Association between inhibited binding of folic acid to folate receptor a in maternal serum and folate-related birth defects in Norway
Association between inhibited binding of folic acid to folate receptor a in maternal serum and folate-related birth defects in Norway
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DOI：
10.1093/humrep/der144
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发表时间：
2011-08-01
影响因子：
6.1
通讯作者：
Finnell, R. H.
中科院分区：
文献类型：
--
作者：
Boyles, A. L.;Ballard, J. L.;Finnell, R. H.
背景：孕期摄入叶酸可以降低神经管畸形(NTDS)的风险，或许还可以降低口腔面部裂隙的风险。母体的叶酸受体自身抗体会损害叶酸的结合。我们探讨了这些出生缺陷与叶酸与叶酸受体α(FRα)结合抑制的关系，以及父母人口统计学或产前暴露的可能影响。方法：我们在挪威母子队列研究中进行了嵌套病例对照研究。这项研究包括患有NTD的儿童(n=11)、伴有或不伴有唇裂(CL/P，n 72)或仅有腭裂(CPO，n=27)的儿童的母亲，以及随机选择的对照组母亲(n=221)。在妊娠17周左右收集的母体血浆中检测叶酸与FRα结合的抑制作用。在既往文献的基础上，母亲的年龄、孕次、教育程度、吸烟、孕周补充叶酸和牛奶摄入量被认为是潜在的混杂因素。结果：随着结合抑制的增加，NTDS的风险增加[调整后的优势比(AOR)1.4，95%可信区间(CI)1.0~1.8]。叶酸与FRα结合受阻并未增加口腔面裂的风险(CL/P AOR 0.7，95%CI 0.6~1.0；CPO AOR 1.1，95%CI 0.8~1.4)。未发现吸烟、补充叶酸或其他辅助因素与抑制叶酸与FRα结合之间的关系。结论：抑制孕期采集的母体血浆中叶酸与FRα的结合与NTDS的风险增加有关，但与口腔面裂无关。
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.