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

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.

Fig 1. PRISMA Flowchart.

Fig 2. Neural Tube Defects Prevalence and Confidence Intervals by World Bank Income Classifications (Log Scale)[18].

Fig 3. Percent of all Neural Tube Defects (NTDs) Attributable to Each Condition for Studies that Reported all Three Types of NTDs: Anencephaly, Spina Bifida, and Encephalocele.

Bars Indicate the Median Percent for Each Condition.

Fig 4. Prevalence per 10,000 Births for Specific Types of Neural Tube Defects by World Bank Income Classifications [18].

Bars Indicate the Median Prevalence for Each Condition.

Fig 5. African Region Neural Tube Defects Prevalence Estimates (Location, Number of Hospitals).

If there were national data available for more than one NTD, the entire country was filled-in based on the prevalence per 10,000 births. In instances where multiple prevalence estimates were available at the national level, the prevalence reported by the study/report with the least risk-of-bias was selected. Countries colored in grey are not a part of the World Health Organization region. Shapefile reprinted from http://www.diva-gis.org under a CC BY license, with permission from DIVA-GIS and Dr. Robert Hijmans.

Fig 6. Eastern Mediterranean Region Neural Tube Defects Prevalence Estimates (Location, Number of Hospitals).

If there were national data available for more than one NTD, the entire country was filled-in based on the prevalence per 10,000 births. In instances where multiple prevalence estimates were available at the national level, the prevalence reported by the study/report with the least risk-of-bias was selected. Countries colored in grey are not a part of the World Health Organization region. Shapefile reprinted from http://www.diva-gis.org under a CC BY license, with permission from DIVA-GIS and Dr. Robert Hijmans.

Fig 7. European Region Neural Tube Defects Prevalence Estimates (Location, Number of Hospitals).

The majority of data from the European region was population based. All data based on hospital studies from regions is indicated with the number of hospitals. If there were national or regional data available for more than one NTD, the entire country or region was filled-in based on the prevalence per 10,000 births. In instances where multiple prevalence estimates were available at the national level, the prevalence reported by the study/report with the least risk-of-bias was selected. Countries colored in grey are not a part of the World Health Organization region. A national study from Israel is not represented on this map since it only provided prevalence by ethnicity. Shapefile reprinted from http://www.gadm.org under a CC BY license, with permission from Global Administrative Areas and Dr. Robert Hijmans.

Fig 8. American Region Neural Tube Defects Prevalence Estimates (Location, Number of Hospitals).

If there were national data available for more than one NTD, the entire country was filled-in based on the prevalence per 10,000 births. In instances where multiple prevalence estimates were available at the national level, the prevalence reported by the study/report with the least risk-of-bias was selected. Shapefile reprinted from http://www.diva-gis.org under a CC BY license, with permission from DIVA-GIS and Dr. Robert Hijmans.

Fig 9. South-East Asian Region Neural Tube Defects Prevalence Estimates (Location, Number of Hospitals).

If there were national data available for more than one NTD, the entire country was filled-in based on the prevalence per 10,000 births. In instances where multiple prevalence estimates were available at the national level, the prevalence reported by the study/report with the least risk-of-bias was selected. North Korea had no reported data and was not shown in map due to scaling considerations. Shapefile reprinted from http://www.diva-gis.org under a CC BY license, with permission from DIVA-GIS and Dr. Robert Hijmans.

Fig 10. Western Pacific Region Neural Tube Defects Prevalence Estimates (Location, Number of Hospitals).

If there were national data available for more than one NTD, the entire country was filled-in based on the prevalence per 10,000 births. In instances where multiple prevalence estimates were available at the national level, the prevalence reported by the study/report with the least risk-of-bias was selected. Countries colored in grey are not a part of the World Health Organization region. Shapefile reprinted from http://www.diva-gis.org under a CC BY license, with permission from DIVA-GIS and Dr. Robert Hijmans.

Fig 11. Data Source: Surveillance/Registry Coverage by Geographic Level.

Shapefile reprinted from http://www.diva-gis.org under a CC BY license, with permission from DIVA-GIS and Dr. Robert Hijmans.

Fig 12. Average Study Risk-of-Bias by World Health Organization Region.

Fig 13. Average Study Risk-of-Bias by World Bank Income Classification [18].