Estimating the Serum Folate Concentration Associated With the Red Blood Cell Folate Threshold for Optimal Neural Tube Defects Prevention: A Population Based Biomarker Survey

Abstract

ObjectivesTo estimate the serum folate insufficiency threshold (sf-IT) corresponding to the red blood cell (RBC) folate insufficiency threshold for optimal neural tube defect (NTD) prevention. MethodsParticipants were 977 women of reproductive age (WRA; 15–40y; not pregnant or lactating) from a population-based biomarker survey in Southern India. Venous blood samples were collected at enrollment. Plasma, serum, and red blood cells were centrifuged, processed, and stored < -80°C until batch analysis. Total vitamin B12 concentrations were measured via chemiluminescence; RBC and serum folate concentrations were measured using the World Health Organization-recommended microbiological assay. Vitamin B12 deficiency was defined as total vitamin B12 < 148 pmol/L. Folate insufficiency was defined as RBC folate < 748 nmol/L, the recommended calibrator-adjusted equivalent of the threshold for population optimal NTD prevention. A previously developed Bayesian model and the RBC and serum folate distributions in this population were used to estimate the sf-IT corresponding to the RBC folate insufficiency threshold for optimal NTD prevention, overall and by age, body mass index (BMI) category, HbA1c, anemia, and vitamin B12 status. ResultsThe overall estimated median sf-IT was 37.8 nmol/L (95% credible interval [33.8–43.3]). This threshold was lower in overweight WRA (BMI: ≥25.0 kg/m2: 32.0 nmol/L [27.3–40.2] vs. BMI < 25.0 kg/m2: 36.2 nmol/L [32.2–43.3]), and varied by age (< 25y: 61.3 nmol/L [44.3–111.8]; 25 to 35y: 35.7 nmol/L [30.8–43.5]; ≥35y: 30.8 nmol/L [26.9–37.2]). The sf-IT was lower in anemic WRA (32.9 nmol/L [28.5–40.1]) compared to non-anemic WRA (42.0 nmol/L [36.1–51.3]), and lower in WRA with elevated HbA1c (≥5.7% to < 6.5: 32.4 nmol/L [27.3–41.6]; ≥6.5%: 20.9 nmol/L [17.8–25.6]) vs. WRA with HbA1c < 5.7% (43.8 nmol/L, [37.5–53.7]). The median sf-IT was higher in WRA with vitamin B12 deficiency (72.1 nmol/L [52.0–126.0]), compared to women who were not vitamin B12 deficient (28.1 nmol/L [25.6–31.5]). ConclusionsThe estimated sf-IT is dependent on anemia, elevated HbA1c, BMI, age, and vitamin B12 status. Funding SourcesCenters for Disease Control and Prevention; AF was supported by the National Institutes of Health #5 T32 HD087137.