Background
Background
Congenital heart defects are the most common single organmalformations in humans.
The estimates of prevalences published during the last 3–4 decades ranged from 4–5
CHD/1 000 live births in the earlier studies up to 12–14/1 000 live births in the
more recent ones [3 ]
[6 ]
[7 ]
[9 ]
[14 ]
[17 ]
[21 ]. Higher prevalences were usually reported by echocardiography screening studies
in newborn nurseries or by registries covering childhood and adolescence [13 ]
[18 ]. Hoffman and Kaplan [9 ] addressed the reasons for the variation in CHD prevalence rates in a meta-analysis
of 62 publications. They pointed out that studies of very large populations tend to
give sufficiently large numbers of live births at the expense of an adequate detection
rate. On the other hand, intensive studies in a restricted region virtually disclose
all CHD, but they are usually not feasible for very large populations. The prevalence
of CHD, and in particular the proportions of single lesions, depend essentially on
the detection rates of mild defects [5 ]
[9 ]
[17 ]
[21 ], and any assessment of CHD prevalence must take into account not only the age of
the patients but, in particular, the ways in which they were entered into the study.
Population-wide data on current CHD prevalence are scarce and a recent review critically
noted that only crude calculations and estimates were available for Germany [10 ]. The PAN (P
raevalenz
a
ngeborener Herzfehler bei
N
eugeborenen ) study is making efforts to remedy the lack of research in this field. It is a nation-wide
epidemiological registry within the German Competence Network for Congenital Heart
Defects, which is funded by the German Federal Ministry of Education and Research
and involves hospitals, cardiac centers and practicing physicians in an interdisciplinary
research structure.
This report summarizes the results of the first registration year of the PAN study.
Data are presented for the whole group of cardiovascular defects as well as for relevant
subgroups. We further provide information on the association of demographic and selected
gestational data with CHD and compare these findings to those provided by official
data for all live births in Germany.
Material and methods
Material and methods
The PAN study is a nationwide investigation in Germany with the aim of a prospective
registration of all congenital cardiovascular malformations diagnosed among live births
during the first year of life. It is based on the resident population of more than
80 million people presently living within the territory of the Federal Republic of
Germany. This report is on the first year of registration which includes the data
for infants with CHD born between 1st July 2006 and 30th June 2007. There were 673 282 live births in Germany during this period.
The study was approved by the ethics committee of the Charité, Berlin. The data protection
officers of all Federal States of Germany agreed with the data sampling procedures.
Signed informed consent was obtained from parents/legal guardians for data acquisition
and handling.
Data acquisition
All German paediatric cardiologists and paediatricians with cardiologic expertise
working in specialized heart centers, children's hospitals and outpatient clinics
were addressed to contribute to the PAN study data base. Finally, 34 out of 35 departments
of paediatric cardiology in university units (97%), 154 out of 192 children's hospitals
(80%) and 72 out of 111 outpatient departments (65%) contributed patients to the study
base.
Data of all patients were submitted in electronic form into a central database by
a remote data entry system. All data were monitored for plausibility and correctness.
To reduce underreporting and to optimize participation, a routine monthly reminder
was sent to all institutions. In cases with loss of contact or non-compliance, an
anonymous registration was offered.
Data sets
The patient data consisted of sets of personal and medical parameters. The Identification
Data set was used to create a unique patient identifier (PID), applying encryption
methods developed by the Telematics Platform for Medical Research Networks [19 ]. The use of PIDs permits linkage of different records by stochastic methods, which
ensure low rates of misclassification and comply with German data protection requirements.
Patient's data were stored in the PAN data base exclusively by their PID.
The Medical Data set consisted of demographic data, birth data, and medical data.
In case of missing consent, only infant's sex, month and year of birth and diagnosis
of CHD were registered anonymously.
The first place of residence of the newborn after birth had to be in Germany.
Diagnosis of CHD
Registration of cases was based on a passive patient collection with diagnosis assessment
on clinical signs rather than on active screening for CHD. Diagnostic procedures included
echocardiography, cardiac catheterization, surgery or autopsy.
All congenital malformations of the heart and the thoracic vessels were recorded with
the following exclusion criteria:
persistent arterial duct in a preterm infant until four weeks after calculated birth
date and in a full-term infant until four weeks after birth;
physiological branch stenosis of the right or left pulmonary artery;
isolated patent foramen ovale;
isolated persistent left superior vena cava;
isolated bicuspid aortic valve;
isolated dextrocardia;
cardiac tumours;
cardiomyopathies;
cardiac arrhythmias.
