NEWBORN SCREENING IN PAKISTAN When & How ? Col Zeeshan Ahmed FCPS(Pediatrics),FCPS(Neonatology) Head Of NICU Military Hospital Rwp.

CAN WE MAKE A DIFFERENCE?

Mission of Newborn Screening: AAP “Newborn screening…aimed at the early identification of conditions for which early and timely interventions can lead to the elimination or reduction of associated mortality, morbidity, and disabilities.”

Mission of Newborn Screening: AAP “Newborn screening…aimed at the early identification of conditions for which early and timely interventions can lead to the elimination or reduction of associated mortality, morbidity, and disabilities.”

Newborn Screening The term is used to refer to two programs that may or may not have linkages: Traditional biochemical screening for inherited conditions (metabolic, endocrine, hematological, etc.) Screening for congenital hearing loss In this presentation, “newborn screening” will refer to the traditional heelstick biochemical testing program.

What is Newborn Screening? An essential public health program that prevents catastrophic health consequences through early detection, diagnosis and treatment. A complex system of testing, evaluation, and treatment that involves families, laboratory personnel, administrative and follow-up personnel, primary and specialty health care professionals, policy makers, sources of payments, manufacturers, and other interested persons or groups.

Newborn Screening Newborn screening developed worldwide from a keen interest and understanding of Inborn Errors of Metabolism- a term introduced by Garrod in 1908 Newborn Screening has focused historically on the identification of conditions that adversely affect the CNS Increasingly, conditions involving other areas, such as the immune and cardiac systems have been recommended for the newborn screening panel Newborn screening has been driven to a considerable extent by available technology, and increasingly by better understanding of conditions as well as by new diagnostic technologies and treatments.

THE US EXPERIENCE

Newborn Screening for Genetic Diseases in the United States Over 4 million infants are screened each year Newborn screening is by far the most commonly performed testing for genetic diseases in the United States

Brief Review: Newborn Screening History Guthrie developed filter paper test for PKU. (Identified newborns with PKU whose diet could be modified thus preventing mental retardation.) Bob Guthrie Guthrie - 1961

Disorders Included Under Current Mission Congenital Hypothyroidism Sickle Cell Disease PKU Late 1970s 1963 1987

Tandem Mass Spec Disorders Cystic Fibrosis ? Tandem Mass Spec Disorders 2003 2004 20??

Selection Criteria For ScreeningPanel Incidence of conditions Identifiable at birth Burden of disease Mortality/ Morbidity prevention Availability of test Test characteristics Diagnostic confirmation Availability of treatment Cost of treatment Efficacy of treatment Benefits of early intervention Benefits of early identification Acute management Simplicity of therapy 13

Uniform Screening Panel 29 Primary (Core) Conditions All result in serious medical complications (e.g., developmental delay) and/or death if not recognized early All children with these conditions benefit from early diagnosis and treatment 14

Expanded NBS – 29 conditions 20 inborn errors of metabolism 9 organic acid disorders 5 fatty acid oxidation disorders 6 amino acid disorders 3 hemoglobinopathies Sickle cell and related disorders 2 endocrine disorders Congenital Hypothyroidism CAH 3 other metabolic disorders Biotinidase deficiency Galactosemia Cystic Fibrosis 1 hearing loss Slide 4: Expanded 29 conditions Inborn errors of metabolism, also known as inherited metabolic diseases, comprise a large class of genetic diseases involving disorders of metabolism. The majority are due to genetic defects in genes that code for enzymes which facilitate conversion of various substances into other products. In the majority of these disorders, problems arise due to accumulation of substances which are toxic or interfere with normal function, or to the effects of reduced ability to synthesize essential compounds. Hemoglobinopathies refer to diseases resulting from genetic alterations in the amount of, and/or structure of the alpha and/or beta chain components of hemoglobin. The clinical picture of hemoglobinopathies varies; ranging from benign (carriers) to transfusion-dependent anemia or lethal in some cases. Endocrine disorders refer to diseases involving the production or metabolism of hormones. Other conditions: galactosemia, biotinidase deficiency, cystic fibrosis and hearing loss. Galactosemia and biotinidase deficiency are both metabolic disorders that are not amino acid, organic acid or fatty acid disorders. Hearing loss will not be discussed in this module.

