Global burden of neural tube defects, risk factors, prevention, and the role of folic acid

National Center on Birth Defects and Developmental Disabilities

Division of Birth Defects and Developmental Disabilities

Joe Sniezek, MD, MPH

Amy Cordero, MPA

Prevention Research Branch

National Center for Birth Defects and Developmental Disabilities

Outline

Definition of birth defects

Global burden

Neural tube defects

Global burden

Risk Factors

Prevention strategies with folic acid

SEARO/CDC collaboration

Defining Birth Defects

Structural or functional abnormalities that are present from birth

Potential for serious adverse effect on health, development, or functional ability

Can be caused by single gene defects, chromosomal disorders, multifactorial inheritance, environmental teratogens or micronutrient deficiencies

Often also referred to as congenital anomalies or congenital malformations

Burden of Birth Defects

1 in 33 infants has a birth defect (~3%)

4.8 million infants globally

1 in 260 infants dies because of a birth defect

0.6 million infants globally

Underestimated

Spontaneous abortion

Stillbirths

Elective Termination of Pregnancy for Fetal Anomaly (ETOPFA)

Birth Defects: Overall Global Burden

3.0 %

340,000

470,000

540,000

820,000

1,130,000

1,500,000

0 500,000 1,000,000 1,500,000

EUROPE

AMERICAS

EAST-MEDITER

WEST PACIFIC

SOUTH-EAST-ASIA

AFRICA

4,800,000 Globally =

Data of Total Births 2010 from WHO Statistics Website

March of Dimes Global Report on Birth Defects (2006): A Paucity of Data

“There is a paucity of data on the birth prevalence of birth defects in middle- and low-income countries”

Why?

Constrained diagnostic capability

Poor health-related statistics

Lack of birth defect surveillance and registries

Reliance on hospital-based rather than population-based studies

Systematic underestimation of the toll of birth defects

Prevalence of Birth Defects (MoD estimates)

0

10

20

30

40

50

60

70

80

Pre

va

len

ce p

er

1,0

00

bir

ths Others ICD-10 Q00-Q99

Estimated number (per 1,000 – per year) of infants with birth defects (BD,Chrom, Single Gene, Genetic/Haemolysis/Jaundice)

Source: March of Dimes Global Report on Birth Defects, 2006

0

10

20

30

40

50

60

70

80

Pre

va

len

ce p

er

1,0

00

bir

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Others ICD-10 Q00-Q99

Estimated number (per 1,000 – per year) of infants with birth defects (BD, Chrom, Single Gene, Genetic-Haemolysis/Jaundice)

Source: March of Dimes Global Report on Birth Defects, 2006

• Congenital heart defects: 1,000,000

• Neural tube defects: 350,000

• Down syndrome: 220,000

Prevalence of Birth Defects (MoD estimates)

Under 5-year Mortality due to BDs by WHO regions: Rate, Percentage and Absolute Numbers

2.0

2.6

3.2

3.8

4.0

5.3

0.0 1.0 2.0 3.0 4.0 5.0 6.0

WEST PACIFIC

EUROPE

AMERICAS

SOUTH-EAST-ASIA

EAST-MEDITER

AFRICA

Rate U-5y-M per 1,000

Globally 3.9 per 1,000

29,000

49,000

56,000

71,000

143,000

263,000

0 50,000 100,000150,000200,000250,000300,000

EUROPE

AMERICAS

WEST PACIFIC

EAST-MEDITER

SOUTH-EAST-ASIA

AFRICA

Number of Deaths Under 5y

Globally 611,000

4.6%

6.7%

6.8%

11.9%

17.3%

18.6%

0.0% 5.0% 10.0% 15.0% 20.0%

AFRICA

EAST-MEDITER

SOUTH-EAST-ASIA

WEST PACIFIC

AMERICAS

EUROPE

% of U-5y death due to BD

Globally 6.2%

2010 Data from WHO Statistics Website

Overall Under 5-year Mortality (line) and % of Deaths due to BDs (bars) by WHO Region and Country Income

0%

10%

20%

30%

40%

0.0

20.0

40.0

60.0

80.0

100.0

120.0

140.0

160.0

180.0

De

ath

s d

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)

Un

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Birth defects Under-5 mortality rate

LegendCountries income: 1= High, 2=Upper-Middle, 3=Lower-Middle , 4=Low

WHO Regions: AFR=Africa, AM= Americas, EM=Eastern Mediterranean, EU=Europe, SE=South East Asia; WP=Western Pacific

World Health Statistics 2010 datahttp://apps.who.int/gho/data/node.main.1?lang=en http://apps.who.int/gho/data/node.main.1?lang=en

Serious birth defects of the brain and spine

Form in the first month of pregnancy

Most common are anencephaly and spina bifida

Neural Tube Defects

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Global Burden of Neural Tube Defects

More than 300,000 neural tube defects each year worldwide*

Occur widely

Different geographical areas

Countries of varying levels of economic development

Among diverse populations

Remain a significant, preventablecause of mortality and morbidity worldwide

* Christianson A, Howson CP, Model B. March of Dimes Global Report on Birth Defects: the hidden toll of dying and disabled children. 2006. March of Dimes Birth Defects Foundation, New York.