Cardiac and extracardiac lesions were recorded in accordance with the Code of the
Association for European Paediatric Cardiology (EPC code) [1 ]. Combined cardiac defects were arranged in a one-dimensional approach with the leading
malformation being either the main anatomical defect or the defect which would require
the earliest intervention (for example, double inlet ventricle with coarctation of
aorta was coded double inlet ventricle as the major cardiovascular malformation, while
coarctation or interrupted aortic arch with ventricular septal defect was coded as
coarctation of the aorta or interrupted aortic arch as the main lesion). The severity
of the CHD was classified as ‘mild’,‘moderate’
‘serve’[Table 1 ]).
Table 1 Baseline characteristics of the PAN study patients.
<TD VALIGN="TOP">
</TD><TD VALIGN="TOP" COLSPAN="2">
Total
</TD><TD VALIGN="TOP" COLSPAN="2">
Complete data set
</TD><TD VALIGN="TOP" COLSPAN="2">
Anonymous data set
</TD>
<TD VALIGN="TOP">
</TD><TD VALIGN="TOP">
n
</TD><TD VALIGN="TOP">
%
</TD><TD VALIGN="TOP">
n
</TD><TD VALIGN="TOP">
%
</TD><TD VALIGN="TOP">
n
</TD><TD VALIGN="TOP">
%
</TD>
<TD VALIGN="TOP">
registered cases with CHD
</TD><TD VALIGN="TOP">
7 245
</TD><TD VALIGN="TOP">
(100)
</TD><TD VALIGN="TOP">
5 251
</TD><TD VALIGN="TOP">
(72.5)
</TD><TD VALIGN="TOP">
1 994
</TD><TD VALIGN="TOP">
(27.5)
</TD>
<TD VALIGN="TOP">
male
</TD><TD VALIGN="TOP">
3 379
</TD><TD VALIGN="TOP">
(46.7)
</TD><TD VALIGN="TOP">
2 474
</TD><TD VALIGN="TOP">
(47.1)
</TD><TD VALIGN="TOP">
905
</TD><TD VALIGN="TOP">
(45.4)
</TD>
<TD VALIGN="TOP">
female
</TD><TD VALIGN="TOP">
3 860
</TD><TD VALIGN="TOP">
(53.3)
</TD><TD VALIGN="TOP">
2 777
</TD><TD VALIGN="TOP">
(52.9)
</TD><TD VALIGN="TOP">
1 083
</TD><TD VALIGN="TOP">
(54.3)
</TD>
<TD VALIGN="TOP">
not specified
</TD><TD VALIGN="TOP">
6
</TD><TD VALIGN="TOP">
(0.08)
</TD><TD VALIGN="TOP">
0
</TD><TD VALIGN="TOP">
</TD><TD VALIGN="TOP">
6
</TD><TD VALIGN="TOP">
(0.3)
</TD>
<TD VALIGN="TOP">
CHD-severity*:
</TD><TD VALIGN="TOP">
</TD><TD VALIGN="TOP">
</TD><TD VALIGN="TOP">
</TD><TD VALIGN="TOP">
</TD><TD VALIGN="TOP">
</TD><TD VALIGN="TOP">
</TD>
<TD VALIGN="TOP">
mild CHD
</TD><TD VALIGN="TOP">
4 372
</TD><TD VALIGN="TOP">
(60.3)
</TD><TD VALIGN="TOP">
3 166
</TD><TD VALIGN="TOP">
(60.3)
</TD><TD VALIGN="TOP">
1 206
</TD><TD VALIGN="TOP">
(60.5)
</TD>
<TD VALIGN="TOP">
moderate CHD
</TD><TD VALIGN="TOP">
1 988
</TD><TD VALIGN="TOP">
(27.4)
</TD><TD VALIGN="TOP">
1 440
</TD><TD VALIGN="TOP">
(27.4)
</TD><TD VALIGN="TOP">
548
</TD><TD VALIGN="TOP">
(27.5)
</TD>
<TD VALIGN="TOP">
severe CHD
</TD><TD VALIGN="TOP">
866
</TD><TD VALIGN="TOP">
(12.0)
</TD><TD VALIGN="TOP">
634
</TD><TD VALIGN="TOP">
(12.1)
</TD><TD VALIGN="TOP">
232
</TD><TD VALIGN="TOP">
(11.6)
</TD>
<TD VALIGN="TOP">
no classification
</TD><TD VALIGN="TOP">
19
</TD><TD VALIGN="TOP">
(0.3)
</TD><TD VALIGN="TOP">
11
</TD><TD VALIGN="TOP">
(0.2)
</TD><TD VALIGN="TOP">
8
</TD><TD VALIGN="TOP">
(0.4)
</TD>
<TD VALIGN="TOP">
*mild CHD include: VSD (small or muscular), ASD (all forms), PDA, PS, other lesions; moderate CHD include: VSD (others than small or muscular), AVSD, AS, CoA, PAPVC, other lesions;
severe CHD include: UVH (all types), ToF, PA/VSD, PA/IVS, DORV, D-TGA, L-TGA, TAC, IAA, TAPVC,
Ebstein's anomaly, other lesions
</TD>
<TD VALIGN="TOP">
For abbrevations see footnote of [Table 2 ]
</TD>
Statistical analyses
Analyses were exclusively descriptive and the observed prevalences are reported. Tests
of statistical significance are not provided as there was no prior study hypothesis
to be tested. Analyses were performed with SPSS statistical software (version 17.0).
