Prognosis for Danish Patients with Congenital Heart Defects Morten Olsen
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Prognosis for Danish patients with congenital heart defects -Mortality, psychiatric morbidity, and educational achievement PhD thesis Morten Olsen Faculty of Health Sciences Aarhus University Department of Clinical Epidemiology and Department of Cardiothoracic and Vascular Surgery & Institute of Clinical Medicine, Aarhus University Hospital, Denmark Supervisors Vibeke Elisabeth Hjortdal Professor, chief cardiac surgeon, MD, DMSc, PhD Department of Cardiothoracic and Vascular Surgery & Institute of Clinical Medicine, Aarhus University Hospital, Skejby Thomas Decker Christensen Senior resident, MD, PhD Department of Cardiothoracic and Vascular Surgery & Institute of Clinical Medicine, Aarhus University Hospital, Skejby Lars Pedersen Chief Statistician, MSc, PhD Department of Clinical Epidemiology Aarhus University Hospital Preface This thesis is based on studies made during my time at the Department of Clinical Epidemiology, Aarhus University Hospital. I would like to thank all the people who helped me throughout my time as a PhD student. In particular I want to thank my supervisors; Vibeke Elisabeth Hjortdal for sharing her clinical expertise and for friendly encouragement, Thomas Decker Christensen for getting me started and helping me along, and Lars Pedersen for his time, statistical support and positive attitude. I wish to thank Henrik Toft Sørensen for providing excellent research facilities, for making this work possible, and for constructive feedback. I also want to thank Søren Påske Johnsen for all his help and his pleasant personality. I thank all my colleagues at the Department of Clinical Epidemiology for an inspiring and friendly working environment. Finally I thank Laust Hvas Mortensen for contributing to the writing of the study on educational attainment. Morten Olsen, Aarhus, 2010 This thesis is based on the following studies I. Morten Olsen, Thomas Decker Christensen, Lars Pedersen, Søren Paaske Johnsen, Vibeke Elisabeth Hjortdal. Late Mortality among Danish Patients with Congenital Heart Defect. Accepted, American Journal of Cardiology. II. Morten Olsen, Henrik Toft Sørensen, Vibeke Elisabeth Hjortdal, Thomas Decker Christensen, Lars Pedersen. Congenital heart defects and psychiatric in- or outpatient admissions: A nationwide cohort study. Accepted, Cardiology in the Young. III. Morten Olsen, Vibeke Elisabeth Hjortdal, Laust Hvas Mortensen, Thomas Decker Christensen, Henrik Toft Sørensen, Lars Pedersen. Educational achievement among long-term survivors of congenital heart defects: A Danish population-based follow-up study. Submitted. CONTENT List of Abbreviations................................................................................................................2 Introduction ..............................................................................................................................3 Congenital heart defects...........................................................................................................3 Prognosis ...................................................................................................................................5 Study I – Mortality ...................................................................................................................8 Congenital heart defects and the brain ................................................................................14 Study II – Psychiatric morbidity...........................................................................................15 Study III – Educational achievement ...................................................................................23 Hypotheses and aims ..............................................................................................................27 Subjects and methods.............................................................................................................28 Data sources ............................................................................................................................28 Variable definitions ................................................................................................................30 Study design ............................................................................................................................34 Statistical analysis...................................................................................................................36 Results......................................................................................................................................38 Study I – Mortality .................................................................................................................38 Study II – Psychiatric morbidity...........................................................................................41 Study III – Educational achievement ...................................................................................44 Methodological considerations ..............................................................................................46 Selection bias...........................................................................................................................46 Information bias .....................................................................................................................47 Confounding............................................................................................................................49 Discussion ................................................................................................................................50 Main conclusions ....................................................................................................................53 Perspectives .............................................................................................................................54 Summary .................................................................................................................................55 Danish summary.....................................................................................................................57 References ...............................................................................................................................59 Appendix .................................................................................................................................75 1 List of Abbreviations CHD Congenital heart defect TOF Tetralogy of Fallot TGA Transposition of great arteries VSD Ventricular septal defect ASD Atrial septal defect PDA Persistent arterial duct PS Pulmonary stenosis AS Aortic stenosis CoA Coarctation of aorta RACHS-1 Risk Adjusted Classification for Congenital Heart Surgery ICD International Classification of Diseases IPCCC International Pediatric and Congenital Cardiac Code CI Confidence interval HR Hazard ratio HKD Hyperkinetic disorder IQ Intelligence quotient ADHD Attention deficit hyperactivity disorder PDD-NOS Pervasive developmental disorder not otherwise specified DSM Diagnostic and Statistical Manual of Mental Disorders ISCED International Standard Classification of Education 2 Introduction Congenital heart defects Congenital heart defects (CHDs) have been defined as gross structural abnormalities of the heart or intrathoracic great vessels that are actually or potentially of functional significance (1). Traditionally, CHDs have been categorized according to whether the defect may cause cyanosis. Cyanotic lesions cause the presence of desaturated blood in the systemic circulation due to right to left shunting and include tetralogy of Fallot (TOF), transposition of the great arteries (TGA), and Ebstein’s anomaly. Acyanotic lesions include ventricular septal defect (VSD), atrial septal defect (ASD), patent arterial duct (PDA), pulmonary stenosis (PS), atrial stenosis (AS), and coarctation of the aorta (CoA) (2, 3). CHD vary immensely in severity, natural history and management. Minor forms of CHD include mild PS, small ASD, and VSD, and they rarely require intervention. More severe CHDs with four heart chambers and 4 heart valves like CoA, severe AS, large VSD, TOF, and TGA require intervention to prevent heart failure, cyanosis, pulmonary hypertension or death. Highly complex CHD include atresia and hypoplasia of valve or chamber (4). Most CHDs are diagnosed in infancy (5), and cyanosis and cardiac failure are the principal signs. Later, in childhood or adolescence, CHD patients may present differently with e.g. a heart murmur, abnormal heart rate, absent pulses or hypertension. Prevalence at birth and aetiology Congenital heart defects comprise the most prevalent group of congenital anomalies. Most studies estimate the live birth prevalence of CHD to be around 6-10 per 1,000 (5-9). The discrepancy in the reported prevalence of CHD may reflect true geographical and or temporal differences in the prevalence, however it is more likely attributable to variations in recording and reporting practices. Thus, there are differences between the studies in e.g. case definition and inclusion/exclusion criteria, follow-up period and age at diagnosis (7). Hoffman et al reviewed 62 studies published after 1952 and found that prevalence estimates were highly dependent on the number of small VSDs included (5). Thus, there is no evidence of temporal variations in the prevalence of CHD. However, elective terminations of pregnancies due to severe CHD, diagnosed in prenatal investigations,