OBJECTIVE

Congenital heart disease (CHD) is a leading cause of premature death in infants and children. Currently limited data are available regarding lesion specific mortality over time. Our study aimed to describe pediatric mortality trends by CHD lesion in the United States.

METHODS

We conducted a 19 year analysis (1999 to 2017) of publicly available, deidentified multiple cause of death data compiled and produced by the National Center for Health Statistics. Analysis was stratified by CHD diagnosis and age using 3 age categories (infants, 1 to 4 years, and 5 to 17 years). Temporal trends of CHD mortality and the effect of contributing risk factors were analyzed by using joinpoint regression.

RESULTS

Mortality was highest for in infants for all CHD lesions, in particular for total anomalous pulmonary venous return. Significant declines in infant CHD mortality occurred for most other lesions. Contributing risk factors, including prematurity, extracardiac birth defects, and genetic conditions, occurred in 19% of infant CHD deaths and demonstrated worse mortality trends in the majority of lesions. Mortality rates remained highest for single ventricle lesions in all ages, with an infant mortality rate plateau in the later half of the study and progressive increasing mortality rates for children 5 to 17 years.

CONCLUSIONS

CHD mortality is decreasing for most lesions. Because of the heterogenicity of CHD lesions, there is expected variability in mortality trends by lesion and age group. Single ventricle lesions continue to contribute most heavily to premature death because of CHD demonstrated by significant increases in mortality rate for children aged 5 to 17 years.

What’s Known on this Subject:

Inpatient databases and single center studies suggest improved survival in children with congenital heart disease, even for the most severe cardiac lesions.

What This Study Adds:

This study provides a modern era population-based examination of national US temporal trends in congenital heart disease specific lesion mortality for infants and children. Our data highlight the population heterogenicity and continued premature death of patients with single ventricle physiology.

Congenital heart disease (CHD) affects as many as 40 000 births per year in the United States and, historically, contributed to a significant proportion of infant mortality across the globe.1,2  As surgical techniques, perioperative care, and long-term CHD management improved, more recent studies demonstrate improvement in mortality for CHD patients. A Canadian group reported a 30% decrease in all-cause mortality among CHD patients between 1987 to 2005.3  Lopez et al demonstrated declining trends in overall United States CHD-attributed mortality (39%) but noted persistent racial and ethnic disparities in mortality trends.4 

Although the trend in overall mortality has been well-corroborated, CHD is a highly heterogeneous group that includes simple lesions with lower need for early interventions, as well as more complex defects necessitating intensive medical and surgical management from birth. A recent national report demonstrated improvement in mortality trends for most CHD lesions in US adults.5  Current United States population-based CHD lesion specific mortality data for infants and children are very limited. Published lesion specific mortality data are often single-center, based on in-hospital mortality data, or on a single age group. A regional United States study from the Metropolitan Atlanta Congenital Defects Program reported significant improvement in 1 year mortality for infants with several different critical congenital heart lesions.6  A national inpatient database study evaluating neonates with hypoplastic left heart syndrome (HLHS) demonstrated a 20% decrease in mortality comparing 1998 to 2005 to 2006 to 2014.7  Small, single center studies demonstrated decreased mortality over time in cases of transposition of the great arteries (TGA) and tetralogy of Fallot (TOF).8,9  Our study aims to describe national childhood mortality trends from 0 to 17 years of age by specific CHD lesion in the United States from 1999 to 2017.

As we did in our previous work on adult CHD mortality trends, we conducted a United States population-based CHD mortality study of infants and children, ages 0 to 17 years from 1999 to 2017. The study sample was obtained using deidentified multiple cause of death (MCOD) data files compiled and produced by the National Center for Health Statistics at the Centers for Disease Control and Prevention.10  MCOD files are publicly available, and our study was deemed exempt by the Baylor College of Medicine institutional review board. MCOD files originate from death certificates filed by registries in all 50 states and the District of Columbia and contain a single underlying cause of death (UCOD) and up to 20 contributing causes of death for each decedent. International Classification of Diseases, Tenth Revision (ICD-10) codes were used to classify all UCOD and contributed causes of death in the MCOD data set. The MCOD data set excludes deaths among non- United States residents, United States nationals living abroad, residents of United States territories, and fetal deaths. We classified subjects based on age (infants, 1 to 4 years of age and 5 to 17 years of age) and CHD diagnosis. CHD mortality was defined as decedent with UCOD containing an ICD-10 code indicative of a CHD lesion (Q20–Q26 range) (Supplemental Table 5). For further analysis of single ventricle (SV) mortality, we created an SV composite comprising HLHS, tricuspid atresia, and double inlet left ventricle. For consistency with previously published MCOD data, multiple CHD diagnoses were grouped together under “Other Specified CHD” for analysis (Supplemental Table 5). We performed a subanalysis of CHD deaths listed as the UCOD by excluding known risk factors to early mortality including prematurity, extracardiac birth defects, and genetic conditions listed as a contributing cause of death.

Population estimates were used as denominators in the calculation of mortality rates for decedents <1 year of age on the basis of live birth data downloaded from the National Center for Health Statistics.11  For decedents 1 year of age and older, the population estimates used as denominators in the calculation of mortality rates were estimates from the US Census Bureau.12  Age-specific mortality rates were then calculated and assessed for specific CHD lesions. Rates were calculated as the number of deaths per 100 000 live births for infants <1 year or per 100 000 population for ages ≥1 year.

We analyzed temporal trends in mortality rates for overall CHD and specific CHD lesions in each age group using joinpoint regression. Joinpoint regression takes the CHD mortality rates and assumes a single trend (ie, a straight line) and tests if there are significant changes in trends over time, called joinpoints.13  Monte Carlo Permutation method is used to test significance of the changes in trend and inclusion of joinpoints in the model.13  The final model provides the annual percent change (APC) and its associated 95% confidence interval, which estimates how mortality changes between each joinpoint.13  Joinpoint also provides an average annual percent change (AAPC), which is a valid estimate based on a weighted average of the APCs during the total 19-year study period.13 

All statistical analysis were performed with SAS version 9.4 (Cary, NC) and Joinpoint Regression Program version 4.9.0.0.13 

Infants demonstrated the highest CHD-related mortality for every lesion when compared to the other age groups. Of the 495 917 infant deaths during the study period, 27 962 deaths (5.6%) had CHD listed as the underlying cause of death, and 14 854 deaths (3.0%) had CHD listed as a contributing cause of death (Table 1). High-risk conditions including prematurity, extracardiac birth defects, and genetic conditions were common among primary CHD infant deaths. Overall, ∼19% of CHD-related infant deaths had at least 1 of these conditions documented as another contributing cause. Over 30% of the deaths attributed to atrioventricular septal defect (AVSD), ventricular septal defect (VSD), and TOF had at least 1 of these factors listed as a contributing cause of death.