Results
Results
A total of 7 245 live births with CHD were registered within the birth period from
1st July 2006 to 30th June 2007. Departments of paediatric cardiology in university hospitals contributed
38%, children's hospitals with cardiologic care 36% and outpatients departments 26%
of all cases. The number of patients included by these three institutional categories
ranged from 6 to 260, 1 to 145 and 1 to 157 with a median of 70, 11 and 18, respectively.
A complete data set was obtained for 5 251 (72.5%) of the patients and an anonymous
data set for 1 994 (27.5%). Patients with complete and anonymous data did not markedly
differ regarding sex or CHD severity ([Table 1 ]
).
Based on the official number of live births in Germany during the study period, the
total prevalence of CHD was calculated as 107.6 per 10 000 live births. Among all
infants with CHD, 60.3% had a mild, 27.4% a moderate and 12.0% a severe cardiovascular
defect; the proportions among full term infants were 59.2%, 27.9% and 12.7%, respectively.
The most common lesion were: ventricular septal defect (48.9%), about two third of
them being small or muscular defects, atrial septal defect (17.0%), valvular pulmonary
stenosis (6.1%), persistent arterial duct (4.3%) and aortic coarctation (3.6%). The
most common cyanotic lesions were tetralogy of Fallot (2.5%) and complete transposition
of the great arteries (2.2%). A single ventricle (all types) was identified in 2.8%,
half of them being a hypoplastic left heart syndrome. While female infants were clearly
more common in mild defects, there was a striking predominance of males with severe
lesions ([Table 2 ]
).
Table 2 Prevalence of categories of CHD severity and of single cardiac lesions. Numbers of
cases, proportion of total numbers, sex ratio and prevalence. The single lesions are
arranged in decreasing frequency.
<TD VALIGN="TOP">
Cardiac Malformation
</TD><TD VALIGN="TOP" COLSPAN="2">
Cases
</TD><TD VALIGN="TOP">
Ratio male/female
</TD><TD VALIGN="TOP">
Prevalence per 10 000 live births
</TD>
<TD VALIGN="TOP">
</TD><TD VALIGN="TOP">
n
</TD><TD VALIGN="TOP">
(%)
</TD><TD VALIGN="TOP">
</TD><TD VALIGN="TOP">
</TD>
<TD VALIGN="TOP">
total
</TD><TD VALIGN="TOP">
7 245
</TD><TD VALIGN="TOP">
</TD><TD VALIGN="TOP">
0.88
</TD><TD VALIGN="TOP">
107.6
</TD>
<TD VALIGN="TOP">
CHD severity*
</TD><TD VALIGN="TOP">
</TD><TD VALIGN="TOP">
</TD><TD VALIGN="TOP">
</TD><TD VALIGN="TOP">
</TD>
<TD VALIGN="TOP">
mild CHD
</TD><TD VALIGN="TOP">
4 372
</TD><TD VALIGN="TOP">
(60.3)
</TD><TD VALIGN="TOP">
0.75
</TD><TD VALIGN="TOP">
64.9
</TD>
<TD VALIGN="TOP">
moderate CHD
</TD><TD VALIGN="TOP">
1 988
</TD><TD VALIGN="TOP">
(27.4)
