title: Maternal hypertension, medication use, and hypospadias in the National Birth Defects Prevention Study.
abstract: OBJECTIVE
  To investigate whether antihypertensive classes and specific medications in early pregnancy increase the risk of severe hypospadias and to assess prior associations detected for late-treated and untreated hypertension in the National Birth Defects Prevention Study.
  
  
  METHODS
  Using telephone interviews from mothers of 2,131 children with severe hypospadias and 5,129 nonmalformed male control children for 1997-2009 births in a population-based case-control study, we estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) with multivariable logistic regression. We adjusted P values to account for multiple testing.
  
  
  RESULTS
  Forty-eight (2.3%) case and 70 (1.4%) control mothers reported early pregnancy antihypertensive treatment, 45 (2.1%) case and 31 (0.6%) control mothers reported late treatment, and 315 (14.8%) case and 394 (7.7%) control mothers reported untreated hypertension. Selective β-blockers, centrally acting agents, renin-angiotensin system-acting agents, diuretics, and specific medications, methyldopa and atenolol, were not associated with hypospadias. Nonselective β-blockers (adjusted OR 3.22, 95% CI 1.47-7.05) were associated with hypospadias; however, P values adjusted for multiple testing were not statistically significant. We confirmed prior findings for associations between hypospadias and untreated hypertension (adjusted OR 2.09, 95% CI 1.76-2.48) and late initiation of treatment (adjusted OR 3.98, 95% CI 2.41-6.55). The increased risks would translate to severe hypospadias prevalences of 11.5, 17.7, and 21.9 per 10,000 births for women with untreated hypertension, nonselective β-blocker use, and late initiation of treatment, respectively.
  
  
  CONCLUSIONS
  Our study suggests a relationship between hypospadias and the severity of hypertension.
  
  
  METHODS
  II.
authors.affiliation: Congenital Malformations Registry, New York State Department of Health, Albany, and the Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, Rensselaer, New York; the Slone Epidemiology Center at Boston University, Boston, Massachusetts; and the Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa.
authors.forename: Alissa R
authors.initials: AR
authors.lastname: Van Zutphen
authors.forename: Martha M
authors.initials: MM
authors.lastname: Werler
authors.forename: Marilyn M
authors.initials: MM
authors.lastname: Browne
authors.forename: Paul A
authors.initials: PA
authors.lastname: Romitti
authors.forename: Erin M
authors.initials: EM
authors.lastname: Bell
authors.forename: Louise-Anne
authors.initials: LA
authors.lastname: McNutt
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Druschel
authors.forename: Allen A
authors.initials: AA
authors.lastname: Mitchell
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000009:adverse effects; D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000013:Congenital Abnormalities / Q000517:prevention & control; D005260:Female; D005865:Gestational Age; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy*; D007021:Hypospadias / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D016017:Odds Ratio; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000188:drug therapy*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents