title: Levels of folate receptor autoantibodies in maternal and cord blood and risk of neural tube defects in a Chinese population.
abstract: BACKGROUND
  After years of periconceptional folic acid supplementation, the prevalence of neural tube defects (NTDs) remains stable following the remarkable reduction observed immediately after the fortification practice. There is accumulating evidence that folate receptor (FR) autoimmunity may play a role in the etiology of folate-sensitive NTDs.
  
  
  METHODS
  From 2011 to 2013, 118 NTD cases and 242 healthy controls were recruited from a population-based birth defects surveillance system in Northern China. Enzyme-linked immunosorbent assay was used to measure FR autoantibodies in maternal and cord blood. Logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (95% CI).
  
  
  RESULTS
  Plasma FR autoantibodies levels were significantly elevated in mothers of infants with NTDs compared with mothers of healthy controls. Using the lowest tertile as the referent group, 2.20-fold (95% CI, 0.71-6.80) and 5.53-fold increased odds (95% CI, 1.90-16.08) of NTDs were observed for the second and third tertile of immunoglobulin G (IgG), respectively, and the odds of NTDs for each successive tertile of IgM was 0.98 (95% CI, 0.35-2.75) and 3.49 (95% CI, 1.45-8.39), respectively. A dose-response relationship was found between FR autoantibodies levels and risk of NTDs (P < 0.001 for IgG, P = 0.002 for IgM). The same pattern was observed in both subtypes of spina bifida and anencephaly. No significant difference in levels of cord blood FR autoantibodies was observed.
  
  
  CONCLUSIONS
  Higher levels of FR autoimmunity in maternal plasma are associated with elevated risk of NTDs in a dose-response manner. Birth Defects Research (Part A) 106:685-695, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Institute of Reproductive and Child Health/Ministry of Health Key Laboratory of Reproductive Health, Department of Epidemiology and Biostatistics, Peking University, Beijing, China.
authors.forename: Na
authors.initials: N
authors.lastname: Yang
authors.affiliation: Institute of Reproductive and Child Health/Ministry of Health Key Laboratory of Reproductive Health, Department of Epidemiology and Biostatistics, Peking University, Beijing, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Dell Pediatric Research Institute, The University of Texas at Austin, Austin, Texas, USA.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Finnell
authors.affiliation: Institute of Reproductive and Child Health/Ministry of Health Key Laboratory of Reproductive Health, Department of Epidemiology and Biostatistics, Peking University, Beijing, China.
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Institute of Reproductive and Child Health/Ministry of Health Key Laboratory of Reproductive Health, Department of Epidemiology and Biostatistics, Peking University, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.affiliation: Institute of Reproductive and Child Health/Ministry of Health Key Laboratory of Reproductive Health, Department of Epidemiology and Biostatistics, Peking University, Beijing, China.
authors.forename: Le
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Dell Pediatric Research Institute, The University of Texas at Austin, Austin, Texas, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Cabrera
authors.affiliation: Institute of Reproductive and Child Health/Ministry of Health Key Laboratory of Reproductive Health, Department of Epidemiology and Biostatistics, Peking University, Beijing, China.
authors.forename: Rongwei
authors.initials: R
authors.lastname: Ye
authors.affiliation: Institute of Reproductive and Child Health/Ministry of Health Key Laboratory of Reproductive Health, Department of Epidemiology and Biostatistics, Peking University, Beijing, China.
authors.forename: Aiguo
authors.initials: A
authors.lastname: Ren
mesh_terms: D000328:Adult; D000757:Anencephaly / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000097:blood*; D015551:Autoimmunity / Q000187:drug effects*; D016022:Case-Control Studies; D002681:China; D004306:Dose-Response Relationship, Immunologic; D004361:Drug Tolerance / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D058975:Folate Receptor 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D005492:Folic Acid / Q000008:administration & dosage / Q000276:immunology*; D015870:Gene Expression; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007223:Infant; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D012306:Risk
chemical_list: D001323:Autoantibodies; D058975:Folate Receptor 1; D007074:Immunoglobulin G; D005492:Folic Acid
keywords: IgG; IgM; autoantibody; folate receptor; neural tube defects