</TD><TD VALIGN="TOP">
1.01
</TD><TD VALIGN="TOP">
29.5
</TD>
<TD VALIGN="TOP">
severe CHD
</TD><TD VALIGN="TOP">
866
</TD><TD VALIGN="TOP">
(12.0)
</TD><TD VALIGN="TOP">
1.41
</TD><TD VALIGN="TOP">
12.9
</TD>
<TD VALIGN="TOP">
no classification
</TD><TD VALIGN="TOP">
19
</TD><TD VALIGN="TOP">
(0.3)
</TD><TD VALIGN="TOP">
0.73
</TD><TD VALIGN="TOP">
0.3
</TD>
<TD VALIGN="TOP">
single CHD entities
</TD><TD VALIGN="TOP">
</TD><TD VALIGN="TOP">
</TD><TD VALIGN="TOP">
</TD><TD VALIGN="TOP">
</TD>
<TD VALIGN="TOP">
VSD (all)
</TD><TD VALIGN="TOP">
3 545
</TD><TD VALIGN="TOP">
(48.9)
</TD><TD VALIGN="TOP">
0.78
</TD><TD VALIGN="TOP">
52.7
</TD>
<TD VALIGN="TOP">
– VSD small or muscular
</TD><TD VALIGN="TOP">
2 260
</TD><TD VALIGN="TOP">
(31.2)
</TD><TD VALIGN="TOP">
0.75
</TD><TD VALIGN="TOP">
33.6
</TD>
<TD VALIGN="TOP">
– VSD all others
</TD><TD VALIGN="TOP">
1 285
</TD><TD VALIGN="TOP">
(17.7)
</TD><TD VALIGN="TOP">
0.83
</TD><TD VALIGN="TOP">
19.1
</TD>
<TD VALIGN="TOP">
ASD (all forms)
</TD><TD VALIGN="TOP">
1 235
</TD><TD VALIGN="TOP">
(17.0)
</TD><TD VALIGN="TOP">
0.70
</TD><TD VALIGN="TOP">
18.3
</TD>
<TD VALIGN="TOP">
– ASD II
</TD><TD VALIGN="TOP">
1 219
</TD><TD VALIGN="TOP">
(16.8)
</TD><TD VALIGN="TOP">
0.69
</TD><TD VALIGN="TOP">
18.1
</TD>
<TD VALIGN="TOP">
– ASD all others
</TD><TD VALIGN="TOP">
16
</TD><TD VALIGN="TOP">
(0.2)
</TD><TD VALIGN="TOP">
1.00
</TD><TD VALIGN="TOP">
0.2
</TD>
<TD VALIGN="TOP">
PS
</TD><TD VALIGN="TOP">
443
</TD><TD VALIGN="TOP">
(6.1)
</TD><TD VALIGN="TOP">
0.74
</TD><TD VALIGN="TOP">
6.6
</TD>
<TD VALIGN="TOP">
PDA
</TD><TD VALIGN="TOP">
310
</TD><TD VALIGN="TOP">
(4.3)
</TD><TD VALIGN="TOP">
0.93
</TD><TD VALIGN="TOP">
4.6
</TD>
<TD VALIGN="TOP">
CoA
</TD><TD VALIGN="TOP">
264
</TD><TD VALIGN="TOP">
(3.6)
</TD><TD VALIGN="TOP">
1.51
</TD><TD VALIGN="TOP">
3.9
</TD>
<TD VALIGN="TOP">
UVH (all types)
</TD><TD VALIGN="TOP">
202
</TD><TD VALIGN="TOP">
(2.8)
</TD><TD VALIGN="TOP">
1.56
</TD><TD VALIGN="TOP">
3.0
</TD>
<TD VALIGN="TOP">
– HLHS
</TD><TD VALIGN="TOP">
101
</TD><TD VALIGN="TOP">
(1.4)
</TD><TD VALIGN="TOP">
1.53
</TD><TD VALIGN="TOP">
1.5
</TD>
<TD VALIGN="TOP">
AVSD
</TD><TD VALIGN="TOP">
183
</TD><TD VALIGN="TOP">
(2.5)
</TD><TD VALIGN="TOP">
1.08
</TD><TD VALIGN="TOP">
2.7
</TD>
<TD VALIGN="TOP">
ToF
</TD><TD VALIGN="TOP">
179
</TD><TD VALIGN="TOP">
(2.5)
</TD><TD VALIGN="TOP">
1.42
</TD><TD VALIGN="TOP">
2.7
</TD>
<TD VALIGN="TOP">
AS
</TD><TD VALIGN="TOP">
161
</TD><TD VALIGN="TOP">
(2.2)
</TD><TD VALIGN="TOP">
2.83
</TD><TD VALIGN="TOP">
2.4
</TD>
<TD VALIGN="TOP">
D-TGA
</TD><TD VALIGN="TOP">
156
</TD><TD VALIGN="TOP">
(2.2)
</TD><TD VALIGN="TOP">
2.90
</TD><TD VALIGN="TOP">
2.3
