Periconceptional folic acid associated with an increased risk of oral clefts relative to non-folate related malformations in the Northern Netherlands: a population based case-control study
Periconceptional folic acid associated with an increased risk of oral clefts relative to non-folate related malformations in the Northern Netherlands: a population based case-control study
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DOI：
10.1007/s10654-013-9849-0
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发表时间：
2013-11-01
影响因子：
13.6
通讯作者：
de Walle, Hermien E. K.
中科院分区：
文献类型：
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作者：
Rozendaal, Anna M.;van Essen, Anthonie J.;de Walle, Hermien E. K.
围受孕期叶酸与神经管缺陷风险降低有关，但其在口腔裂中的作用的研究结果在很大程度上是不确定的。这项病例对照研究评估了围受孕期叶酸对唇裂风险的影响，使用了荷兰口腔裂登记处和基于人口的出生缺陷登记处（Eurocat）的补充数据，这些数据来自1997年至2009年期间在荷兰北方出生的儿童和胎儿。病例为非综合征性唇腭裂的活产婴儿（n = 367），对照组为染色体/综合征性（n = 924）或非叶酸相关异常（n = 2，021）的婴儿或胎儿。我们分析了与传统裂缝类别相关的补充剂使用的类型/时间/持续时间以及它们的时间（早期/晚期胚胎期）和潜在的胚胎学过程（融合/分化缺陷）。在病因相关时期（受孕后0-12周）持续使用补充剂与唇腭裂风险增加相关（调整后比值比1.72，95%置信区间1.19-2.49），特别是唇裂/牙槽嵴（3.16，1.69-5.91）。进一步的系统性分析显示晚期分化缺陷的风险增加了2 - 3倍，主要是唇/牙槽裂，与早期/晚期融合缺陷没有显著相关性。影响归因于叶酸，而不是其他多种维生素成分，包括部分使用（不包括完整的病因相关时期）通常会削弱相关性。总之，这项研究提出了几条证据，表明在荷兰北方的围受孕期叶酸与唇腭裂风险增加有关，特别是唇裂/齿槽裂。我们的研究结果的特异性、一致性、系统性模式和缓解-反应关系的持续时间加强了这种关联，强调了评估叶酸相关公共卫生策略和进一步调查潜在不良反应的必要性。
Periconceptional folic acid has been associated with a reduced risk of neural tube defects, but findings on its effect in oral clefts are largely inconclusive. This case-control study assesses the effects of periconceptional folic acid on cleft risk, using complementary data from the Dutch Oral Cleft Registry and a population-based birth defects registry (Eurocat) of children and foetuses born in the Northern Netherlands between 1997 and 2009. Cases were live-born infants with non-syndromic clefts (n = 367) and controls were infants or foetuses with chromosomal/syndromal (n = 924) or non-folate related anomalies (n = 2,021). We analyzed type/timing/duration of supplement use related to traditional cleft categories as well as to their timing (early/late embryonic periods) and underlying embryological processes (fusion/differentiation defects). Consistent supplement use during the aetiologically relevant period (weeks 0-12 postconception) was associated with an increased risk of clefts (adjusted odds ratio 1.72, 95 % confidence interval 1.19-2.49), especially of cleft lip/alveolus (3.16, 1.69-5.91). Further analysis systematically showed twofold to threefold increased risks for late differentiation defects-mainly clefts of the lip/alveolus-with no significant associations for early/late fusion defects. Effects were attributable to folic acid and not to other multivitamin components, and inclusion of partial use (not covering the complete aetiologically relevant period) generally weakened associations. In conclusion, this study presents several lines of evidence indicating that periconceptional folic acid in the Northern Netherlands is associated with an increased risk of clefts, in particular of cleft lip/alveolus. This association is strengthened by the specificity, consistency, systematic pattern, and duration of exposure-response relationship of our findings, underlining the need to evaluate public health strategies regarding folic acid and to further investigate potential adverse effects.