Journal of the American Heart Association

ORIGINAL RESEARCH

Survival in Children With Congenital Heart

Disease: Have We Reached a Peak at
97%?
Zacharias Mandalenakis , MD, PhD; Kok Wai Giang, PhD; Peter Eriksson, MD, PhD; Hans Liden, MD, PhD;
Mats Synnergren, MD, PhD; Håkan Wåhlander, MD, PhD; Maria Fedchenko, MD, PhD; Annika Rosengren , MD, PhD;
Mikael Dellborg, MD, PhD

BACKGROUND: Despite advances in pediatric health care over recent decades, it is not clear whether survival in children with
congenital heart disease (CHD) is still increasing.

METHODS AND RESULTS: We identified all patients with CHD using nationwide Swedish health registries for 1980 to 2017. We
examined the survival trends in children with CHD; we investigated the mortality risk in patients with CHD compared with
matched controls without CHD from the general population using Cox proportional regression models and Kaplan–Meier
survival analysis. Among 64 396 patients with CHD and 639 012 matched controls without CHD, 3845 (6.0%) and 2235 (0.3%)
died, respectively. The mean study follow-up (SD) was 11.4 (6.3) years in patients with CHD. The mortality risk was 17.7 (95%
CI, 16.8–18.6) times higher in children with CHD compared with controls. The highest mortality risk was found during the first
4 years of life in patients with CHD (hazard ratio [HR], 19.6; 95% CI, 18.5–20.7). When stratified by lesion group, patients with
non-conotruncal defects had the highest risk (HR, 97.2; 95% CI, 80.4–117.4). Survival increased substantially according to
birth decades, but with no improvement after the turn of the century where survivorship reached 97% in children with CHD
born in 2010 to 2017.
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CONCLUSIONS: Survival in children with CHD has increased substantially since the 1980s; however, no significant improvement
has been observed this century. Currently, >97% of children with CHD can be expected to reach adulthood highlighting the
need of life-time management.

Key Words: congenital heart disease ■ nationwide ■ pediatric ■ registry study ■ survivorship

C
ongenital heart disease (CHD) is the most com- of aortic coartation7; repair of atrioventricular septal
mon major congenital malformation, having a defects8; Mustard and Senning atrial corrections9,10;
prevalence of ≈9 per 1000 live births.1,2 Thanks to Rastelli procedure11; the arterial switch12; and the cre-
the development of pediatric health care over the past ation of single-ventricle Fontan circulation.13 Despite
70 years, survival among patients with CHD has ef- this improvement, the mortality during the first 4 years
fectively increased: >90% of such children born in the of life among patients with CHD remains comparatively
early 1990s reached adulthood.3–5 The improvement high3,14–17; the need for further improvement in pediat-
has been based on developments in diagnostic tech- ric care persists.
niques, catheter interventions,6 and several surgical Advances in pediatric cardiovascular surgery and
innovations, such as the following: surgical treatment cardiac interventional catheterization since the new

Correspondence to: Zacharias Mandalenakis, MD, PhD, Department of Molecular and Clinical Medicine/Cardiology, Sahlgrenska University Hospital,
Diagnosvägen 11, SE-416 50 Gothenburg, Sweden. E-mail: [email protected]
Supplementary Material for this article is available at https://www.ahajo​urnals.org/doi/suppl/​10.1161/JAHA.120.017704
Preprint posted on SSRN June 23, 2020. doi: http://dx.doi.org/10.2139/ssrn.3566151.
For Sources of Funding and Disclosures, see page 7.
© 2020 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative
Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use
is non-commercial and no modifications or adaptations are made.
JAHA is available at: www.ahajournals.org/journal/jaha