</TD>
<TD VALIGN="TOP">
DORV
</TD><TD VALIGN="TOP">
76
</TD><TD VALIGN="TOP">
(1.0)
</TD><TD VALIGN="TOP">
0.90
</TD><TD VALIGN="TOP">
1.1
</TD>
<TD VALIGN="TOP">
PA/VSD
</TD><TD VALIGN="TOP">
44
</TD><TD VALIGN="TOP">
(0.6)
</TD><TD VALIGN="TOP">
1.20
</TD><TD VALIGN="TOP">
0.7
</TD>
<TD VALIGN="TOP">
TAPVC
</TD><TD VALIGN="TOP">
43
</TD><TD VALIGN="TOP">
(0.6)
</TD><TD VALIGN="TOP">
1.15
</TD><TD VALIGN="TOP">
0.6
</TD>
<TD VALIGN="TOP">
TAC
</TD><TD VALIGN="TOP">
33
</TD><TD VALIGN="TOP">
(0.5)
</TD><TD VALIGN="TOP">
1.06
</TD><TD VALIGN="TOP">
0.5
</TD>
<TD VALIGN="TOP">
Ebstein's anomaly
</TD><TD VALIGN="TOP">
27
</TD><TD VALIGN="TOP">
(0.4)
</TD><TD VALIGN="TOP">
0.93
</TD><TD VALIGN="TOP">
0.4
</TD>
<TD VALIGN="TOP">
PAPVC
</TD><TD VALIGN="TOP">
26
</TD><TD VALIGN="TOP">
(0.4)
</TD><TD VALIGN="TOP">
1.00
</TD><TD VALIGN="TOP">
0.4
</TD>
<TD VALIGN="TOP">
L-TGA
</TD><TD VALIGN="TOP">
25
</TD><TD VALIGN="TOP">
(0.3)
</TD><TD VALIGN="TOP">
0.92
</TD><TD VALIGN="TOP">
0.4
</TD>
<TD VALIGN="TOP">
IAA
</TD><TD VALIGN="TOP">
22
</TD><TD VALIGN="TOP">
(0.3)
</TD><TD VALIGN="TOP">
0.69
</TD><TD VALIGN="TOP">
0.3
</TD>
<TD VALIGN="TOP">
PA/IVS
</TD><TD VALIGN="TOP">
21
</TD><TD VALIGN="TOP">
(0.3)
</TD><TD VALIGN="TOP">
1.10
</TD><TD VALIGN="TOP">
0.3
</TD>
<TD VALIGN="TOP">
AVSD partial
</TD><TD VALIGN="TOP">
18
</TD><TD VALIGN="TOP">
(0.2)
</TD><TD VALIGN="TOP">
1.57
</TD><TD VALIGN="TOP">
0.3
</TD>
<TD VALIGN="TOP">
misc., specific lesions
</TD><TD VALIGN="TOP">
223
</TD><TD VALIGN="TOP">
(3.1)
</TD><TD VALIGN="TOP">
0.78
</TD><TD VALIGN="TOP">
3.3
</TD>
<TD VALIGN="TOP">
misc., not specified
</TD><TD VALIGN="TOP">
9
</TD><TD VALIGN="TOP">
(0.1)
</TD><TD VALIGN="TOP">
0.50
</TD><TD VALIGN="TOP">
0.1
</TD>
<TD VALIGN="TOP">
Abbreviations : VSD: ventricular septal defect; ASD II: atrial septal defect, secundum type; PS:
valvular pulmonary stenosis; PDA: persistent arterial duct; CoA: coarctation of aorta;
UVH: univentricular heart; HLHS: hypoplastic left heart syndrome; AVSD: atrioventricular
septal defect; ToF: tetralogy of Fallot; AS: valvular aortic stenosis; D-TGA: complete
transposition of the great arteries; DORV: double outlet right ventricle; PA/VSD:
pulmonary atresia with ventricular septal defect; TAPVC: total anomalous pulmonary
venous connection; TAC: truncus arteriosus communis; PAPVC: partial anomalous pulmonary
venous connection; L-TGA: congenitally corrected transposition of the great arteries;
IAA: interrupted aortic arch; PA/IVS: pulmonary atresia with intact ventricular septum;
misc.: miscellaneous
</TD>
Associated genetic anomalies were reported in 5.3% and extracardiac organ malformations
in 2.3% of the patients.
