Kate Best 1, Judith Rankin 1 LONG-TERM SURVIVAL OF CHILDREN BORN WITH CONGENITAL HEART DISEASE: A SYSTEMATIC REVIEW 1 Institute of Health & Society, Newcastle University, UK

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.

BACKGROUND  Prevalence of CHD: 80 per 10,000 total births

 Infant survival has been frequently reported  But after infancy, mortality remains higher than that of the general population 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 BACKGROUND

PREVIOUS RESEARCH  In 2008, a systematic review on the long-term prognosis of CHD was published BUT it included hospital-based studies Survival %

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

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

METHODS  Exclusion criteria Studies not available from the British Library Studies not written in English

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.

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

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

RESULTS 6,269 citation identified from electronic database searching 1,178 duplicates 5,091 titles reviewed 88 abstracts reviewed 35 full papers 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 10 studies included

RESULTS Dastgiri, Gilmour et al Fixler, Nembhard et al Frid, Bjorkhem et al Garne 2004 Miller, Siffel et al Moons, Sluysmans et al Olsen, Christensen et al Samanek and Voriskova 1999 Tennant, Pearce et al Wang, Hu et al  Study periods

RESULTS Dastgiri, Gilmour et al Fixler, Nembhard et al Frid, Bjorkhem et al Garne 2004 Miller, Siffel et al Moons, Sluysmans et al Olsen, Christensen et al Samanek and Voriskova 1999 Tennant, Pearce et al Wang, Hu et al  Follow-up periods

RESULTS Dastgiri, Gilmour et al Fixler, Nembhard et al Frid, Bjorkhem et al Garne 2004 Miller, Siffel et al Moons, Sluysmans et al Olsen, Christensen et al Samanek and Voriskova 1999 Tennant, Pearce et al Wang, Hu et al  Follow-up periods Max age

RESULTS Fixler Dastgiri Frid Garne Miller Moons Olsen Samanek Tennant Wang

RESULTS StudyCHD subtypes Dastgiri et al. 2003All subtypes combined Fixler et al. 2010Single Ventricle, Hypoplastic left heart, Pulmonary atresia, Tricuspid atresia Frid, et al. 2004AVSD Garne et al 2004All subtypes combined and individually Miller et al. 2010AVSD Moons et al. 2009All subtypes combined and individually Olsen et al. 2010All subtypes combined and individually Samanek et al 1999All subtypes combined and individually Tennant et al. 2010All subtypes combined and individually Wang et al. 2011Hypoplastic left heart, TGV, ToF, Common Trunkus, CoA, AVSD, Aortic atresia/stenosis

RESULTS StudyCHD subtypes Dastgiri et al. 2003All subtypes combined Fixler et al. 2010Single Ventricle, Hypoplastic left heart, Pulmonary atresia, Tricuspid atresia Frid, et al. 2004AVSD Garne et al 2004All subtypes combined and individually Miller et al. 2010AVSD Moons et al. 2009All subtypes combined and individually, including VSD Olsen et al. 2010All subtypes combined and individually Samanek et al 1999All subtypes combined and individually Tennant et al. 2010All subtypes combined and individually Wang et al. 2011Hypoplastic left heart, TGV, ToF, Common Trunkus, CoA, AVSD, Aortic atresia/stenosis

RESULTS: VSD

RESULTS: AVSD

RESULTS AVSD 69 (55-81) 64 (48-79) 68 (41-89) 65 (58-71) 61 (56-67) 60 (56-64) 51 (41-61)

RESULTS: HLH

18 (1-66) 18 (3.5-39) 9 (8-59)

RESULTS: ALL CHD SUBTYPES

87 (86-88) 84 (67-96) 86 (72-96) 76 (74-79)

RESULTS  Sources of heterogeneity Study period Ascertainment of milder forms Ascertainment of cases with extra-cardiac anomalies Coding of cases with multiple CHD

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)

RESULTS Maternal age at delivery (2 studies) ◦ No association (SV physiology) ◦ Increased survival with increasing maternal age (All CHD) RR < Maternal age 95% CIRR

STRENGTHS & LIMITATIONS  Strengths: Restricted to population-based studies Separated studies including/excluding extra-cardiac anomalies Systematic search strategy ◦ Authors contacted ◦ 2 data extractors

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

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

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

ACKNOWLEDGEMENTS  Thank-you to the British Heart Foundation for funding this study  Thank-you for listening!