J Am Heart Assoc. 2020;9:e017704. DOI: 10.1161/JAHA.120.0177041

 Mandalenakis et alSurvival in Children With Congenital Heart Diseas

were recorded at any time with a diagnosis of CHD

CLINICAL PERSPECTIVE with at least 1 of the following registers: National
Hospital Inpatient (complete since 1987, but with
What Is New? coverage of all hospitals performing thoracic surgery
• We report for the first time in a large, national since 1970); National Hospital Outpatient (complete
cohort study the survival in children with con- since 2001); and National Cause of Death Registers
genital heart disease born until the late 2010s. in Sweden (complete since 1968). All diagnoses
• The overall mortality risk was 18 times higher were coded according to the International Statistical
in children with congenital heart disease com- Classification of Diseases, Eighth, Ninth, and Tenth
pared with matched controls without congenital Revisions (ICD-8, ICD-9, ICD-10). Follow-up and co-
heart disease during a period of almost 40 years morbidity data were collected until December 31,
follow-up. 2017 or death.
• Survival increased substantially according to
Each patient with CHD was matched by birth year and
birth decades, but no further overall improve-
ment was noticed after the turn of the century. sex with 10 control individuals without diagnosis of CHD
from the Total Population Register in Sweden.25 We used
What Are the Clinical Implications? hierarchical CHD categorization to classify patients with
• Children with the most complex congenital mal- CHD into different groups according to CHD lesions. The
formations, such as non-conotruncal defects, study design has been described previously.3,26,27
had the highest risk of mortality and could be The study was conducted according to the ethical
considered a risk group. guidelines of the Declaration of Helsinki and it was ap-
• The mortality was still high during the first proved by the Gothenburg Regional Research Ethics
4 years of life in children with congenital heart Board (Gpg 912-16, T 616-18). All national registration
disease which indicates that continuous moni- numbers were replaced with a unique code for every
toring and early intervention may be beneficial. individual in the final data set by the Swedish National
• Over 97% of children with congenital heart dis-
Board of Health and Welfare and under collaboration
ease expected to reach adulthood and the need
of lifetime management is mandatory. with the Statistics Sweden. The requirement for in-
formed consent was waived. The data, methods used
in the analysis, and study materials used to conduct
the present study will not be made available to other
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millennium have shown improved outcomes in se- researchers for purposes of reproducing the results or
lected groups of patients with CHD.18–23 In addition, the replicating the procedure.
antenatal diagnosis of congenital heart malformations
has been introduced; currently 37% of all CHD is diag-
Definitions
nosed prenatally.24 However, it is unclear whether re-
cent developments have had an effect on the survival We defined patients with CHD as having at least 1 hos-
of pediatric patients with CHD over the past decade. pital discharge, an outpatient visit, or a death certificate
Accordingly, we examined the survival trends and risk with a registered ICD-8, ICD-9, and ICD-10 diagnosis of
of mortality in children with CHD compared with con- CHD (Table S1). To categorize CHD into different lesion
trols without CHD from the general population within groups according to severity, we used the hierarchic
a nationwide, registry-based cohort in Sweden from classification initially suggested by Botto et al and sub-
1980 to 2017. sequently used in observational studies,27–30 (Table S2).
Lesion group 1 was defined as patients with conotrun-
cal defects (such as common arterial trunk, transposi-
METHODS tion of the great vessels, double-outlet right ventricle,
double-outlet left ventricle, discordant atrioventricular
Data Source and Study Population connection, tetralogy of Fallot, and aortopulmonary sep-
Sweden is a northern European country of almost tal defect). Lesion group 2 was defined as patients with
10 million inhabitants with a through taxation publicly non-conotruncal defects (such as endocardial cushion
financed healthcare system. There are 70 acute care defects, common ventricle, and hypoplastic left heart
hospitals, all publicly financed and all but a handful syndrome). We defined lesion group 3 as patients with
also run by the regional authorities. Two complete coarctation of the aorta. Lesion group 4 was defined as
university affiliated congenital heart care units exist patients with ventricular septal defect. Lesion group 5
where all congenital heart surgery, pediatric and was defined as patients with atrial septal defect. Lesion
adult, is performed. We linked data from Swedish group 6 included all other heart and circulatory system
health registers to identify patients who were born anomalies and all other CHD diagnoses not included in
from January 1, 1980 to December 31, 2017 and who lesion groups 1 to 5.