As depicted in [Table 3 ]
the proportion of a gestational age of less than 37 weeks was substantially higher
in newborns with CHD compared with all live births in Germany (18.7% vs. 9.1%). Similarly,
a birth weight below 2 500 g was more common in patients with CHD than in the average
newborn (17.5% vs.6.8%). The rate of multiple births was nearly doubled in patients
with CHD compared to all live births (6.2% vs. 3.3%).
Table 3 Numbers and proportions of birth weight <2 500 g, gestational age <37 weeks and multiple
births among all live births in Germany and PAN patients born from July 2006 to June
2007.
<TD VALIGN="TOP">
</TD><TD VALIGN="TOP">
</TD><TD VALIGN="TOP">
Birth weight <2 500 g
</TD><TD VALIGN="TOP">
Gestational age <37 weeks
</TD><TD VALIGN="TOP">
Multiple birth
</TD>
<TD VALIGN="TOP">
</TD><TD VALIGN="TOP">
Numbers
</TD><TD VALIGN="TOP">
(%)
</TD><TD VALIGN="TOP">
(%)
</TD><TD VALIGN="TOP">
(%)
</TD>
<TD VALIGN="TOP">
Total live births per year in Germany*
</TD><TD VALIGN="TOP">
669 298
</TD><TD VALIGN="TOP">
6.8
</TD><TD VALIGN="TOP">
9.1
</TD><TD VALIGN="TOP">
3.3
</TD>
<TD VALIGN="TOP">
PAN patients**
</TD><TD VALIGN="TOP">
5 172
</TD><TD VALIGN="TOP">
17.5
</TD><TD VALIGN="TOP">
18.7
</TD><TD VALIGN="TOP">
6.2
</TD>
<TD VALIGN="TOP">
– Single CHD entities:
</TD><TD VALIGN="TOP">
</TD><TD VALIGN="TOP">
</TD><TD VALIGN="TOP">
</TD><TD VALIGN="TOP">
</TD>
<TD VALIGN="TOP">
– VSD
</TD><TD VALIGN="TOP">
2 598
</TD><TD VALIGN="TOP">
14.0
</TD><TD VALIGN="TOP">
15.2
</TD><TD VALIGN="TOP">
5.2
</TD>
<TD VALIGN="TOP">
– ASD II
</TD><TD VALIGN="TOP">
816
</TD><TD VALIGN="TOP">
26.0
</TD><TD VALIGN="TOP">
29.3
</TD><TD VALIGN="TOP">
9.3
</TD>
<TD VALIGN="TOP">
– PS
</TD><TD VALIGN="TOP">
295
</TD><TD VALIGN="TOP">
15.9
</TD><TD VALIGN="TOP">
18.4
</TD><TD VALIGN="TOP">
7.6
</TD>
<TD VALIGN="TOP">
– PDA
</TD><TD VALIGN="TOP">
241
</TD><TD VALIGN="TOP">
29.0
</TD><TD VALIGN="TOP">
33.1
</TD><TD VALIGN="TOP">
9.0
</TD>
<TD VALIGN="TOP">
– CoA
</TD><TD VALIGN="TOP">
184
</TD><TD VALIGN="TOP">
17.9
</TD><TD VALIGN="TOP">
15.2
</TD><TD VALIGN="TOP">
6.9
</TD>
<TD VALIGN="TOP">
– UVH
</TD><TD VALIGN="TOP">
138
</TD><TD VALIGN="TOP">
10.9
</TD><TD VALIGN="TOP">
12.8
</TD><TD VALIGN="TOP">
4.4
</TD>
<TD VALIGN="TOP">
– AVSD
</TD><TD VALIGN="TOP">
126
</TD><TD VALIGN="TOP">
23.8
</TD><TD VALIGN="TOP">
21.5
</TD><TD VALIGN="TOP">
4.5
</TD>
<TD VALIGN="TOP">
– TOF
</TD><TD VALIGN="TOP">
135
</TD><TD VALIGN="TOP">
20.0
</TD><TD VALIGN="TOP">
14.9
</TD><TD VALIGN="TOP">
5.1
</TD>
<TD VALIGN="TOP">
– AS
</TD><TD VALIGN="TOP">
120
</TD><TD VALIGN="TOP">
17.5
</TD><TD VALIGN="TOP">
19.8
</TD><TD VALIGN="TOP">
5.6
</TD>
<TD VALIGN="TOP">
– D-TGA
</TD><TD VALIGN="TOP">
123
</TD><TD VALIGN="TOP">
6.5
</TD><TD VALIGN="TOP">
8.9
</TD><TD VALIGN="TOP">
3.2
</TD>
<TD VALIGN="TOP">
– DORV
</TD><TD VALIGN="TOP">
56
</TD><TD VALIGN="TOP">
21.4
</TD><TD VALIGN="TOP">
20.4
</TD><TD VALIGN="TOP">
7.1
</TD>
<TD VALIGN="TOP">
– PA/VSD
</TD><TD VALIGN="TOP">
37
</TD><TD VALIGN="TOP">
24.3
</TD><TD VALIGN="TOP">
16.7
</TD><TD VALIGN="TOP">
2.9
</TD>
<TD VALIGN="TOP">
