title: Association between inhibited binding of folic acid to folate receptor alpha in maternal serum and folate-related birth defects in Norway.
abstract: BACKGROUND
  Folic acid intake during pregnancy can reduce the risk of neural tube defects (NTDs) and perhaps also oral facial clefts. Maternal autoantibodies to folate receptors can impair folic acid binding. We explored the relationship of these birth defects to inhibition of folic acid binding to folate receptor α (FRα), as well as possible effects of parental demographics or prenatal exposures.
  
  
  METHODS
  We conducted a nested case-control study within the Norwegian Mother and Child Cohort Study. The study included mothers of children with an NTD (n = 11), cleft lip with or without cleft palate (CL/P, n= 72), or cleft palate only (CPO, n= 27), and randomly selected mothers of controls (n = 221). The inhibition of folic acid binding to FRα was measured in maternal plasma collected around 17 weeks of gestation. On the basis of prior literature, the maternal age, gravidity, education, smoking, periconception folic acid supplement use and milk consumption were considered as potential confounding factors.
  
  
  RESULTS
  There was an increased risk of NTDs with increased binding inhibition [adjusted odds ratio (aOR) = 1.4, 95% confidence interval (CI) 1.0-1.8]. There was no increased risk of oral facial clefts from inhibited folic acid binding to FRα (CL/P aOR = 0.7, 95% CI 0.6-1.0; CPO aOR = 1.1, 95% CI 0.8-1.4). No association was seen between smoking, folate supplementation or other cofactors and inhibition of folic acid binding to FRα.
  
  
  CONCLUSIONS
  Inhibition of folic acid binding to FRα in maternal plasma collected during pregnancy was associated with increased risk of NTDs but not oral facial clefts.
authors.affiliation: Epidemiology Branch, NIEHS/NIH, Durham, NC 27709, USA. boylesa@niehs.nih.gov
authors.forename: A L
authors.initials: AL
authors.lastname: Boyles
authors.forename: J L
authors.initials: JL
authors.lastname: Ballard
authors.forename: E B
authors.initials: EB
authors.lastname: Gorman
authors.forename: D R
authors.initials: DR
authors.lastname: McConnaughey
authors.forename: R M
authors.initials: RM
authors.lastname: Cabrera
authors.forename: A J
authors.initials: AJ
authors.lastname: Wilcox
authors.forename: R T
authors.initials: RT
authors.lastname: Lie
authors.forename: R H
authors.initials: RH
authors.lastname: Finnell
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000032:analysis; D016022:Case-Control Studies; D002971:Cleft Lip / Q000209:etiology; D002972:Cleft Palate / Q000209:etiology; D005260:Female; D058975:Folate Receptor 1 / Q000097:blood* / Q000276:immunology; D005492:Folic Acid / Q000378:metabolism*; D005494:Folic Acid Deficiency / Q000150:complications; D006801:Humans; D009436:Neural Tube Defects / Q000209:etiology*; D009664:Norway; D011247:Pregnancy
chemical_list: D001323:Autoantibodies; D058975:Folate Receptor 1; D005492:Folic Acid