Association between Early Pregnancy Maternal Folate and Glycemic Indices at Oral Glucose Tolerance Test: A Systematic Review and Meta-analysis
Bibliographic record
Abstract
<h2>Abstract</h2><h3>Background</h3> Folate plays a crucial role in foetal development, but its relationship with maternal glucose metabolism remains inconclusive. Recent meta-analyses have suggested a correlation between high folate and the risk of GDM in pregnancy, however its association with different glycaemic parameters have not yet been explored. <h3>Objective</h3> To comprehensively synthesise evidence and test the association between early pregnancy circulating folate (<16 weeks of gestation) and glycaemic indices measured during oral glucose tolerance testing (OGTT) at 24-28 weeks. <h3>Methods</h3> We conducted a systematic search of databases up to 25<sup>th</sup> June 2025 examining the relationship between early pregnancy folate and maternal glycaemic indices. Study quality was assessed by Newcastle-Ottawa Scale (NOS). Standardised effect sizes (std. β coefficients) for serum/plasma folate were pooled using a random-effects model. Subgroup and sensitivity analyses were performed to account for between- study heterogeneity. <h3>Results</h3> Ten studies were included in this meta-analysis. Early pregnancy maternal folate levels were positively associated with glycaemic indices measured at the time of OGTT. One standard deviation (SD nmol/l) increase in early pregnancy serum folate was associated with 0.01 (95% CI: -0.001, 0.01) mmol/l higher fasting, 0.17 (95% CI: 0.15; 0.18) mmol/l higher 1-hour glucose, and 0.10 (95% CI: 0.05, 0.15) mmol/l higher 2-hour glucose levels during OGTT Subgroup analyses revealed similar positive association between mid-pregnancy circulating folate and glucose levels measured at the time of OGTT despite substantial between-study heterogeneity (<i>I</i><sup>2</sup>>70%). <h3>Conclusions</h3> Our analysis suggests a possible association between higher early pregnancy folate levels and higher glucose levels at the time of OGTT. However, these findings should be interpreted cautiously given the methodological limitations and limited number of studies included in this review. <h3>Registry number for systematic reviews and meta-analysis</h3> Systematic review was registered in PROSPERO with registry number CRD42021255022 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021255022).
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.006 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".