J Am Heart Assoc. 2020;9:e017704. DOI: 10.1161/JAHA.120.0177042

 Mandalenakis et alSurvival in Children With Congenital Heart Diseas

Cardiac intervention was defined as patients with

CHD having undergone at least 1 cardiovascular sur- RESULTS
gery or cardiac interventional catheterization related We identified 64 396 patients with CHD and 639 012
to CHD, according to the classification of operations matched controls; the characteristics of the study pop-
(Sixth edition, Swedish version)31 or following the clas- ulation appear in Table 1. The majority of the patients
sification of surgical procedures (1.9 edition, Swedish with CHD and matched controls were born in Sweden;
version).32 94.8% and 83.2% respectively. From birth and with a
mean (SD) follow-up of 11.4 (6.3) years in patients with
Statistical Analysis CHD and 12.2 (6.0) years in matched controls, 3845
Baseline characteristics were reported as propor- (6.0%) and 2235 (0.3%) respectively, died. The charac-
tions and percentages of sex, birth period, and num- teristics were similar for male and females in the study
ber of deaths for patients with CHD and controls population (Table S3).
separately. For continuous variables, mean and me- Overall, the risk of mortality was 17.7 times higher for
dian with SD and interquartile range were reported. patients with CHD (95% CI, 16.8–18.6; P<0.001) than in
We used survival analysis techniques to compare matched controls (Table 2). All the lesion groups in pa-
patients with CHD and matched controls in terms of tients with CHD had increased mortality risk compared
mortality outcomes. Incidence rate was estimated as with matched controls. The highest relative risk of mor-
the number of deaths divided by total follow-up time tality was found in patients with non-conotruncal de-
and reported as per 10 000 person-years. We esti- fects (such as endocardial cushion defects, common
mated survival by means of the Kaplan–Meier esti- ventricle, and hypoplastic left heart syndrome) with an
mator; we compared patients with CHD with controls HR of 97.2 (95% CI, 80.4–117.4; P<0.001).
(both overall and within groups) from birth until the Overall survival probability in patients with CHD and
age of 18 years. We compared the survival curves matched controls appear in Figure S1. The survival
using non-parametric log-rank tests. We did not ad- curve in patients with CHD diverged within from the sur-
just for any confounders such as comorbidities be- vival curve for controls, mostly within the first 4 years
cause the follow-up of the study started at birth and of life when mortality was higher for patients with CHD.
there were no recorded comorbidities at that time. However, the survival curves continued to separate
Patients with CHD and matched controls that died more modestly until the age of 18 years (P<0.001).
The survival trends for patients with CHD and
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shortly after birth were accounted in the present

study; however, those who died the same date as matched controls according to birth period are shown
their date of birth, were given 1 day of follow-up. in Figure 1. Survival increased markedly in patients
Hazard ratios (HRs) and the associated 95% CIs with CHD that were born in the 1980s, 1990s, and
were calculated by means of the Cox proportional haz- 2000s. However, we did not observe any change in
ards model. We used 2-sided P values and considered survival in patients with CHD born in the 2010s com-
a P value of <0.05 as statistically significant. Statistical pared with such patients born in the 2000s: there was
analyses were conducted with SAS software (version practically identical survival (almost 97%) over the first
9.4; SAS institute, Cary, NC, USA) or R software (ver- years in the 2 birth cohorts. We did not find any sig-
sion 3.6.1; Free Software Foundation for Statistical nificant difference in the survival trends between male
Computing, Vienna, Austria). and female patients with CHD (Figure S2).

Table 1. Study Population Characteristics

Patients With Congenital Heart Disease Controls

Characteristics (n=64 396) (n=639 012)

Male, n (%) 32 334 (50.2) 323 340 (50.6)

Mean follow-up, y (SD) 11.4 (6.3) 12.2 (6.0)
Median follow-up, y (IQR) 12.5 (5.6–18.0) 13.7 (6.8–18.0)
Born in Sweden, n (%) 61 054 (94.8) 531 866 (83.2)
Deaths, n (%) 3845 (6.0) 2235 (0.3)
Birth period
Born 1980–1989, n (%) 9814 (15.2) 98 140 (15.4)
Born 1990–1999, n (%) 13 997 (21.7) 139 970 (21.9)
Born 2000–2009, n (%) 21 459 (33.3) 212 177 (33.2)
Born 2010–2017, n (%) 19 126 (29.7) 188 725 (29.5)

IQR indicates interquartile range.

