title: Prenatal exposure to nitrosatable drugs, vitamin C, and risk of selected birth defects.
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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Prenatal dietary and vitamin C supplement intake may diminish the association between nitrosatable drug exposure during pregnancy and selected birth defects.
authors.affiliation: Texas A&M Health Science Center, School of Rural Public Health, College Station, Texas 77843-1266, USA. shinde@srph.tamhsc.edu
authors.forename: Mayura U
authors.initials: MU
authors.lastname: Shinde
authors.forename: Ann M
authors.initials: AM
authors.lastname: Vuong
authors.forename: Jean D
authors.initials: JD
authors.lastname: Brender
authors.forename: Martha M
authors.initials: MM
authors.lastname: Werler
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Kelley
authors.forename: John C
authors.initials: JC
authors.lastname: Huber
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Sharkey
authors.forename: Qi
authors.initials: Q
authors.lastname: Zheng
authors.forename: Lucina
authors.initials: L
authors.lastname: Suarez
authors.forename: Peter H
authors.initials: PH
authors.lastname: Langlois
authors.forename: Mark A
authors.initials: MA
authors.lastname: Canfield
authors.forename: Paul A
authors.initials: PA
authors.lastname: Romitti
authors.forename: Sadia
authors.initials: S
authors.lastname: Malik
mesh_terms: D001205:Ascorbic Acid / Q000378:metabolism*; D001921:Brain / Q000002:abnormalities; D016022:Case-Control Studies; D002971:Cleft Lip / Q000139:chemically induced / Q000209:etiology; D002972:Cleft Palate / Q000139:chemically induced / Q000209:etiology; D019587:Dietary Supplements; D005260:Female; D006330:Heart Defects, Congenital / Q000139:chemically induced; D006801:Humans; D017880:Limb Deformities, Congenital / Q000139:chemically induced; D018811:Maternal Exposure / Q000009:adverse effects*; D015538:Nitrosation / Q000187:drug effects*; D009603:Nitroso Compounds / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D009603:Nitroso Compounds; D001205:Ascorbic Acid
keywords: birth defects; dietary vitamin C; heart defects; limb deficiencies; nitrosatable drug; oral clefts; vitamin C