TABLE 1

Number of Deaths and Mortality Rates for Infants, Children, and Adolescents Stratified by Age of Death and Diagnosis from 1999 to 2017

Age of Death
<1 Year1–4 Year5–17 Year
DiagnosisnRateanRatebnRateb
All diagnosis 495 917 643.09 85 781 24.48 220 829 21.67 
 Prematurity listed as primary or contributing cause of death 2634 3.42 58 0.02 0.00 
 Extracardiac birth defect listed as primary or contributing cause of death 13 534 17.55 1211 0.40 649 0.06 
 Genetic condition listed as primary or contributing cause of death 6699 8.69 603 0.20 326 0.03 
All CHD       
 Any CHD listed as a contributing cause of death 14 854 19.26 1295 0.43 972 0.10 
 Any CHD listed as UCOD 27 962 36.26 3696 1.23 3494 0.34 
 Any CHD listed as UCOD with contributing prematurity, extracardiac birth defects, or genetic conditions 5265 6.83 N/A N/A N/A N/A 
 Any CHD listed as UCOD with contributing extracardiac birth defects or genetic conditions N/A N/A 485 0.16 251 0.02 
 Any CHD listed as UCOD excluding prematurity 26 369 34.19 N/A N/A N/A N/A 
 Any CHD listed as UCOD excluding extracardiac defects or genetic conditions 24 025 31.15 3211 1.07 3243 0.32 
 Any CHD listed as UCOD excluding prematurity, extracardiac birth defects, or genetic conditions 22 697 29.43 3211 1.07 3243 0.32 
By lesion listed as the underlying cause of death 
Aortic valve stenosis
Including contributing risk factors
Excluding contributing risk factors 

449
402 

0.58
0.52 

20
20 

0.01
0.01 

52
51 

0.01
0.01 
Atrial septal defect
Including contributing risk factors
Excluding contributing risk factors 

332
259 

0.43
0.34 

53
42 

0.02
0.01 

62
55 

0.01
0.01 
Atrioventricular septal defect
Including contributing risk factors
Excluding contributing risk factors 

606
404 

0.79
0.52 

126
82 

0.04
0.03 

55
41 

0.01
0.00 
Coarctation
Including contributing risk factors
Excluding contributing risk factors 

504
371 

0.65
0.48 

22
20 

0.01
0.01 

40
38 

0.00
0.00 
Double outlet right ventricle
Including contributing risk factors
Excluding contributing risk factors 

385
275 

0.50
0.36 

57
52 

0.02
0.02 

50
47 

0.00
0.00 
Ebstein anomaly
Including contributing risk factors
Excluding contributing risk factors 

485
392 

0.63
0.51 

23
22 

0.01
0.01 

52
49 

0.01
0.00 
Hypoplastic left heart syndrome
Including contributing risk factors
Excluding contributing risk factors 

5626
4940 

7.30
6.41 

520
502 

0.17
0.17 

279
273 

0.03
0.03 
Other specified CHD
Including contributing risk factors
Excluding contributing risk factors 

2311
1880 

3.00
2.44 

326
287 

0.11
0.10 

758
721 

0.07
0.07 
Patent ductus arteriosus
Including contributing risk factors
Excluding contributing risk factors 

879
707 

1.13
0.92 

11

0.00
0.00 

13
13 

0.00
0.00 
Pulmonary artery atresia or stenosis
Including contributing risk factors
Excluding contributing risk factors 

855
689 

1.11
0.89 

169
150 

0.06
0.05 

79
71 

0.01
0.01 
Pulmonary valve abnormalities
Including contributing risk factors
Excluding contributing risk factors 

128
99 

0.17
0.13 

9

0.00
0.00 

4

0.00
0.00 
Single ventricle composite
Including contributing risk factors
Excluding contributing risk factors 

6051
5289 

7.85
6.86 

612
581 

0.20
0.19 

375
364 

0.04
0.04 
Tetralogy of Fallot
Including contributing risk factors
Excluding contributing risk factors 

1176
806 

1.53
1.05 

264
215 

0.09
0.07 

232
196 

0.02
0.02 
Total anomalous pulmonary venous return
Including contributing risk factors
Excluding contributing risk factors 

329
289 

0.43
0.37 

12
11 

0.00
0.00 

2

0.00
0.00 
Transposition of the great arteries
Including contributing risk factors
Excluding contributing risk factors 

1243
1039 

1.16
1.35 

132
125 

0.04
0.04 

150
147 

0.01
0.01 
Tricuspid valve stenosis
Including contributing risk factors
Excluding contributing risk factors 

165
136 

0.21
0.18 

31
29 

0.01
0.01 

39
38 

0.00
0.00 
Truncus arteriosus
Including contributing risk factors
Excluding contributing risk factors 

619
452 

0.80
0.59 

31
25 

0.01
0.01 

48
45 

0.00
0.00 
Unspecified CHD
Including contributing risk factors
Excluding contributing risk factors 

11 134
8977 

14.44
11.64 

1778
1541 

0.59
0.51 

1472
1361 

0.14
0.13 
Ventricular septal defect
Including contributing risk factors
Excluding contributing risk factors 

592
403 

0.77
0.52 

87
59 

0.03
0.02 

92
79 

0.01
0.01 
Age of Death
<1 Year1–4 Year5–17 Year
DiagnosisnRateanRatebnRateb
All diagnosis 495 917 643.09 85 781 24.48 220 829 21.67 
 Prematurity listed as primary or contributing cause of death 2634 3.42 58 0.02 0.00 
 Extracardiac birth defect listed as primary or contributing cause of death 13 534 17.55 1211 0.40 649 0.06 
 Genetic condition listed as primary or contributing cause of death 6699 8.69 603 0.20 326 0.03 
All CHD       
 Any CHD listed as a contributing cause of death 14 854 19.26 1295 0.43 972 0.10 
 Any CHD listed as UCOD 27 962 36.26 3696 1.23 3494 0.34 
 Any CHD listed as UCOD with contributing prematurity, extracardiac birth defects, or genetic conditions 5265 6.83 N/A N/A N/A N/A 
 Any CHD listed as UCOD with contributing extracardiac birth defects or genetic conditions N/A N/A 485 0.16 251 0.02 
 Any CHD listed as UCOD excluding prematurity 26 369 34.19 N/A N/A N/A N/A 
 Any CHD listed as UCOD excluding extracardiac defects or genetic conditions 24 025 31.15 3211 1.07 3243 0.32 
 Any CHD listed as UCOD excluding prematurity, extracardiac birth defects, or genetic conditions 22 697 29.43 3211 1.07 3243 0.32 
By lesion listed as the underlying cause of death 
Aortic valve stenosis
Including contributing risk factors
Excluding contributing risk factors 

449
402 

0.58
0.52 

20
20 

0.01
0.01 

52
51 

0.01
0.01 
Atrial septal defect
Including contributing risk factors
Excluding contributing risk factors 

332
259 

0.43
0.34 

53
42 

0.02
0.01 

62
55 

0.01
0.01 
Atrioventricular septal defect
Including contributing risk factors
Excluding contributing risk factors 

606
404 

0.79
0.52 

126
82 

0.04
0.03 

55
41 

0.01
0.00 
Coarctation
Including contributing risk factors
Excluding contributing risk factors 

504
371 

0.65
0.48 

22
20 

0.01
0.01 

40
38 

0.00
0.00 
Double outlet right ventricle
Including contributing risk factors
Excluding contributing risk factors 

385
275 

0.50
0.36 

57
52 

0.02
0.02 

50
47 

0.00
0.00 
Ebstein anomaly
Including contributing risk factors
Excluding contributing risk factors 

485
392 

0.63
0.51 

23
22 

0.01
0.01 

52
49 

0.01
0.00 
Hypoplastic left heart syndrome
Including contributing risk factors
Excluding contributing risk factors 

5626
4940 

7.30
6.41 

520
502 

0.17
0.17 

279
273 

0.03
0.03 
Other specified CHD
Including contributing risk factors
Excluding contributing risk factors 

2311
1880 

3.00
2.44 

326
287 

0.11
0.10 

758
721 

0.07
0.07 
Patent ductus arteriosus
Including contributing risk factors
Excluding contributing risk factors 

879
707 

1.13
0.92 

11

0.00
0.00 

13
13 

0.00
0.00 
Pulmonary artery atresia or stenosis
Including contributing risk factors
Excluding contributing risk factors 