J Am Heart Assoc. 2020;9:e017704. DOI: 10.1161/JAHA.120.0177043

 Mandalenakis et alSurvival in Children With Congenital Heart Diseas

Table 2. Mortality Risk in Patients With Congenital Heart Disease Compared With Matched Controls According to Lesion
Group

Categorical Hierarchy Deaths in Patients With CHD/All Patients Deaths in Controls/All Controls,
Group With CHD, n (%) n (%) HR (95%, CI)*

Lesion group 1 764/4593 (16.63) 171/45 710 (0.37) 48.8 (41.3–57.6)

Lesion group 2 972/3081 (31.55) 121/30 700 (0.39) 97.2 (80.4–117.4)
Lesion group 3 199/2773 (7.18) 112/27 610 (0.41) 18.4 (14.6–23.2)
Lesion group 4 525/21 649 (2.43) 690/214 296 (0.32) 7.6 (6.8–8.6)
Lesion group 5 271/13 376 (2.03) 398/132 561 (0.29) 6.8 (5.8–8.0)
Lesion group 6 1114/18 924 (5.87) 743/188 135 (0.39) 15.4 (14.0–16.9)
All groups 3845/64 396 (5.97) 2235/639 012 (0.35) 17.7 (16.8–18.6)

CHD indicates congenital heart disease; and HR, hazard ratio.

*All P<0.001

The risk of mortality according to birth period in Altogether, 23.2% (n=14 971) of patients with CHD
patients with CHD relative to that of controls appears underwent a cardiac intervention related to their CHD
in Table 3. In all birth periods, patients with CHD had between birth and the age of 18 years. Survival in-
higher risk of mortality than matched controls; that dif- creased in patients with CHD with and without cardiac
ference decreased over the birth period. Patients with intervention until the 2000s (Figure 2). However, in the
CHD born in the 1980s had the highest relative mortal- past decade, no further improvement in survival ap-
ity: HR, 29.0; 95% CI, 26.2 to 31.9; P<0.001. However, peared in patients with CHD who had undergone at
the risk was similar in patients with CHD born during least 1 cardiac intervention: the mortality was up to
the 2000s and 2010s: HR, 10.7 (95% CI, 9.6–11.9; 4.5% at the age of 7 years.
P<0.001) and HR, 11.4 (95% CI, 10.0–13.0; P<0.001) Survival showed a significant improvement in patients
respectively. with CHD who were born between the 1980s and 2010s,
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Figure 1. Kaplan–Meier survival curves of patients with congenital heart disease and matched controls according to birth period.
CHD indicates congenital heart disease.

J Am Heart Assoc. 2020;9:e017704. DOI: 10.1161/JAHA.120.0177044

 Mandalenakis et alSurvival in Children With Congenital Heart Diseas

Table 3. Risk of All-Cause Mortality in Patients With Congenital Heart Disease Compared With Matched Controls
According to Birth Period and Sex

Deaths in Patients With CHD, No./All Patients Deaths in Controls, No./All

Birth Period With CHD, n (%) Controls, n (%) HR (95%, CI)*

Birth period
Born 1980–1989 1452/9814 (14.80) 542/98 140 (0.55) 29.0 (26.2–32.0)
Born 1990–1999 1248/13 997 (8.92) 647/139 970 (0.46) 20.2 (18.4–22.2)
Born 2000–2009 688/21 459 (3.21) 646/212 177 (0.30) 10.7 (9.6–11.9)
Born 2010–2017 457/19 126 (2.39) 400/188 725 (0.22) 11.4 (10.0–13.0)
Sex
Male 2026/32 334 (6.27) 1276/323 340 (0.39) 16.4 (15.3–17.6)
Female 1819/32 062 (5.67) 958/315 672 (0.30) 19.3 (17.9–20.9)

CHD indicates congenital heart disease; and HR, hazard ratio.

*All P<0.001

particularly in those with complex congenital malforma- and by birth period (Table S4). The highest mortality
tions (Figure S3). Among complex lesion groups, survival was found during the first 4 years of life in patients with
improved from about 70% and 50%, respectively, at the CHD born in the 1980s (HR, 34.3, 95% CI, 30.7–38.3,
age of 18 years to >90% in lesion group 1 and >80% in P<0.001); however, the HRs decreased by two thirds in
lesion group 2; the latter included highly complex condi- the most recent birth period cohort (2010–2017).
tions such as hypoplastic left heart syndrome. However, A sensitivity analysis was performed after exclud-
survival was stable and similar in all lesion groups after ing individuals that were not born in Sweden and the
the millennium: no further improvement was evident. overall risk of mortality in patients with CHD born in
The risk of mortality in patients with CHD, compared Sweden was 15.7 times higher (95% CI, 14.9–16.5)
with controls, declined dramatically with increasing age compared with matched controls.
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Figure 2. Kaplan–Meier survival curves of patients with congenital heart disease with or without a cardiac intervention
according to birth period.

