Long-term survival of children born with congenital heart disease: a systematic review

1. Long-term survival of children born with congenital heart disease: a systematic review Kate Best1, Judith Rankin1 1 Institute of Health & Society, Newcastle University, UK

2. Background • Objectives of PhD • Describe the prevalence of CHD, trends and risk factors using BINOCAR data. • Conduct a systematic review on the long-term survival of children born with CHD. • Analyse survival and predictors of survival of children born with CHD using BINOCAR data linked to death registrations. • Predict the future prevalence/survival of CHDs.

3. Background • Prevalence of CHD: 80 per 10,000 total births

4. background • Infant survival has been frequently reported • But after infancy, mortality remains higher than that of the general population

5. background • Individuals with CHD require highly specialised healthcare • Long-term follow-up of children born with CHD is important in predicting life time healthcare requirements

6. Previous research • In 2008, a systematic review on the long-term prognosis of CHD was published it included hospital-based BUT studies Survival % 97.2 99.6 98.1 95.4 96.9 95.7 93.5 98.5 87.4 97.5 90.2 96.8 92.9

7. Aim • To conduct a systematic review of all population-based studies that report the long-term survival of individuals born with CHD. • Compare survival estimates • Examine predictors of survival

8. methods • MEDLINE, EMBASE and Scopus from their inception to October 2013 • Inclusion criteria: • Population-based studies • Cases ascertained at birth • Survival estimates reported at age ≥5 • Survival estimates correspond to all CHD combined or by subtype

9. methods • Exclusion criteria • Studies not available from the British Library • Studies not written in English

10. methods • Search strategy: • MeSH-terms (e.g. “exp Heart Defects, Congenital/ep, mo”) and key words (e.g. “congenital” and “heart” or “cardiac”) • Core journals & reference lists were searched • Titles and abstracts were screened according to the inclusion criteria and irrelevant citations were excluded. Full articles were then retrieved.

11. methods • Data extraction • Two data extractors • Study descriptions extracted • Kaplan-Meier survival estimates and 95% confidence intervals (CIs) were extracted from each included study • Authors contacted for clarification

12. methods • Data summary/ Analysis • Studies that included and excluded cases with extra-cardiac anomalies grouped separately • Summary estimates were estimated using meta-analyses.

13. Results 6,269 citation identified from electronic database searching 1,178 duplicates 5,091 titles reviewed 88 abstracts reviewed 25 studies excluded 10 were not population-based studies 5 reported infant survival only 3 reported mortality rates by year of death 2 reported survival of all congenital anomalies only 2 did not report survival estimates at the specified ages 2 reported survival categorised by another variable only 1 excluded cases of certain ethnicities 35 full papers reviewed 10 studies included

14. Wang, Hu et al. 2011 Tennant, Pearce et al. 2010 Samanek and Voriskova 1999 Olsen, Christensen et al. 2010 Moons, Sluysmans et al. 2009 Miller, Siffel et al. 2010 Garne 2004 Frid, Bjorkhem et al. 2004 Fixler, Nembhard et al. 2010 Dastgiri, Gilmour et al. 2003 1970 1980 1990 2000 2010 Results • Study periods

15. Wang, Hu et al. 2011 Tennant, Pearce et al. 2010 Samanek and Voriskova 1999 Olsen, Christensen et al. 2010 Moons, Sluysmans et al. 2009 Miller, Siffel et al. 2010 Garne 2004 Frid, Bjorkhem et al. 2004 Fixler, Nembhard et al. 2010 Dastgiri, Gilmour et al. 2003 1970 1980 1990 2000 2010 Results • Follow-up periods

16. Wang, Hu et al. 2011 Tennant, Pearce et al. 2010 Samanek and Voriskova 1999 Olsen, Christensen et al. 2010 Moons, Sluysmans et al. 2009 Miller, Siffel et al. 2010 Garne 2004 Frid, Bjorkhem et al. 2004 Fixler, Nembhard et al. 2010 Dastgiri, Gilmour et al. 2003 1970 1980 1990 2000 2010 Results Max age • Follow-up periods

