TABLE 2.
Estimated serum folate insufficiency threshold corresponding to the RBC folate threshold for optimal NTD prevention: Overall and by sociodemographic, biochemical, and metabolic characteristics1.
| Serum folate, nmol/L | Difference | ||
|---|---|---|---|
| Variables | n2 | Median (95% Credible Interval) | Median (95% Credible Interval) |
| Overall | 977 | 37.8 (33.9, 43.3) | n/a |
| Sociodemographic characteristics | |||
| Age, y | |||
| <26 | 277 | 54.0 (41.8, 81.5) | 21.9 (6.6, 49.8) |
| 26–36 | 452 | 33.9 (29.7, 40.5) | 2.0 (-7.9, 10.2) |
| ≥36 | 248 | 31.9 (26.9, 41.1) | Reference |
| Iron status | |||
| Hemoglobin3, g/dL | |||
| <12.0 | 405 | 32.8 (28.5, 40.2) | -9.1 (-19.7, 0.4) |
| ≥12.0 | 572 | 42.0 (36.0, 51.4) | Reference |
| Serum ferritin4, μg/L | |||
| <15.0 | 599 | 34.4 (30.7, 39.8) | -10.6 (-28.1, -0.5) |
| ≥15.0 | 376 | 45.2 (36.4, 62.1) | Reference |
| <20.0 | 709 | 36.4 (32.2, 42.6) | -4.4 (-19.1, 5.1) |
| ≥20.0 | 266 | 40.8 (33.4, 55.8) | Reference |
| <25.0 | 790 | 37.3 (33.0, 43.2) | -1.8 (-18.9, 7.8) |
| ≥25.0 | 185 | 39.1 (31.7, 55.9) | Reference |
| Body iron index5, mg/kg | |||
| <0.0 | 378 | 32.9 (29.2, 38.3) | -12.3 (-27.5, -3.0) |
| ≥0.0 | 597 | 45.3 (37.4, 59.9) | Reference |
| Specifically, for serum ferritin, CRP, serum B12, MMA, cB12, and HbA1c | |||
| Serum CRP 6, mg/L | |||
| ≤1.0 | 425 | 41.6 (35.6, 51.4) | Reference |
| >1.0 to ≤3.0 | 261 | 36.6 (30.7, 47.4) | -4.9 (-16.5, 7.3) |
| >3.0 to ≤5.0 | 123 | 28.8 (23.9, 38.4) | -12.7 (-23.7, -1.7) |
| >5.0 | 168 | 29.3 (23.4, 42.8) | -12.2 (-23.8, 1.8) |
| >1.0 | 552 | 33.4 (29.5, 39.4) | -8.1 (-19.2, 0.7) |
| ≤1.0 | 425 | 41.5 (35.4, 52.0) | Reference |
| >3.0 | 291 | 29.5 (25.2, 36.9) | -10.3 (-18.3, -1.6) |
| ≤3.0 | 686 | 39.8 (35.2, 46.8) | Reference |
| >5.0 | 168 | 29.3 (23.3, 43.7) | -8.8 (-17.0, 5.1) |
| ≤5.0 | 809 | 38.1 (34.2, 43.7) | Reference |
| Serum α-1 acid glycoprotein7, g/L | |||
| >1.0 | 216 | 33.5 (26.9, 48.1) | -4.7 (-13.6, 10.6) |
| ≤1.0 | 759 | 38.2 (34.1, 44.2) | Reference |
| Vitamin B12status | |||
| Serum vitamin B128, pmol/L | |||
| <148 | 472 | 72.5 (52.1, 125.1) | 44.2 (23.6, 97.3) |
| ≥148 | 505 | 28.1 (25.7, 31.5) | Reference |
| <221 | 727 | 48.7 (41.0, 61.3) | 24.3 (15.9, 37.5) |
| ≥221 | 250 | 24.3 (21.7, 27.8) | Reference |
| Plasma MMA8, μmol/L | |||
| >0.26 | 592 | 55.6 (44.8, 75.7) | 29.6 (18.3, 49.8) |
| ≤0.26 | 545 | 25.9 (23.5, 29.3) | Reference |
| >0.37 | 432 | 68.3 (50.1, 115.7) | 39.9 (21.5, 87.6) |
| ≤0.37 | 545 | 28.2 (25.7, 31.6) | Reference |
| Impaired vitamin B12status8 | |||
| Vitamin B12 <148 pmol/L and MMA >0.26 μmol/L | 370 | 78.0 (53.7, 154.9) | 48.5 (24.1, 125.3) |
| Not impaired vitamin B12 status | 607 | 29.3 (26.7, 32.8) | Reference |
| Plasma homocysteine9, μmol/L | |||
| >10.0 | 157 | 114.9 (60.3, 485.3) | 79.7 (25.3, 451.3) |
| ≤10.0 | 820 | 34.7 (31.2, 39.6) | Reference |
| cB128 | |||
| ≥1.5 | 20 | 14.6 (9.3, 22.4) | -14.7 (-21.5, -6.5) |
| -0.5 to <1.5 | 517 | 29.4 (26.6, 33.0) | Reference |
| -1.5 to <-0.5 | 333 | 54.2 (46.0, 66.5) | 24.9 (17.6, 35.5) |
| -2.5 to <-1.5 | 100 | 70.7 (55.3, 94.6) | 41.3 (26.9, 63.5) |
| <-2.5 | 7 | 123.2 (57.4, 280.1) | 93.8 (28.8, 250.0) |
| ≥-0.5 | 537 | 28.4 (25.8, 31.8) | Reference |
| <-0.5 | 440 | 57.4 (48.9, 70.0) | 28.9 (21.3, 40.1) |
| BMI10,11, kg/m2 | |||