– TAPVC
</TD><TD VALIGN="TOP">
28
</TD><TD VALIGN="TOP">
17.9
</TD><TD VALIGN="TOP">
21.4
</TD><TD VALIGN="TOP">
3.6
</TD>
<TD VALIGN="TOP">
– TAC
</TD><TD VALIGN="TOP">
24
</TD><TD VALIGN="TOP">
33.3
</TD><TD VALIGN="TOP">
20.8
</TD><TD VALIGN="TOP">
4.2
</TD>
<TD VALIGN="TOP">
– Ebstein's anomaly
</TD><TD VALIGN="TOP">
22
</TD><TD VALIGN="TOP">
22.7
</TD><TD VALIGN="TOP">
27.3
</TD><TD VALIGN="TOP">
4.5
</TD>
<TD VALIGN="TOP">
*Source: German Federal Statistical Office and the German National Institution for
Quality Assessment with data on birth weight, gestational age and multiple pregnancy
</TD>
<TD VALIGN="TOP">
**PAN registered patients with complete information on birth weight, gestational age
and multiple pregnancy
</TD>
<TD VALIGN="TOP">
For abbreviations see footnote of [Table 2 ]
</TD>
According to parents’ self reports, a prenatal diagnosis of CHD by echocardiography
was made in 12.1% of all CHD cases ([Fig. 1 ]). The prenatal detection rates were strongly affected by the type of defect. They
were highest for univentricular hearts (68.4%) and Ebstein's anomaly (59.1%).
Fig. 1 Proportion of prenatal screening by echocardiography and of subsequent CHD diagnosis.
Included are infants with complete data set and with information on prenatal screening
given by the parents (n=4 796). For abbreviations see footnote of [Table 2 ]
.
Postnatal diagnoses were made in 52.6% of the patients within the first month of life
and in 82.1% within the first three months. The time of diagnostic ascertainment varied
by the type of defect, severe CHD lesions were usually detected earlier than the mild
ones ([Fig. 2 ]).
Fig. 2 Time of postpartal diagnostic assessment, by type of CHD. Included are infants with
complete data set and information on time of diagnosis (n=4 494). For abbreviations
see footnote of [Table 2 ]
.
Discussion
Discussion
The PAN register covers all of Germany with more than 670 000 live births per year.
The observed prevalence of CHD between July 2006 and June 2007 was 1.08 per 100 live
births.
The PAN study involved nearly all institutions in Germany with a sizable CHD case
load. All university departments treating in particular the moderate and severe CHD
patients, participated in the PAN study with the exception of one department. Only
a minority of children's hospitals and outpatient clinics refrained from active participation,
mostly due to care of very low numbers or of a complete lack of patients with CHD.
Internal quality checks were applied to avoid underreporting as well as multiple reporting
of identical cases. Using automated PID checks in the remote data entry system and
cross-checking of anonymous reports with complete records for variable identity, we
could rule out duplicate registrations in at least 97.5% of severe and over 95% of
moderate CHD cases. Based on design, conduct, participation, performance and quality
control, there is evidence that the PAN study enrolled more than 90% of the CHD patients
born during the study period, and that the prevalences reported here are representative
for Germany.