J Am Heart Assoc. 2020;9:e017704. DOI: 10.1161/JAHA.120.0177045

 Mandalenakis et alSurvival in Children With Congenital Heart Diseas

and detection can be translated into a better sur-

DISCUSSION vival, on a national level, is still unclear. Variations in
In Sweden, survival among pediatric patients with CHD the rate of antenatal screening have not been tied
has increased dramatically since the 1980s; currently, to variations in outcome for children with CHD and
>97% can be expected to reach adulthood. However, improvements in general in outcome because of an-
no further improvement in survivorship was observed tenatal screening remains unproven.43,44
in children with CHD over the past decade. Although Mortality has declined for patients with CHD who
declining, mortality remains comparatively high in rela- underwent cardiac intervention (surgical or catheter
tive as well as absolute terms with the most complex intervention) from the early (1980–1989) to the latest
conditions and during the first years of life: the mortal- era (2010–2017); despite the introduction and expan-
ity in patients with complex CHD lesions born 1980s sion of complicated and high-risk procedures, such
and 2000s decreased from almost 50% to <20%, re- as Fontan palliation for univentricular heart defects
spectively, at the age of 18 years. and Norwood surgery for hypoplastic left heart syn-
We observed an increase in the number of patients drome during this period. This strongly implies that
with CHD over time which is explained by population improved therapy was an important explanation
growth. This may in part be explained by increased diag- for the improved survival seen in the entire popula-
nosis of less severe CHD cases. However, also among tion. However, we have also observed that mortal-
complex CHD we observed no further improvement in ity among children who did not undergo a cardiac
prognosis in recent years (Figure S3). This is also re- intervention decreased over time. This may reflect
flected in the comparatively stable level of interventions. improved selection of patients with CHD for car-
Numerous studies have reported outcomes with diovascular surgery or catheter interventions; but it
particular diagnostic groups for post-surgical re- may, also reflect improved diagnostic techniques,
sults.22,23,33–35 However, our study is the first nation- especially on echocardiography, for example an in-
wide report to cover recent trends and examine an creased rate of diagnosis of less complex congenital
unselected, broad, representative population of chil- heart malformations such as mild shunts.1
dren with CHD (including matched controls), including During the last study period cohort (2010–2017),
patients where no cardiac interventions took place. we observed a worse outcome among children with
The use of antenatal screening for CHD diagno- CHD who underwent a cardiac intervention, different
sis have increased over the past decade36,37; though from results from earlier birth periods. This most likely
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feasible, it is not clear whether the use of antenatal reflects an increase in detection of mild conditions of
CHD diagnosis leads to improved care or survival. CHD where no intervention is needed, and the condi-
There are several reports indicating that in some tion has little if any impact on the health of the child. It
countries including Sweden, increasing prenatal di- may also reflect a further improvement in interventional
agnosis of highly complex malformations such as techniques with CHD children with extremely high risk
hypoplastic left heart syndrome will lead to more fre- undergoing reparative or palliative procedures. This
quent terminations of pregnancy and fewer live born is further supported by results from patients with the
children with this condition.38,39 Prenatal screening most complex CHD groups, such as the lesion group
currently detects almost 40% of fetuses with major 1 and lesion group 2, doing better until the turn of
CHD in Sweden. However, that trend does not ap- the millennium, after which no further improvement
pear to translate into increased survival—at least not is observed. Sweden’s 6 cardiothoracic surgery clin-
on a national level. Improved detection rates, particu- ics have registered all hospitalizations and interven-
larly with major CHD, lead to increased rates of preg- tions since 1970. Swedish hospital records have been
nancy termination, with a subsequent decrease in the mandatory since 1987, based on each individual in
incidence of the most severe complex CHD.38,40,41 the country having a unique 10-digit personal identity
Also in Sweden, data indicate that increased ante- number, which includes their sex and date of birth.
natal CHD diagnosis leads to more pregnancy ter- Administrative health databases have become a pow-
minations, with little—if any—effect on the overall erful resource for studying several medical conditions;
survivorship in children born with CHD.39 Live births they are valuable owing to the large sample sizes and
with the most complex CHD may have become less possibility of long observation periods. The strength of
frequent; however, other moderately complex con- the present report is that it is a nationwide study based
genital heart conditions, related to increasing mater- on the Swedish healthcare system, which is mainly
nal age and obesity, may increase.42 In the present government funded, universal, and offers free access
study, we did not observe any further improvement in to all citizens. The current data are representative for
survivorship after the new millennium in children with Sweden but may be less applicable to other countries
CHD in general–particularly in those with complex with different access to and organization and financing
CHD. Whether a higher rate of antenatal screening of the healthcare system. Our data may be considered