| <18.5 | 176 | 43.3 (34.4, 63.3) | 9.5 (-1.5, 30.0) |
| 18.5 to <25.0 | 440 | 33.7 (29.6, 39.9) | Reference |
| 25.0 to <30.0 | 213 | 37.4 (29.4, 55.5) | 3.7 (-6.4, 22.3) |
| ≥30.0 | 88 | 25.3 (21.1, 32.9) | -8.4 (-16.0, 0.0) |
| Waist circumference10,12, cm | |||
| >88.9 | 123 | 26.6 (22.6, 33.7) | -10.5 (-17.6, -2.4) |
| ≤88.9 | 794 | 37.1 (33.1, 43.0) | Reference |
| Waist-hip ratio10,12 | |||
| ≥0.85 | 191 | 30.5 (25.2, 41.0) | -5.6 (-13.2, 5.4) |
| <0.85 | 726 | 36.0 (32.3, 41.4) | Reference |
| Whole body fat10,12, % | |||
| >35 | 360 | 31.0 (27.1, 37.4) | -7.1 (-15.4, 0.8) |
| ≤35 | 559 | 38.1 (33.3, 45.6) | Reference |
| Trunk fat10,12, % | |||
| >35 | 332 | 30.7 (26.7, 37.1) | -7.3 (-15.6, 0.7) |
| ≤35 | 587 | 38.1 (33.4, 45.4) | Reference |
| HbA1c13, % | |||
| <5.7 | 732 | 43.8 (37.5, 53.7) | Reference |
| ≥5.7 | 245 | 28.2 (24.9, 33.3) | -15.5 (-25.9, -7.5) |
| <6.5 | 928 | 40.5 (35.8, 47.3) | Reference |
| ≥6.5 | 49 | 21.0 (17.8, 25.6) | -19.5 (-27.2, -13.0) |
Results outside assay LOD were set to ½ LOD (if below LOD) or 2 ×LOD (if above LOD); Results outside assay LODs: serum folate (n = 1 below LOD), vitamin B12 (n = 4 below LOD, n = 6 above LOD). BRINDA, Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia; cB12, combined B12; LOD, limit of detection; sTfR, soluble transferrin receptor; WHO, World Health Organization; 95% CI, 95% credible interval.
Individuals contributing data to the Bayesian simulations by strata; reported results are summarizing the posterior distributions of 10,000 iterations
Hemoglobin values from complete blood count; adjusted for smoking status [29]
Serum ferritin concentrations were adjusted for inflammation via BRINDA methods [41]; cutoffs for iron deficiency (serum ferritin <15.0 μg/L) and iron insufficiency (serum ferritin <20.0 and <25.0 μg/L) from [33,34]
Body iron index (mg/kg) was estimated using Cook’s equation after adjusting serum ferritin for inflammation via BRINDA methods [41] and converting sTfR to Flowers Ramco equivalents (Ramco = 1.5 × Roche + 0.35) [35].
CRP cutoffs for inflammation (>5.0 mg/L) and metabolic risk (>3.0 mg/L and >1.0 mg/L) from [33]
α-1 acid glycoprotein cutoff (>1.0 g/L) based on WHO criteria [33]
Cutoffs for vitamin B12 deficiency (<148 pmol/L) and vitamin B12 insufficiency (<221 pmol/L) from (30); cB12 was calculated using vitamin B12, MMA, and homocysteine and categorized (i.e., ≥1.5, -0.5 to <1.5, -1.5 to <-0.5, -2.5 to <-1.5, <-2.5) using methods developed by Fedosov et al. [32]
Elevated vitamin B12 (≥1.5), Adequate vitamin B12 (-0.5 to <1.5), Decreased vitamin B12 (-1.5 to <-0.5) , Possibly deficient (-2.5 to <-1.5) , Probably deficient (<-2.5) Sufficient vitamin B12 (-0.5 to >1.5), Deficient vitamin B12 (<-0.5).
Homocysteine cutoffs (>15.0 and >10.0 μmol/L) from [6]
Among adult participants (≥18 y; n = 928)
BMI categories (<18.5, 18.5 to <25.0, 25.0 to <30.0, and ≥30.0 kg/m2) as defined by the WHO [37]
Anthropometric cutoffs (waist circumference >88.9 cm and waist-hip ratio ≥ 0.85) were defined based on WHO criteria [38]; elevated whole body (>35%) and trunk fat (>35%) were defined based on criteria suggested by the American Association of Clinical Endocrinology [39]
HbA1c cutoffs (<5.7%, ≥5.7% to <6.5%, and ≥6.5%) were defined using the American Diabetes Association criteria [40]