CDC Presentation

Global Overview of Birth Defects Workshop on Birth Defects Surveillance Disclaimer: The findings and conclusions in this presentation have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. Not all children are born healthy Congenital conditions Cleft lip Down syndrome Neural tube defect Metabolic disease Mucopolysaccharidosis

Premature birth Thalassemia Global Overview Sickle cell anemia Intrauterine growth retardation (IUGR) Cerebral palsy | 2 Birth defects: five take home messages 1. Birth defects: a specific group under the category congenital conditions 2. Etiology: increasing knowledge allows for new opportunities for prevention 3. Burden: high globally; proportionally increasing in low

and middle resource countries 4. Interventions: decrease the burden, implement widely 5. Public health surveillance: a necessary and powerful tool Congenital conditions Birth defects Structural Functional IUGR Other Preterm birth Birth defects: classification Abnormalities of body structure

Abnormalities of function ICD-10 Chapter XVII Q00-Q99 Deafness Cerebral palsy Developmental disabilities Inborn error of metabolism Hematologic diseases Birth defects: definition Abnormalities of body structure or function that are present at birth and are of prenatal origin

Focus of this presentation is on abnormalities of body structure (Included in Chapter XVII of ICD-10 Classification of Diseases) Sometimes also called: Congenital anomalies Congenital abnormalities Congenital malformations Birth defects: Classification Location

Pathogenesis External Internal Malformation Deformation Dysplasia Disruption Health impact Clinical presentation Major Minor Isolated Multiple

Location of Birth Defects External: Example: Spina Bifida Easily recognizable at birth Best choice when starting a surveillance program Internal: Example: Tetralogy of Fallot Frequently delayed diagnosis Requires imaging and/or other technology Birth defects according to health impact Major: Significant medical, cosmetic and social impact Focus of care, prevention and surveillance Examples: spina bifida, cleft lip, amelia

Minor: No significant medical, cosmetic and social impact May accompany major malformations May provide useful clues for diagnosing syndromes Examples: clinodactyly, small nevi, lop ears Malformations Structural defect of an organ, part of an organ, or larger region of the body that arises during organogenesis, or during the initial formation of a structure as a result of an intrinsically abnormal process Some malformations can be prevented Neural tube defect Deformations Abnormal shape, form or position of a part of the body caused by mechanical forces Initial formation of the structures is normal but mechanical

forces affect their development Potter sequence http://library.med.utah.edu/WebPath/jpeg3/PERI230.jpg Disruptions Structural defect of an organ, part of an organ, or larger region for the body resulting from the extrinsic breakdown of, or interference with an originally normal developmental process Initial development is normal, but the process is interrupted or normally developed parts disrupted Amniotic band sequence CDC-Beijing Medical University collaborative project Dysplasias Abnormalities of histogenesis or formation of tissues Dysplasias generally affect the skin, brain, cartilage or bone

and can either be localized (confined to one area of the body) or be generalized Achondroplasia Hemangioma Clinical presentation: Isolated and multiple defects Isolated birth defect Single major defect 75% of major birth defects are isolated Sequence Multiple birth defect More than one major unrelated defect Associations pattern of multiple anomalies that occur with a higher than random frequency and that is not a sequence or a syndrome

Syndromes pattern of multiple anomalies thought to be pathogenically related, but not representing a sequence Birth defects: five take home messages 1. Birth defects: a specific group under the category congenital conditions 2. Etiology: increasing knowledge allows for new opportunities for prevention 3. Burden: high globally; proportionally increasing in low and middle resource countries 4. Interventions: decrease the burden, implement widely 5. Public health surveillance: a necessary and powerful tool Etiology of birth defects Single gene (14%)

* Includes multifactorial determination Chromosomal (10%) Environmental (10%) Unknown* (66%) Source: Nelson K, Holmes LB. Malformations due to presumed spontaneous mutations in newborn infants. N. Engl. J. Med. 1989;320:1923. ; Brent RL. Environmental causes of human congenital malformations: the pediatricians role in dealing with these complex clinical problems caused by a multiplicity of environmental and genetic factors. Pediatrics. 2004;113:95768. Examples of known modifiable risk factors for birth defects

Infections Rubella Varicella Lifestyle and vitamins

Medications Alcohol Cigarette smoke Folate insufficiency Retinoic acid Antiseizure medications Maternal Diseases and Conditions

Diabetes Obesity, overweight Others Hyperthermia Mercury Birth defects: five take home messages 1. Birth defects: a specific group under the category congenital conditions 2. Etiology: increasing knowledge allows for new opportunities for prevention 3. Burden: high globally; proportionally increasing in low and middle resource countries

4. Interventions: decrease the burden, implement widely 5. Public health surveillance: a necessary and powerful tool Risk factors and relative risks Related Birth Defect Relative Risk * (95% CI) Insufficient folic acid Neural tube defects 3.57 (1.92-6.67) Hyperthermia Neural tube defects

2.90 (2.22-3.79) Valproic acid Spina bifida 12.7 (7.7-20.7) [email protected], severe (BMI35) Congenital heart defects 1.38 (1.20-1.59) Diabetes Congenital heart defects 3.8 (3.0-4.9)

