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.
Am J Clin Nutr. 2019 May 1;109(5):1452-1461. doi: 10.1093/ajcn/nqz027.
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.
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.
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.
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).
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.
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。
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。
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。
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）。
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。