21 9 10 9 >30 >30 >30 9 26 26 >30 >30 12 >30 19 29 >30 >30 DC >30 9 14 29 >30 >30 >30 27 >30 10 40 13 >30 >30 More than 8 Disorders (32) [More than 30 Disorders (15)] 8 Disorders (2) U.S. Newborn Screening Mandated Disorders – Nov. 2004 (Note: Other disorders may be offered but are not mandated and some mandated may yet not be implemented) 7 Disorders (4) 6 Disorders (4) 5 Disorders (2) 4 Disorders (6) 3 Disorders (1)

Disorders Mandated in United States November 2004

Burden of the Core Panel Conditions in the U.S. All conditions are rare Over 4 million babies screened annually Estimated annual number confirmed (most common) Hearing loss: 5,064 Primary congenital hypothyroidism: 2,156 Sickle cell disease: 1,775 Cystic fibrosis: 1,248 Medium-chain acyl-CoA dehydrogenase deficiency: 239 A total of about 12,500 infants are diagnosed with the core conditions and treated each year in the US with the current newborn screening panel 18

Burden of the Core Panel Conditions in the US Untreated persons suffer enormous burdens Persons with phenylketonuria have relatively normal lifespan Untreated: IQ that are under 20 Identified and Treated: Normal IQ Persons with medium-chain acyl-CoA dehydrogenase deficiency, the most common disorder of fatty acid oxidation, are at substantial risk for sudden death

IT’S NOT JUST THE TEST!

Evaluation: Management: Treatment Screening: Sample collection Sample submission Laboratory testing Follow-up: Obtain test results Get results to family Repeat test(s) if needed Ensure diagnostic testing Diagnosis: Subspecialist Assessment Results shared with family Counseling if necessary Management: Treatment Long-term follow-up Specimen storage Evaluation: Quality assurance Outcome evaluation Cost effectiveness

Education Management: Evaluation: Follow-up: Quality assurance Screening: Sample collection Sample submission Laboratory testing Follow-up: Obtain test results Get results to family Repeat test(s) if needed Ensure diagnostic testing Diagnosis: Subspecialist Assessment Results shared with family Counseling if necessary Management: Treatment Long-term follow-up Specimen storage Evaluation: Quality assurance Outcome evaluation Cost effectiveness Education

Metabolic Team Child Age-appropriate self-management skills Parents Monitoring health status, teaching, advocacy Nutritionist Nutrition therapy, feeding skills Geneticist Medical monitoring Social Worker Family support, counseling Lab Laboratory monitoring Medical Home Well child care, family support Psychologist Developmental monitoring, counseling PHN, others Family support in community School Educational programs, treatment monitoring Community Support of family and friends Therapists (OT, PT, SLP, etc.) Developmental monitoring, intervention

SITUATION IN OTHER DEVELOPING COUNTRIES

ASIA PACIFIC NEWBORN SCREENING COLLABORATIVE Two workshops - facilitate formation of the Asia Pacific Newborn Screening Collaborative. The 1st Workshop on Consolidating Newborn Screening Efforts in the Asia Pacific Region in Cebu, Philippines, on March 30–April 1, 2008. The second workshop was held on June 4–5, 2010, in Manila, Philippines. Newborn screening activities in the Asia Pacific Region are particularly important since births there account for approximately half of the world’s births.

Workshop participants included Key policy-makers, Service providers, Researchers, and Consumer advocates From 11 countries with 50% or less newborn screening coverage. 

s. No. Country NBS INITIATED NATIONAL COVERAGE DISORDER (s) 1. Bangladesh 1999 ≤ 5% CH 2. China 1981 59% CH, PKU 3. India 2007-8 70-86% (local) CH,CAH, G6PD DEF, CF, GAL, Various metabolic 4. Indonesia 2000 ≤ 1% 5. Laos 2008 7% 6. Mongolia 6% CH,CAH 7. Pakistan 2007 8. Palau 2009 50% As per Phillipines panel 9. Philippines 1996 28% CH,CAH,GAL,PKU, G6PD Def 10. Sri Lanka 2005 2.8% 11. Vietnam 1998 CH,CAH, G6PD Def

BARRIERS IN COMMON Lack of political awareness/will (Bangladesh, India, Pakistan, Indonesia, Mongolia, Sri Lanka) Lack of physician awareness/ training and lack of subject specialists (Sri Lanka, Philippines, Pakistan, Mongolia, Indonesia, Bangladesh) Lack of consistent source of funds (Bangladesh, India, Pakistan, Philippines, Sri Lanka, Vietnam) Economic variations/inhibiting fee (Bangladesh, China, Indonesia, Pakistan, Philippines)

Lack of infrastructure/labs (Indonesia, Laos, Pakistan, Sri Lanka) Logistic problems (Vietnam, Sri Lanka, Mongolia, Pakistan ) Competition with other health priorities ( mentioned by India only but likely to be a universal reality)

CONCLUSIONS ON REGIONAL STATUS All 11 countries report progress despite significant barriers Infrastructure exists though limited in scope (not national) All programs include NBS for congenital hypothyroidism. China – Approx half population has access to screening for CH, PKU. Laws on mandated NBS exist in some countries only

THE PRESENT: WHERE DO WE STAND?

NBS: Challenges and future goals Barriers Govt support uncertain Prohibitive NBS fee ($2.35?) Universal lack of awareness Very limited screening coverage Lack of standardized procedures No consensus on treatment /followup strategies Subject experts lacking High home births (65%) and consanguinity (60%) Lack of dedicated screening laboratories

THE BURDEN OF UNTREATED DISEASE CORE QUESTION: The cost burden of NBS and treatment versus The burden of untreated preventable conditions whose cost in terms of medical services provision and loss of human resource potential is difficult to estimate

OUR HEALTH PRIORITIES Study: Setting Health Care Priorities in Pakistan. Khan KS. J Pak Med Assoc. 1995 Aug;45(8):222-7 OBJECTIVE: To describe a health priority setting exercise in Pakistan and its relevance to traditional medical care and care providers. METHODS: Literature search of local and regional data was performed to identify priority health problems, those with high disease burden and with cost-effective interventions.

RESULTS Major causes of ill-health were Communicable ( Diarrhoea, ARI, childhood immunizable diseases, malaria, tuberculosis) Pregnancy related diseases. Factors that contributed to these disorders included Malnutrition, Anemia, Poor sanitation and water supply, Low level of education, High fertility rates and Poverty

For these conditions, cost-effective interventions for prevention included Environmental control (provision of clean water and sanitation), Education programmes, Expanded programme of immunization and Family planning For treatment included case management of diarrhoea, respiratory infections, tuberculosis and complications of pregnancy and childbirth.

CONCLUSION Priority health problems include factors outside the domain of traditional medical care. Their definition is important for directing policy reform, medical curricula and health research.

THE FUTURE OF NBS IN PAKISTAN: WAY FORWARD Balance health priorities with need for NBS Sustained (Decades) Awareness program targeted to health professionals, public and policy makers. Start with one test (e.g. CH) but establish nation wide infrastructure which will serve as springboard for future expansion

THANK YOU

THE PRESENT: WHERE DO WE STAND? Many of the countries in the Asia Pacific Region, particularly those with depressed and developing economies, are just initiating newborn screening programs for selected metabolic and other congenital disorders. The cultural, geographic, language, and economic differences that exist throughout the region add to the challenges of developing sustainable newborn screening systems. There are currently more developing programs than developed programs within the region. Newborn screening activities in the Asia Pacific Region are particularly important since births there account for approximately half of the world’s births. To date, there have been two workshops to facilitate formation of the Asia Pacific Newborn Screening Collaboratives. The 1st Workshop on Consolidating Newborn Screening Efforts in the Asia Pacific Region occurred in Cebu, Philippines, on March 30–April 1, 2008, as a satellite meeting to the 7th Asia Pacific Conference on Human Genetics. The second workshop was held on June 4–5, 2010, in Manila, Philippines. Workshop participants included key policy-makers, service providers, researchers, and consumer advocates from 11 countries with 50% or less newborn screening coverage. Expert lectures included experiences in the United States and the Netherlands, international quality assurance activities and ongoing and potential research activities. Additional meeting support was provided by the U.S. National Institutes of Health, the Centers for Disease Control and Prevention, the U.S. National Newborn Screening and Genetics Resource Center, the International Society for Neonatal Screening, and the March of Dimes. As part of both meeting activities, participants shared individual experiences in program implementation with formal updates of screening information for each country. This report reviews the activities and country reports from two Workshops on Consolidating Newborn Screening Efforts in the Asia Pacific Region with emphasis on the second workshop. It also updates the literature on screening activities and implementation/expansion challenges in the participating countries.