855
689 

1.11
0.89 

169
150 

0.06
0.05 

79
71 

0.01
0.01 
Pulmonary valve abnormalities
Including contributing risk factors
Excluding contributing risk factors 

128
99 

0.17
0.13 

9

0.00
0.00 

4

0.00
0.00 
Single ventricle composite
Including contributing risk factors
Excluding contributing risk factors 

6051
5289 

7.85
6.86 

612
581 

0.20
0.19 

375
364 

0.04
0.04 
Tetralogy of Fallot
Including contributing risk factors
Excluding contributing risk factors 

1176
806 

1.53
1.05 

264
215 

0.09
0.07 

232
196 

0.02
0.02 
Total anomalous pulmonary venous return
Including contributing risk factors
Excluding contributing risk factors 

329
289 

0.43
0.37 

12
11 

0.00
0.00 

2

0.00
0.00 
Transposition of the great arteries
Including contributing risk factors
Excluding contributing risk factors 

1243
1039 

1.16
1.35 

132
125 

0.04
0.04 

150
147 

0.01
0.01 
Tricuspid valve stenosis
Including contributing risk factors
Excluding contributing risk factors 

165
136 

0.21
0.18 

31
29 

0.01
0.01 

39
38 

0.00
0.00 
Truncus arteriosus
Including contributing risk factors
Excluding contributing risk factors 

619
452 

0.80
0.59 

31
25 

0.01
0.01 

48
45 

0.00
0.00 
Unspecified CHD
Including contributing risk factors
Excluding contributing risk factors 

11 134
8977 

14.44
11.64 

1778
1541 

0.59
0.51 

1472
1361 

0.14
0.13 
Ventricular septal defect
Including contributing risk factors
Excluding contributing risk factors 

592
403 

0.77
0.52 

87
59 

0.03
0.02 

92
79 

0.01
0.01 

Contributing risk factors include prematurity, extracardiac birth defects, and/or genetic conditions listed as a contributing cause of death. N/A, not available.

a

Infant mortality rate calculated per 100 000 live births

b

Mortality rates for decedents >1 y of age calculated per 100 000 population of that age

The SV composite group accounted for the highest mortality rates for infants among specific CHD lesions at 7.85 per 100 000 live births (n = 6051) attributed to HLHS and 7.30 per 100 000 live births (n = 5626) attributed to the SV composite over the 19-year study period (Table 1). HLHS made up 93% of all SV deaths, and the SV composite deaths accounted for 23% of infant CHD deaths.

When evaluating temporal trends, almost all lesions had improvement in mortality trends if decedents with contributing risk factors were excluded (Fig 1, Table 2). The exceptions to this finding include Ebstein anomaly, patent ductus arteriosus, and total anomalous pulmonary venous return (TAPVR), which had better or no change in trends if infants with contributing risk factors were included (Fig 1, Table 2). TAPVR was the only lesion that had persistent increases in mortality throughout the study period with an AAPC 5.7% irrespective of inclusion or exclusion of contributing risk factors (Fig 1, Table 2). Truncus arteriosus had the largest discrepancy in mortality trend with an AAPC of -1.9% (P = .259) compared to -4.0% (<0.001) if contributing risk factors were excluded (Table 1, Table 2). SV Composite and HLHS mortality trend had significant declines for the first half of the study period followed by plateauing of trend regardless if contributing factors were included or excluded (Fig 2, Table 2). AVSD, double outlet right ventricle, patent ductus arteriosus, pulmonary valve abnormalities mortality had no significant trends in mortality throughout the study period (Table 2). The remaining lesions had significant AAPCs (Table 2).

FIGURE 1

Joinpoint infant mortality for different congenital heart disease lesions from 1999 to 2017. Specific congenital heart disease temporal mortality. The black line represents the APC of lesions including contributing risk factors. The blue line represents the APC of lesions excluding contributing risk factors. Contributing risk factors include prematurity, extracardiac birth defects, and/or genetic conditions listed as a contributing cause of death.

FIGURE 1

Joinpoint infant mortality for different congenital heart disease lesions from 1999 to 2017. Specific congenital heart disease temporal mortality. The black line represents the APC of lesions including contributing risk factors. The blue line represents the APC of lesions excluding contributing risk factors. Contributing risk factors include prematurity, extracardiac birth defects, and/or genetic conditions listed as a contributing cause of death.

Close modal
FIGURE 2

Joinpoint single ventricle mortality from 1999 to 2017. Single ventricle temporal mortality stratified by age group. Infant mortality rate calculated per 100 000 live births. Mortality rates for decedents >1 year of age calculated per 100 000 persons on the basis of the population of that age. The black line represents the APC of lesions including contributing risk factors. The blue line represents the APC of lesions excluding contributing risk factors. Contributing risk factors include prematurity, extracardiac birth defects, and/or genetic conditions listed as a contributing cause of death.

FIGURE 2

Joinpoint single ventricle mortality from 1999 to 2017. Single ventricle temporal mortality stratified by age group. Infant mortality rate calculated per 100 000 live births. Mortality rates for decedents >1 year of age calculated per 100 000 persons on the basis of the population of that age. The black line represents the APC of lesions including contributing risk factors. The blue line represents the APC of lesions excluding contributing risk factors. Contributing risk factors include prematurity, extracardiac birth defects, and/or genetic conditions listed as a contributing cause of death.

Close modal
TABLE 2

Trends in Infant Congenital Heart Disease Mortality Stratified by Contributing Risk Factors using Joinpoint Regression

DiagnosisAverage Annual Percent Change (95% Confidence Interval)PSignificant Change in Mortality Trend During Study: Annual Percent Change by Time Period (95% Confidence Interval)P
Any CHD
Including contributing risk factors
Excluding contributing risk factors 

−2.2% (−2.6% to −1.8%)
−2.9% (−3.1% to −2.6%) 

<.001
<.001 
1999 to 2009: −2.9% (−3.4% to −2.5%)
2009 to 2017: −1.4% (−2.1% to −0.6%)
– 
<.001
.002
– 
Aortic valve stenosis
Including contributing risk factors
Excluding contributing risk factors 

−4.9% (−6.6% to −3.2%)
−5.3% (−6.9% to −3.5%) 

<.001
<.001 

– 

– 
Atrial septal defect
Including contributing risk factors
Excluding contributing risk factors 

−2.4% (−4.2% to −0.5%)
−3.8% (−5.8% to −1.8%) 

.014
.001 

– 

– 
Atrioventricular septal defect
Including contributing risk factors
Excluding contributing risk factors 

0.6% (−2.5% to 3.8%)
−1.0% (−3.3% to 1.3%) 

.719
.370 
1999 to 2011: −3.6% (−6.5% to −0.6%)
2011 to 2017: 9.5% (18.9% to 2.4%)
– 
.022
.032
– 
Coarctation
Including contributing risk factors
Excluding contributing risk factors 

−3.0% (−4.9% to −1.1%)
−3.4% (−5.2% to −1.5%) 

.004
.001 

– 

– 
Double outlet right ventricle
Including contributing risk factors
Excluding contributing risk factors 

1.1% (−1.2% to 3.6%)
0.7% (−3.6% to 5.2%) 

.321
.758 

1999 to 2009: −6.1% (−11.1 to −0.8%)
2009 to 2017: 9.9% (1.0% to 19.4%) 

.028
.030 
Ebstein anomaly
Including contributing risk factors
Excluding contributing risk factors 

−1.7% (−2.8% to −0.6%)
−1.6% (−2.8% to −0.3%) 

