Evidence map›Paper›PMID 31005964›Full record

Trial reportThe American journal of clinical nutrition2019

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.

Meng-Yu Chen, Charles E Rose, Yan Ping Qi, Jennifer L Williams, Lorraine F Yeung, Robert J Berry, Ling Hao, Michael J Cannon, Krista S Crider

2 registry-linked trialsAbstract readRandomized Controlled Trial
In one paragraph

Trial report in The American journal of clinical nutrition, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 58 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed, 3 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00207558 nacompletednot on this map

Blood Folate and Homocysteine Levels Following Administration of Folic Acid According to Different Daily Dosing Schedules:a Simulation of Food Fortification

TypeinterventionalSponsorCenters for Disease Control and PreventionEnrolled1,100ConditionsNeural Tube Defects - Spina Bifida and AnencephalyArmsfolic acid
NCT05935631 nacompletednot on this mapstarted 2023, after this paper: background citation

Feasibility, Acceptability and Directional Signal Effect on Blood Folate Levels of Iodized Salt Fortified With Folic Acid: Clinical Study

TypeinterventionalSponsorUniversity of Alabama at BirminghamRan2023 to 2023Enrolled32ConditionsNeural Tube Defects, Folic Acid Deficiency, FortificationArmsSalt with folic acid and iodine
3 · Its place in the literature

Who cites it

58 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. The Roles of Reduced Folate Carrier-1 (RFC1) A80G (rs1051266) Polymorphism in Congenital Heart Disease: A Meta-Analysis.Medical science monitor : international medical journal of experimental and clinical research · 2021
    Pooled it
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  18. Nicotine consumption and folate insufficiency in pregnancy: a population-based cross-sectional study.The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians · 2025
    Article
  19. Article
  20. Vitamin BClinical nutrition ESPEN · 2025
    Observational
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Meng-Yu ChenEpidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, GA.
Charles E RoseNational Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA.
Yan Ping QiNational Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA.
Jennifer L WilliamsNational Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA.
Lorraine F YeungNational Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA.
Robert J BerryNational Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA.
Ling HaoChina Office, Centers for Disease Control and Prevention, US Embassy, Beijing, China.
Michael J CannonNational Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA.
Krista S CriderNational Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA.

Funding

Intramural CDC HHS CC999999
6 · The paper itself

Abstract

backgroundFor 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.

objectiveThe 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.

methodsWe 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.

resultsUsing 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).

conclusionsThe 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.

Indexed as

Dietary SupplementsAdultBayes TheoremBody Mass IndexChinaErythrocytesFemaleFolic AcidFolic Acid DeficiencyGenotypeHumansMethylenetetrahydrofolate Reductase (NADPH2)Neural Tube DefectsNutrition TherapyPopulation HealthPreconception CareFolic AcidMethylenetetrahydrofolate Reductase (NADPH2)MTHFR protein, humanVitamin B 12Bayesianfolic acidneural tube defectsplasma folatered blood cell folatevitamin B-12

Identifiers

PMID31005964
PMCPMC7099800

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.