1. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Newborn Screening: The Future Revolution Beth A. Tarini, MD, MS Assistant Professor Child Health Evaluation and Research Unit University of Michigan Assistant Professor Child Health Evaluation and Research Unit University of Michigan

2. Treuman Katz Center for Pediatric Bioethics - 2008 Conference “If you don't know where you are going, any road will get you there.” - Lewis Carroll “If you don't know where you are going, any road will get you there.” - Lewis Carroll

3. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Where do we want to go with newborn screening?

4. Treuman Katz Center for Pediatric Bioethics - 2008 Conference What do we want the ultimate goal of newborn screening to be?

5. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Outline Newborn screening of the present Newborn screening of the future Implications of future system Newborn screening of the present Newborn screening of the future Implications of future system

6. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Outline Newborn screening of the present Newborn screening of the future Implications of future system Newborn screening of the present Newborn screening of the future Implications of future system

7. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Newborn Screening Now Public health program Newborns screened after birth for inherited, treatable disorders Examples –Phenylketonuria (PKU) –Congenital Hypothyroidism –Sickle Cell Disease Public health program Newborns screened after birth for inherited, treatable disorders Examples –Phenylketonuria (PKU) –Congenital Hypothyroidism –Sickle Cell Disease

8. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Newborn Screening Policy Mandated

9. Treuman Katz Center for Pediatric Bioethics - 2008 Conference

10. Newborn Screening Policy State regulated

11. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Copyright ©2006 American Academy of Pediatrics Tarini, B.A. et al. Pediatrics 2006;118:448- 456 Increase in newborn screening testing across states: 1995-2005

12. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Mission of Newborn Screening: ACMG “…newborn screening programs are designed to provide early diagnosis and treatment before significant, irreversible damage occurs.”

13. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Mission of Newborn Screening: ACMG “…newborn screening programs are designed to provide early diagnosis and treatment before significant, irreversible damage occurs.”

14. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Mission of Newborn Screening: ACMG “…newborn screening programs are designed to provide early diagnosis and treatment before significant, irreversible damage occurs.”

15. Treuman Katz Center for Pediatric Bioethics - 2008 Conference 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.”

16. Treuman Katz Center for Pediatric Bioethics - 2008 Conference 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.”

17. Treuman Katz Center for Pediatric Bioethics - 2008 Conference 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.”

18. Treuman Katz Center for Pediatric Bioethics - 2008 Conference 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.”

19. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Mission of Newborn Screening EARLY IDENTIFICATION IMPROVED INFANT OUTCOMES INTERVENTION

20. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Disorders Added Under Current Mission PKU 1963 1987 Sickle Cell Disease Congenital Hypothyroidism Late 1970s

21. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Cystic Fibrosis 2003 Tandem Mass Spec Disorders 2005 Disorders Added Under Current Mission 20?? ? ?

22. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Outline Newborn screening of the present Newborn screening of the future Implications of future system Newborn screening of the present Newborn screening of the future Implications of future system

23. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Disorders for the Future 20?? Duchenne’s Muscular Dystrophy Spinal Muscular Atrophy Duchenne’s Muscular Dystrophy Spinal Muscular Atrophy Cystic Fibrosis 2003 Tandem Mass Spec Disorders 2005

24. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Treatment for Duchenne’s?

25. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Should we screen only when an effective treatment exists?

26. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Screening only when effective treatment exists is… “outmoded because it fails to consider other benefits of diagnosis in the newborn period”

27. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Screening only when effective treatment exists is… “outmoded because it fails to consider other benefits of diagnosis in the newborn period”

28. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Screening only when effective treatment exists is… “outmoded because it fails to consider other benefits of diagnosis in the newborn period”

29. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Screening only when effective treatment exists… “dooms us to continued ignorance and unavailability of treatment because affected individuals are not identified until they exhibit symptoms, too late for effective preventive interventions to be tested or applied.”

30. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Screening only when effective treatment exists… “dooms us to continued ignorance and unavailability of treatment because affected individuals are not identified until they exhibit symptoms, too late for effective preventive interventions to be tested or applied.”

31. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Current Mission of Newborn Screening EARLY IDENTIFICATION IMPROVED INFANT OUTCOMES INTERVENTION

32. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Future Mission of Newborn Screening EARLY IDENTIFICATION “OTHER BENEFITS” RESEARCH

33. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Screening only when effective treatment exists… “outmoded because it fails to consider other benefits of diagnosis in the newborn period”

34. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Other Benefits: Future Newborn Screening Avoid diagnostic odyssey “Prepare” for disease Reproductive decision making Early access to promising therapies Avoid diagnostic odyssey “Prepare” for disease Reproductive decision making Early access to promising therapies

35. Treuman Katz Center for Pediatric Bioethics - 2008 Conference No Benefits Without Harms HARMS BENEFITS

36. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Other Harms: Future Newborn Screening More Tests, More False Positives –Parental anxiety –Lingering doubts about test result –Later increased healthcare utilization More Tests, More False Positives –Parental anxiety –Lingering doubts about test result –Later increased healthcare utilization

37. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Other Harms: Future Newborn Screening Ambiguous results –Parental anxiety –Labeling effect –Unnecessary treatment Ambiguous results –Parental anxiety –Labeling effect –Unnecessary treatment

38. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Consequences of Screening Disease that will become symptomatic Disease detected clinically “Pseusodisease” Disease detected by screening Disease that will remain asymptomatic Wolf, BMJ, 2003

39. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Screening only when effective treatment exists “…because affected individuals are not identified until they exhibit symptoms, too late for effective preventive interventions to be tested or applied.”

40. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Newborn Screening as Research

41. Treuman Katz Center for Pediatric Bioethics - 2008 Conference To benefit from research… Establish research infrastructure –National or regional –Address medical and social outcomes –Requires resources –Takes time Establish research infrastructure –National or regional –Address medical and social outcomes –Requires resources –Takes time

42. Treuman Katz Center for Pediatric Bioethics - 2008 Conference To benefit from research… 2005, ACMG NBS recommendation –“develop national systems for the collection of clinical information about those individuals identified in screening” 2008 –Development of infrastructure in process 2005, ACMG NBS recommendation –“develop national systems for the collection of clinical information about those individuals identified in screening” 2008 –Development of infrastructure in process

43. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Outline Newborn screening of the present Newborn screening of the future Implications of future system Newborn screening of the present Newborn screening of the future Implications of future system

44. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Future Newborn Screening as Mandatory Research Current newborn screening is mandatory…

45. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Can you mandate based on these benefits? Avoid diagnostic odyssey “Prepare” for disease onset Reproductive decision making Early access to promising therapies Avoid diagnostic odyssey “Prepare” for disease onset Reproductive decision making Early access to promising therapies

46. Treuman Katz Center for Pediatric Bioethics - 2008 Conference

47. Parental Consent Process Current process needs modification –Many states don’t obtain active consent Focus on parental education Address needs of research subjects Current process needs modification –Many states don’t obtain active consent Focus on parental education Address needs of research subjects

48. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Expansion of newborn screening requires expansion of resources

49. Treuman Katz Center for Pediatric Bioethics - 2008 Conference More than a test…

50. Treuman Katz Center for Pediatric Bioethics - 2008 Conference More than a test… Follow-up testing & evaluation Education Screening Treatment & long-term management

51. Treuman Katz Center for Pediatric Bioethics - 2008 Conference More than a test… Public Health Primary Care Physicians Specialty Physicians FAMILIES

52. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Public Health Services PKU Congenital Hypothyroidism Sickle Cell Cystic Fibrosis EmergencyUrgency Public Health Clinical Service

53. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Where do we put Duchenne’s? EmergencyUrgency Public Health Clinical Service Duchenne’s X X X X

54. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Where will it end?

55. Treuman Katz Center for Pediatric Bioethics - 2008 Conference What disorders will we NOT add?

56. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Julia 5 day old female term infant Being seen at her pediatrician’s office for check-up Pediatrician reviews newborn screening results with family Julia 5 day old female term infant Being seen at her pediatrician’s office for check-up Pediatrician reviews newborn screening results with family Newborn Screening 2020

57. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Positive screen for congenital hypothyroidism Carrier for Fragile X Genetic mutations that increase her risk for autism, depression, type 2 diabetes Positive screen for congenital hypothyroidism Carrier for Fragile X Genetic mutations that increase her risk for autism, depression, type 2 diabetes Julia’s newborn screening results…

58. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Where do we want to go with newborn screening?

59. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Acknowledgements Treuman Katz Center for Pediatric Bioethics Duane Alexander, MD Ben Wilfond, MD Wylie Burke, MD, PhD Child Health Evaluation & Research Unit, University of Michigan Treuman Katz Center for Pediatric Bioethics Duane Alexander, MD Ben Wilfond, MD Wylie Burke, MD, PhD Child Health Evaluation & Research Unit, University of Michigan