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

Details

• Journal Article:
  Am J Clin Nutr
• Personal Author:
  Chen, Meng-Yu ; Rose, Charles E ; Qi, Yan Ping ; Williams, Jennifer L ; Yeung, Lorraine F ; Berry, Robert J ; Hao, Ling ; Cannon, Michael J ; Crider, Krista S
• Description:
  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 NCT00207558.
• Subjects:
  • Adult
  • Bayes Theorem
  • Body Mass Index
  • China
  • Dietary Supplements
  • Erythrocytes
  • Female
  • Folic Acid
  • Folic Acid Deficiency
  • Genotype
  More +
• Keywords:
  • neural tube defects
  • folic acid
  • plasma folate
  • red blood cell folate
  • vitamin B-12
  • Bayesian
• Source:
  Am J Clin Nutr. 109(5):1452-1461
• DOI:
  http://dx.doi.org/10.1093/ajcn/nqz027
• Pubmed ID:
  31005964
• Pubmed Central ID:
  PMC7099800
• Document Type:
  Text ; Journal Article
• Funding:
  CC999999/ImCDC/Intramural CDC HHSUnited States/
• Genre:
  Journal Article
• Volume:
  109
• Issue:
  5
• Download URL:
  https://stacks.cdc.gov/view/cdc/86189/cdc_86189_DS1.pdf
• File Type:
  [PDF - 1.05 MB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:4f56ffef396d039599910b895c53bb05ba3ceeba6286ad6aa9b3660e5b6bb8cbf5f8ea9269709e9e0063c3926bacd1002df49b1fb3d788f620c9e262335d6aef