Ann. N.Y. Acad. Sci. ISSN 0077-8923
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
Special Issue: Folate Status in Women and Neural Tube Defect Risk Reduction
Framework for laboratory harmonization of folate
measurements in low- and middle-income countries
Christine M. Pfeiffer, Mindy Zhang, and Shameem Jabbar
Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention,
Address for correspondence: Christine M. Pfeiffer, Division of Laboratory Sciences, National Center for Environmental Health,
Centers for Disease Control and Prevention, 4770 Buford Hwy NE, Atlanta, GA 30341. firstname.lastname@example.org
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 labora-
tories, 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: microbiologic assay; folic acid; 5-methyltetrahydrofolate; serum folate; red blood cell folate; cutoff value
Folate status can be assessed through dietary intake,
blood biomarker concentrations, or a combination
of both. The measurement of biochemical indica-
tors is considered to be more objective than dietary
assessment, as it is not affected by recall or underre-
porting bias. The two main biochemical indicators
of folate status are serum and red blood cell (RBC)
folate, and these indicators have also been recom-
mended by the Biomarkers on Nutrition and Devel-
opment folate expert panel.
RBC folate has recently
also been recommended by the World Health Orga-
nization (WHO) as a biomarker for neural tube
defect (NTD) risk in women of reproductive age.
Assessing folate status through the measurement of
biochemical indicators is subject to numerous ana-
lytical and data interpretation challenges. A recent
article on challenges and lessons learned in gener-
ating and interpreting nutritional biomarker data
from the U.S. National Health and Nutrition Exam-
ination Survey provides several examples related to
folate as well as general information on laboratory
logistics and quality assurance.
There are no validated ﬁeld techniques to reliably
assess folate status in low-resource environments
at the point of specimen collection. Blood samples
have to be processed, transported, and stored while
maintaining uninterrupted cold chain, owing to
the labile nature of this vitamin, before they can
be analyzed at a central laboratory that has access
to continuous electrical power, speciﬁc instru-
mentation and reagents, and well-trained staff.
Furthermore, folate results show poor comparabil-
ity across laboratories, sometimes even using the
same analytical technique.
This makes it difﬁcult
to compare folate concentrations across surveys. It
Ann. N.Y. Acad. Sci. 1414 (2018) 96–108
2018 This article is a U.S. Government work and is in the public domain in the USA.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in
any medium, provided the original work is properly cited.