The proportion of mild cardiac lesions was comparatively high in the PAN study, indicating
a high sensitivity of identifying minor lesions early in life despite being a nation-wide
investigation without active screening modalities. These data are in line with other
studies that noticed a significant increase in the prevalence of mild CHD, in particular
of ventricular septal defects, and attributed this fact mainly to changes in the diagnostic
facilities [4 ]
[21 ]. Likewise, severe cardiac malformations accounted for 12.0% of all cardiac defects
in the PAN study, a finding that again is within the range of previous reports [9 ]
[21 ]. We are unable to present a prevalence trend over time for severe cardiac defects
but it should be noted that prenatal detection of the lesion and consecutive intervention
may have influenced the prevalence, resulting in a decrease of severe defects [8 ]
[15 ].
The overall male/female ratio was 0.88 in the PAN study, compared to a ratio of 1.05
for all live births in the general population during this study period. It is noteworthy
that this ratio was 1.41 for infants with severe cardiac lesions. This result closely
agrees with a ratio of 1.45 reported by Pradat et al. in their study based on registries
of three countries [17 ]. Similarly, the particularly high predominance of males observed in complete transposition
of the great arteries (m/f ratio 2.90) and in aortic valve stenosis (m/f ratio 2.83)
corresponds with results of other studies [11 ]
[12 ]
[17 ].
Prematurity as well as a low birth weight, which are partly associated, are more frequent
among infants of all severity categories of CHD when compared to the national average.
We further noted that patients with a univentricular heart or a transposition of the
great arteries were more frequently born at term and with a normal birth weight than
patients with other CHD, confirming previous observations [20 ].
The numbers of associated extracardiac organ malformations or genetic anomalies reported
by us are lower than those mostly reported by others [16 ], which is probably due to the diagnosis assessment made very early within the first
year of life.
We further report on a relatively high occurrence of multiple births in newborns with
CHD which was particularly common in mild lesions as found before by Pradat et al.
[17 ]. The reasons for high rates of multiples among CHD births remain unexplained as
data on fertilization modalities or the proportion of monochorionic/diamniotic twins
[2 ] were not available in our study.
Based on the parents’ own reports of prenatal history, the detection rates for univentricular
heart and other severe lesions by echocardiography were fairly high while the general
detection rate of CHD was as low as reported by others [15 ].
CHD was diagnosed early after birth: more than one half of the patients were detected
within the first month and more than 80% within three months of life. These numbers
may be taken to reflect the qualified postnatal diagnostic care in Germany. As could
be expected, the diagnosis was made earlier in infants with more severe cardiac defects.
It is a strength of the PAN study that it covers a large European country with a high
level of completeness. To our knowledge this study enrolls the largest number of CHD
within a one year period of data acquisition ever reported. Furthermore, the EPC-code
was used for classifying cardiovascular lesions which offers advantages over the widely
used international code of diseases (ICD) with its restricted differentiation of the
single malformations. As a limitation, the proportion of anonymous reports – though
containing full medical diagnoses – limited some subgroup analyses, e. g. influence
of birth weight and gestational age. However, since baseline characteristics were
equally distributed between complete and anonymous cases, it is unlikely that selection
bias has influenced these results.
Conclusion
Conclusion
The PAN study reports a prevalence of 1.08% of CHD among all live births in a German
national register.
The high proportion of mild CHD indicates a good diagnostic coverage early in life.
The prevalence of severe malformations is concordant with reports of others. CHD in
live births is associated with a high proportion of prematurity, low birth weight
and multiple births. The ongoing data acquisition of the PAN study will stabilize
estimates of prevalence in particular for the rare cardiac lesions and will provide
a basis for follow-up studies on etiological and prognostic factors.
This study is being supported by the Competence Network for Congenital Heart Defects
funded by the Federal Ministry of Education and Research, [FKZ 01GI0601].
This publication is dedicated to P. E. Lange, the founder of the Competence Network
for Congenital Heart Defects, for his constant encouragement and support of the study.
Acknowledgements
Acknowledgements
The authors are grateful to the following:
– All institutions participating in the PAN study. They are listed in the e “Supporting
Information”.
– J. Frei, M. A. Körten, J. Olchvary and A. Meyer-Rapp for their assistance in data
collection and management.
– The Network Central Office, Berlin, the CIO-Office, University of Göttingen and
the Biostatistics Department, University of Magdeburg for providing infrastructural
facilities and support.
We wish to thank G. Graham for his critical reading of the manuscript.
Conflict of Interest: The authors have no conflict of interest to disclose.