基于队列的围孕期叶酸补充剂服用安全性评价及作用机制研究

叶酸是人体必需的微量营养素，围孕期补充叶酸预防神经管缺陷已成为全球共识。化学合成的叶酸性质稳定、用于食品强化和膳食补充剂。研究发现围孕期服用叶酸与妊娠期糖尿病、高血压等风险增加有关，并影响胎儿出生结局和儿童生长发育与健康。合成叶酸需经酶催化还原为四氢叶酸，并转化为5-甲基四氢叶酸发挥生理作用，这一过程受酶饱和限制，叶酸摄入超过其代谢能力致未代谢叶酸积聚，对孕妇和胎儿影响的安全性值得关注。本项目拟基于“同济母婴健康队列”，开展以下研究：1.检测孕妇早、中、晚期血样及脐血中各叶酸组分浓度，分析未代谢叶酸及其它组分与妊娠期并发症、不良妊娠结局、儿童生长发育与健康的关系；2.比较叶酸代谢关键酶基因多态性对叶酸摄入与母体及胎儿叶酸水平关系的影响，揭示不同叶酸代谢能力人群叶酸摄入量与未代谢叶酸的剂量反应关系；3.探讨围孕期补充叶酸促进母体及胎儿近、远期健康的有效和安全剂量，明确监测指标和安全域值。

Folate is an essential micronutrient for human health. Folic acid (FA) is the stable, synthetic form of folate , which is recommended as a supplement worldwide among women of childbearing age for preventing neural tube defects. Recent studies suggested that FA supplement use was associated with increased risk of gestational diabetes mellitus, gestational hypertension and adverse birth outcomes, and adversely affected the growth and health of the children. FA, unlike folate, requires reduction to tetrahydrofolate in order to be further metabolized to 5-methyltetrahydrofloate, the biological active form of folate. The metabolism of FA modulated by several enzymes has limited capacity in humans and is overwhelmed when FA intake exceeds and resulting in circulating unmetabolized FA (UMFA). Concerns have been raised over whether high synthetic folic acid intakes and circulating UMFA concentrations pose health risk to pregnant women and their offspring. This project is based on the "Tongji Maternal and Child Health Cohort" and aims to focus on the following: 1.To exam the concentrations of total folate, UMFA and other foate metabolites of maternal and cord blood, and demonstrate their effects on adverse outcomes during pregnancy and childhood growth and health; 2. To evaluate the effects of the related gene polymorphisms on the capacity of FA metabolism and the implications on the association between folic acid intake and the concentrations of total folate, UMFA and other form of folate, as well as the correlation with adverse outcomes of pregnancy and newborn; 3. To explore the adequate dosage and duration for the effectiveness and safety of preiconceptional FA supplement use, and determine the reliable indicator of FA metabolism and optimal range.