Nitrosatable drug exposure during the first trimester of pregnancy and selected congenital malformations

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

doi:10.1002/bdra.23060

Back

Nitrosatable drug exposure during the first trimester of pregnancy and selected congenital malformations

Journal article

Open access

Peer reviewed

Nitrosatable drug exposure during the first trimester of pregnancy and selected congenital malformations

Jean D Brender, Martha M Werler, Mayura U Shinde, Ann M Vuong, Katherine E Kelley, John C Huber Jr, Joseph R Sharkey, John S Griesenbeck, Paul A Romitti, Sadia Malik, …

Birth defects research. A Clinical and molecular teratology, Vol.94(9), pp.701-713

09/2012

DOI: 10.1002/bdra.23060

PMCID: PMC3488451

PMID: 22903972

Files and links (1)

url

https://www.ncbi.nlm.nih.gov/pmc/articles/3488451View

Open Access

Abstract

Nitrosatable drugs can react with nitrite in the stomach to form N-nitroso compounds, and results from animal studies suggest that N-nitroso compounds are teratogens. With data from the National Birth Defects Prevention Study, the relation between prenatal exposure to nitrosatable drugs and limb deficiencies, oral cleft, and heart malformations in offspring was examined. Maternal reports of drugs taken during the first trimester of pregnancy were classified with respect to nitrosatability for mothers of 741 babies with limb deficiencies, 2774 with oral cleft malformations, 8091 with congenital heart malformations, and 6807 without major congenital malformations. Nitrite intake was estimated from maternal responses to a food frequency questionnaire. Isolated transverse limb deficiencies and atrioventricular septal defects were associated with secondary amine drug exposures (adjusted odds ratios [aORs], 1.51; 95% confidence limit [CI], 1.11-2.06 and aOR, 1.97; 95% CI, 1.19-3.26, respectively). Tertiary amines were associated with hypoplastic left heart syndrome (aOR, 1.50; 95% CI, 1.10-2.04) and single ventricle (aOR, 1.61; 95% CI, 1.06-2.45). These two malformations were also significantly associated with amide drugs. For several malformations, the strongest associations with nitrosatable drug use occurred among mothers with the highest estimated dietary nitrite intake, especially for secondary amines and atrioventricular septal defects (highest tertile of nitrite, aOR, 3.30; 95% CI, 1.44-7.58). Prenatal exposure to nitrosatable drugs may be associated with several congenital malformations, especially with higher nitrite intake. The possible interaction between nitrosatable drugs and dietary nitrite on risk of congenital malformations warrants further attention.

Pregnancy

United States - epidemiology

Prenatal Exposure Delayed Effects - epidemiology

Humans

Infant

Male

Nitroso Compounds - toxicity

Risk

Pregnancy Trimester, First

Amides - toxicity

Nitrites - toxicity

Adult

Female

Odds Ratio

Amines - toxicity

Abnormalities, Drug-Induced - epidemiology

Maternal-Fetal Exchange

Heart Defects, Congenital - pathology

Abnormalities, Drug-Induced - pathology

Nitrosation

Limb Deformities, Congenital - epidemiology

Cleft Palate - pathology

Adolescent

Heart Defects, Congenital - epidemiology

Cleft Palate - epidemiology

Prenatal Exposure Delayed Effects - pathology

Limb Deformities, Congenital - pathology

Details

Title: Subtitle: Nitrosatable drug exposure during the first trimester of pregnancy and selected congenital malformations
Creators: Jean D Brender - Texas A&M Health Science Center, School of Rural Public Health, College Station, Texas 77843-1266, USA. jdbrender@srph.tamhsc.edu
Martha M Werler
Mayura U Shinde
Ann M Vuong
Katherine E Kelley
John C Huber Jr
Joseph R Sharkey
John S Griesenbeck
Paul A Romitti
Sadia Malik
Lucina Suarez
Peter H Langlois
Mark A Canfield
National Birth Defects Prevention Study
Resource Type: Journal article
Publication Details: Birth defects research. A Clinical and molecular teratology, Vol.94(9), pp.701-713
DOI: 10.1002/bdra.23060
PMID: 22903972
PMCID: PMC3488451
NLM abbreviation: Birth Defects Res A Clin Mol Teratol
ISSN: 1542-0752
eISSN: 1542-0760
Publisher: Wiley; United States
Grant note: U50/CCU613232 / PHS HHS 3R01ES015634-03S1 / NIEHS NIH HHS R01 ES015634 / NIEHS NIH HHS 5R01ES015634 / NIEHS NIH HHS
Language: English
Date published: 09/2012
Academic Unit: Epidemiology; Biostatistics
Record Identifier: 9983995049102771

Metrics

16 Record Views

28 Times Cited - Web of Science