The prevalence and survival of children with congenital septal defects in the UK using CPRD

Background Congenital heart disease (CHD) is a major contributor to infant mortality worldwide, accounting for a third of total congenital defects and a fifth of total global early neonatal mortality. Congenital septal defects (SD) are the most common CHD. This study assesses the prevalence and survival of children diagnosed with congenital septal defects in the UK. Methods All children who survived to at least the first 30 days after birth and registered with a GP within their first year of birth diagnosed with any CHD at any time in England between January 1998 and June 2017 were extracted from Clinical Practice Research Datalink (CPRD). Similar records for children diagnosed with other congenital anomalies were also obtained as well as children without any congenital anomaly constituting as the control group. These records were matched with the Office for National Statistics (ONS) death registration data, and the Index of Multiple Deprivation (IMD) data to allow assessment of death records and deprivation records, respectively. Prevalence risk ratios were calculated according to specific sociodemographic factors such as gender, year of birth, ethnicity, socioeconomic status, and geographical location for SD and its variants. Mortality risk ratios were calculated by gender, ethnicity, and socioeconomic status for SD and its variants. Also, in the absence of Hospital Episode Statistics (HES) data, I assessed the recording of CHD-related procedures/interventions in children’s GP records as a measure of disease severity within the CPRD-based birth cohort used in this thesis. Results The prevalence of any CHD was 86.1 per 10,000 live GP-registered births (95% CI, 83.7 – 88.4). SD accounted for 53.4% of the total CHD within this population and the overall prevalence of SD was 48.64 per 10,000 live GP-registered births (95% CI 46.90-50.44). Of all SD diagnosis identified, 59.1% had a VSD diagnosis (35.50 per 10,000 live GP-registered births, 95% CI 34.02-37.04), 28.8% ASD (17.31 per 10,000 live GP-registered births, 95% CI 16.29-18.40), 6.5% for ToF (3.91 per 10,000 live GP-registered births, 95% CI 3.44-4.45), 0.3% for AoSD (0.17 per 10,000 live GP-registered births, 95% CI 0.09-0.31), 3.2% for AVSD (1.93 per 10.000 live GP-registered births, 95% CI 1.61-2.32), and 2.1% for unspecified SD (1.28 per 10.000 live GP-registered births, 95% CI 1.02-1.60). For any SD, gender was significantly associated with occurrence, with the prevalence in females being 15% more than males (PR (Male-Female) 1.15, 95% CI 1.07-1.24), however, there was considerable variation across specific SD variants. Whilst there was no evidence of an association with the year of birth, ethnicity, or socioeconomic status on the prevalence of overall SD, specific sub-analysis of the SD variants showed some associations. The prevalence of SD and its variants varied by geographical regions in England with the highest prevalence of any SD observed in the East Midlands. The total number of deaths due to CHD from 30 days after birth to 19 years between January 1998 and June 2017 was 166 and the mortality rate was 5.6 (95% CI, 4.8-6.5) per 1,000 person-years. By SD variants, children with Aortopulmonary septal defect (54.9; 95% CI 13.7-219.6), Atrioventricular septal defect (7.2; 95% CI, 3.0-17.3), and Tetralogy of Fallot (8.1; 95% 4.6-14.3) had the highest mortality rates compared to other defects, although small numbers of children resulted in large confidence limits for some of these estimations. The hazard of death for children with any septal defect was over 16-fold higher than for children without a CA (HR 16.2; 95% CI, 12.8-20.6); aHR 16.4, 95% CI, 13.0-20.9, p<0.001). Of this, children with Aortopulmonary septal defect had the highest hazard of death with a 160-fold increase compared to children without a CA (HR, 164.6, 95% CI, (41.1-659.5); aHR 159.3, 95% CI, 39.7-641.4, p<0.001) and was lowest for children with VSD (HR, 15.5, 95% CI, (11.7-20.5); aHR 14.9, 95% CI, 12.0-21.0, p