ArticleThe American journal of clinical nutrition2022
Associations between folic acid supplement use and folate status biomarkers in the first and third trimesters of pregnancy in the Maternal-Infant Research on Environmental Chemicals (MIREC) Pregnancy Cohort Study.
Article in The American journal of clinical nutrition, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 2 of them syntheses that pooled it.
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Who cites it
12 citing papers in PubMed, 2 syntheses or guidelines pooled it, 22 citations in OpenAlex.
- Unmetabolized Folic Acid: Biology, Epidemiology, and Clinical Consequences: A Systematic Review.Nutrients · 2026Pooled it
- Does previous pregnancy experience improve folic acid supplementation uptake? A systematic review and meta-analysis.BMJ open · 2026Pooled it
- Human milk unmetabolized folic acid is increased following supplementation with synthetic folic acid as compared to (6S)-5-methyltetrahydrofolic acid.Scientific reports · 2023Trial
- Air Pollution Mixture and Folate Status Indicators among Pregnant Women in Canada: Maternal-Infant Research on Environmental Chemicals (MIREC) Study, 2008 to 2011.Current developments in nutrition · 2026Article
- Reassessing Mandatory Folic Acid Fortification for Neural Tube Defect Prevention: Evidence, Uncertainty, and Policy Implications.Nutrients · 2026Review
- Excess folic acid disrupts placental endocrine functionFrontiers in nutrition · 2026Article
- Prenatal fluoride exposure and autistic behaviors in preschool-aged children: the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort study.Environmental health : a global access science source · 2025Article
- Association between gestational environmental chemical mixtures and folate exposures with autistic behaviors in a Canadian birth cohort.Environmental epidemiology (Philadelphia, Pa.) · 2025Article
- Prenatal Intake of High Multivitamins or Folic Acid With or Without Choline Contributes to Gut Microbiota-Associated Dysregulation of Serotonin in Offspring.Molecular nutrition & food research · 2025Article
- Uptake of iron and folic acid supplements among pregnant women in Dar es Salaam, Tanzania.PLOS global public health · 2025Article
- Combined Exposure to Folate and Lead during Pregnancy and Autistic-Like Behaviors among Canadian Children from the MIREC Pregnancy and Birth Cohort.Environmental health perspectives · 2024Article
- Gestational exposure to organochlorine compounds and metals and infant birth weight: effect modification by maternal hardships.Environmental health : a global access science source · 2024Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundAchieving optimal folate status during early gestation reduces the risk of neural tube defects (NTDs). While inadequate folate intake remains a concern, it is becoming increasingly common for individuals to consume higher than recommended doses of folic acid (FA) with minimal additional benefit.
objectiveHere, we sought to investigate the determinants, including FA supplement dose and use, of plasma total and individual folate vitamer concentrations in the first and third trimesters of pregnancy.
methodsUsing data from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a cohort exposed to mandatory FA fortification, we measured plasma total folate and individual folate vitamer [5-methyltetrahydrofolate (5-methylTHF), unmetabolized FA (UMFA), and non-methyl folates (sum of THF, 5-formylTHF, 5,10-methenyl-THF)] concentrations in the first and third trimesters (n = 1,893). Using linear mixed models, we estimated associations between plasma folate concentrations, total daily supplemental FA intake, plasma vitamin B-12 concentrations, and multiple demographic, maternal, and reproductive factors.
resultsAlmost 95% of MIREC study participants met or exceeded the recommended daily supplemental FA intake from supplements (≥400 μg/d), with approximately 25% consuming more than the Tolerable Upper Intake Level (>1000 μg/d). Over 99% of MIREC participants had a plasma total folate status indicative of maximal NTD risk reduction (25.5 nmol/L) regardless of FA supplement dose. UMFA was detected in almost all participants, with higher concentrations associated with higher FA doses. Determinants of adequate FA supplement intake and folate status associated with reduced NTD risk included indicators of higher socioeconomic position, higher maternal age, nulliparity, and lower prepregnancy BMI.
conclusionsIn the context of mandatory FA fortification, our data indicate that higher-than-recommended FA doses are unwarranted, with the exception of individuals at higher risk for NTDs. Ideally, prenatal supplements would contain 400 rather than 1000 µg FA, thereby enabling the consumption of optimal and safe FA doses.
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