Krista S. Crider

Background: Maternal folate and vitamin B₁₂ deficiency can lead to serious adverse pregnancy outcomes. There are no nationally representative estimates on folate and vitamin B₁₂ status among women of reproductive age (WRA) in Malawi.Objective: We assessed folate and vitamin B₁₂ status among nonpregnant WRA in Malawi and predicted the risk of folate‐sensitive neural tube defects (NTDs) were they to become pregnant.Methods: Using data from the cross‐sectional, nationally representative 2015–2016 Malawi Micronutrient Survey, we calculated the proportion of folate and vitamin B₁₂ deficiency and insufficiency by demographic characteristics among 778 nonpregnant WRA (15–49 years). We predicted NTD prevalence using red blood cell (RBC) folate distributions and a published Bayesian model of the association between RBC folate and NTD risk. Analyses accounted for complex survey design.Results: Among WRA, 8.5% (95% CI: 6.2, 11.6) and 13.3% (10.0, 17.4) had serum (12 deficiency (12 nutrition among Malawian WRA.

Folate, including the folic acid form, is a key component of the one-carbon metabolic pathway used for DNA methylation. Changes in DNA methylation patterns during critical development periods are associated with disease outcomes and are associated with changes in nutritional status in pregnancy. The long-term impact of periconceptional folic acid supplementation on DNA methylation patterns is unknown. To determine the long-term impact of periconceptional folic acid supplementation on DNA methylation patterns, we examined the association of the recommended dosage (400 μg/d) and time period (periconceptional before pregnancy through first trimester) of folic acid supplementation with the DNA methylation patterns in the offspring at age 14–17 y compared with offspring with no supplementation. Two geographic sites in China from the 1993–1995 Community Intervention Program of folic acid supplementation were selected for the follow-up study. DNA methylation at 402,730 CpG sites was assessed using saliva samples from 89 mothers and 179 adolescents (89 male). The mean age at saliva collection was 40 y among mothers (range: 35–54 y) and 15 y among adolescents (range: 14–17 y). Epigenome-wide analyses were conducted to assess the interactions of periconceptional folic acid exposure, the 5,10-methylenetetrahydrofolate reductase (MTHFR)-C677T genotype, and epigenome-wide DNA methylation controlling for offspring sex, geographic region, and background cell composition in the saliva. In the primary outcome, no significant differences were observed in epigenome-wide methylation patterns between adolescents exposed and those non-exposed to maternal periconceptional folic acid supplementation after adjustment for potential confounders [false discovery rate (FDR) P values < 0.05]. The MTHFR-C677T genotype did not modify this lack of association (FDR P values < 0.05). Overall, there were no differences in DNA methylation between adolescents who were exposed during the critical developmental window and those not exposed to the recommended periconceptional/first-trimester dosage of folic acid.

For three decades, the US Public Health Service has recommended that all persons capable of becoming pregnant consume 400 μg/day of folic acid (FA) to prevent neural tube defects (NTDs). The neural tube forms by 28 days after conception. Fortification can be an effective NTD prevention strategy in populations with limited access to folic acid foods and/or supplements. This review describes the status of mandatory FA fortification among countries that fortify ( n = 71) and the research describing the impact of those programs on NTD rates (up to 78% reduction), blood folate concentrations [red blood cell folate concentrations increased ∼1.47-fold (95% CI, 1.27, 1.70) following fortification], and other health outcomes. Across settings, high-quality studies such as those with randomized exposures (e.g., randomized controlled trials, Mendelian randomization studies) are needed to elucidate interactions of FA with vitamin B₁₂as well as expanded biomarker testing.

To evaluate anemia screening via portable hemoglobinometer (HemoCue 301) compared to automated hematology analyzer (AHA) reference, using paired venous samples from a population-based biomarker survey in Southern India. Participants were women of reproductive age (WRA; 15–40 y) who were not pregnant or lactating. Paired venous whole blood samples (n = 896) were analyzed for hemoglobin (Hb) via HemoCue 301 and Coulter Counter AHA, as the gold standard. Serum ferritin (SF) was measured by electrochemiluminescence. Anemia and severe anemia were defined as Hb < 12.0 and < 8.0 g/dL, respectively. SF was adjusted for inflammation using BRINDA methods; iron deficiency (ID) was defined as SF < 15.0 μg/L. Bland-Altman methods were used to assess level of agreement between Hb results (i.e., mean difference, standard deviation of differences, limits of agreement). Diagnostic accuracy parameters (i.e., sensitivity, specificity, positive predictive value, negative predictive value, accuracy) were calculated to evaluate HemoCue performance compared to the AHA reference, overall and by sociodemographic (e.g., age, parity), nutritional (e.g., iron, vitamin B12, folate status), and metabolic (e.g., HbA1c, body mass index (BMI)) characteristics. The estimated prevalence of anemia (36.3% vs. 41.6%, p < 0.0001) was significantly lower via HemoCue compared to the AHA reference. A total of 84.4% of anemia and 98.8% of severe anemia screening results were concordant. HemoCue had 74.8% sensitivity and 91.2% specificity, compared to AHA. HemoCue sensitivity was higher in women with iron deficiency (SF < 15.0 μg/L: 81.6% vs. ≥15.0 μg/L: 41.3%; p < 0.0001), and lower in WRA who were overweight (BMI ≥ 25.0 kg/m²: 63.9% vs. < 25.0 kg/m²: 78.8%; p = 0.004) or had elevated C-reactive protein (CRP) (CRP > 1.0 mg/L: 67.2% vs. ≤1.0 mg/L: 82.9%; p = 0.001; CRP > 3.0 mg/L: 62.2% vs. ≤3.0 mg/L: 79.3%; p = 0.001). Findings suggest the estimated prevalence of anemia evaluated via portable hemoglobinometer (HemoCue) was lower compared to the AHA reference. HemoCue sensitivity varied by iron status and metabolic risk factors in this population. Centers for Disease Control and Prevention (5U01DD001007), University of South Carolina Disability Research and Dissemination Center; NIH 5T32HD087137 (AF); NIH T32DK007158 (HMG); Cornell DNS.