J Am Heart Assoc. 2020;9:e017704. DOI: 10.1161/JAHA.120.0177046

 Mandalenakis et alSurvival in Children With Congenital Heart Diseas

as support for regionalization and centralization of the the dramatic improvement in congenital heart care over
care of the complex congenital heart conditions.45 By the last decades of the 19th century, even further.
using national registers, we were able to achieve al- Furthermore, our results point to the obvious need
most complete follow-up, with limited risk because of for more cardiologists, nurses, physiotherapist to de-
emigration as a possible cause of the loss to follow-up. velop skills and knowledge of how to care for adults
One of the study’s limitations is that administrative with CHD, since they are increasing in number and will
data from Swedish outpatient clinics before 2001 and continue to do so in the future.
data for primary care were unavailable. Thus, they In summary, our study shows that survival among
were not included in this study: that could have led patients with CHD has improved dramatically in the past
to an underestimation of the mortality of patients with 40 years. Over the past decade, no further improvement
less severe lesions that were not detected at birth or has been observed, and survivorship in children with
detected during follow-up at outpatient clinics or by CHD has been at about 97% since the beginning of this
primary care physicians. Another limitation is that century. Despite these trends, the most complex con-
there have been no published formal validations of ditions are still characterized by a high early mortality.
CHD diagnostic codes in the Swedish registry sys- For patients with less complex conditions, focusing on
tem; however, several cardiovascular and other med- lifetime management and preventing acquired diseases
ical conditions or interventions have been shown to may be the key to future improvement.
have high validity.46,47 The limited number of variables
available for analysis may also limit the assertation of
both cases and causes of death. One should also ac-
knowledge that our results may be less valid in a dif- ARTICLE INFORMATION
ferent healthcare setting with less centralization and Received June 9, 2020; accepted September 29, 2020.

different access to care, different rate of antenatal di- Affiliations

agnosis as well as differences in public opinion and From the Department of Molecular and Clinical Medicine, Institute of Medicine
regulations on termination of pregnancy. The classi- (Z.M., K.W.G., P.E., M.F., A.R., M.D.) and Department of Paediatrics, Institute
of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg,
fication and grouping of CHD into larger groups such Sweden (H.L., M.S., H.W.).
as the 6 lesion groups used in the present study will
by definition group together conditions that may have Sources of Funding
This work was funded by the Swedish state under an agreement between
had different evolution over the last decades. Our data
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the Swedish Government and County Councils (the Avtal om Läkarutbildning

may be an example of Simpson paradox i.e., that while och Forskning agreement, Grant Number: 236611), the Swedish Heart-Lung
prognosis improves for some of the CHD conditions Foundation (Grant Number: 20090724), and the Swedish Research Council
(2019-00193 SIMSAM).
included in e.g., lesion group 1, other conditions in the
same group may have changed in a different direction. Disclosures
Dividing, congenital cardiac malformations into smaller None.
or more distinct groups may provide further insights Supplementary Material
but at the cost of statistical power. Tables S1–S4
The significant improvements made in cardiovas- Figures S1–S3
cular care since the 1970s and 1980s have resulted
in a dramatic improvement in survival for children with
CHD. Further advances in the past 2 decades have not
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J Am Heart Assoc. 2020;9:e017704. DOI: 10.1161/JAHA.120.0177048

SUPPLEMENTAL MATERIAL
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 Table S1. Diagnosis of congenital heart disease according to the International
Statistical Classification of Diseases and Related Health Problems .

