Date Published: June 5, 2019
Publisher: Public Library of Science
Author(s): Elizabeth G. Rey, Julia L. Finkelstein, David Erickson, Richard C. Willson.
Folate is a micronutrient required for the production of new cells, making it a key factor in early fetal development and ensuring normal growth and maintenance of health. The increase in consumption of folate due to increased periconceptional supplementation and fortification of grains in many countries has led to a decrease in occurrence of folate deficiency and a class of birth defects called neural tube defects. However, an opportunity remains to further improve folate status of populations in areas with limited access to fortified foods and supplementation. Screening of women of reproductive age and other vulnerable populations for folate status would increase our understanding of the magnitude of the burden of folate deficiency and inform monitoring of public health programs. Current gold standard methods for folate assessment are time-intensive and require cold chain, sophisticated laboratory infrastructure, and highly-trained personnel. Our lateral flow assay is low-cost, easy to use, and allows a user to assess folate insufficiency at the point of care in less than 40 minutes. We evaluated the sensitivity and specificity of our assay in 24 human serum samples, including 8 samples with folate concentrations less than 10.0 nmol/L and 14 samples less than 13.4 nmol/L using the Immulite 2000 commercial assay as a reference standard. The sensitivity and specificity were found to be 93% (95% CI: 54.7–100.0) and 91% (95% CI: 80.0–100.0), respectively, when using our test to determine folate insufficiency based on a cutoff of 13.4 nmol/L. Our point-of-care diagnostic test for folate concentrations could inform screening and public health programs in at-risk populations.
Folate is a B-vitamin which is essential for DNA synthesis and cellular division, including fetal growth and development. Factors that can lead to insufficient folate status include inadequate intake, increased requirements (e.g., pregnancy), conditions which inhibit absorption, and antifolate medications (e.g., pyrimethamine, methotrexate). Folate deficiency can lead to megaloblastic anemia, which can cause symptoms of weakness, fatigue, and shortness of breath. Folate requirements are increased during pregnancy and lactation, to support cell replication in fetal, placental, and maternal tissues; inadequate maternal folate status during pregnancy has been associated with increased risk of adverse pregnancy outcomes, including pregnancy loss, low birth weight, and premature delivery.
This LFA platform could be used at the point of care and in field settings to detect concentrations of folate in serum. This assay delivers an accurate result regarding serum folate concentration in less than 40 minutes without the use of sophisticated laboratory equipment. Although sample preparation steps are required beyond that of traditional LFAs, we have developed a protocol which could be used in limited-resource settings. This point-of-care diagnostic method would inform screening for folate insufficiency in vulnerable populations, including women of reproductive age, and programs for anemia and birth defects prevention. This test could also inform assessment of folate status and representative population data worldwide. Along with appropriate folic acid supplementation and fortification programs, a folate diagnostic test at the point of care could help to reduce the burden of anemia and NTDs globally.