Department of Nutrition, University of California, Davis, CA, USA.
Institute for Global Nutrition, University of California, Davis, CA, USA.
Adv Nutr. 2021 Dec 1;12(6):2401-2414. doi: 10.1093/advances/nmab083.
Several models have been developed to predict the effects of folic acid fortification programs on prevention of neural tube defects (NTDs), but each relies on different assumptions and data inputs. We identified and reviewed 7 models that predict the effects of folic acid intake or status on NTD risk. We applied 4 of these models [the original and a modified version of the Lives Saved Tool (LiST) and models developed by Arth et al. and Wald et al.] to predict the effect of folic acid fortification of wheat flour on reduction of NTDs using national survey data from Cameroon. The estimated percentage of NTDs averted due to fortified wheat flour (5.0 μg folic acid/g flour) varied by predictive model, with a 21-31% reduction in LiST to 83% in Arth's model, and 15% in Wald's model. As the simulated fortification level was increased from 1.0 to 7.0 μg folic acid/g flour, the pattern of change in estimated numbers of NTDs averted differed due to different model assumptions: the number of NTDs averted increased and then reached a plateau in the modified LiST model (as would be expected in real-world conditions), increased sharply in Arth's model, and increased continuously in Wald's model. This wide variation in predicted effects, and implausible results in some cases, undermines the models' utility for users of model outputs. Concurrent collection of dietary and biomarker data, including plasma and RBC folate concentrations, and NTD outcomes, is necessary to validate these models and monitor change in folic acid intake, folate-related biomarkers, and reduced NTD risk due to fortification. In the meantime, models based on erythrocyte folate concentration are recommended, based on biological plausibility and consistency with empirical evidence. Where erythrocyte folate data are unavailable, sensitivity analyses (using several models) could be conducted to examine the range of possible outcomes.
已经开发了几种模型来预测叶酸强化计划对预防神经管缺陷 (NTD) 的效果，但每种模型都依赖于不同的假设和数据输入。我们确定并审查了 7 种预测叶酸摄入量或状况对 NTD 风险影响的模型。我们应用了其中的 4 种模型[原始的和修改后的 Lives Saved Tool (LiST) 以及 Arth 等人和 Wald 等人开发的模型]来预测叶酸强化面粉对减少喀麦隆全国调查数据中 NTD 的影响。由于强化面粉 (5.0μg 叶酸/g 面粉)，LiST 估计的 NTD 减少比例在 21-31%之间，Arth 的模型为 83%，Wald 的模型为 15%。随着模拟强化水平从 1.0μg 叶酸/g 面粉增加到 7.0μg 叶酸/g 面粉，由于不同模型的假设不同，估计的 NTD 减少数量的变化模式也有所不同：在修改后的 LiST 模型中，NTD 减少数量增加，然后达到一个平台（在实际情况下预期会如此）；在 Arth 的模型中急剧增加；而在 Wald 的模型中则持续增加。这种预测效果的广泛差异，以及在某些情况下不合理的结果，削弱了模型输出使用者对模型的实用性。同时收集饮食和生物标志物数据，包括血浆和 RBC 叶酸浓度以及 NTD 结果，对于验证这些模型以及监测叶酸摄入量、叶酸相关生物标志物和强化叶酸导致的 NTD 风险降低的变化是必要的。同时，基于红细胞叶酸浓度的模型是推荐的，因为它们具有生物学合理性并与经验证据一致。在没有红细胞叶酸数据的情况下，可以进行敏感性分析（使用几种模型）来检查可能的结果范围。