.004
.017 

– 

– 
Hypoplastic left heart syndrome
Including contributing risk factors
Excluding contributing risk factors 

−2.8% (−3.6% to −1.9%)
−3.1% (−4.0% to −2.3%) 

<.001
<.001 
1999 to 2008: −4.5% (−5.7% to −3.3%)
2008 to 2017: −1.0% (−2.4% to 0.5%)
1999 to 2008: −4.9% (−6.1% to −3.7%)
2008 to 2017: −1.4% (2.8% to 0.1%) 
<.001
.165
<.001
.065 
Other specified CHD
Including contributing risk factors
Excluding contributing risk factors 

−2.0% (−2.8% to −1.2%)
−2.1% (−3.7% to −0.4%) 

<.001
.014 

1999 to 2011: −4.1% (−5.4% to −2.7%)
2011 to 2017: 2.1% (−2.5% to 6.9%) 

<.001
.356 
Patent ductus arteriosus
Including contributing risk factors
Excluding contributing risk factors 

−0.8% (−5.1% to 3.8%)
−0.2% (−4.2% to 3.9%) 

.742
.908 
1999 to 2004: 22.7% (5.5% to 42.8%)  2004 to 2017: −8.5% (−11.8% to −5.2%)
1999 to 2004: 27.6% (11.1% to 46.5%)
2004 to 2017: −9.2% (−12.1% to −6.3%) 
.012
<.001
.002
<.001 
Pulmonary atresia or stenosis
Including contributing risk factors
Excluding contributing risk factors 

−1.6% (−2.9% to −0.3%)
−1.7% (−2.9% to −0.4%) 

.019
.011 

– 

– 
Pulmonary valve abnormalities
Including contributing risk factors
Excluding contributing risk factors 

0.7% (−2.7% to 4.1%)
N/A 

.690
N/A 

N/A 

N/A 
Single ventricle composite
Including contributing risk factors
Excluding contributing risk factors 

−2.8% (−3.5% to −2.0%)
−3.4% (−4.2% to −2.6%) 

<.001
<.001 
1999 to 2008: −4.5% (−5.5% to −3.5%)
2008 to 2017: −1.0% (−3.5% to 0.2%)
1999 to 2006: −5.6% (−7.1% to −4.0%)
2006 to 2017: −2.0% (−2.9% to −1.0%) 
<.001
.101
<.001
.001 
Tetralogy of Fallot
Including contributing risk factors
Excluding contributing risk factors 

−0.9% (−3.2% to 1.5%)
−2.7% (−4.1% to −1.2%) 

.469
.001 
1999 to 2013: −3.1% (−4.6% to −1.6%)
2013 to 2017: 7.4% (−3.3% to 19.3%)
– 
.001
.165
– 
Total anomalous pulmonary venous return
Including contributing risk factors
Excluding contributing risk factors 

5.7% (2.1%–9.5%)
5.7% (1.5%–10.0%) 

.003
.010 

– 

– 
Transposition of the great arteries
Including contributing risk factors
Excluding contributing risk factors 

−3.1% (−4.3% to −2.0%)
−3.8% (−4.8% to −2.8%) 

<.001
<.001 

– 

– 
Tricuspid valve stenosis
Including contributing risk factors
Excluding contributing risk factors 

−2.3% (−5.8% to 1.5%)
−3.9% (−7.3% to −0.4%) 

.217
.032 

– 

– 
Truncus arteriosus
Including contributing risk factors
Excluding contributing risk factors 

−1.9% (−5.1% to 1.4%)
−4.0% (−5.9% to −2.1%) 

.259
<.001 
1999 to 2011: −5.8% (−8.4% to −3.0%)
2011 to 2017: 6.3% (−3.1% to 16.7%)
– 
.001
.178
– 
Unspecified CHD
Including contributing risk factors
Excluding contributing risk factors 

−1.9% (−2.4% to −1.4%)
−2.4% (−2.9% to −1.9%) 

<.001
<.001 

– 

– 
Ventricular septal defect
Including contributing risk factors
Excluding contributing risk factors 

−5.6% (−7.5% to −3.7%)
−7.5% (−9.4% to −5.4%) 

<.001
<.001 

– 

– 
DiagnosisAverage Annual Percent Change (95% Confidence Interval)PSignificant Change in Mortality Trend During Study: Annual Percent Change by Time Period (95% Confidence Interval)P
Any CHD
Including contributing risk factors
Excluding contributing risk factors 

−2.2% (−2.6% to −1.8%)
−2.9% (−3.1% to −2.6%) 

<.001
<.001 
1999 to 2009: −2.9% (−3.4% to −2.5%)
2009 to 2017: −1.4% (−2.1% to −0.6%)
– 
<.001
.002
– 
Aortic valve stenosis
Including contributing risk factors
Excluding contributing risk factors 

−4.9% (−6.6% to −3.2%)
−5.3% (−6.9% to −3.5%) 

<.001
<.001 

– 

– 
Atrial septal defect
Including contributing risk factors
Excluding contributing risk factors 

−2.4% (−4.2% to −0.5%)
−3.8% (−5.8% to −1.8%) 

.014
.001 

– 

– 
Atrioventricular septal defect
Including contributing risk factors
Excluding contributing risk factors 

0.6% (−2.5% to 3.8%)
−1.0% (−3.3% to 1.3%) 

.719
.370 
1999 to 2011: −3.6% (−6.5% to −0.6%)
2011 to 2017: 9.5% (18.9% to 2.4%)
– 
.022
.032
– 
Coarctation
Including contributing risk factors
Excluding contributing risk factors 

−3.0% (−4.9% to −1.1%)
−3.4% (−5.2% to −1.5%) 

.004
.001 

– 

– 
Double outlet right ventricle
Including contributing risk factors
Excluding contributing risk factors 

1.1% (−1.2% to 3.6%)
0.7% (−3.6% to 5.2%) 

.321
.758 

1999 to 2009: −6.1% (−11.1 to −0.8%)
2009 to 2017: 9.9% (1.0% to 19.4%) 

.028
.030 
Ebstein anomaly
Including contributing risk factors
Excluding contributing risk factors 

−1.7% (−2.8% to −0.6%)
−1.6% (−2.8% to −0.3%) 

.004
.017 

– 

– 
Hypoplastic left heart syndrome
Including contributing risk factors
Excluding contributing risk factors 

−2.8% (−3.6% to −1.9%)
−3.1% (−4.0% to −2.3%) 

<.001
<.001 
1999 to 2008: −4.5% (−5.7% to −3.3%)
2008 to 2017: −1.0% (−2.4% to 0.5%)
1999 to 2008: −4.9% (−6.1% to −3.7%)
2008 to 2017: −1.4% (2.8% to 0.1%) 
<.001
.165
<.001
.065 
Other specified CHD
Including contributing risk factors
Excluding contributing risk factors 

−2.0% (−2.8% to −1.2%)
−2.1% (−3.7% to −0.4%) 

<.001
.014 

1999 to 2011: −4.1% (−5.4% to −2.7%)
2011 to 2017: 2.1% (−2.5% to 6.9%) 

<.001
.356 
Patent ductus arteriosus
Including contributing risk factors
Excluding contributing risk factors 

−0.8% (−5.1% to 3.8%)
−0.2% (−4.2% to 3.9%) 

.742
.908 
1999 to 2004: 22.7% (5.5% to 42.8%)  2004 to 2017: −8.5% (−11.8% to −5.2%)
1999 to 2004: 27.6% (11.1% to 46.5%)
2004 to 2017: −9.2% (−12.1% to −6.3%) 
.012
<.001
.002
<.001 
Pulmonary atresia or stenosis
Including contributing risk factors
Excluding contributing risk factors 

