Describing the Prevalence of Neural Tube Defects Worldwide: A Systematic Literature Review

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Abstract

Background

Folate-sensitive neural tube defects (NTDs) are an important, preventable cause of morbidity and mortality worldwide. There is a need to describe the current global burden of NTDs and identify gaps in available NTD data.

Methods and Findings

We conducted a systematic review and searched multiple databases for NTD prevalence estimates and abstracted data from peer-reviewed literature, birth defects surveillance registries, and reports published between January 1990 and July 2014 that had greater than 5,000 births and were not solely based on mortality data. We classified countries according to World Health Organization (WHO) regions and World Bank income classifications. The initial search yielded 11,614 results; after systematic review we identified 160 full text manuscripts and reports that met the inclusion criteria. Data came from 75 countries. Coverage by WHO region varied in completeness (i.e., % of countries reporting) as follows: African (17%), Eastern Mediterranean (57%), European (49%), Americas (43%), South-East Asian (36%), and Western Pacific (33%). The reported NTD prevalence ranges and medians for each region were: African (5.2–75.4; 11.7 per 10,000 births), Eastern Mediterranean (2.1–124.1; 21.9 per 10,000 births), European (1.3–35.9; 9.0 per 10,000 births), Americas (3.3–27.9; 11.5 per 10,000 births), South-East Asian (1.9–66.2; 15.8 per 10,000 births), and Western Pacific (0.3–199.4; 6.9 per 10,000 births). The presence of a registry or surveillance system for NTDs increased with country income level: low income (0%), lower-middle income (25%), upper-middle income (70%), and high income (91%).

Conclusions

Many WHO member states (120/194) did not have any data on NTD prevalence. Where data are collected, prevalence estimates vary widely. These findings highlight the need for greater NTD surveillance efforts, especially in lower-income countries. NTDs are an important public health problem that can be prevented with folic acid supplementation and fortification of staple foods.

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Most cited references 74

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Prevention of neural-tube defects with folic acid in China. China-U.S. Collaborative Project for Neural Tube Defect Prevention.

Robert J. Berry, Zhu Hua Li, J Erickson … (1999)

Periconceptional administration of folic acid can reduce a woman's risk of having a fetus or infant with a neural-tube defect. As part of a public health campaign conducted from 1993 to 1995 in an area of China with high rates of neural-tube defects (the northern region) and one with low rates (the southern region), we evaluated the outcomes of pregnancy in women who were asked to take a pill containing 400 microg of folic acid alone daily from the time of their premarital examination until the end of their first trimester of pregnancy. Among the fetuses or infants of 130,142 women who took folic acid at any time before or during pregnancy and 117,689 women who had not taken folic acid, we identified 102 and 173, respectively, with neural-tube defects. Among the fetuses or infants of women who registered before their last menstrual period and who did not take any folic acid, the rates of neural-tube defects were 4.8 per 1000 pregnancies of at least 20 weeks' gestation in the northern region and 1.0 per 1000 in the southern region. Among the fetuses or infants of the women with periconceptional use of folic acid, the rates were 1.0 per 1000 in the northern region and 0.6 per 1000 in the southern region. The greatest reduction in risk occurred among the fetuses or infants of a subgroup of women in the northern region with periconceptional use who took folic acid pills more than 80 percent of the time (reduction in risk, 85 percent as compared with the fetuses or infants of women who registered before their last menstrual period and who took no folic acid; 95 percent confidence interval, 62 to 94 percent) [corrected]. In the southern region the reduction in risk among the fetuses or infants of women with periconceptional use of folic acid was also significant (reduction in risk, 41 percent; 95 percent confidence interval, 3 to 64 percent). Periconceptional intake of 400 microg of folic acid daily can reduce the risk of neural-tube defects in areas with high rates of these defects and in areas with low rates.

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Reduction in neural-tube defects after folic acid fortification in Canada.

Philippe De Wals, Fassiatou Tairou, Margot I. Van Allen … (2007)

