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

EpiFASSTT：孕中期和孕晚期补充叶酸的随机试验中表观遗传对儿童社会心理发展的影响

• 批准号: ES/N000323/1
• 负责人: Colum Walsh
• 金额: $ 51.01万
• 依托单位: University of Ulster
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=ES%2FN000323%2F1
• 关键词: EpiFASSTT; Epigenetic; effects; children; psychosocial

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.

对人类一生中健康状况越来越精确的调查使专家们提出，婴儿在母亲子宫内时所受的压力会影响其日后的健康。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群中进行彻底检查，因此研究结果主要基于观察工作。已知影响儿童健康的具体因素之一是必需营养素叶酸，已被证明在怀孕前三个月（前三个月）缺乏叶酸时在预防神经管闭合缺陷（例如脊柱裂）方面发挥作用。因此，目前英国的指导方针是仅在妊娠早期补充叶酸。然而，其他观察性研究表明，在妊娠期第二和第三阶段叶酸缺乏也会影响儿童的大脑发育。这一点的证据只能通过金标准测试提供，这是一项随机对照试验，其中一半的参与者在妊娠期2和3服用叶酸，一半不服用，参与者随机分配补充或不补充。我们最近进行了这样一项试验（第二和第三个三个月的叶酸补充剂（FASSTT）），并表明接受补充剂的母亲及其子女的血液中叶酸水平得到了大幅改善。对7岁儿童的后续工作显示，在智力和情感发展的几项指标方面，包括言语推理能力和情感弹性，结果有所改善。这种对健康的长期影响被认为是由受影响的人的基因上的半永久性痕迹介导的，称为表观遗传标记（来自epi-（上文）和基因）。在这里，我们计划在FASSTT试验的孩子和他们的母亲中进行一次彻底的搜索，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，将告诉我们环境压力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指标。我们的研究结果还将为有关食品补充剂和怀孕/早期生活社会护理的政策提供信息，为儿童及其母亲以及为他们提供支持的更广泛的社会和卫生服务带来切实利益。

项目成果

Effects of maternal folic acid supplementation during the second and third trimesters of pregnancy on neurocognitive development in the child: an 11-year follow-up from a randomised controlled trial.

• DOI: 10.1186/s12916-021-01914-9
• 发表时间: 2021-03-10
• 期刊: BMC medicine
• 影响因子: 9.3
• 作者: Caffrey A;McNulty H;Rollins M;Prasad G;Gaur P;Talcott JB;Witton C;Cassidy T;Marshall B;Dornan J;Moore AJ;Ward M;Strain JJ;Molloy AM;McLaughlin M;Lees-Murdock DJ;Walsh CP;Pentieva K
• 通讯作者: Pentieva K