Epidemiology Branch, NIEHS/NIH, Durham, NC 27709, USA.
Hum Reprod. 2011 Aug;26(8):2232-8. doi: 10.1093/humrep/der144. Epub 2011 May 15.
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.
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.
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.
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.
孕妇叶酸摄入可降低神经管缺陷（NTD）的风险，或许也可降低口腔面裂的风险。母体抗叶酸受体抗体可损害叶酸结合。我们探究了这些出生缺陷与叶酸结合到叶酸受体α（FRα）的抑制作用之间的关系，以及父母人口统计学特征或产前暴露的可能影响。
我们在挪威母婴队列研究中进行了一项巢式病例对照研究。该研究纳入了 NTD 患儿的母亲（n=11）、唇裂伴或不伴腭裂（CL/P，n=72）或单纯腭裂（CPO，n=27），以及随机选择的对照组母亲（n=221）。在妊娠约 17 周时采集母体血浆以测量叶酸对 FRα 的结合抑制作用。根据既往文献，母体年龄、孕次、教育程度、吸烟、受孕前叶酸补充剂使用情况和牛奶摄入量被认为是潜在的混杂因素。
叶酸与 FRα 结合的抑制作用增加与 NTD 风险增加相关[校正比值比（aOR）=1.4，95%置信区间（CI）1.0-1.8]。FRα 上叶酸结合的抑制与口腔面裂无关（CL/P 的 aOR=0.7，95%CI 0.6-1.0；CPO 的 aOR=1.1，95%CI 0.8-1.4）。未发现吸烟、叶酸补充剂或其他因素与叶酸结合到 FRα 的抑制作用之间存在关联。
妊娠期间采集的母体血浆中叶酸与 FRα 结合的抑制与 NTD 风险增加相关，但与口腔面裂无关。
