定义与红细胞叶酸浓度阈值相关的血浆叶酸浓度，以达到最佳神经管缺陷预防效果：一项基于人群的叶酸补充随机试验。
Defining the plasma folate concentration associated with the red blood cell folate concentration threshold for optimal neural tube defects prevention: a population-based, randomized trial of folic acid supplementation.
机构信息
Epidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, GA.
National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA.
出版信息
Am J Clin Nutr. 2019 May 1;109(5):1452-1461. doi: 10.1093/ajcn/nqz027.
BACKGROUND
For women of reproductive age, a population-level red blood cell (RBC) folate concentration below the threshold 906 nmol/L or 400 ng/mL indicates folate insufficiency and suboptimal neural tube defect (NTD) prevention. A corresponding population plasma/serum folate concentration threshold for optimal NTD prevention has not been established.
OBJECTIVE
The aim of this study was to examine the association between plasma and RBC folate concentrations and estimated a population plasma folate insufficiency threshold (pf-IT) corresponding to the RBC folate insufficiency threshold (RBCf-IT) of 906 nmol/L.
METHODS
We analyzed data on women of reproductive age (n = 1673) who participated in a population-based, randomized folic acid supplementation trial in northern China. Of these women, 565 women with anemia and/or vitamin B-12 deficiency were ineligible for folic acid intervention (nonintervention group); the other 1108 received folic acid supplementation for 6 mo (intervention group). We developed a Bayesian linear model to estimate the pf-IT corresponding to RBCf-IT by time from supplementation initiation, folic acid dosage, methyltetrahydrofolate reductase (MTHFR) genotype, body mass index (BMI), vitamin B-12 status, or anemia status.
RESULTS
Using plasma and RBC folate concentrations of the intervention group, the estimated median pf-IT was 25.5 nmol/L (95% credible interval: 24.6, 26.4). The median pf-ITs were similar between the baseline and postsupplementation samples (25.7 compared with 25.2 nmol/L) but differed moderately (±3-4 nmol/L) by MTHFR genotype and BMI. Using the full population-based baseline sample (intervention and nonintervention), the median pf-IT was higher for women with vitamin B-12 deficiency (34.6 nmol/L) and marginal deficiency (29.8 nmol/L) compared with the sufficient group (25.6 nmol/L).
CONCLUSIONS
The relation between RBC and plasma folate concentrations was modified by BMI and genotype and substantially by low plasma vitamin B-12. This suggests that the threshold of 25.5 nmol/L for optimal NTD prevention may be appropriate in populations with similar characteristics, but it should not be used in vitamin B-12 insufficient populations. This trial was registered at clinicaltrials.gov as NCT00207558.
背景
对于育龄妇女，红细胞（RBC）叶酸浓度低于 906 nmol/L（或 400ng/ml）的人群阈值表明叶酸不足和神经管缺陷（NTD）预防效果不佳。尚未确定最佳 NTD 预防的相应人群血浆/血清叶酸浓度阈值。
目的
本研究旨在探讨血浆和 RBC 叶酸浓度与估计人群血浆叶酸不足阈值（pf-IT）与 RBC 叶酸不足阈值（RBCf-IT）906 nmol/L 的关系。
方法
我们分析了中国北方一项基于人群的随机叶酸补充试验中育龄妇女（n=1673）的数据。其中，565 名患有贫血和/或维生素 B-12 缺乏症的妇女不符合叶酸干预条件（非干预组）；其余 1108 名妇女接受了 6 个月的叶酸补充（干预组）。我们建立了一个贝叶斯线性模型，通过补充起始时间、叶酸剂量、亚甲基四氢叶酸还原酶（MTHFR）基因型、体重指数（BMI）、维生素 B-12 状态或贫血状态来估计与 RBCf-IT 相对应的 pf-IT。
结果
使用干预组的血浆和 RBC 叶酸浓度，估计中位数 pf-IT 为 25.5 nmol/L（95%可信区间：24.6，26.4）。基线和补充后样本的中位数 pf-IT 相似（分别为 25.7 和 25.2 nmol/L），但 MTHFR 基因型和 BMI 略有不同（±3-4 nmol/L）。使用基于全人群的基线样本（干预组和非干预组），维生素 B-12 缺乏（34.6 nmol/L）和边缘缺乏（29.8 nmol/L）的妇女的中位数 pf-IT 高于充足组（25.6 nmol/L）。
结论
RBC 和血浆叶酸浓度之间的关系受 BMI 和基因型以及低血浆维生素 B-12 的显著影响。这表明，对于具有相似特征的人群，25.5 nmol/L 是预防最佳 NTD 的阈值，但不应用于维生素 B-12 不足的人群。该试验在 clinicaltrials.gov 上注册为 NCT00207558。
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