1. TM National Center on Birth Defects and Developmental Disabilities Kernicterus Surveillance Presented at the FDA Pediatric Advisory Committee Meeting on Current Epidemiology and Therapeutic Interventions Relevant to Hyperbilirubinemia in the Term & Near-term Newborn Washington DC: June 11, 2003

2. TM Overview: Framework for DD surveillance Health education & prevention strategies Public policy Monitor prevalence rates, trends, & prevention programs Provide registry of cases Surveillance Systems Epidemiological Studies Prevention Programs Identify risk & protective factors Address public concerns

3. TM  Definitions – Attributable to an impairment in physical, cognitive, speech or language, psychological, or self-care areas  Measurement – Not always straight forward, especially for conditions that rely on a behavioral patterns  Population-based – Limited surveillance and not always well defined Above issues can make generalizing results difficult or impossible to interpret Overview: Complexities of DD surveillance

4. TM Issues: Complexities of KI surveillance Range of impairment and associated conditions – Brain damage that is associated with athetoid cerebral palsy, hearing loss, vision impairment, dental dysplasia, and sometimes mental retardation Changes in level of awareness and use of diagnosis over time Variability in how cases are diagnosed – Physical markers and behavioral pattern utilized for identification Early onset but often delayed diagnosis

5. TM  No systematic population-based surveillance in place to monitor kernicterus or hyperbilirubinemia  Case reports from convenience samples or select populations (e.g., medical insurance records)  No accepted standard for surveillance definition Historical perspectives: KI surveillance

6. TM  True population estimates unknown to date  Case reports from a convenience sample – Johnson, Bhutani, Brown (2002). 90 cases reported from 1984-Jan 2001  Rates versus numbers Prevalence of kernicterus – Rate = # of people with condition # of people in the population Is kernicterus on the rise?

7. TM Summary of issues for KI surveillance Case definition – Debate over cut-offs for inclusion Low prevalence condition – Requires a substantial population to detect cases Lack of recognition – Acute event with specific features – Permanent damage, long-term clinical features Litigation – Possible deterrent for case identification

8. TM  Evaluation of extant databases – National Hospital Discharge Data  Preponderance of hyperbilirubinemia codes  KI codes not readily used – MADDSP surveillance  Examined athetoid CP cases Kernicterus is not a reportable condition – CSTE approached regarding national reporting Managed Care System – Proposed cooperative agreement – Limited interest Preliminary actions: CDC

9. TM  PERT announcement 2002  Objectives – Applicant should seek to review cases of extreme jaundice in otherwise healthy full-term infants – Provide a body of evidence to inform why cases of extreme jaundice may lead to kernicterus and why kernicterus may be re-emerging – A forum of concerned scientists and health-care professionals will be convened to develop a strategic plan for national kernicterus prevention Current activities: CDC surveillance efforts

10. TM UMDNJ Robert Wood Johnson Medical School Principal Investigators: T. Hegyi, B. Ostfeld, A. Petrova Infant mortality and morbidity of kernicterus Surveillance Identification of risk factors (clinical & systemic) Support network Objectives of award recipient

11. TM UMDNJ Robert Wood Johnson Medical School Principal Investigators: T. Hegyi, B. Ostfeld, A. Petrova IRB submissions and approvals Initial discussion & process for population-based surveillance with the NJ Dept of Health Analyses of extant data on infant morbidity and mortality due to kernicterus Progress to date

12. TM Preliminary results: Morbidity UMDNJ Robert Wood Johnson Medical School Principal Investigators: T. Hegyi, B. Ostfeld, A. Petrova 1992 – 2001(NJ Hospital Discharge Data) – 82 cases of kernicterus – 7.5/100,000 live births (cumulative incidence) – Significant variation by race and ethnicity with the lowest rate among Hispanics and the highest rate among Asians

13. TM Pennsylvania Hospital, University of Pennsylvania Principal Investigators: V. Bhutani & L. Johnson Surveillance Identification of risk factors (clinical & systemic) Prevention Taskforce/Steering Committee National Prevention Campaign Objectives of award recipient

14. TM Pennsylvania Hospital, University of Pennsylvania Principal Investigators: V. Bhutani & L. Johnson Initial Advisory Board teleconference Peer Review Group meeting for consensus on kernicterus definition (planned) Database development Collaboration with PICK on kernicterus educational video Progress to date

15. TM Future directions Partner for prevention – American Academy of Pediatrics, AWHONN, HRSA, JCAHO, March of Dimes, NICHD, PICK, University researchers, others… Forum for developing consensus on surveillance case definition Identify a mechanism for population-based surveillance – State – National

16. TM Working to prevent kernicterus

17. TM