Swammerdam Institute for Life Sciences, Center for Neuroscience, Brain plasticity group, University of Amsterdam, Amsterdam, Netherlands.
Division of Human Nutrition and Health, Wageningen University, Wageningen, Netherlands.
Adv Nutr. 2019 May 1;10(3):502-519. doi: 10.1093/advances/nmy120.
The importance of an adequate periconceptional maternal folate status to prevent fetal neural tube defects has been well demonstrated and resulted in the recommendation for women to use folic acid supplements during the periconception period. The importance of maternal folate status for offspring neurodevelopment and brain health is less well described. We reviewed the current evidence linking maternal folate status before conception and during pregnancy with neurodevelopment and cognition of the offspring. We discuss both animal and human studies. Preclinical research revealed the importance of maternal folate status for several key processes required for normal neurodevelopment and brain functioning in the offspring, including DNA synthesis, regulation of gene expression, synthesis of phospholipids and neurotransmitters, and maintenance of healthy plasma homocysteine concentrations. Human observational studies are inconclusive; about half have shown a positive association between maternal folate status and cognitive performance of offspring. Whereas some studies suggest a positive association between maternal folate intake and cognition of offspring during childhood, data from interventional studies are too limited to conclude that there is a direct effect. Future preclinical studies are needed to help us characterize the behavioral effects, understand the underlying mechanisms, and to establish an optimal dosage and time window of folate supplementation. Moreover, more conclusive data from well-designed human observational studies and randomized controlled trials are needed to determine whether current recommendations for folic acid supplementation during pregnancy cover the needs for normal cognitive development in the offspring.
充分的围孕期母体叶酸状态对于预防胎儿神经管缺陷的重要性已得到充分证实，并促成了建议女性在围孕期使用叶酸补充剂。母体叶酸状态对后代神经发育和大脑健康的重要性则描述得较少。我们回顾了目前的证据，这些证据将受孕前和孕期母体叶酸状态与后代的神经发育和认知能力联系起来。我们讨论了动物和人类研究。临床前研究揭示了母体叶酸状态对于正常神经发育和后代大脑功能所需的几个关键过程的重要性，包括 DNA 合成、基因表达调控、磷脂和神经递质合成以及维持健康的血浆同型半胱氨酸浓度。人类观察性研究尚无定论；约有一半研究表明母体叶酸状态与后代的认知表现之间存在正相关。虽然一些研究表明，母体叶酸摄入与儿童时期后代的认知之间存在正相关，但干预性研究的数据有限，无法得出直接影响的结论。未来的临床前研究将有助于我们描述行为影响，了解潜在机制，并确定叶酸补充的最佳剂量和时间窗。此外，还需要更多来自精心设计的人类观察性研究和随机对照试验的更具结论性的数据，以确定目前在孕期补充叶酸的建议是否满足后代正常认知发育的需要。