−1.6% (−2.9% to −0.3%)
−1.7% (−2.9% to −0.4%) 

.019
.011 

– 

– 
Pulmonary valve abnormalities
Including contributing risk factors
Excluding contributing risk factors 

0.7% (−2.7% to 4.1%)
N/A 

.690
N/A 

N/A 

N/A 
Single ventricle composite
Including contributing risk factors
Excluding contributing risk factors 

−2.8% (−3.5% to −2.0%)
−3.4% (−4.2% to −2.6%) 

<.001
<.001 
1999 to 2008: −4.5% (−5.5% to −3.5%)
2008 to 2017: −1.0% (−3.5% to 0.2%)
1999 to 2006: −5.6% (−7.1% to −4.0%)
2006 to 2017: −2.0% (−2.9% to −1.0%) 
<.001
.101
<.001
.001 
Tetralogy of Fallot
Including contributing risk factors
Excluding contributing risk factors 

−0.9% (−3.2% to 1.5%)
−2.7% (−4.1% to −1.2%) 

.469
.001 
1999 to 2013: −3.1% (−4.6% to −1.6%)
2013 to 2017: 7.4% (−3.3% to 19.3%)
– 
.001
.165
– 
Total anomalous pulmonary venous return
Including contributing risk factors
Excluding contributing risk factors 

5.7% (2.1%–9.5%)
5.7% (1.5%–10.0%) 

.003
.010 

– 

– 
Transposition of the great arteries
Including contributing risk factors
Excluding contributing risk factors 

−3.1% (−4.3% to −2.0%)
−3.8% (−4.8% to −2.8%) 

<.001
<.001 

– 

– 
Tricuspid valve stenosis
Including contributing risk factors
Excluding contributing risk factors 

−2.3% (−5.8% to 1.5%)
−3.9% (−7.3% to −0.4%) 

.217
.032 

– 

– 
Truncus arteriosus
Including contributing risk factors
Excluding contributing risk factors 

−1.9% (−5.1% to 1.4%)
−4.0% (−5.9% to −2.1%) 

.259
<.001 
1999 to 2011: −5.8% (−8.4% to −3.0%)
2011 to 2017: 6.3% (−3.1% to 16.7%)
– 
.001
.178
– 
Unspecified CHD
Including contributing risk factors
Excluding contributing risk factors 

−1.9% (−2.4% to −1.4%)
−2.4% (−2.9% to −1.9%) 

<.001
<.001 

– 

– 
Ventricular septal defect
Including contributing risk factors
Excluding contributing risk factors 

−5.6% (−7.5% to −3.7%)
−7.5% (−9.4% to −5.4%) 

<.001
<.001 

– 

– 

CHD Contributing risk factors include prematurity, extracardiac birth defects, and/or genetic conditions listed as a contributing cause of death. AAPC is the weighted average of the annual changes throughout the 19-y study period. – Represents that there is no significant change in trend through the study period and the average annual percent change is the same value as the annual percent change from 1999 to 2017. P-vale represents if the annual percent change is significantly different from zero at the α = .05 level. N/A, not available; Joinpoint unable to analyze trend because of mortality rate value of zero.

1 to 4 years

Of the 85 781 deaths in children 1 year to 4 years, CHD occurred as the underlying cause of death in 3696 deaths (4.3%) and as a contributing cause in 1295 deaths (1.5%) (Table 1). An extracardiac birth defect or genetic condition occurred as a contributing cause of death in ∼13% (n = 485) of the primary CHD deaths. Over 30% of the deaths attributed to AVSD, VSD, and pulmonary valve abnormalities had at least 1 associated risk factor listed as a contributing cause of death (Table 1).

Single ventricle lesions remained the leading cause of death in 1 to 4 years with 0.17 per 100 000 persons (n = 502) attributed to HLHS and 0.19 per 100 000 persons (n = 581) attributed to the SV composite over the 19-year study period (Table 1). HLHS made up 86% of the SV composite deaths, and SV lesions accounted for 18% of early childhood CHD deaths.

When evaluating temporal trends, contributing risk factors had less effect on mortality trends compared the infant group. The SV composite and HLHS demonstrated persistent increases to their mortality rates from 1999 to 2012 followed by persistent declines in their mortality rates for the remaining study period resulting in nonsignificant AAPCs irrespective of presence of contributing risk factors (Fig 2, Table 3). TOF demonstrated a steady mortality decline with an AAPC of -3.6% (P = .014) and -3.7% (P = .011) if contributing risk factors were excluded (Fig 3). No significant trends occurred in mortality for the remaining lesions, or the lesions experienced too few deaths per year for meaningful interpretation (Table 3).

FIGURE 3

Joinpoint tetralogy of Fallot mortality from 1999 to 2017. Tetralogy of Fallot temporal mortality stratified by age group. Infant mortality rate calculated per 100 000 live births. Mortality rates for decedents >1 year of age calculated per 100 000 persons on the basis of the population of that age. The black line represents the annual percent change (APC) of lesions including contributing risk factors. The blue line represents the APC of lesions excluding contributing risk factors. Contributing risk factors include prematurity, extra cardiac birth defects, and/or genetic conditions listed as a contributing cause of death.

FIGURE 3

Joinpoint tetralogy of Fallot mortality from 1999 to 2017. Tetralogy of Fallot temporal mortality stratified by age group. Infant mortality rate calculated per 100 000 live births. Mortality rates for decedents >1 year of age calculated per 100 000 persons on the basis of the population of that age. The black line represents the annual percent change (APC) of lesions including contributing risk factors. The blue line represents the APC of lesions excluding contributing risk factors. Contributing risk factors include prematurity, extra cardiac birth defects, and/or genetic conditions listed as a contributing cause of death.

Close modal
TABLE 3

Trends in Congenital Heart Disease Mortality of Children Age 1 to 4 Years at Time of Death Stratified by Contributing Risk Factors using Joinpoint Regression

DiagnosisAverage Annual Percent Change (95% Confidence Interval)PSignificant Change in Mortality Trend During Study: Annual Percent Change by Time Period (95% Confidence Interval)P
Any CHD
Including contributing risk factors
Excluding contributing risk factors 

−2.0% (−2.7% to −1.2%)
−2.1% (−2.9% to −1.2%) 
<.001
<.001 

– 

– 
Aortic valve stenosis
Including contributing risk factors
Excluding contributing risk factors 
N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Atrial septal defect
Including contributing risk factors
Excluding contributing risk factors 

−1.0% (−4.8% to 2.9%)
N/A 
.587
N/A 

N/A 

N/A 
Atrioventricular septal defect
Including contributing risk factors
Excluding contributing risk factors 

0.2% (−3.1% to 3.7%)
−0.5% (−4.3% to 3.5%) 
.879
.799 

– 

– 
Coarctation
Including contributing risk factors
Excluding contributing risk factors 

N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Double outlet right ventricle
Including contributing risk factors
Excluding contributing risk factors 

N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Ebstein anomaly
Including contributing risk factors
Excluding contributing risk factors 
N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Hypoplastic left heart syndrome
Including contributing risk factors
Excluding contributing risk factors 
1.0% (−2.5% to 4.5%)
0.9% (−2.5% to 4.3%) 
.585
.621 
1999 to 2012: 6.2% (3.3%–9.2%)
2012 to 2017: −11.5% (−21.1% to -0.7%)
1999 to 2012: 5.8% (3.0%–8.7%)
2012 to 2017: −10.9% (−20.4% to -0.3%) 
<.001
.039
.001
.045 
Other specified CHD
Including contributing risk factors
Excluding contributing risk factors 

