Folic acid supplementation and dietary folate intake in children with sickle cell disease : a double-blind randomized non-inferiority cross-over trial
Bibliographic record
Abstract
Supplementation with 1-5 mg/d folic acid, a synthetic form of folate, is the routine recommendation for Canadian individuals with sickle cell disease (SCD), an inherited hemoglobin disorder thought to increase requirements for folate due to chronic hemolysis and increased folate-dependent erythropoiesis. There is concern about whether children with SCD need such high doses of folic acid following mandatory folic acid fortification of refined grains and advancements in medical therapies for SCD in Canada. Thus, I conducted a double-blind randomized cross-over trial to determine the efficacy of folic acid supplementation by measuring the effect of folic acid, compared to placebo, on the primary outcome of red blood cell (RBC) folate concentrations in children with SCD. Children with SCD (n=31) in British Columbia were randomized to either 1 mg/d folic acid (current standard of care), or a placebo for 12 ± 1 weeks. After a 12 ± 1 week washout period, treatments were reversed. RBC folate concentrations were measured via microbiological assay and serum folate concentrations were measured via LC-MS/MS at baseline and after treatment periods. Mean differences in RBC and serum folate concentrations by treatment were evaluated using generalized linear regression models. Dietary intake was collected and analyzed from non-consecutive 24-hour dietary recalls. Inadequate dietary folate intake, defined as below the Estimated Average Requirement, was observed in 31% (n=8/26) of participants. In intention-to-treat analyses, the adjusted mean difference in RBC folate concentrations across treatments (placebo vs. folic acid) was -248 (95% CI: -367, -129) nmol/L (p<0.001). In per-protocol analyses (excluding periods with >1 RBC transfusion), the mean adjusted difference was -224 (95% CI: -336, -111) nmol/L (p<0.001). As per the ‘a priori’ defined non-inferiority margin of -227 nmol/L, the results were equivocal regarding non-inferiority of placebo in comparison to folic acid for the maintenance of RBC folate concentrations over 12 weeks. There was no significant difference in adjusted mean serum folate concentrations across treatments (-7 [95% CI: -35, 21] nmol/L, p=0.610). Future in vitro work in which the folate capacity of sickled red blood cells is tested could further inform interpretation of folate status in this population with abnormally shaped RBCs.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.005 | 0.002 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.004 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".