Diagnosis ICD 8 ICD 9 ICD 10

Common arterial trunk 746,09 745A Q200

Transposition of the great vessels 746,19 745B Q203

Tetralogy of Fallot 746,29 745C Q213

Ventricular septal defect 746,39 745E Q210

Atrial septal defect or patent foramen ovale 746,42 745F Q211

Congenital tricuspid stenosis or atresia 746,54 746B Q224

Ebstein’s anomaly 746,54 746C Q225

Congenital stenosis of the aortic valve 746,73 746D Q230

Congenital insufficiency of the aortic valve 746,79 746E Q231

Congenital mitral stenosis 746,59 746F Q232

Congenital mitral insufficiency 746,59 746G Q233

Hypoplastic left heart syndrome 746,74 746H Q234

Congenital subaortic stenosis 746,79 746W Q244

Cor triatriatum 746,89 746W Q242

Infundibular pulmonic stenosis 746,63 746W Q243

Congenital coronary vessel anomalies 747,69 746W Q245

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Congenital heart block 746,89 746W Q246

Coarctation of the aorta 747,19 747B Q251

Interruption of the aortic arch 747,19 747B Q252

Q253

Other unspecified congenital malformations of the aorta 747,29 747C Q254

Q258
Q259

Congenital malformations of the pulmonary artery 747,34 747D Q255

747,39 Q256
Q257

Congenital malformations of the great veins 747,49 747E Q260

747,59 Q261
Q262
Q263
Q264

Cor biloculare 746,89 745H Q208

Double outlet right ventricle 746,19 745B Q201

Double outlet left ventricle 746,19 745B Q202

Double inlet ventricle 746,37 745D Q204

Discordant atrioventricular connection 746,19 745B Q205

Isomerism of atrial appendages 746,89 745W Q206

 Unspecified congenital malformations of the cardiac chambers 746,89 746X Q208
Q209

Atrioventricular septal defect 746,47 745G Q212

746,46
746,43

Aortopulmonary septum defect 746,09 745A Q214

Other congenital malformations of the cardiac septum 746,89 745W Q218

Unspecified congenital malformations of the cardiac septum 746,99 745X Q219

Pulmonary valve atresia 746,64 746A Q220

Congenital stenosis of the pulmonary valve 746,63 746A Q221

Congenital pulmonary valve insufficiency 746,69 746A Q222

Other congenital malformations of the pulmonary valve 746,69 746A Q223

Hypoplastic right heart syndrome 746,69 746B Q226

Other congenital malformations of the tricuspid valve 746,54 746B Q228

Q229

Other congenital malformations of aortic and mitral valves 746,89 746W Q238
Q239

Other specified congenital malformations of the heart 746,89 746W Q248

Unspecified congenital malformations of the heart 746,99 746X Q249

Patent ductus arteriosus 747,09 747A Q250

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 Table S2. Hierarchic classification of congenital heart disease according to the
International Statistical Classification of Diseases and Related Health Problems.

Categorical hierarchy group CHD diagnosis ICD-8 ICD-9 ICD-10

Lesion group 1. Conotruncal Common arterial trunk 746.09 745A Q200

defects
Aortopulmonary septum defect 746.09 745A Q214

Double outlet right ventricle 746.19 745B Q201

Double outlet left ventricle 746.19 745B Q202

Transposition of great vessels 746.19 745B Q203

Discordant atrioventricular connection 746.19 745B Q205

(ccTGA)

Tetralogy of Fallot 746.29 745C Q213

Lesion group 2. Severe non- Endocardial cushion defects 746.43, 745G Q212
conotruncal defects 746.46,
746.47

Common ventricle 746.37 745D Q204

Hypoplastic left heart syndrome 746.74 746H Q234

Lesion group 3. Coartation of the Coarctation of the aorta 747.19 747B Q251
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aorta
Lesion group 4. Ventricular Ventricular septal defect 746.39 745E Q210
septal defect

Lesion group 5. Atrial septal Atrial septal defect 746.42 745F Q211
defect

Lesion group 6. Other heart and All other congenital heart disease diagnoses that are not included in the above five lesion groups
circulatory system anomalies

ccTGA, congenitally corrected transposition of the great arteries

 Table S3. Characteristics of the study population according to sex.

