Association of Maternal Folate and Vitamin B12 in Early Pregnancy With Gestational Diabetes Mellitus: A Prospective Cohort Study
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Abstract
OBJECTIVE: To investigate the association of folate and vitamin B12 in early pregnancy with gestational diabetes mellitus (GDM) risk. RESEARCH DESIGN AND METHODS: The data of this study were from a subcohort within the Shanghai Preconception Cohort Study. We included pregnancies with red blood cell (RBC) folate and vitamin B12 measurements at recruitment (between 9 and 13 gestational weeks) and those with three samples available for glucose measurements under an oral glucose tolerance test. GDM was diagnosed between 24 and 28 weeks’ gestation. Odds ratio (OR) and 95% CI of having GDM was used to quantify the association. RESULTS: A total of 1,058 pregnant women were included, and GDM occurred in 180 (17.01%). RBC folate and vitamin B12 were significantly higher in pregnancies with GDM than those without GDM (P values were 0.045 and 0.002, respectively) and positively correlated with 1-h and 2-h serum glucose. Daily folic acid supplementation in early pregnancy increases the risk of GDM; OR (95% CI) was 1.73 (1.19–2.53) (P = 0.004). Compared with RBC folate <400 ng/mL, pregnancies with RBC folate ≥600 ng/mL were associated with ∼1.60-fold higher odds of GDM; the adjusted OR (95% CI) was 1.58 (1.03–2.41) (P = 0.033). A significant trend of risk effect on GDM risk across categories of RBC folate was observed (Ptrend = 0.021). Vitamin B12 was significantly associated with GDM risk (OR 1.14 per 100 pg/mL; P = 0.002). No significant association of serum folate and percentile ratio of RBC folate/vitamin B12 with GDM was observed. CONCLUSIONS: Higher maternal RBC folate and vitamin B12 levels in early pregnancy are significantly associated with GDM risk, while the balance of folate/vitamin B12 is not significantly associated with GDM.
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Higher vitamin B12 levels at 9 to 13 weeks' gestation are associated with a ~1.14-fold risk of GDM.
“Chen et al. reported that higher vitamin B12 levels at 9 to 13 weeks’ gestation were associated with a ~1.14-fold risk of GDM [145].”
From Medical Nutrition Therapy for Women with Gestational Diabetes: Current Practice and Future Perspectives (2025) · cites this paper as [145]
The Study Population section places vitamin B12 measurement at 9–13 gestational weeks, and the Results report a positive association with GDM. However, the reported 1.14-fold figure is an odds ratio per 100 pg/mL increase in vitamin B12, not an unqualified increase in risk; the citing sentence omits that essential unit and calls odds risk. Page numbers were not available in our copy. (LLM, conf=0.87)
Experimental — accuracy not yet measuredWomen with higher red blood cell folate ≥ 600 ng/mL at 9 to 13 weeks' gestation have ∼1.60-fold the odds of developing GDM (aOR 1.58, 95% CI 1.03-2.41; p = 0.033) compared with women who had RBC folate levels < 400 ng/mL.
“Women with higher red blood cell folate ≥ 600 ng/mL at 9 to 13 weeks’ gestation were associated with ∼1.60-fold the odds of developing GDM (aOR 1.58 (95% CI 1.03–2.41); p = 0.033) compared with women who had RBC folate levels < 400 ng/mL [145].”
From Medical Nutrition Therapy for Women with Gestational Diabetes: Current Practice and Future Perspectives (2025) · cites this paper as [145]
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- Authors
- Chen, X., Zhang, Y., Chen, H., Jiang, Y., Wang, Y., Wang, D., Li, M., Dou, Y., Sun, X., Huang, G., & Yan, W.
- Affiliations
- Fudan University (CN)
- Corresponding author
- Huang, Guoying
- Yan, Weili
- ORCID
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2020-11-06
- Volume
- 44
- Issue
- 1
- Pages
- 217-223
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC7783943
- OpenAlex
- W3096767488
- Cited by
- 100
- References
- 33
- Citations by year
- 2026: 6 · 2025: 20 · 2024: 19 · 2023: 23 · 2022: 23 · 2021: 8
- FWCI
- 10.17
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Diabetes Care (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Key Research and Development Program (2016YFC1000500)
- CAMS Innovation Fund for Medical Sciences (2019-I2M-5-001)
- Three-year Action Plan for Strengthening the Construction of Public Health System in Shanghai (GWIV-24)
- Topics
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Keywords
- gestational diabetes mellitus, maternal folate, vitamin B12, red blood cell folate, early pregnancy, folic acid supplementation, serum glucose, oral glucose tolerance test, preconception cohort
- MeSH terms
- China, Female, Folic Acid, Humans, Pregnancy, Prospective Studies, Vitamin B 12, Vitamins, Cohort Studies, Diabetes, Gestational
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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