title: Nitrosatable Drug Exposure during Pregnancy and Preterm and Small-for-Gestational-Age Births.
abstract: BACKGROUND
  Nitrosatable drugs react with nitrite in the stomach to form N-nitroso compounds, observed in animal models to result in adverse pregnancy outcomes, such as birth defects and reduced fetal weight. Previous studies examining prenatal exposure to medications classified as nitrosatable have reported an increased risk of preterm births (PTBs) and small-for-gestational-age (SGA) infants.
  
  
  METHODS
  Using data from mothers (controls) of babies without major birth defects from the National Birth Defects Prevention Study, prenatal nitrosatable drug usage by trimester and month of gestation was examined in relation to PTBs and SGA infants.
  
  
  RESULTS
  Positive associations were observed with nitrosatable drug use and PTBs, with the strongest relationship with second trimester exposure (adjusted hazard ratio [aHR] 1.37, [95% confidence interval (CI) 1.10, 1.70]). Of the nitrosatable functional groups, secondary amines were the most notable, with a higher association among women with second (aHR 1.37, [95% CI 1.05, 1.79]) and third (aHR 1.34, [95% CI 1.02, 1.76]) trimester exposure compared with women with no prenatal nitrosatable drug use. Among SGA infants, a borderline association was noted with amide exposure during the third trimester (adjusted odds ratio 1.43 [95% confidence interval [CI] 1.00, 2.05]).
  
  
  CONCLUSIONS
  Prenatal exposure to nitrosatable drugs during the second and third trimester of pregnancy, particularly secondary amines, might increase the risk of PTBs. However, prenatal exposure to nitrosatable drugs was not associated with SGA infants, with the exception of amide drugs.
authors.affiliation: Division of Epidemiology, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Vuong
authors.forename: Mayura U
authors.initials: MU
authors.lastname: Shinde
authors.forename: Jean D
authors.initials: JD
authors.lastname: Brender
authors.forename: Eva M
authors.initials: EM
authors.lastname: Shipp
authors.forename: John C
authors.initials: JC
authors.lastname: Huber
authors.forename: Qi
authors.initials: Q
authors.lastname: Zheng
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: McDonald
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Sharkey
authors.forename: Adrienne T
authors.initials: AT
authors.lastname: Hoyt
authors.forename: Martha M
authors.initials: MM
authors.lastname: Werler
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Kelley
authors.forename: Peter H
authors.initials: PH
authors.lastname: Langlois
authors.forename: Mark A
authors.initials: MA
authors.lastname: Canfield
mesh_terms: D000293:Adolescent; D000328:Adult; D000577:Amides / Q000008:administration & dosage / Q000009:adverse effects*; D000588:Amines / Q000008:administration & dosage / Q000009:adverse effects*; D001205:Ascorbic Acid / Q000008:administration & dosage; D016022:Case-Control Studies; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D008297:Male; D011247:Pregnancy; D011264:Pregnancy Trimesters; D047928:Premature Birth / Q000139:chemically induced* / Q000453:epidemiology; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000577:Amides; D000588:Amines; D001205:Ascorbic Acid
keywords: Nitrosatable drug; adverse pregnancy outcomes; preterm birth; small for gestational age; vitamin C