Characteristics Patients with congenital heart disease Controls

Men Women Men Women

no. (%) 32,334 (50.2) 32,062 (49.8) 323,340 (50.6) 315,672 (49.4)
Mean follow-up, years (SD) 11.4 (6.4) 11.3 (6.3) 12.2 (6.0) 12.1 (5.9)

Median follow-up, years (IQR) 12.5 (5.6–18.0) 12.5 (5.7–18.0) 13.8 (6.8–18.0) 13.6 (6.8–18.0)

Born in Sweden, no. (%) 30,734 (95.1) 30,320 (94.6) 268,221 (83.0) 263,645 (83.5)

Birth Period

Born 1980–1989, no. (%) 5,001 (15.5) 4,813 (15.0) 50,010 (15.5) 48,130 (15.2)

Born 1990–1999, no. (%) 7,266 (22.5) 6,731 (21.0) 72,660 (22.5) 67,310 (21.3)

Born 2000–2009, no. (%) 10,610 (32.8) 10,855 (33.9) 106,040 (32.8) 106,137 (33.6)

Born 2010–2017, no. (%) 9,463 (29.3) 9,663 (30.1) 94,630 (29.3) 94,095 (29.8)
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SD, standard deviation; IQR, interquartile range

 Table S4. Risk of all-cause mortality in patients with congenital heart disease
compared to matched controls according to birth period and age.

Birth period and age No. of deaths in CHD Incidence rate of death in HR (95%, CI) †
patients / Controls CHD patients / Controls *

Born 1980–1989

0 – 4 year 1,314 / 409 303.36 / 8.38 34.3 (30.7–38.3)

5 – 9 year 66 / 40 15. 59 / 0.82 19.04 (12.9–28.2)

10 – 14 year 42 / 35 9.99 / 0.71 13.9 (8.9–21.8)

15 – 18 year 30 / 58 11.94 / 1.95 6.1 (3.9–9.5)

Born 1990–1999

0 – 4 year 1,118 / 489 172.20 / 7.02 23.7 (21.4–26.4)

5 – 9 year 48 / 54 7.62 / 0.76 10.0 (6.8–14.8)

10 – 14 year 47 / 43 7.34 / 0.63 11.6 (7.7–17.5)

15 – 18 year 35 / 61 9.14 / 1.46 6.3 (4.1–9.5)

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Born 2000–2009

0 – 4 year 627 / 541 60.05 / 5.12 11.6 (10.3–13.0)

5 – 9 year 33 / 56 3.29 / 0.55 6.0 (3.9–9.2)

10 – 14 year 26 / 35 4.79 / 0.63 7.6 (4.6–12.7)

15 – 18 year 2 / 14 2.61 / 1.74 NA

Born 2010–2017

0 – 4 year 450 / 389 66.18 / 5.69 11.5 (10.1–13.2)

5 – 9 year 7 / 11 5.77 / 0.90 6.4 (2.5–16.5)

10 – 14 year -/- -/- NA

15 – 18 year -/- -/- NA

CHD, congenital heart disease; HR, hazard ratio; CI, confidence interval
*Incidence rate per 10,000 person-years
†All P <0.001
 Figure S1. Kaplan-Meier survival curves of the study population.
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 Figure S2. Kaplan-Meier survival curves of the patients with congenital heart disease
and matched controls according birth period and sex.
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 Figure S3. Kaplan-Meier survival curves of the patients with congenital heart disease
and matched controls according to lesion group and birth period.
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Lesion group 1 was defined as patients with conotruncal defects (such as common arterial trunk, transposition of the great vessels, double-
outlet right ventricle, double-outlet left ventricle, discordant atrioventricular connection, tetralogy of Fallot, and aortopulmonary septal
defect). Lesion group 2 was defined as patients with non-conotruncal defects (such as endocardial cushion defects, common ventricle, and
hypoplastic left heart syndrome). Lesion group 3 was defined as patients with coarctation of the aorta. Lesion group 4 was defined as patients
with ventricular septal defect. Lesion group 5 was defined as patients with atrial septal defect. Lesion group 6 included all other heart and
circulatory system anomalies and all other CHD diagnoses not included in lesion groups 1–5.