Quinn Matthew, Halsey Jim, Sherliker Paul, Pan Hongchao, Chen Zhengming, Bennett Derrick A, Clarke Robert
Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Medical Research Council Population Health Research Unit of University of Oxford, United Kingdom.
EClinicalMedicine. 2023 Dec 12;67:102366. doi: 10.1016/j.eclinm.2023.102366. eCollection 2024 Jan.
Folic acid (pteroylmonoglutamic acid) supplements are highly effective for prevention of neural tube defects (NTD) prompting implementation of mandatory or voluntary folic acid fortification for prevention of NTDs. We used plasma folate levels in population studies by country and year to compare effects of folic acid fortification types (mandatory or voluntary folic acid fortification policies) on plasma folate levels, NTD prevalence and stroke mortality rates.
We conducted systematic reviews of (i) implementation of folic acid fortification in 193 countries that were member states of the World Health Organization by country and year, and (ii) estimated population mean plasma folate levels by year and type of folic acid fortification. We identified relevant English language reports published between Jan 1, 1990 and July 31, 2023 using Google Scholar, Medline, Embase and Global Health. Eligibility criteria were observational or interventional studies with >1000 participants. Studies of pregnant women or children <15 years were excluded. Using an ecological study design, we examined the associations of folic acid fortification types with NTD prevalence (n = 108 studies) and stroke mortality rates (n = 3 countries).
Among 193 countries examined up to 31 July 2023, 69 implemented mandatory folic acid fortification, 47 had voluntary fortification, but 77 had no fortification (accounting for 32%, 53% and 15% of worldwide population, respectively). Mean plasma folate levels were 36, 21 and 17 nmol/L in populations with mandatory, voluntary and no fortification, respectively (and proportions with mean folate levels >25 nmol/L were 100%, 15% and 7%, respectively). Among 75 countries with NTD prevalence, mean (95% CI) prevalence per 10,000 population were 4.19 (4.11-4.28), 7.61 (7.47-7.75) and 9.66 (9.52-9.81) with mandatory, voluntary and no folic acid fortification, respectively. However, age-standardised trends in stroke mortality rates were unaltered by the introduction of folic acid fortification.
There is substantial heterogeneity in folic acid fortification policies worldwide where folic acid fortification are associated with 50-100% higher population mean plasma folate levels and 25-50% lower NTD prevalence compared with no fortification. Many thousand NTD pregnancies could be prevented yearly if all countries implemented mandatory folic acid fortification. Further trials of folic acid for stroke prevention are required in countries without effective folic acid fortification policies.
Medical Research Council (UK) and British Heart Foundation.
叶酸（蝶酰单谷氨酸）补充剂对预防神经管缺陷（NTD）非常有效，这促使许多国家实施强制性或自愿性叶酸强化措施以预防NTD。我们利用不同国家和年份的人群研究中的血浆叶酸水平，比较叶酸强化类型（强制性或自愿性叶酸强化政策）对血浆叶酸水平、NTD患病率和中风死亡率的影响。
我们对以下内容进行了系统评价：（i）按国家和年份统计世界卫生组织193个成员国实施叶酸强化的情况，以及（ii）按年份和叶酸强化类型估计人群平均血浆叶酸水平。我们使用谷歌学术、医学索引、荷兰医学文摘数据库和全球健康数据库，检索了1990年1月1日至2023年7月31日期间发表的相关英文报告。纳入标准为参与者超过1000人的观察性或干预性研究。排除孕妇或15岁以下儿童的研究。采用生态研究设计，我们研究了叶酸强化类型与NTD患病率（n = 108项研究）和中风死亡率（n = 3个国家）之间的关联。
截至2023年7月31日，在193个接受调查的国家中，69个国家实施了强制性叶酸强化，47个国家实施了自愿性强化，但77个国家未实施强化（分别占全球人口的32%、53%和15%）。强制性、自愿性和未强化人群的平均血浆叶酸水平分别为36、21和17 nmol/L（平均叶酸水平>25 nmol/L的比例分别为100%、15%和7%）。在有NTD患病率数据的75个国家中，每10000人口的平均（95%可信区间）患病率在强制性、自愿性和未进行叶酸强化的情况下分别为4.19（4.11 - 4.28）（每万人口）、7.61（7.47 - 7.75）和9.66（9.52 - 9.81）。然而，叶酸强化措施的实施并未改变中风死亡率的年龄标准化趋势。
全球叶酸强化政策存在很大差异，与未强化相比，叶酸强化使人群平均血浆叶酸水平提高50 - 100%，NTD患病率降低25 - 50%。如果所有国家都实施强制性叶酸强化，每年可预防数千例NTD妊娠。在没有有效叶酸强化政策的国家，需要进一步开展叶酸预防中风的试验。
英国医学研究理事会 和 英国心脏基金会
Zotero 插件