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Global Burden of Neural Tube DefectsMarch of Dimes Global Report on Birth Defects, 2006

* Christianson A, Howson CP, Model B. March of Dimes Global Report on Birth Defects: the hidden toll of dying and disabled children. 2006. March of Dimes Birth Defects Foundation, New York.

Global Burden of Neural Tube Defects:Systematic review (1990-2004)

Objectives

To assess the extent to which neural tube defects are a global public health problem

Summarize prevalence estimates of NTDs at the greatest population representation available

Assess differences in NTDs prevalence by WHO regions and country income level (low, medium and high)

Identify gaps in information

Global Burden of Neural Tube Defects:Systematic review (1990-2004)

Methods

Search• Database search of PubMed, Google Scholar, EUROCAT, ICBDSR

registries

• Observational studies and reports published during 1990 -2014

• Observational studies and registry reports and databases

Included studies• NTD diagnosis, reported number of cases and total number of births

• Reported at least spina bifida or total NTD cases

• Registries were pre-identified

Excluded: studies • No reported # NTD cases, mortality reports only, ≤ 5,000 live births per

year

Global Burden of Neural Tube Defects:Systematic review (1990-2004)

Preliminary Results Records identified through database searching (n = ~11,000)

Records screened ~1,100

Full articles revised ~ 100

Records included – 173 (multiple records/ country)

Countries by WHO region

• AFRO 9

• EMRO 11

• EURO 28

• PAHO 14

• SEARO 4

• WPRO 9

Global NTD Prevalence Range

• 4.5 – 199.4 per 10,000 live births

Risk Factors for Neural Tube Defects

Nutritional (Folate insufficiency; Vitamin B-12 deficiency

Environmental (hyperthermia)

Behavioral (medications e.g. valproic acid, some narcotics)

Maternal conditions (Obesity, diabetes )

Folic Acid and Neural Tube Defects Prevention

Role of folic acid in preventing neural tube defects is well known

The majority of neural tube defects can be prevented with 400 micrograms (mcg) of folic acid daily before and during early pregnancy

Globally many women of reproductive age do not consume enough folic acid for prevention

4CDC. www.cdc.gov/mmwr/mmwrrhtml/mmm5931a2.htm. CDC Grand Rounds: Additional Opportunities to Prevent NTD with Folic Acid Fortification

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Diet…natural foods such as vegetables, fruits, beans, yeast, liver

Fortification … folic acid added to foods - flour, rice, pasta, breakfast cereals

Pills… folic acid-containing dietary supplements

Approaches to Increase Folate/Folic Acid Intake

Source: CDC. MMWR Recomm Rep 1992 Sep 11;41(RR-14):1-7

Neural Tube Defects Prevalence Changes:Before and After Folic Acid Fortification

10.8

15.817.1

9.7

14.1

6.9

8.6 8.6

6.3

9.8

0

5

10

15

20

US Canada Chile Costa Rica South Africa

Before fortification

After fortification

-31%

Sources: US: CDC. CDC grand rounds: additional opportunities to prevent neural tube defects with folic acid fortification. MMWR. 2010;59(31):980-4.Canada: De Wals et al. 2007. Reduction in neural-tube defects after folic acid fortification in Canada. N Engl J Med357: 135–142.Chile: Cortes F et al. Wheat flour fortification with folic acid: changes in neural tube defects rates in Chile. Amer Jnl Med Genet A. 2012 Aug;158A(8):1885-90. Costa Rica; Tacsan Chen L. The Costa Rican experience: Reduction of neural tube defects following food fortification program. Nutr Revs. 2004: 62(6):S40-S43.South Africa: Sayed AR. Decline in the prevalence of neural tube defects following folic acid fortification and its cost-benefit in South Africa. Birth Defects Res A Clin MolTeratol. 2008:82(4): 211-6.

Rate per 10,000 births

-36%-46% -50%

-35%

5

Year of Fortification

Return on Investment

South Africa 2003 30 to 1

Chile 1998 12 to 1

US 1996 150 to 1

Fortification: Cost Effectiveness

Sources:• South Africa – Sayed AR, et al. Decline in the prevalence of neural tube defects following folic acid fortification and its

cost-benefit in South Africa . Birth Defects Research Part a-Clinical and Molecular Teratology2008 Apr;82(4):211-6.• Chile – Llanos A, et al. Cost-effectiveness of a folic acid fortification program in Chile. Health Policy2007;83(2-3):295-303• US – Grosse S et al. Assessing the health and economic impacts of prevention: A case study of folic acid fortification in

the United States. Unpublished manuscript. 2014

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Birth Defects COUNTCountries and Organizations United for Neural Tube Defects Prevention

CDC is working with partners to advance neural tube defects prevention globally through folic acid food fortification and supplementation

Contribute to the achievement of the Millennium Development Goal 4 (reduce under-5 mortality)

Support the 63rd World Health Assembly resolution on birth defects

Focus on regions where prevention opportunities will have greatest impact

South-East Asia and Africa

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Birth Defects COUNTSouth-East Asia

WHO-SEARO and Member States working together to move forward birth defects prevention and surveillance

Regional Strategic Framework for Birth

Defects Prevention and Control 8 countries have held national meetings to adapt

into national action plan

The findings and conclusions in this presentation are those of the presenters and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

National Center on Birth Defects and Developmental Disabilities

Division of Birth Defects and Developmental Disabilities

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