Cognitive health is a public health concern among older adults. Dietary supplement (SUP) use is common and concerns have been raised about high folic acid intake among those with vitamin B-12 deficiency and exacerbation of poor cognitive performance (PCP). We evaluated SUP use, usual folic acid intake, and blood folate and vitamin B-12 concentrations in relation to cognitive performance. We used NHANES 2011–2014 data on adults aged ≥60 y (n = 2867) and estimated total usual folic acid intake from diet and supplements, vitamin B-12 intake from SUPs, blood folates, vitamin B-12 concentrations, vitamin B-12 insufficiency (≤258 pmol/L), high folate (serum folate ≥59 nmol/L or RBC folate ≥1609 nmol/L), and PCP (<34 on the Digit Symbol Substitution Test). We assessed folate distributions adjusted for multiple variables, including renal function. Compared with persons without PCP, adults with PCP were less likely to use supplements containing folic acid (mean ± SEE: 34.4% ± 2.4%) or vitamin B-12 (mean ± SEE: 47.5% ± 1.6%). Among vitamin B-12–insufficient adults, 18.0% ± 1.6% (mean ± SEE) reported taking a vitamin B-12 supplement. Among participants with high folate and insufficient vitamin B-12 concentrations, 34.3% ± 11.5% (mean ± SEE) reported taking vitamin B-12–containing supplements. Persons with high folate and normal vitamin B-12 concentrations had lower odds of PCP [aOR (adjusted odds ratio): 0.61; 95% CI: 0.45, 0.83] than persons with normal folate and vitamin B-12. Persons with high folate and normal methylmalonic acid (MMA) had lower odds of PCP (OR: 0.56; 95% CI: 0.40, 0.78) than those with normal folate and MMA concentrations. After adjustment for renal function, elevated risk of PCP was attenuated among persons with high folate and MMA. Concurrent high folate and insufficient vitamin B-12 concentrations were not associated with PCP. Differential associations between vitamin B-12 and MMA highlight the need to consider renal function in studies of high folate and low vitamin B-12 status. Consumption of vitamin B-12 supplements concurrent with low vitamin B-12 status may indicate vitamin B-12 malabsorption.

Background: Current studies examining the effects of high concentrations of red blood cell (RBC) or serum folates assume that high folate concentrations are an indicator of high folic acid intakes, often ignoring the contributions of other homeostatic and biological processes, such as kidney function. Objective: The current study examined the relative contributions of declining kidney function, as measured by the risk of chronic kidney disease (CKD), and usual total folic acid intake on the concentrations of RBC folate and serum folate (total as well as individual folate forms). Design: Cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) collected in 2-year cycles were combined from 2011 to 2018. A total of 18,127 participants aged ≥16 years with available folate measures, kidney biomarker data (operationalized as a categorical CKD risk variable describing the risk of progression), and reliable dietary recall data were analyzed. Results: RBC folate concentrations increased as CKD risk increased: low risk, 1089 (95% CI: 1069, 1110) nmol/L; moderate risk, 1189 (95% CI: 1158, 1220) nmol/L; high risk, 1488 (95% CI: 1419, 1561) nmol/L; and highest risk, 1443 (95% CI: 1302, 1598) nmol/L (p < 0.0001). Similarly, serum total folate concentrations increased as CKD risk increased: low risk: 37.1 (95% CI: 26.3, 38.0) nmol/L; moderate risk: 40.2 (95% CI: 38.8, 41.7) nmol/L; high risk: 48.0 (95% CI: 44.3, 52.1) nmol/L; the highest Risk: 42.8 (95% CI: 37.8, 48.4) nmol/L (p < 0.0001). The modeled usual intake of folic acid showed no difference among CKD risk groups, with a population median of 225 (interquartile range: 108–390) µg/day. Conclusion: Both RBC and serum folate concentrations increased with declining kidney function without increased folic acid intake. When analyzing associations between folate concentrations and disease outcomes, researchers may want to consider the confounding role of kidney function.