School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ontario, Canada.
Faculty of Medicine, University of Ottawa, Ontario, Canada.
Birth Defects Res. 2020 Nov;112(19):1699-1719. doi: 10.1002/bdr2.1827. Epub 2020 Oct 29.
There has been a longstanding debate about the role of folate in the etiology of orofacial clefts (OFCs). Studies of different measures of nutritional intake or folate status have been done to investigate the possible role of folate in the prevention of OFC. Only one knowledge synthesis has attempted to bring together different types of evidence. The aim of the present work was to update it.
Evidence for associations between OFC and dietary folate, supplement use, folic acid fortification, biomarkers of folate status, and variants of MTHFR (C677T and A1298C) were included. Potentially eligible articles were systematically identified from PubMed, Medline, Embase, and Web of Science (2007-2020) and combined using random-effects meta-analysis when appropriate. Quality assessments were conducted using the Newcastle-Ottawa scale and Cochrane's risk of bias tool.
Sixty-four studies published since the previous knowledge synthesis were identified, with eight of these identified through a supplementary search from October, 2018 to August, 2020. There was an inverse association between folic acid-containing supplement use before or during pregnancy and cleft lip with or without cleft palate (CL/P) (OR 0.60, 95% CI 0.51-0.69), with considerable between-study heterogeneity. The prevalence of CL/P showed a small decline post-folic acid fortification in seven studies (OR 0.94, 95% CI 0.86-1.02). No association was found between OFC and genetic markers of folate status. The coronavirus-19 pandemic has threatened food availability globally and therefore there is a need to maintain and even enhance surveillance concerning maternal intake of folate and related vitamins.
The risk of non-syndromic OFC was reduced among pregnant women with folic acid-containing supplements during the etiologically relevant period. However, high heterogeneity between included studies, incomplete reporting of population characteristics and variation in timing of exposure and supplement types mean that conclusions should be drawn with caution.
叶酸在口面裂（OFC）病因学中的作用一直存在争议。已经进行了多项关于营养摄入或叶酸状态不同测量的研究，以探讨叶酸在预防 OFC 中的可能作用。只有一项知识综合尝试将不同类型的证据汇集在一起。本研究旨在更新它。
纳入了与 OFC 与饮食叶酸、补充剂使用、叶酸强化、叶酸状态生物标志物以及 MTHFR（C677T 和 A1298C）变体之间的关联的证据。从 PubMed、Medline、Embase 和 Web of Science（2007-2020 年）系统地识别潜在合格的文章，并在适当的情况下使用随机效应荟萃分析进行组合。使用纽卡斯尔-渥太华量表和 Cochrane 的偏倚风险工具进行质量评估。
自上次知识综合以来，共确定了 64 项已发表的研究，其中 8 项是通过 2018 年 10 月至 2020 年 8 月的补充搜索确定的。在妊娠前或妊娠期间使用含有叶酸的补充剂与唇裂伴或不伴腭裂（CL/P）之间存在反比关系（OR 0.60，95%CI 0.51-0.69），存在较大的研究间异质性。在 7 项研究中，在叶酸强化后 CL/P 的患病率显示出略有下降（OR 0.94，95%CI 0.86-1.02）。OFC 与叶酸状态的遗传标志物之间没有关联。冠状病毒-19 大流行已威胁到全球的食物供应，因此需要维持甚至加强对孕妇叶酸和相关维生素摄入的监测。
在相关的病因学时期，孕妇使用含有叶酸的补充剂可降低非综合征性 OFC 的风险。然而，纳入研究之间存在高度异质性、人群特征的不完全报告以及暴露和补充类型的时间变化，这意味着应谨慎得出结论。
