title: Oral clefts and maternal biomarkers of folate-dependent one-carbon metabolism in Utah.
abstract: BACKGROUND
  Maternal folate intake and related biomarkers have been inconsistently associated with a risk of oral clefts.
  
  
  METHODS
  Maternal concentrations of plasma folate (PF) and erythrocyte folate (EF), plasma pyridoxal-5'-phosphate (PLP; active vitamin B(6) ) and total plasma homocysteine (tHcy) were measured in a Utah study with 347 cases and 469 controls.
  
  
  RESULTS
  Risk of all clefts combined, including cleft lip with or without cleft palate (CL/P) and cleft palate only (CP), was 65% lower in the highest versus lowest PF quartile (odds ratio [OR], 0.35; 95% confidence interval [CI], 0.23-0.53; p-trend < 0.001). Results remained significant in the subgroups with isolated CL/P and CP (p-trend < 0.001 in each). EF results were similar. In the highest versus lowest PLP quartile, risk of CP with other malformations was lower (OR, 0.25; 95% CI, 0.07-0.95); however, no other associations were significant for PLP or tHcy. Differences in mean biomarker levels between cases and controls widened with an increasing interval between delivery and maternal blood collection. Decreased cleft risk with increasing quartiles of PF, EF, and PLP and decreasing tHcy was more apparent in mothers with a longer versus shorter interval between the index child delivery and blood collection.
  
  
  CONCLUSIONS
  Low maternal blood folate concentration was associated with an increased risk of clefts, and the differences in mean case and control PF, EF, PLP, and tHcy concentrations widened over time. Additional mechanistic studies are warranted to elucidate whether an acquired or inherited disorder of folate metabolism plays a role in the etiology of clefts.
authors.affiliation: Department of Nutrition, Dietetics, and Food Sciences, Center for Epidemiologic Studies, Utah State University, Logan, UT 84322, USA. ron.munger@usu.edu
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Munger
authors.forename: Tsunenobu
authors.initials: T
authors.lastname: Tamura
authors.forename: Kelley E
authors.initials: KE
authors.lastname: Johnston
authors.forename: Marcia L
authors.initials: ML
authors.lastname: Feldkamp
authors.forename: Roxane
authors.initials: R
authors.lastname: Pfister
authors.forename: Richard
authors.initials: R
authors.lastname: Cutler
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Murtaugh
authors.forename: John C
authors.initials: JC
authors.lastname: Carey
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000097:blood*; D002244:Carbon / Q000378:metabolism*; D016022:Case-Control Studies; D002971:Cleft Lip / Q000453:epidemiology / Q000209:etiology*; D002972:Cleft Palate / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D005494:Folic Acid Deficiency / Q000097:blood* / Q000150:complications / Q000453:epidemiology; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008661:Metabolism, Inborn Errors / Q000097:blood* / Q000150:complications / Q000453:epidemiology; D009035:Mothers; D011247:Pregnancy; D012307:Risk Factors; D014589:Utah / Q000453:epidemiology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D002244:Carbon; D005492:Folic Acid