−2.4% (−4.2% to -0.6%)
−2.3% (−4.3% to -0.4%) 
.013
.022 

– 

– 
Patent ductus arteriosus
Including contributing risk factors
Excluding contributing risk factors 

N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Pulmonary atresia or stenosis
Including contributing risk factors
Excluding contributing risk factors 

−0.7% (−4.5% to 3.3%)
−0.8% (−4.8% to 3.4%) 
.726
.685 

– 

– 
Pulmonary valve abnormalities
Including contributing risk factors
Excluding contributing risk factors 

N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Single ventricle composite
Including contributing risk factors
Excluding contributing risk factors 

−1.0% (−5.3% to 3.6%)
0.1% (−3.2% to 3.5%) 
.673
.964 
1999 to 2014: 3.6% (1.3%–5.8%)
2014 to 2017: −20.8% (−39.8% to 4.3%)
1999 to 2012: 4.2% (1.5%–6.9%)
2012 to 2017: −9.9% (−19.5% to 0.9%) 
.004
.091
.004
.069 
Tetralogy of Fallot
Including contributing risk factors
Excluding contributing risk factors 

−3.6% (−6.4% to -0.8%)
−3.7% (−6.4% to −1.0%) 
.014
.011 

– 

– 
Total anomalous pulmonary venous return
Including contributing risk factors
Excluding contributing risk factors 

N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Transposition of the great arteries
Including contributing risk factors
Excluding contributing risk factors 

1.0% (−1.4% to 3.6%)
0.7% (−1.7% to 3.1%) 
.369
.551 

– 

– 
Tricuspid valve stenosis
Including contributing risk factors
Excluding contributing risk factors 

N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Truncus arteriosus
Including contributing risk factors
Excluding contributing risk factors 
N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Unspecified CHD
Including contributing risk factors
Excluding contributing risk factors 

−2.8% (−4.0% to −1.7%)
−2.9% (−4.2% to −1.6%) 
<.001
<.001 

– 

– 
Ventricular septal defect
Including contributing risk factors
Excluding contributing risk factors 
−3.2% (−6.7% to 0.4%)
N/A 
.080
N/A 

N/A 

N/A 
DiagnosisAverage Annual Percent Change (95% Confidence Interval)PSignificant Change in Mortality Trend During Study: Annual Percent Change by Time Period (95% Confidence Interval)P
Any CHD
Including contributing risk factors
Excluding contributing risk factors 

−2.0% (−2.7% to −1.2%)
−2.1% (−2.9% to −1.2%) 
<.001
<.001 

– 

– 
Aortic valve stenosis
Including contributing risk factors
Excluding contributing risk factors 
N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Atrial septal defect
Including contributing risk factors
Excluding contributing risk factors 

−1.0% (−4.8% to 2.9%)
N/A 
.587
N/A 

N/A 

N/A 
Atrioventricular septal defect
Including contributing risk factors
Excluding contributing risk factors 

0.2% (−3.1% to 3.7%)
−0.5% (−4.3% to 3.5%) 
.879
.799 

– 

– 
Coarctation
Including contributing risk factors
Excluding contributing risk factors 

N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Double outlet right ventricle
Including contributing risk factors
Excluding contributing risk factors 

N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Ebstein anomaly
Including contributing risk factors
Excluding contributing risk factors 
N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Hypoplastic left heart syndrome
Including contributing risk factors
Excluding contributing risk factors 
1.0% (−2.5% to 4.5%)
0.9% (−2.5% to 4.3%) 
.585
.621 
1999 to 2012: 6.2% (3.3%–9.2%)
2012 to 2017: −11.5% (−21.1% to -0.7%)
1999 to 2012: 5.8% (3.0%–8.7%)
2012 to 2017: −10.9% (−20.4% to -0.3%) 
<.001
.039
.001
.045 
Other specified CHD
Including contributing risk factors
Excluding contributing risk factors 

−2.4% (−4.2% to -0.6%)
−2.3% (−4.3% to -0.4%) 
.013
.022 

– 

– 
Patent ductus arteriosus
Including contributing risk factors
Excluding contributing risk factors 

N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Pulmonary atresia or stenosis
Including contributing risk factors
Excluding contributing risk factors 

−0.7% (−4.5% to 3.3%)
−0.8% (−4.8% to 3.4%) 
.726
.685 

– 

– 
Pulmonary valve abnormalities
Including contributing risk factors
Excluding contributing risk factors 

N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Single ventricle composite
Including contributing risk factors
Excluding contributing risk factors 

−1.0% (−5.3% to 3.6%)
0.1% (−3.2% to 3.5%) 
.673
.964 
1999 to 2014: 3.6% (1.3%–5.8%)
2014 to 2017: −20.8% (−39.8% to 4.3%)
1999 to 2012: 4.2% (1.5%–6.9%)
2012 to 2017: −9.9% (−19.5% to 0.9%) 
.004
.091
.004
.069 
Tetralogy of Fallot
Including contributing risk factors
Excluding contributing risk factors 

−3.6% (−6.4% to -0.8%)
−3.7% (−6.4% to −1.0%) 
.014
.011 

– 

– 
Total anomalous pulmonary venous return
Including contributing risk factors
Excluding contributing risk factors 

N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Transposition of the great arteries
Including contributing risk factors
Excluding contributing risk factors 

1.0% (−1.4% to 3.6%)
0.7% (−1.7% to 3.1%) 
.369
.551 

– 

– 
Tricuspid valve stenosis
Including contributing risk factors
Excluding contributing risk factors 

N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Truncus arteriosus
Including contributing risk factors
Excluding contributing risk factors 
N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Unspecified CHD
Including contributing risk factors
Excluding contributing risk factors 

−2.8% (−4.0% to −1.7%)
−2.9% (−4.2% to −1.6%) 
<.001
<.001 

– 

– 
Ventricular septal defect
Including contributing risk factors
Excluding contributing risk factors 
−3.2% (−6.7% to 0.4%)
N/A 
.080
N/A 

N/A 

N/A 

CHD (congenital heart disease) Contributing risk factors include prematurity, extracardiac birth defects, and/or genetic conditions listed as a contributing cause of death. AAPC is the weighted average of the annual changes throughout the 19-y study period. – Represents that there is no significant change in trend through the study period and the average annual percent change is the same value as the annual percent change from 1999 to 2017. P-vale represents if the annual percent change is significantly different from zero at the α = .05 level. N/A, not available; Joinpoint unable to analyze trend because of mortality rate value of zero.

5 to 17 years

Of the 220 829 deaths in children aged 5 to 17 years, CHD was listed as the underlying cause of death in 3494 deaths (1.6%) and as a contributing cause of death in 972 deaths (0.4%) (Table 1). Extracardiac birth defects or genetic conditions occurred as a contributing cause of death in 251 primary CHD deaths (7.2%) (Table 2). Twenty-five percent of deaths attributed to AVSD and pulmonary valve abnormalities had at least 1 associated risk factor listed as a contributing cause of death (Table 1).

Single ventricle lesions again were the leading causes of death in 5 to 17 years with 0.03 per 100 000 persons (n = 273) attributed to HLHS and 0.04 per 100 000 persons (n = 364) over the 19 year study period (Table 2). HLHS made up 75% of SV composite deaths and the SV composite made up 11% of CHD deaths in later childhood and adolescence.

