EpiFASSTT: Epigenetic effects on children's psychosocial development in a randomised trial of Folic Acid Supplementation in Second and Third Trimester

对整个生命过程中人类健康的调查越来越准确，这导致专家们提出，在母亲子宫中对孩子施加压力可能会影响其晚年的健康。虽然许多因素可能会成为压力源，但其中大多数因素很难在人类群体中进行彻底检查，因此研究结果主要是基于观察工作。在已知的影响儿童健康的具体因素中，基本营养素叶酸已被证明在怀孕前三个月(前三个月)缺乏时在预防神经管闭合缺陷(如脊柱裂)方面发挥作用。因此，英国目前的指导方针是只在怀孕前三个月补充叶酸。然而，其他观察性研究表明，两个月和三个月的叶酸缺乏也会影响儿童的大脑发育。这一点只能通过黄金标准测试提供证据，这是一项随机对照试验，其中一半的参与者在第二和第三个月服用叶酸，另一半不服用，参与者随机分配到补充或不补充。我们最近进行了这样一项试验(孕中期和孕晚期补充叶酸(FASSTT))，结果显示，接受补充剂的母亲和她们的孩子血液中的叶酸水平都得到了显著改善。对7岁儿童的跟踪研究显示，在智力和情绪发展的几个指标上，包括言语推理能力和情绪弹性，结果都有所改善。这种对健康的长期影响被认为是通过在患者基因上的一种称为表观遗传标记的半永久性痕迹(来自表观遗传标记和基因)来调节的。在这里，我们计划在FASSTT试验的儿童及其母亲中彻底寻找可能的表观遗传标记。检测到的这种标记的水平，以及受其影响的基因，将告诉我们环境应激源对一个人未来健康的影响程度。同样，它将为我们评估营养投入等因素对儿童健康的影响提供具体的标志。我们的研究结果还将为有关食品补充剂和孕期/早期社会护理的政策提供参考，为儿童及其母亲带来实实在在的好处，并在更广泛的领域为他们提供支助的社会和卫生服务。

Increasingly accurate surveys of human health throughout the course of life has led experts to propose that stresses on the child while still in the mother's womb can affect its health much later in life. While many factors can potentially act as stressors, the majority of these are difficult to examine thoroughly in human populations and so findings are based largely on observational work. Among concrete factors known to affect child health is the essential nutrient folate, which has been proven to play a role in preventing neural tube closure defects (e.g. Spina bifida) when deficient during the first three months (first trimester) of pregnancy. Current UK guidance is therefore to supplement with folate during first trimester only. However other observational studies suggest that folate deficiency in trimesters two and three also affects children's brain development. Proof for this can only be provided by the gold standard test which is a Randomised Control Trial, where half the participants take folate in trimesters 2 and 3 and half do not, with participants assigned randomly to supplement or no supplement. We recently conducted such a trial (Folic Acid Supplementation in the Second and Third Trimester (FASSTT)) and showed that folate levels in blood were substantially improved in mothers receiving the supplement and in their children. Follow-up work with the children at age seven showed improved outcomes with regard to several measures of intellectual and emotional development, including verbal reasoning ability and emotional resilience. Such long-term effects on health are thought to be mediated by a semi-permanent trace on the genes of the affected person called an epigenetic mark (from epi- (above) and gene). Here we plan to do a thorough search for possible epigenetic marks in the children from the FASSTT trial and their mothers. The levels of such marking detected, and the genes affected by it, will tell us much about the extent to which environmental stressors can affect a person's future health. Likewise it will give us concrete markers for assessing the impact of factors such as nutritional inputs on the health of the child. The results of our study will also inform policy regarding food supplements and pregnancy/early life social care, with tangible benefits for children, their mums, and in the wider sphere the social and health services which provide them with support.