Abate Biruk Beletew, Kumsa Henok, Kibret Gebremeskel Abebe, Wodaynew Tilahun, Habtie Tesfaye Engdaw, Kassa Muluemebet, Munie Melesse Abiye, Temesgen Dessie, Tilahun Befkad Derese, Merchaw Abebe, Alamaw Addis Wondimagegn, Zemariam Alemu Birara, Kitaw Tegene Atamenta, Kassaw Amare, Kassie Ayelign Mengesha, Yilak Gizachew, Kassa Mulat Awoke, Kebede Fasikaw, Moges Solomon, Adisu Molalign Aligaz, Azmeraw Molla
Department of Nursing, College of Health Science, Woldia University, Weldiya, Ethiopia.
Department of Midwifery, College of Health Science, Woldia University, Weldiya, Ethiopia.
Neuroepidemiology. 2024 Jul 29:1-14. doi: 10.1159/000539803.
Previous reviews explored the association between maternal use of folic acid and multivitamin supplements and risk of neural tube defect (NTD) in children, with no definitive conclusion. These reviews had produced contradictory results, and there had been no umbrella review. Therefore, the objective of this umbrella review is to combine the inconsistent data on the effect of prenatal folic acid and/or multivitamin supplementation for the prevention of NTD in offspring.
Using the PRISMA guideline, PubMed, Embase, Scopus, Web of Sciences, Cochrane Database of Systematic Reviews, Scopus, and Google Scholar reported that the effects of folic acid and/or multivitamin supplementation for the prevention of NTD in offspring were searched. The quality of the included studies was assessed using Assessment of Multiple Systematic Reviews (AMSTAR). A weighted inverse variance random-effects model was applied to find the pooled estimates. The subgroup analysis, heterogeneity, publication bias, and sensitivity analysis were also assessed.
Ten SRM with 296,816 study participants were included. The random-effects model analysis from 10 included systematic review and meta-analysis revealed that the pooled effect of either folic acid or multivitamin supplementation for the prevention of NTD globally is found to be 0.43 (95% CI: 0.29, 0.58) (I2 = 93.50%; p ≤0.001). In the subgroup analysis, the pooled effect was found to be 0.23 (0.09, 0.37) in folic acid group, while this estimate is 0.63 (0.53, 0.72) and 0.61 (0.46, 0.75) in groups who took multivitamin. The pooled effect of prevention of NTD was found to be 0.50 (0.34, 0.66) in SRMs aimed at occurrence prevention (primary prevention) group, while this estimate is 0.20 (-0.01, 0.41) among SRMs, which aimed at reoccurrence (secondary) prevention, and 0.61 (0.46, 0.75) among those SRMs aimed to assess the effect folic acid or multivitamin for the prevention of both occurrence and reoccurrence. The pooled effect of either folic acid or multivitamin supplementation for the prevention of NTD was found to be 0.45 (0.03, 0.87) in SRMs of observational studies, while this estimate is 0.43 (0.32, 0.54) among SRMs of randomized controlled trials.
This umbrella review of systematic review and meta-analysis found that prenatal folic acid and/or multivitamin supplementation was associated with a 57% reduction in NTD. Participants who took folic acid supplementation were associated with a slightly higher (77%) percentage of reduction in NTD compared with those who took multivitamin (37%). Reductions of 80% and 50% were observed for reoccurrence and occurrence prevention of NTD. Reductions of 57% and 55% of NTD have been found in SRM of RCTs and observational studies. This umbrella review revealed that both folic acid and multivitamin were associated with significantly lower levels of NTD in children. Considering the incorporation of those supplements in NTD prevention strategies during the preconception period is recommended. More large-scale prospective cohort and RCTs are needed to understand the protective effect of multivitamins and/or folic acid on NTD risk addressing the molecular mechanisms and to determine the optimal dose, duration, and timing of maternal multivitamin and folic acid intake for best child NTD risk reduction.
以往的综述探讨了孕妇使用叶酸和多种维生素补充剂与儿童神经管缺陷（NTD）风险之间的关联，但尚无定论。这些综述结果相互矛盾，且未进行过综合评价。因此，本综合评价的目的是整合关于产前叶酸和/或多种维生素补充剂预防后代神经管缺陷效果的不一致数据。
按照PRISMA指南，检索了PubMed、Embase、Scopus、Web of Sciences、Cochrane系统评价数据库以及Scopus和谷歌学术，以获取叶酸和/或多种维生素补充剂预防后代神经管缺陷效果的相关报道。采用多种系统评价评估工具（AMSTAR）对纳入研究的质量进行评估。应用加权逆方差随机效应模型计算合并估计值。同时还进行了亚组分析、异质性分析、发表偏倚分析和敏感性分析。
纳入了10项系统评价和荟萃分析（SRM），涉及296,816名研究参与者。对10项纳入的系统评价和荟萃分析进行随机效应模型分析发现，全球范围内叶酸或多种维生素补充剂预防神经管缺陷的合并效应值为0.43（95%可信区间：0.29，0.58）（I² = 93.50%；p≤0.001）。亚组分析中，叶酸组的合并效应值为0.23（0.09，0.37），而服用多种维生素的组分别为0.63（0.53，0.72）和0.61（0.46，0.75）。在旨在预防发生（一级预防）的SRM中，预防神经管缺陷的合并效应值为0.50（0.34，0.66），而在旨在预防复发（二级预防）的SRM中该估计值为0.20（-0.01，0.41），在旨在评估叶酸或多种维生素预防发生和复发效果的SRM中为0.61（0.46，0.75）。在观察性研究的SRM中，叶酸或多种维生素补充剂预防神经管缺陷的合并效应值为0.45（0.03，0.87），而在随机对照试验的SRM中该估计值为0.43（0.32，0.54）。
本对系统评价和荟萃分析的综合评价发现，产前叶酸和/或多种维生素补充剂可使神经管缺陷风险降低57%。与服用多种维生素的参与者相比，服用叶酸补充剂的参与者神经管缺陷降低比例略高（77%）。神经管缺陷复发预防和发生预防分别降低了80%和50%。在随机对照试验和观察性研究的SRM中，神经管缺陷分别降低了57%和55%。本综合评价表明，叶酸和多种维生素均与儿童神经管缺陷水平显著降低相关。建议在孕前将这些补充剂纳入神经管缺陷预防策略。需要更多大规模的前瞻性队列研究和随机对照试验，以了解多种维生素和/或叶酸对神经管缺陷风险的保护作用及其分子机制，并确定孕妇摄入多种维生素和叶酸的最佳剂量、持续时间和时间，以最大程度降低儿童神经管缺陷风险。