Again, contributing risk factors had less significant changes to mortality trends compared to the infant group when included in mortality analysis. Consistent increases in single ventricle mortality occurred throughout the 19 years in this age group (Fig 2, Table 4). HLHS demonstrated an AAPC of 7.6% (P < .001) in mortality regardless if contributing risk factors were included. Similarly, the SV composite demonstrated persistent increases with an AAPC of 4.8% (P < .001) and increased to 4.9% if those with contributing risk factors were excluded (P < .001, Table 4). Unlike the other 2 age groups, TOF mortality rate trend failed to reach statistical significance (Fig 3). The remaining specific lesions experienced too few deaths per year for meaningful interpretation (Table 4).

TABLE 4

Trends in Congenital Heart Disease Mortality of Children and Adolescents Age 5 to 17 Years at Time of Death Stratified by Contributing Risk Factors using Joinpoint Regression

DiagnosisAverage Annual Percent Change (95% Confidence Interval)PSignificant Change in Mortality Trend During Study: Annual Percent Change by Time Period (95% Confidence Interval)P
Any CHD
Including contributing risk factors
Excluding contributing risk factors 

−2.9% (−3.5% to −2.3%)
−3.1% (−3.8% to −2.5%) 

<.001
<.001 


– 

– 
Aortic valve stenosis
Including contributing risk factors
Excluding contributing risk factors 

N/A
N/A 

N/A
N/A 

N/A
N/A 
N/A
N/A 
Atrial septal defect
Including contributing risk factors
Excluding contributing risk factors 
N/A
N/A 

N/A
N/A 

N/A
N/A 
N/A
N/A 
Atrioventricular septal defect
Including contributing risk factors
Excluding contributing risk factors 
N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Coarctation
Including contributing risk factors
Excluding contributing risk factors 

N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Double outlet right ventricle
Including contributing risk factors
Excluding contributing risk factors 

N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Ebstein anomaly
Including contributing risk factors
Excluding contributing risk factors 
N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Hypoplastic left heart syndrome
Including contributing risk factors
Excluding contributing risk factors 

7.6% (5.0%–10.2%)
7.6% (4.8%–10.5%) 

<.001
<.001 

– 

– 
Other specified CHD
Including contributing risk factors
Excluding contributing risk factors 

−4.4% (−5.6% to −3.2%)
−4.0% (−5.2% to −2.7%) 
<.001
<.001 

– 

– 
Patent ductus arteriosus
Including contributing risk factors
Excluding contributing risk factors 

N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Pulmonary atresia or stenosis
Including contributing risk factors
Excluding contributing risk factors 
N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Pulmonary valve abnormalities
Including contributing risk factors
Excluding contributing risk factors 
N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Single ventricle composite
Including contributing risk factors
Excluding contributing risk factors 

4.8% (2.9%–6.8%)
4.9% (2.8%–3.5%) 
<.001
<.001 

– 

– 
Tetralogy of fallot
Including contributing risk factors
Excluding contributing risk factors 

−1.8% (−4.2% to 0.7%)
−3.0% (−6.7% to 0.8%) 
.142
.111 

– 

– 
Total anomalous pulmonary venous return
Including contributing risk factors
Excluding contributing risk factors 

N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Transposition of the great arteries
Including contributing risk factors
Excluding contributing risk factors 
N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Tricuspid valve stenosis
Including contributing risk factors
Excluding contributing risk factors 
N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Truncus arteriosus
Including contributing risk factors
Excluding contributing risk factors 
N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Unspecified CHD
Including contributing risk factors
Excluding contributing risk factors 

−3.9% (−4.7% to −3.1%)
−4.3% (−5.1% to −3.5%) 
<.001
<.001 

– 

– 
Ventricular septal defect
Including contributing risk factors
Excluding contributing risk factors 
N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
DiagnosisAverage Annual Percent Change (95% Confidence Interval)PSignificant Change in Mortality Trend During Study: Annual Percent Change by Time Period (95% Confidence Interval)P
Any CHD
Including contributing risk factors
Excluding contributing risk factors 

−2.9% (−3.5% to −2.3%)
−3.1% (−3.8% to −2.5%) 

<.001
<.001 


– 

– 
Aortic valve stenosis
Including contributing risk factors
Excluding contributing risk factors 

N/A
N/A 

N/A
N/A 

N/A
N/A 
N/A
N/A 
Atrial septal defect
Including contributing risk factors
Excluding contributing risk factors 
N/A
N/A 

N/A
N/A 

N/A
N/A 
N/A
N/A 
Atrioventricular septal defect
Including contributing risk factors
Excluding contributing risk factors 
N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Coarctation
Including contributing risk factors
Excluding contributing risk factors 

N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Double outlet right ventricle
Including contributing risk factors
Excluding contributing risk factors 

N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Ebstein anomaly
Including contributing risk factors
Excluding contributing risk factors 
N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Hypoplastic left heart syndrome
Including contributing risk factors
Excluding contributing risk factors 

7.6% (5.0%–10.2%)
7.6% (4.8%–10.5%) 

<.001
<.001 

– 

– 
Other specified CHD
Including contributing risk factors
Excluding contributing risk factors 

−4.4% (−5.6% to −3.2%)
−4.0% (−5.2% to −2.7%) 
<.001
<.001 

– 

– 
Patent ductus arteriosus
Including contributing risk factors
Excluding contributing risk factors 

N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Pulmonary atresia or stenosis
Including contributing risk factors
Excluding contributing risk factors 
N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Pulmonary valve abnormalities
Including contributing risk factors
Excluding contributing risk factors 
N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Single ventricle composite
Including contributing risk factors
Excluding contributing risk factors 

4.8% (2.9%–6.8%)
4.9% (2.8%–3.5%) 
<.001
<.001 

– 

– 
Tetralogy of fallot
Including contributing risk factors
Excluding contributing risk factors 

−1.8% (−4.2% to 0.7%)
−3.0% (−6.7% to 0.8%) 
.142
.111 

– 

– 
Total anomalous pulmonary venous return
Including contributing risk factors
Excluding contributing risk factors 

N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Transposition of the great arteries
Including contributing risk factors
Excluding contributing risk factors 
N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Tricuspid valve stenosis
Including contributing risk factors
Excluding contributing risk factors 
N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Truncus arteriosus
Including contributing risk factors
Excluding contributing risk factors 
N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 
Unspecified CHD
Including contributing risk factors
Excluding contributing risk factors 

−3.9% (−4.7% to −3.1%)
−4.3% (−5.1% to −3.5%) 
<.001
<.001 

– 

– 
Ventricular septal defect
Including contributing risk factors
Excluding contributing risk factors 
N/A
N/A 
N/A
N/A 
N/A
N/A 
N/A
N/A 

CHD (congenital heart disease) contributing risk factors include prematurity, extracardiac birth defects, and/or genetic conditions listed as a contributing cause of death. AAPC is the weighted average of the annual changes throughout the 19-y study period. – Represents there is no significant change in trend through the study period and the average annual percent change is the same value as the annual percent change from 1999 to 2017. P-vale represents if the annual percent change is significantly different from zero at the α = 0.05 level.

N/A, not available; Joinpoint unable to analyze trend because of mortality rate value of zero.

This study provides a national update on mortality trends because of CHD by lesion type in United States children. Like previously published data using the MCOD dataset, our study shows that overall CHD mortality rates continue to decrease across infancy, childhood, and adolescence.4,14  This data set is unique allowing for the evaluation of infant, child, and adolescent CHD mortality compared to the general United States population, versus deaths within the CHD population. CHD-related mortality remains highest in infants consistent with previously published data.3,4,14  The overall CHD mortality rate demonstrated plateauing in the later part of the study for infants when high-risk conditions were not excluded. Potential reasons for mortality rate plateau include an increased percentage of high-risk CHD patients or a decrease in surgical and medical innovation in the most recent years of the study. The large variation seen in those with contributing risk factors is likely related to the inherent heterogeneity of CHD lesions themselves and the heterogeneity of the contributing factors.