Smoking Cleft lip w/out palate 1.62 (1.35-1.95) Risk factor * Relative risk is usually given by metanalysis or other robust studies. @ Without diabetes Etiologic heterogeneity of spina bifida Give Protection

Manage Conditions Micronutrient supplementation Previous NTD-affected pregnancy Gene mutations (e.g., VANGL1, MTHFR) Diabetes and obesity Avoid Exposure Valproate (anti-seizure medications)

Environmental toxins (e.g., fumonisins) Important concepts related to risk factors Increasing knowledge allows for new opportunities for prevention Known and modifiable risk factors can be: qualified (birth defects; IUGR, preterm) o quantified o

population prevalence risk magnitude for each related outcome population attributable fraction Impact of preventive interventions varies according to etiologic heterogeneity of birth defects Birth defects: five take home messages 1. Birth Defects: a specific group under category congenital conditions 2. Etiology: increasing knowledge allows for new opportunities for prevention 3. Burden: high globally; proportionally increasing in low and middle resource countries 4. Interventions: decrease the burden, implement widely 5. Public health surveillance: a necessary and powerful tool

One or more risk factor: Effect of primary prevention One causal factor, e.g.: cong. rubella syndrome Factor A Factor A Multiple causal factors, e.g.: spina bifida Disease B Disease B

X = Effect of the preventive intervention Disease B Disease B Hidden burden of birth defects Prevalence Mortality: Easier to measure

Metrics readily avaiable Neonatal Infant Under-5 Difficult to measure Evaluated less frequently Elective terminations Spontaneous abortions Stillbirths Co-morbidities Medical/surgical treatment Hospitalizations Long term disability Quality of life Social/emotional impact Economic cost

Prevalence of birth defects The prevalence of birth defects around the world shows a wide variation, which can be due to: real population differences methodological issues (e.g., definition, case ascertainment) Notable variations in prevalence that appear to be real: NTDs Oral clefts Gastroschisis Down syndrome & other trisomies (maternal age) Mortality

ETOPFA* Stillbirths Perinatal mortality Neonatal mortality Infant mortality

Under-five years mortality Elective termination of pregnancy for fetal anomalies U n d e r -5 m o r t a lit y r a t e ( p e r 1 ,0 0 0 b ir t h s ) Overall under 5 year mortality (line) and % of deaths due to birth defects (bars) by WHO region and country income 180.0 35.0% 160.0 30.0% 140.0

120.0 25.0% 20.0% 100.0 15.0% 80.0 60.0 40.0 20.0 0.0 10.0% 5.0% 0.0% -5.0% Legend

Countries income: H= High, UM=Upper-Middle, LM=Lower-Middle , L=Low WHO Regions: AFR=Africa, AM= Americas, EM=Eastern Mediterranean, EUR=Europe, SEA=South East Asia; WP=Western Pacific World Health Statistics 2010 data http://apps.who.int/gho/data/view.main.POP2020?lang=en Accurate diagnosis Prenatal Post-natal Anomalies (external/internal) Syndromes Experience, team, clinical geneticist, diagnostic help network http://www.skeldys.org/

Effective counseling Before birth At birth or at time of diagnosis Recurrence risk counseling Counseling is an art, but can be learned: Guidelines Skotko GB et al. Pediatrics 2009;124;e751; Sheets BK et al. J Genet Counsel (2011) 20:432441 Treatment Options Surgical Before birth (e.g., spina bifida, diaphragmatic hernia)

Soon after birth After birth Medical treatment (examples) Neonatal Intensive Care Unit Palliative care (life-limiting illness) Supportive care and management* Provision of primary care as for any child Anticipatory guidance (e.g., feeding, toileting, behavior) Early diagnosis of co-morbidities

Individualized education program and family supportive plan, including leisure and recreational activities Physical and/or speech treatment Guidelines available for some conditions) Social integration issues Help when joining the community Parent associations Mainstreaming (school) Sports Work Rights of Persons with Disabilities 13 Dec 2006, UN, New York www.un.org/disabilities/default.asp?id=150

Prevention opportunities Primary Avoidance / management of recognized protective and modifiable risk factors Reproductive health promotion and preconception care Folic acid, vaccines, avoid alcohol, smoking, and use of certain medicines Secondary Newborn screening Metabolic diseases Before conception or after a prenatal diagnosis

Counseling Birth defects: five take home messages 1. Birth defects: a specific group under the category congenital conditions 2. Etiology: increasing knowledge allows for new opportunities for prevention 3. Burden: high globally; proportionally increasing in low and middle resource countries 4. Interventions: decrease the burden, implement widely 5. Public health surveillance: a necessary and powerful tool Public health surveillance: a necessary tool Defined as the ongoing and systematic collection, analysis, and interpretation of health data essential to the planning, implementation and evaluation of public

health practice Essentials: ongoing, systematic, linked to public health practice (information for action) Acknowledgements International Clearinghouse on Birth Defects Surveillance and Research Pierpaolo Mastroiacovo Lorenzo Botto World Health Organization/Headquarters Juan Pablo Pea- Rosas CDC National Center for Birth Defects and Developmental Disabilities Surveillance Working Group Questions? If you have any questions, please send an email to

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