Yu Miao, Hu Yiming, Hou Lei, Wu Xiaomin, Chen Xiangxin, Yan Ruohan, Dong Jie, Wu Jing
School of Public Health, Inner Mongolia Medical University, Hohhot 010110, China.
National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100050, China.
Nutrients. 2025 Oct 31;17(21):3443. doi: 10.3390/nu17213443.
: Maternal folic acid supplementation is recommended to prevent neural tube defects (NTDs), yet its influence on offspring neurodevelopmental disorders (NDDs) remains uncertain. This umbrella review aims to evaluate whether maternal folic acid supplementation before and/or during pregnancy affects the risk of NDDs. We conducted a systematic search in MEDLINE, Cochrane Library, EMBASE, PubMed, and Web of Science from inception to 30 June 2025, to identify systematic reviews (SRs) and meta-analyses (MAs) that synthesized evidence from non-randomized studies on maternal folic acid supplementation and NDDs. Methodological quality was assessed using the AMSTAR-2 assessment and evidence certainty using the GRADE framework. A total of 23 SRs/MAs were included, of which 14 did not perform meta-analysis. Most included SRs/MAs were methodologically limited, with 50.00% rated as very low quality and only 36.37% achieving high or moderate quality. MAs indicated a protective effect of supplementation, with odds ratio (OR) of 0.66 (95% confidence interval (CI): 0.55-0.79) for autism spectrum disorder (ASD), 0.86 (95% CI: 0.78-0.95) for attention-deficit/hyperactivity disorder (ADHD), and 0.75 (95% CI: 0.63-0.91) for behavioral problems. No significant associations were found for motor, intellectual/cognitive, or language development. SRs reported inconsistent conclusions across most outcomes. In summary, maternal folic acid supplementation may reduce the risk of ASD, ADHD, and behavioral problems in offspring. Although the current evidence is of low quality, supplementation guidelines are justified by the well-established benefits for NTDs. Further research is required to address remaining uncertainties.
推荐孕妇补充叶酸以预防神经管缺陷（NTD），但其对后代神经发育障碍（NDD）的影响仍不确定。本综述旨在评估孕期前后补充叶酸是否会影响NDD的风险。我们在MEDLINE、Cochrane图书馆、EMBASE、PubMed和Web of Science数据库中进行了系统检索，检索时间从建库至2025年6月30日，以确定对关于孕妇补充叶酸与NDD的非随机研究证据进行综合分析的系统评价（SR）和荟萃分析（MA）。采用AMSTAR-2评估法评估方法学质量，采用GRADE框架评估证据确定性。共纳入23项SR/MA，其中14项未进行荟萃分析。大多数纳入的SR/MA在方法学上存在局限性，50.00%被评为极低质量，只有36.37%达到高质量或中等质量。MA表明补充叶酸有保护作用，自闭症谱系障碍（ASD）的优势比（OR）为0.66（95%置信区间（CI）：0.55-0.79），注意力缺陷多动障碍（ADHD）的OR为0.86（95%CI：0.78-0.95），行为问题的OR为0.75（95%CI：0.63-0.91）。未发现与运动、智力/认知或语言发育有显著关联。SR在大多数结局上报告了不一致的结论。总之，孕妇补充叶酸可能会降低后代患ASD、ADHD和行为问题的风险。尽管目前的证据质量较低，但鉴于补充叶酸对预防NTD有明确益处，补充指南是合理的。需要进一步研究以解决剩余的不确定性。