17. Results Dastgiri Frid Tennant Olsen Garne Moons Samanek Wang Miller Fixler

18. results

19. results

20. Excluding extra-cardiac anomalies Including extra-cardiac anomalies 100 Moons Tennant Tennant Tennant Tennant Garne 95 Percentage Survived 90 Olsen Samanek Olsen 85 5 10 15 20 25 5 10 15 20 25 Age 95% CI Survival estimate Results: vsd

21. Excluding extra-cardiac anomalies Including extra-cardiac anomalies 100 Moons 80 Tennant Tennant Tennant Tennant Olsen Frid Frid Frid Percentage Survived Frid Wang 60 Miller Wang Olsen Miller Wang Samanek Samanek Samanek Frid Frid Garne 40 20 5 10 15 20 25 5 10 15 20 25 Age Survival estimate 95% CI Results: AVSD

22. Excluding extra-cardiac anomalies Including extra-cardiac anomalies 100 80 Percentage Survived 60 40 20 5 10 15 20 25 5 10 15 20 25 Age Survival estimate 95% CI Results AVSD 69 (55-81) 61 (56-67) 65 (58-71) 60 (56-64) 51 (41-61) 64 (48-79) 68 (41-89)

23. Excluding extra-cardiac anomalies Including extra-cardiac anomalies 80 60 Percentage Survived 40 Moons Fixler Fixler Wang Wang Wang 20 Tennant Garne 0 Samanek Samanek Samanek 5 10 15 20 25 5 10 15 20 25 Age Survival estimate 95% CI Results: HLH

24. Excluding extra-cardiac anomalies Including extra-cardiac anomalies 80 60 Percentage Survived 40 20 0 5 10 15 20 25 5 10 15 20 25 Age Survival estimate 95% CI Results: HLH 18 (1-66) 18 (3.5-39) 9 (8-59)

25. Results: all CHD subtypes Including extra-cardiac anomalies Excluding extra-cardiac anomalies 100 Moons Tennant 90 Tennant Tennant Tennant Garne Percentage Survived Garne 80 Samanek Samanek Samanek Olsen Olsen Dastgiri Olsen Olsen 70 5 10 15 20 25 5 10 15 20 25 Age Survival estimate 95% CI

26. Results: all CHD subtypes Including extra-cardiac anomalies Excluding extra-cardiac anomalies 100 90 Percentage Survived 87 (86-88) 80 84 (67-96) 70 76 (74-79) 86 (72-96) 5 10 15 20 25 5 10 15 20 25 Age Survival estimate 95% CI

27. results • Sources of heterogeneity • Study period • Ascertainment of milder forms • Ascertainment of cases with extra-cardiac anomalies • Coding of cases with multiple CHD

28. results • Predictors of survival • Year of birth (5 studies) • All 5 studies reported improved survival over time • Sex (2 studies) • No association (AVSD only) (Frid) • Females increased risk of death (All CHD) (Wang)

29. 1.4 1.2 RR 1 .8 <20 20-24 25-29 30-34 35+ Maternal age 95% CI RR results • Maternal age at delivery (2 studies) • No association (SV physiology) • Increased survival with increasing maternal age (All CHD)

30. Strengths & Limitations • Strengths: • Restricted to population-based studies • Separated studies including/excluding extra-cardiac anomalies • Systematic search strategy • Authors contacted • 2 data extractors

31. Strengths & Limitations • Limitations: • Survival up to age 25 only • 4 studies up to age 5 only • Most studies included cases with extra-cardiac anomalies • No studies from low income populations • Small sample sizes for individual subtypes • Doesn’t account for morbidity • Little information on surgeries

32. Further research • Further research is required into the long-term survival: • Subtypes separately • Of isolated cases of CHD in particular • Predictors of survival (in particular socioeconomic position) • Survival in low income populations • Survival associated with surgeries

33. conclusion • Survival varies substantially by CHD subtype • Further research into long-term survival and predictors is required • This information would inform health service planning and for informing parents when a CHD is detected antenatally or in early childhood

34. Acknowledgements • Thank-you to the British Heart Foundation for funding this study • Thank-you for listening!