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
Historical perspective on folic acid and challenges in
estimating global prevalence of neural tube defects
and Robert E. Black
Department of Epidemiology, Emory University, Rollins School of Public Health, Atlanta, Georgia.
International Health, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland
Address for correspondence: Vijaya Kancherla, Ph.D., Department of Epidemiology, Emory University, Rollins School of Public
Health, 1518 Clifton Rd. NE, Atlanta, GA 30322. email@example.com
Neural tube defects (NTD) are major congenital malformations affecting births worldwide. NTD are associated
with life-long disability, signiﬁcant medical care costs, and child mortality. Their prevalence varies worldwide. We
conducted a review of published literature and surveillance systems to examine challenges in estimating an overall
global prevalence estimate for NTD. Our review showed that most low- and middle-income countries do not track
NTD and indicate a high prevalence of these malformations where data are available. Challenges in global NTD
prevalence estimation include (1) quality of surveillance methods, (2) existing risk factors (including geographic or
socioeconomic factors, availability and use of folic acid, and racial–ethnic and genetic factors), and (3) limitations in
education and access to care. We recommend population-based surveillance systems tracking all pregnancy outcomes
and major risk factors. Countries should invest in sustainable, multisource surveillance systems, in parallel to folic
acid interventions, for gaining a more accurate knowledge of global prevalence of NTD than we currently have. Such
efforts will assist in both global prevention of NTD and periodic evaluation of folic acid interventions for NTD
reduction. Global NTD prevalence data can drive political will and accelerate the implementation and evaluation of
NTD prevention programs.
Keywords: anencephaly; neural tube defects; prevalence; spina biﬁda; surveillance
Neural tube defects (NTD) are one of the most com-
mon types of congenital malformations character-
ized by incomplete closure of the embryonic neural
Anencephaly and spina biﬁda are the two
most common types of NTD that affect the brain
and spinal cord, respectively.
These defects occur
between 21 and 28 days after conception when most
women are unaware of their pregnancies.
contribute to stillbirths, as well as neonatal, infant,
and under-ﬁve mortality; along with life-long dis-
ability and substantial health care costs among those
The March of Dimes Global Report on Birth
Defects, using methods developed by Modell and
colleagues, published a global estimate of num-
ber of live births with NTD.
According to this
report, an estimated 324,000 births (2.4 per 1000
live births) were affected by NTD globally during
the year 2001, which contributed to over 2.3 million
disability-adjusted life years.
et al. extended the Modell methodology and esti-
mated 260,100 NTD-affected pregnancies world-
wide in 2015, of which approximately 50% were
Over 75% of NTD-affected
births resulted in death by 5 years of age.
prevalence of NTD was estimated by Blencowe and
colleagues to be 1.86 per 1000 live births in 2015,
while varying in different regions of the world
between 0.75 and 3.12 per 1000 live births.
A comprehensive systematic review of peer-
reviewed literature, birth defects surveillance reg-
istries, and reports published between January 1990
and July 2014 on the prevalence of NTD worldwide
by Zaganjor and colleagues listed many limitations
Ann. N.Y. Acad. Sci. 1414 (2018) 20–30
2018 The Authors. Annals of the New York Academy of Sciences
published by Wiley Periodicals, Inc. on behalf of New York Academy of Sciences.
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