1. Signs, Symptoms and Findings: Towards an Ontology for Clinical Phenotypes Milan, September 4-5, 2009 Structured Representation of Disorders of the Newborn Infant Andrew James MBChB MBI The Hospital for Sick Children, Toronto Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada

2. Signs, Symptoms and Findings: Towards an Ontology for Clinical Phenotypes Milan, September 4-5, 2009 Canadian Neonatal Network... Enables and promotes evidence-based intensive care in all neonatal intensive care units within Canada Clinical, epidemiological, outcome and health services research aimed at improving both the efficacy and efficiency of neonatal care ICD-9-CM for the representation of disorders of the newborn infant Canada Health Infoway: SNOMED CT as pan-Canadian standard [ICD-10 also].

3. Signs, Symptoms and Findings: Towards an Ontology for Clinical Phenotypes Milan, September 4-5, 2009 Disorders of the newborn infant... Perinatal events [labour and delivery, postnatal transition to extrauterine environment] Immaturity Respiratory disorders Jaundice Infection Low birth weight [preterm infant, small mature infant ] Congenital malformations

4. Signs, Symptoms and Findings: Towards an Ontology for Clinical Phenotypes Milan, September 4-5, 2009 Representation of Disorders... Aetiology Pathology [abnormal morphology, location] Pathophysiology [disturbance of biological process, abnormal function] Clinical features [symptoms, signs] Investigations [laboratory, imaging, other... ] Natural history [duration, progression …] Interventions [physical, pharmacological, biological, behavioural... ]

5. Signs, Symptoms and Findings: Towards an Ontology for Clinical Phenotypes Milan, September 4-5, 2009 Challenges for representation... Origin in embryonic, fetal, perinatal or neonatal period Transient disturbances of function Predisposition to a disorder Outcome of a disorder that no longer exists Resolution of disorder but persistence of consequences into infancy, childhood, and beyond Congenital malformations may not be detectable Genetically determined conditions asymptomatic

6. Signs, Symptoms and Findings: Towards an Ontology for Clinical Phenotypes Milan, September 4-5, 2009 Representation by SNOMED CT... Systematic examination of SNOMED CT July 2006 release to determine whether 434 terms for disorders of the newborn infant are represented SNOMED CT Complete representation 90.8% Partial representation 6.4% No representation 2.8% Nearly 40% fully defined, nearly 50% have synonyms

7. Signs, Symptoms and Findings: Towards an Ontology for Clinical Phenotypes Milan, September 4-5, 2009 Respiratory distress... Commonest presenting problem in neonatal period Constellation of respiratory signs tachypnoea grunting chest wall indrawing [subcostal, intercostal...] cyanosis Abnormal CXR Respiratory distress syndrome... three distinct causes

8. Signs, Symptoms and Findings: Towards an Ontology for Clinical Phenotypes Milan, September 4-5, 2009 Respiratory distress... Primary surfactant deficiency Developmental, functional disorder associated with immaturity Genetically determined disorder Secondary surfactant deficiency Inhibition of surfactant function by protein [albumin, meconium and blood]

9. Signs, Symptoms and Findings: Towards an Ontology for Clinical Phenotypes Milan, September 4-5, 2009 9 SCT’s representation of RDS...

10. Signs, Symptoms and Findings: Towards an Ontology for Clinical Phenotypes Milan, September 4-5, 2009 10 Ontological anomalies...

11. Signs, Symptoms and Findings: Towards an Ontology for Clinical Phenotypes Milan, September 4-5, 2009 Temporal environment...

12. Signs, Symptoms and Findings: Towards an Ontology for Clinical Phenotypes Milan, September 4-5, 2009 The neonatal periods... LateEarly

13. Signs, Symptoms and Findings: Towards an Ontology for Clinical Phenotypes Milan, September 4-5, 2009 13 The root anomaly...

14. Signs, Symptoms and Findings: Towards an Ontology for Clinical Phenotypes Milan, September 4-5, 2009 RefSet for Respiratory Disorders Three neonatologists identified 348 candidate disorders for inclusion in a RefSet for structured representation of respiratory disorders of the newborn infant Criteria for inclusion included congenital, perinatal and neonatal disorders 348 candidate respiratory conditions 288 terms selected for inclusion in the RefSet (83%) 57% terms were congenital 27% terms were general terms

15. Signs, Symptoms and Findings: Towards an Ontology for Clinical Phenotypes Milan, September 4-5, 2009 RefSet for Respiratory Disorders 46% terms fully defined, 33% have synonyms Long tail phenomenon 9% of these terms used at least once per month 23% used at least once per six months 60% used less than once per year 74% of the infrequently used terms were terms for the representation of congenital disorders of the respiratory system

16. Signs, Symptoms and Findings: Towards an Ontology for Clinical Phenotypes Milan, September 4-5, 2009 Emphasis upon function... Abnormal

17. Signs, Symptoms and Findings: Towards an Ontology for Clinical Phenotypes Milan, September 4-5, 2009 Functional perspective...

18. Signs, Symptoms and Findings: Towards an Ontology for Clinical Phenotypes Milan, September 4-5, 2009 RDS: Structural perspective... is_a disorder of the alveolus is_a disorder of the lung is_a disorder of the lower respiratory system is_a disorder of the respiratory system is_a disorder is_a finding

19. Signs, Symptoms and Findings: Towards an Ontology for Clinical Phenotypes Milan, September 4-5, 2009 RDS: Functional perspective... is_a disorder of surfactant function is_a disorder of stability of the alveolus is_a disorder of alveolar function is_a disorder of pulmonary gas exchange is_a disorder of the respiratory system is_a disorder is_a finding