In 1998, folic acid fortification of a large variety of cereal products became mandatory in Canada, a country where the prevalence of neural-tube defects was historically higher in the eastern provinces than in the western provinces. We assessed changes in the prevalence of neural-tube defects in Canada before and after food fortification with folic acid was implemented. The study population included live births, stillbirths, and terminations of pregnancies because of fetal anomalies among women residing in seven Canadian provinces from 1993 to 2002. On the basis of published results of testing of red-cell folate levels, the study period was divided into prefortification, partial-fortification, and full-fortification periods. We evaluated the relationship between baseline rates of neural-tube defects in each province and the magnitude of the decrease after fortification was implemented. A total of 2446 subjects with neural-tube defects were recorded among 1.9 million births. The prevalence of neural-tube defects decreased from 1.58 per 1000 births before fortification to 0.86 per 1000 births during the full-fortification period, a 46% reduction (95% confidence interval, 40 to 51). The magnitude of the decrease was proportional to the prefortification baseline rate in each province, and geographical differences almost disappeared after fortification began. The observed reduction in rate was greater for spina bifida (a decrease of 53%) than for anencephaly and encephalocele (decreases of 38% and 31%, respectively). Food fortification with folic acid was associated with a significant reduction in the rate of neural-tube defects in Canada. The decrease was greatest in areas in which the baseline rate was high. Copyright 2007 Massachusetts Medical Society.

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Birth defects surveillance in China.

Li M. Dai, Jun Zhu, Juan Liang … (2011)

Birth defects are a global public health problem because of their large contribution to infant mortalities and disabilities. It is estimated that 4%-6% of Chinese newborns are affected by birth defects every year. Surveillance is a basic approach to understanding the occurrence and associated factors of birth defects. The Ministry of Health of China initiated a national hospital-based birth defects monitoring system 20 years ago. Nearly every province in this country has established its own surveillance system in the past. The authors reviewed the result of the monitoring system at different administrative levels in China. Available publications on the surveillance of birth defects and data from national and provincial birth defects surveillance systems were reviewed to evaluate the effectiveness of the surveillance systems. According to the 2009 data, the national hospital-based birth defects surveillance system monitored over 1.3 million births, which accounted for more than 8% of births in China. In addition, 30 provincial hospital-based surveillance programs covered a birth population of more than 3.6 million (22% of births in China). Great achievements have been made in terms of case ascertainment, data quality control, and online reporting. But the surveillance systems in China still have some limitations. A short ascertainment period may miss some internal anomalies, inherited metabolic diseases, and malformed fetus aborted before the 28th gestational week. Discrepancies in antenatal or postnatal diagnosis of birth defects between surveillance institutes may affect the detection rate and introduce biases. Absence of baseline data and lack of integrated database systems limit the application of surveillance data to etiological studies and affect the process of decision-making. The surveillance system for birth defects is prerequisite to propose, conduct and assess any interventions for the disease. To meet the need of study and prevention of birth defects, measures should be taken to improve the national and provincial birth defects surveillance systems in China.

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Author and article information

Contributors

Rogelio Cruz-Martinez: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, CA USA )

ISSN (Electronic): 1932-6203

Publication date (Electronic): 11 April 2016

Publication date Collection: 2016

Volume: 11

Issue: 4

Electronic Location Identifier: e0151586

Affiliations

[1 ]National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America

[2 ]Carter Consulting Inc., Atlanta, Georgia, United States of America

Hospital de Especialidades del Niño y la Mujer de Queretaro, MEXICO

Author notes

Competing Interests: The commercial company, Carter Consulting Inc., provided support in the form of salaries for authors [HR, JM], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Conceived and designed the experiments: IZ AS BLT JW HR JM JES MJC JR. Performed the experiments: IZ AS BLT JW HR JM JES MJC JR. Analyzed the data: IZ AS MJC JR. Wrote the paper: IZ AS BLT JW HR JM JES MJC JR.

‡ These authors contributed equally to this work as co-first authors.

* E-mail: wwa3@ 123456cdc.gov

Article

Publisher ID: PONE-D-15-43398

DOI: 10.1371/journal.pone.0151586

PMC ID: 4827875

PubMed ID: 27064786

SO-VID: a8876849-4fd8-4a3e-9e1b-005b81d2f367

License:

This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

History

Date received : 1 October 2015

Date accepted : 29 February 2016

Page count

Figures: 13, Tables: 1, Pages: 31

Funding

AS, IZ, and BLT were supported in part by an appointment to the Research Participation Program at the CDC administered by the Oak Ridge Institute for Science and Education (ORISE). The commercial company, Carter Consulting Inc., provided support in the form of salaries for authors [HR, JM]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Data Availability All relevant data are within the paper and its Supporting Information files.

Describing the Prevalence of Neural Tube Defects Worldwide: A Systematic Literature Review

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Abstract

Background

Methods and Findings

Conclusions

Related collections

PLOS Climate

Most cited references 74

Prevention of neural-tube defects with folic acid in China. China-U.S. Collaborative Project for Neural Tube Defect Prevention.

Reduction in neural-tube defects after folic acid fortification in Canada.

Birth defects surveillance in China.

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