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
A public health approach for preventing neural tube
defects: folic acid fortiﬁcation and beyond
Greg S. Garrett
and Lynn B. Bailey
Program Services, Global Alliance for Improved Nutrition, Geneva, Switzerland.
Department of Foods and Nutrition, College
of Family and Consumer Sciences, University of Georgia, Athens, Georgia
Address for correspondence: Greg S. Garrett, Program Services, Global Alliance for Improved Nutrition, Geneva 1211,
In this paper we review the evidence basis for prevention of folic acid–sensitive neural tube defects (NTDs) through
public health interventions in women of reproductive age (WRA), the proven vehicles for delivery of folic acid,
and what is needed to effectively scale these, and provide a snapshot of potential innovations that require future
research. Our primary focus is on the global situation affecting large-scale food fortiﬁcation (LSFF) with folic acid, in
particular the fortiﬁcation of wheat ﬂour and maize meal. Our overarching conclusion is that folic acid fortiﬁcation
is an evidence-based intervention that reduces the prevalence of NTDs, and that LSFF with folic acid is underutilized.
Thus, food fortiﬁcation with folic acid should be a component of most national public health strategies, in particular
where folate status is insufﬁcient and a fortiﬁable food vehicle, processed by a centralized industry, is consumed
regularly by WRA. The evidence shows that there is still much work needed (1) to build the enabling environment
and expand programs where there is currently no legislation, (2) to improve the low quality of delivery of existing
programs, and (3) to measure and sustain programs by generating new coverage data and demonstrating evidence
of impact in low- and middle-income countries.
Keywords: fortiﬁcation; folic acid; coverage; NTD prevention
Neural tube defects (NTDs), a group of severe birth
defects resulting from abnormal neural tube (i.e.,
spinal cord and brain) formation during embryonic
development, are associated with fetal and infant
mortality, morbidity, severe lifelong disability, psy-
chological maladjustment, and staggering economic
Globally, more than 260,000 pregnancies
are estimated to be affected by NTDs, and of the
NTD live births, 75% result in under-5 deaths.
largest percentage of NTDs are folic acid sensitive,
with much of the NTD burden preventable through
consumption of mandatory folic acid–fortiﬁed sta-
ple food products before conception.
An association between low folate status of
women of reproductive age (WRA) and risk of
NTD-affected pregnancy was ﬁrst proposed in
This hypothesis was substantiated by results
of pivotal randomized controlled trials demonstrat-
ing the effectiveness of folic acid supplementa-
tion before and during early pregnancy (pericon-
ceptional) in preventing the recurrence
of NTDs. These results, published in
the early 1990s, were subsequently followed by a
recommendation by the U.S. Public Health Service
in 1992 that all women capable of becoming preg-
nant consume 400 g of folic acid daily to prevent
ﬁrst occurrence of an NTD-affected pregnancy.
This recommendation and others globally
supported by a large-scale folic acid intervention
study conducted in China that demonstrated the
efﬁcacy of a daily periconceptional supplement of
400 g in preventing a large percentage of NTDs.
To ensure adequate folate status for neural tube
closure that occurs in early embryonic develop-
ment (22–28 days, post conception), a woman
should begin folic acid supplementation before
becoming pregnant. The recommendation of
Ann. N.Y. Acad. Sci. 1414 (2018) 47–58
2018 The Authors. Annals of the New York Academy of Sciences
published by Wiley Periodicals, Inc. on behalf of New York Academy of Sciences.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in
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