Association between inhibited binding of folic acid to folate receptor a in maternal serum and folate-related birth defects in Norway

作者：Boyles A L^*; Ballard J L; Gorman E B; McConnaughey D R; Cabrera R M; Wilcox A J; Lie R T; Finnell R H

来源：Human Reproduction, 2011, 26(8): 2232-2238.

DOI：10.1093/humrep/der144

• neural tube defects
• oral facial clefts
• folic acid
• folate receptor
• maternal autoantibodies

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 alpha (FR alpha), 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 FR alpha 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 FR alpha (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 FR alpha.
CONCLUSIONS: Inhibition of folic acid binding to FR alpha in maternal plasma collected during pregnancy was associated with increased risk of NTDs but not oral facial clefts.

• 出版日期2011-8