title: The association between neonatal thyroxine and craniosynostosis, Texas, 2004-2007.
abstract: BACKGROUND
  Craniosynostosis (CS), a structural anomaly characterized by premature fusion of cranial sutures, occurs in 1 in 2000 live births. Associations of CS with the thyroid have been reported. Neonatal thyroid hormone (T4) is evaluated nationally at birth by the Newborn Screening Program (NBS). This study evaluated the relationship between NBS T4 levels and craniosynostosis.
  
  
  METHODS
  Live-born singleton babies born in 2004 through 2007 were identified through the Texas Birth Defects Registry (499 cases) and Texas Bureau of Vital Statistics (3570 controls) and successfully linked to analyte data available in the Texas NBS Database. Cases were classified based on the absence of other major defects (isolated cases, n = 382) and suture(s) involved. Mean T4 levels were compared between controls and cases (overall and stratified by classification). T4 levels were stratified by quintiles to evaluate differences between cases and controls within quintiles. The diagnostic utility of NBS T4 was evaluated using receiver operator characteristic (ROC) curves.
  
  
  RESULTS
  Mean T4 levels were lower in isolated cases (16.89 μg/dl) than in controls (17.77 μg/dl; p = 0.0004). This trend persisted for sagittal (16.69 μg/dl; p = 0.002) and metopic (16.83 μg/dl; p = 0.042) CS. When stratified by quintiles, 54% of isolated lambdoid CS were in the first quintile compared to controls (p = 0.012). ROC area under the curve (AUC) was approximately 0.55 for all classifications except lambdoid (AUC = 0.73).
  
  
  CONCLUSIONS
  NBS T4 levels were slightly lower among cases with nearly half of all lambdoid CS having T4 levels in the lowest quintile. However, overall NBS T4 levels are not suitable for potential screening or diagnostic application.
authors.affiliation: The University of Texas Medical School, Houston, Texas, USA. Syed.S.Hashmi.1@uth.tmc.edu
authors.forename: Syed Shahrukh
authors.initials: SS
authors.lastname: Hashmi
authors.forename: Mark A
authors.initials: MA
authors.lastname: Canfield
authors.forename: Lisa
authors.initials: L
authors.lastname: Marengo
authors.forename: Karen B
authors.initials: KB
authors.lastname: Moffitt
authors.forename: John W
authors.initials: JW
authors.lastname: Belmont
authors.forename: Debra
authors.initials: D
authors.lastname: Freedenberg
authors.forename: Susan M
authors.initials: SM
authors.lastname: Tanksley
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Lupo
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003398:Craniosynostoses / Q000175:diagnosis / Q000453:epidemiology*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D015997:Neonatal Screening; D012372:ROC Curve; D013781:Texas / Q000453:epidemiology; D013974:Thyroxine / Q000097:blood*; D055815:Young Adult
chemical_list: D013974:Thyroxine