Kihlberg R, Bui T H, Jörgensen C, Söderhjelm L
Institutionen för molekylär medicin, kliniskt genetiska avdelningen, Karolinska sjukhuset, Stockholm.
Lakartidningen. 1999 Apr 21;96(16):1961-3.
The involvement of folic acid in the aetiology of neural tube defects (NTDs) has been discussed for decades. Both observational and controlled intervention trials have shown periconceptional folic acid supplementation (PFAS) to significantly reduce the incidence both of first-time and recurrent NTDs. PFAS may also be associated with reduction in the incidence of certain other congenital malformations, preterm delivery, and intra-uterine growth retardation. However, the mechanism whereby folic acid exerts its protective effect remains unclear. Thermolabile 5,10-methyl-enetetrahydrofolate reductase was the first folate-related enzyme to be associated with an increased risk of NTDs. This genetic variant may result in increased plasma homocysteine levels, which have been linked to an increased risk of NTDs. The folate-dependent genetic variants known today can explain no more than 30-50 per cent of the observed protective effect of folate. However, available evidence suggests low maternal folate status itself to be the major determinant of NTD risk. Since the vast majority of NTDs are first occurrences, and in Sweden a large proportion of fetuses with spina bifida remain undetected at routine ultrasonography during pregnancy, primary prevention by means of PFAS represents a major potential public health asset, capable of reducing both mortality and morbidity due to NTDs. Accordingly, implementation of a national strategy to reduce the incidence of NTDs, and promote awareness among health care providers and women of reproductive age of the benefits of PFAS is strongly to be recommended. Although supplemental folic acid tablets are the best proven means of improving folate status, compliance may be a problem, which emphasises the importance of considering a nutrient fortification programme as a complementary strategy for reducing the incidence of NTDs.
叶酸与神经管缺陷（NTDs）病因学的关联已被讨论了数十年。观察性研究和对照干预试验均表明，孕前补充叶酸（PFAS）可显著降低首次发生和复发性NTDs的发生率。PFAS还可能与某些其他先天性畸形、早产和宫内生长迟缓的发生率降低有关。然而，叶酸发挥其保护作用的机制仍不清楚。热不稳定的5,10-亚甲基四氢叶酸还原酶是首个被发现与NTDs风险增加相关的叶酸相关酶。这种基因变异可能导致血浆同型半胱氨酸水平升高，而这已与NTDs风险增加相关联。目前已知的依赖叶酸的基因变异最多只能解释观察到的叶酸保护作用的30%至50%。然而，现有证据表明，孕妇叶酸水平低本身是NTDs风险的主要决定因素。由于绝大多数NTDs是首次发生，且在瑞典，很大一部分脊柱裂胎儿在孕期常规超声检查中仍未被发现，通过PFAS进行一级预防是一项重要的潜在公共卫生资产，能够降低NTDs导致的死亡率和发病率。因此，强烈建议实施一项国家战略以降低NTDs的发生率，并提高医疗保健提供者和育龄妇女对PFAS益处的认识。尽管补充叶酸片是改善叶酸水平的最佳已证实方法，但依从性可能是个问题，这凸显了考虑将营养强化计划作为降低NTDs发生率的补充策略的重要性。
