National Center on Birth Defects and Developmental Disabilities

Global Situation of Birth Defects and Initiatives for Prevention

Mike Cannon, PhD

Team Lead, Prevention Research Team

National Center on Birth Defects and Developmental Disabilities, CDC

August 9, 2016

Metabolic disease Mucopolysaccharidosis

Cerebral palsy Thalassemia

Cleft lip

Down syndrome

Neural tube defect Congenital syphilis

Congenital rubella syndrome

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 Burden of Birth Defects

0

10

20

30

40

50

60

70

80P

reva

len

ce

per

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

• Congenital heart defects: 1,000,000

• Neural tube defects: 350,000

• Down syndrome: 220,000

Prevalence of Birth Defects (MoD estimates)

Reports of Neural Tube Defects in SE Asia

Zaganjor et al., PLOS ONE, 2016

Deaths Due to Birth Defects

2.0

2.6

3.2

3.8

4.0

5.3

0.0 2.0 4.0 6.0

WEST PACIFIC

EUROPE

AMERICAS

SOUTH-EAST-ASIA

EAST-MEDITER

AFRICA

Rate U-5y Deaths 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 U-5y Deaths

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 Deaths due to Birth Defects

Globally 6.2 %

2010 Data from WHO Statistics Website

Burden of Birth Defects in South-East Asia

0%

10%

20%

30%

40%

50%

60%

0.0

10.0

20.0

30.0

40.0

50.0

60.0

70.0

80.0

90.0

Dis

trib

utio

n o

f ca

use

s o

f d

ea

ths (

%)

Und

er-

5 m

ort

alit

y r

ate

(p

er

1,0

00 b

irth

s)

Birth defects Prematurity Birth asphyxia Under-5 mortality rate

Source: World Health Statistics 2011 - http://www.who.int/whosis/whostat/2011/en/index.html

Hidden burden of birth defects

Elective terminations

Spontaneous abortions

Stillbirths

Co-morbidities

Medical/surgical treatment

Hospitalizations

Long term disability

Quality of life

Social/emotional impact

Economic cost

Easier to measure Metrics readily available

Difficult to measure Evaluated less frequently

Prevalence, Mortality: Neonatal Infant Under-5

Many birth defects can be

swept away

Calls on Member States to prevent birth defects wherever possible, implement screening programs, and provide ongoing support and care to children with birth defects and their families.

CDC and WHO are providing support to Member States in SEAR

to improve birth defects data collection and implement prevention activities.

Risk Factors for Birth Defects • Nutrition

• Folate, vitamin B-12, iodine, or other micronutrient insufficiency; PKU

• Behavioral factors • Smoking, medications, recreational drugs, alcohol

• Maternal conditions • Obesity, epilepsy, mood disorders/mental health, diabetes, hypothyroidism,

thalassemia, age

• Infectious disease • TORCH infections (e.g., congenital syphilis, congenital rubella syndrome)

• Environmental factors • Heat, radiation, industrial solvents, mercury

Goals and targets

•Reduce the prevalence of folic acid-preventable neural tube defects by 35%

•Reduce the number of thalassaemia births by 50%

•Reduce congenital rubella

• Eliminate congenital syphilis

Source: Prevention and Control of Birth Defects in South-East Asia Region: Strategic Framework (2013-2017)

Source: MMWR, Vol. 16, No. 4

Introduction of rubella vaccine

Source: MMWR, Vol. 59, No. 14

The Global Challenge of Neural Tube Defects • Each year there are more than 300,000 babies born with a neural tube defect

(NTD). • NTDs include spina bifida, anencephaly, and other related defects • NTDs cause death, paralysis, or life-long disability – but, many are preventable!

Anencephaly Encephalocele Spina bifida

Global Burden of Neural Tube Defects

Source: Center for Spina Bifida Research, Emory University

Prevention Strategy:

• Childbearing aged women

should consume 400 mcg

of folic acid for the

prevention of neural tube

defects.

1

Intervention = 400 µg Daily Folic Acid Supplement Alone

NTDs

per

10,000

pregnancies

48

7 10 6

85%

41%

Periconceptional Folic Acid Community Trial to Prevent NTDs, China, 1993 – 1996

Neural Tube Defects Prevention | 10

22

Diet…natural foods,

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

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

Neural Tube Defects Prevention | 122

1

Challenges to Preventing

Neural Tube Defects (NTDs)

• It is difficult to get sufficient folate

from dietary sources alone

• NTDs result from the failure of

closure of the neural tube by the

4th week of conception

• Women need sufficient blood

folate concentrations before

conception

• Prenatal vitamins are too late to

prevent NTDs

http://www.who.int/nutrition/publications/birthdefects_atlas/en/

1

Are You Hungry?

Daily Intake Equivalent of 400 µg of Folic Acid

4 slices of fried beef liver

44½ medium ripe tomatoes

14½ cups of raw broccoli

17½ cups of orange juice

19½ cups of raw green beans

5½ cups of black beans

200 medium red apples

Neural Tube Defects Prevention | 13

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

10.8

15.8 17.1

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

Rate per

10,000

births -36%

-46% -50%

-35%

-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 Mol Teratol. 2008:82(4): 211-6.

Year of

Fortification

Return on

Investment

South Africa 2003 30 to 1

Chile 1998 12 to 1

US 1996 150 to 1

Cost Effectiveness of Fortification with Folic Acid

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

Summary

Birth defects are an important cause of morbidity and mortality in SE Asia

Effective interventions can be implemented to prevent • Neural tube defects

• Congenital rubella

• Congenital syphilis

• Thalassaemia

Surveillance is a key piece of prevention

For more information, contact CDC 1-800-CDC-INFO (232-4636) TTY: 1-888-232-6348 www.cdc.gov The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Questions?

Mike Cannon mcannon@cdc.gov