title: Differences in risk factors for second and third degree hypospadias in the national birth defects prevention study.
abstract: BACKGROUND
  Hypospadias is a frequent birth defect with three phenotypic subtypes. With data from the National Birth Defects Prevention Study, a large, multi-state, population-based, case-control study, we compared risk factors for second and third degree hypospadias.
  
  
  METHODS
  A wide variety of data on maternal and pregnancy-related risk factors for isolated second and third degree hypospadias was collected by means of computer-assisted telephone interviews to identify potential etiological differences between the two phenotypes. Logistic regression was used to calculate odds ratios including a random effect by study center.
  
  
  RESULTS
  In total, 1547 second degree cases, 389 third degree cases, and 5183 male controls were included in our study. Third degree cases were more likely to have a non-Hispanic black or Asian/Pacific Islander mother, be delivered preterm, have a low birth weight, be small for gestational age, and be conceived with fertility treatments than second degree cases and controls. Associations with both second and third degree hypospadias were observed for maternal age, family history, parity, plurality, and hypertension during pregnancy. Risk estimates were generally higher for third degree hypospadias except for family history.
  
  
  CONCLUSIONS
  Most risk factors were associated with both or neither phenotype. Therefore, it is likely that the underlying mechanism is at least partly similar for both phenotypes. However, some associations were different between second and third degree hypospadias, and went in opposite directions for second and third degree hypospadias for Asian/Pacific Islander mothers. Effect estimates for subtypes of hypospadias may be over- or underestimated in studies without stratification by phenotype.
authors.affiliation: National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia; Department for Health Evidence, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Sander Groen In 't
authors.initials: SG
authors.lastname: Woud
authors.forename: Iris A L M
authors.initials: IA
authors.lastname: van Rooij
authors.forename: Marleen M H J
authors.initials: MM
authors.lastname: van Gelder
authors.forename: Richard S
authors.initials: RS
authors.lastname: Olney
authors.forename: Suzan L
authors.initials: SL
authors.lastname: Carmichael
authors.forename: Nel
authors.initials: N
authors.lastname: Roeleveld
authors.forename: Jennita
authors.initials: J
authors.lastname: Reefhuis
mesh_terms: D000328:Adult; D044466:Asian People; D016022:Case-Control Studies; D005260:Female; D006306:Health Surveys; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000453:epidemiology* / Q000208:ethnology; D007021:Hypospadias / Q000145:classification / Q000453:epidemiology* / Q000208:ethnology; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007234:Infant, Premature; D016015:Logistic Models; D008297:Male; D044468:Native Hawaiian or Pacific Islander; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D010641:Phenotype; D011247:Pregnancy; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
keywords: birth defects; hypospadias; pregnancy; risk factors