Similar to our previous study of adults evaluating lesion-specific CHD mortality, trends varied by age and specific lesion throughout childhood.5  Mortality rates for the most severe forms of CHD, SV physiology, demonstrated persistent decreases in infancy and increases for the older children and adolescent groups. Improved infant single ventricle mortality trend may result from improved prenatal diagnosis allowing for birth at a cardiac center and improved survival in infancy because of advances in operative and peri-operative, with older children and adolescents potentially experiencing more complications from a failing Fontan (final stage of repair for single ventricle lesions) physiology.7,15,16  Potential reasons for increased mortality in childhood may be early timing of Fontan surgical palliation, development of failing Fontan physiology, and challenges accessing care because of insurance issues.

The other CHD lesions resulting in the highest mortality rates typically require intervention during infancy or early childhood. TAPVR demonstrated a significant increase in infant mortality rate throughout the study period. Studies demonstrate various outcomes on the basis of associated cardiac lesions like heterotaxy, type of TAPVR, preoperative pulmonary vein obstruction, and postoperative pulmonary vein obstruction.1720  The MCOD database is unable to provide the granularity of these different factors, but the increased mortality may be a representation of higher proportion of known risk factors for worse outcomes like those with venous obstruction or more complex anatomy like those with heterotaxy. TOF demonstrated consistent mortality decline in infants and young children, consistent with improved outcomes reported from other single center studies and inpatient databases.9,21,22  Improvements in TOF mortality are likely a combination of advancements in surgical repair, postoperative management, and more consistent cardiac follow-up with close monitoring for need of further intervention. TGA demonstrated significant declines in infant mortality. In the 1 year to 4 years group, there was significant variation in mortality attributed to TGA with no significant trend. In the 5 years to 17 years group, mortality attributed to TGA was too low for meaningful interpretation. This makes sense clinically because patients with TGA need early intervention in the first days of life experience a much lower risk of reintervention than patients with single ventricle physiology or tetralogy of Fallot, so significant changes in mortality outside of infancy would not be expected.

Higher prevalence of CHD lesions are reported in patients born premature and multiple studies have reported worse outcomes in this patient population.2326  Our data corroborates these previous studies showing infants born prematurely have higher rates of CHD-related mortality compared to their term counterparts.23,25,26  Higher mortality rates among premature infants are likely multifactorial, with contributions from low birth weight, impaired maternal-fetal environment resulting in infants small for gestational age, higher surgical technical difficulty because of patient size, and other associated morbidities of prematurity including premature lung mechanics.27 

Our data indicated higher CHD mortality when patients with genetic conditions and extracardiac birth defects were included. This was demonstrated most predominantly in the infant cohort. Patel et al found that 3% of patients in the Society of Thoracic Surgeons Congenital Heart Surgery Database (STS-CHSD) who underwent surgical repair for CHD had an additional noncardiac anomaly, and this increased to 18% when genetic abnormalities and noncardiac anomalies were included.28  Although infants with trisomy 21 and AVSD have similar mortality rates to infants with AVSD without trisomy 21, infants with trisomy 21 or Turner syndrome experience higher rates of mortality with single ventricle anatomy compared to those without genetic syndromes.29,30  Goldmuntz et al reported infants with 22q11.2 deletion syndrome experience higher mortality with pulmonary atresia and VSD and have higher rates of morbidity after most cardiac surgical interventions compared to patients with similar lesions without 22q11.2 deletion.31  A study using the Pediatric Cardiac Care Consortium reported increased risk of death in the early and late postoperative phases in patients with tetralogy of Fallot with an underlying genetic condition.21  Another study showed 6% higher rates of in-hospital mortality for patients for patients undergoing staged palliation for HLHS if they had an additional extracardiac anomaly.32  Potential hypotheses for these findings include extracardiac birth defects, and genetic conditions may delay surgical repair or make the repair more technically challenging. Extracardiac birth defects and genetic conditions may also make medical management of these patients more challenging.

The MCOD data set, although 1 of the best sources of national mortality data in the US, does have limitations. Multiple studies have shown the cause of death listed on death certificates may be nonspecific or even at times incorrect.3335  Studies have suggested lack of training for physicians or providers filling out the death certificates as a contributor to error, but with improved education measures, such as formal training programs, there are less errors in completing certificates of death.36,37  Congenital heart disease is complex and heterogenous in nature which makes it especially susceptible to errors in coding, or coding generically, including codes such as “unspecified cardiac disease.” Another limitation to this study is the use of ICD-10 codes to classify different diagnoses of CHD. ICD-10 codes are helpful for classifying diagnoses, but at times they can also be nonspecific especially for children with more complex anatomy. One recent study showed significant error and underreporting in discharge codes for congenital heart disease, which can be extrapolated the codes use in death certificates.38  In our study, unspecified CHD was the leading ICD-10 code for CHD mortality for each age group, and this poses a limitation to understanding the most complete analysis of mortality rates. Mortality rates for the specific lesions may have had more dramatic declines if there was more specification in diagnosis on death certificates. In the United States, we do not have a centralized database to capture all CHD patients, thus national databases like the MCOD are important for tracking health care trends.

Our data provide an update to national mortality trends for CHD during infancy, childhood, and adolescence in the United States by specific CHD lesion. Significant declines occurred for infant mortality in most CHD lesions. Surgical techniques and aggressive medical management are likely large contributing factors to this success. Because of the heterogenicity of CHD lesions, there is expected variability in mortality trends by lesion and age group. Single ventricle lesions continue to contribute most heavily to premature death because of CHD demonstrated by significant increases in mortality rate for children aged 5 to 17 years. Patients with CHD need lifelong cardiology care to monitor for morbidities and modifying risk factors as they age to prevent premature mortality. Data reporting needs to be more accurate to get the truest picture of mortality for CHD lesions for infants, children, and adolescents. A centralized national database of CHD patients would allow for more in-depth monitoring and research of this growing population.

We acknowledge the National Center for Health Statistics for the production of the Multiple Cause of Death Dataset.

Dr Lynn collected data, carried out the initial analyses, drafted the initial manuscript, and reviewed and revised the manuscript; Dr Salemi conceptualized and designed the study, designed the data collection instruments, collected data, carried out the initial analyses, and reviewed and revised the manuscript; Drs Lopez, Morris, and Tejtel conceptualized and designed the study and reviewed and revised the manuscript; Dr Kostelyna drafted the initial manuscript and reviewed and revised the manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

FUNDING: This project was supported by grant number K23 HL127164 (Primary Investigator: Dr Lopez) from the National Institutes of Health or National Heart Lung and Blood Institute. The content is sole the responsibility of the authors and does not necessary represent the official views of the Nation Institutes of Health.

CONFLICT OF INTEREST DISCLOSURES: The authors have no conflict of interest relevant to this article to disclose.

AAPC

average annual percent change

APC

annual percent change

AVSD

atrioventricular septal defect

CHD

congenital heart disease

HLHS

hypoplastic left heart disease

ICD-10/9

International Classification of Diseases, 10th Revision/9th Revision

MCOD

multiple cause of death

SV

single ventricle

TGA

transposition of great arteries

TOF

tetralogy of Fallot

UCOD

underlying cause of death

VSD

ventricular septal defect

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Supplementary data