 10.1002/bdra.23137

PMCID: PMC5893146

PMID: 23716465

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Abstract

Nitrosatable drugs, such as secondary or tertiary amines and amides react with nitrite in an acidic environment to form N-nitroso compounds, teratogens in animal models. Vitamin C is a known nitrosation inhibitor. Using data from the National Birth Defects Prevention Study, we assessed nitrosatable drug exposure and vitamin C intake during the first trimester among 11,606 case-mothers of infants with oral clefts, limb deficiencies (LDs), or congenital heart defects and 6807 control-mothers of infants without major birth defects during 1997-2005. Daily intake of vitamin C was estimated from maternal interviews that elicited information about supplement use and dietary intake. With no reported use of nitrosatable drugs as the referent group, a lower odds ratio (OR) was observed for transverse LDs among births to mothers exposed to secondary amine drugs and daily vitamin C supplementation (adjusted odds ratio [aOR] 1.2, 95% confidence interval [CI] 0.83-1.8) compared with women taking these drugs and no supplementation (aOR 2.7, 95% CI 1.5-4.6). The OR for longitudinal LDs associated with secondary amine exposure was lower with daily dietary vitamin C intake ≥85 mg (aOR 1.2, 95% CI 0.68-2.0) compared with <85 mg (aOR 1.9, 95% CI 1.2-3.1). Daily vitamin C supplementation in combination with higher dietary vitamin C intake reduced associations between nitrosatable drug exposures and limb deficiencies and atrial septal defects not otherwise specified. Prenatal dietary and vitamin C supplement intake may diminish the association between nitrosatable drug exposure during pregnancy and selected birth defects.

Pregnancy

Limb Deformities, Congenital - chemically induced

Cleft Palate - chemically induced

Cleft Lip - chemically induced

Heart Defects, Congenital - chemically induced

Humans

Brain - abnormalities

Case-Control Studies

Ascorbic Acid - metabolism

Nitroso Compounds - metabolism

Cleft Palate - etiology

Nitrosation - drug effects

Maternal Exposure - adverse effects

Female

Dietary Supplements

Cleft Lip - etiology

Details

Title: Subtitle: Prenatal exposure to nitrosatable drugs, vitamin C, and risk of selected birth defects
Creators: Mayura U Shinde - Texas A&M Health Science Center, School of Rural Public Health, College Station, Texas 77843-1266, USA. shinde@srph.tamhsc.edu
Ann M Vuong
Jean D Brender
Martha M Werler
Katherine E Kelley
John C Huber Jr
Joseph R Sharkey
Qi Zheng
Lucina Suarez
Peter H Langlois
Mark A Canfield
Paul A Romitti
Sadia Malik
National Birth Defects Prevention Study
Resource Type: Journal article
Publication Details: Birth defects research. A Clinical and molecular teratology, Vol.97(8), pp.515-531
DOI: 10.1002/bdra.23137
PMID: 23716465
PMCID: PMC5893146
NLM abbreviation: Birth Defects Res A Clin Mol Teratol
ISSN: 1542-0752
eISSN: 1542-0760
Publisher: Wiley; United States
Grant note: U01 DD000492 / NCBDD CDC HHS U01 DD000494 / NCBDD CDC HHS 3R01ES015634-03S1 / NIEHS NIH HHS R01 ES015634 / NIEHS NIH HHS U01DD000494 / NCBDD CDC HHS 5R01ES015634 / NIEHS NIH HHS
Language: English
Date published: 08/2013
Academic Unit: Epidemiology; Biostatistics
Record Identifier: 9983995135102771

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