Framework for laboratory harmonization of folate measurements in low- and middle-income countries and regions

Ann N Y Acad Sci. 2018 Feb;1414(1):96-108. doi: 10.1111/nyas.13532. Epub 2018 Jan 29.


The measurement of serum and red blood cell folate, two commonly used biomarkers of folate status in populations, is complicated by analytical and data interpretation challenges. Folate results show poor comparability across laboratories, even using the same analytical technique. The folate microbiologic assay produces accurate results and requires simple instrumentation. Thus, it could be set up and maintained in low- and middle-income country laboratories. However, the assay has to be harmonized through the use of common critical reagents (e.g., microorganism and folate calibrator) in order to produce comparable results across laboratories and over time, so that the same cutoff values can be applied across surveys. There is a limited need for blood folate measurements in a country owing to the periodic nature of surveys. Having a network of regional resource laboratories proficient in conducting the folate microbiologic assay and willing and able to perform service work for other countries will be the most efficient way to create an infrastructure wherein qualified laboratories produce reliable blood folate data. Continuous participation of these laboratories in a certification program can verify and document their proficiency. If the resource laboratories conduct the work on a fee-for-service basis, they could become self-sustaining in the long run.

Keywords: 5-methyltetrahydrofolate; cutoff value; folic acid; microbiologic assay; red blood cell folate; serum folate.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers / blood
  • Blood Chemical Analysis / methods*
  • Blood Chemical Analysis / standards
  • Developing Countries
  • Erythrocytes / metabolism
  • Folic Acid / blood*
  • Humans
  • Laboratories
  • Lacticaseibacillus rhamnosus / growth & development
  • Microbiological Techniques / methods
  • Microbiological Techniques / standards
  • Nutritional Status
  • Quality Control


  • Biomarkers
  • Folic Acid