title: Polytomous logistic regression as a tool for exploring heterogeneity across birth defect subtypes: an example using anencephaly and spina bifida.
abstract: BACKGROUND
  In birth defect epidemiology, phenotypic subgroups are often combined into a composite phenotype in an effort to increase statistical power. Although the validity of using composite phenotypes has been questioned, formal evaluations of the underlying assumption of effect homogeneity across component phenotypes have not been conducted.
  
  
  METHODS
  Polytomous logistic regression was used to assess effect heterogeneity of several generally accepted neural tube defect (NTD) risk factors across the component phenotypes of anencephaly and spina bifida. Data for these analyses were obtained from the National Birth Defects Prevention Study.
  
  
  RESULTS
  The use of a composite phenotype has the potential to mask associations specific to a component phenotype and in some cases the effect of a variable may be misattributed to the composite phenotype. For example, an association between infant sex and anencephaly (adjusted odds ratio [AOR], 1.5; 95% CI, 1.1-1.9) was masked when data from all NTDs were analyzed (AOR, 1.1; 95% CI, 0.9-1.3), whereas an association with maternal body mass index that was specific to spina bifida (AOR, 1.9; 95% CI, 1.6-2.4) was attributed to all NTDs (AOR, 1.6; 95% CI, 1.4-2.0). Furthermore, conclusions regarding effect heterogeneity based on ad hoc comparisons, rather than some formal assessment, may be vulnerable to considerable subjectivity, as was the case for the association of maternal Hispanic ethnicity with spina bifida (AOR, 1.4; 95% CI, 1.2-1.8) and anencephaly (AOR, 2.0; 95% CI, 1.5-2.8).
  
  
  CONCLUSIONS
  Polytomous logistic regression provides a useful tool for evaluating putative risk factors for which there is no a priori basis for assuming effect homogeneity across component phenotypes.
authors.affiliation: Division of Epidemiology and Disease Control, University of Texas School of Public Health, Houston, Texas, USA.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Lupo
authors.forename: Elaine
authors.initials: E
authors.lastname: Symanski
authors.forename: D Kim
authors.initials: DK
authors.lastname: Waller
authors.forename: Wenyaw
authors.initials: W
authors.lastname: Chan
authors.forename: Mark A
authors.initials: MA
authors.lastname: Canfield
authors.forename: Peter H
authors.initials: PH
authors.lastname: Langlois
authors.forename: Laura E
authors.initials: LE
authors.lastname: Mitchell
mesh_terms: D000757:Anencephaly / Q000453:epidemiology*; D015992:Body Mass Index; D016022:Case-Control Studies; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage; D056726:Genetic Association Studies / Q000706:statistics & numerical data; D006630:Hispanic or Latino / Q000706:statistics & numerical data; D006801:Humans; D007223:Infant; D016015:Logistic Models; D008297:Male; D010641:Phenotype; D012307:Risk Factors; D016135:Spinal Dysraphism / Q000453:epidemiology*
chemical_list: D005492:Folic Acid