Pediatr Cardiol 8:247-256, 1987

Pediatric Cardiology
9 Springer-VerlagNew YorkInc. 1987

Monitoring of Congenital Cardiac Defects

Lars Erik Carlgren, t Anders Ericson, 2 and Bengt K~llrn 3
~Department of Pediatrics I, Division of Cardiology, University of Gothenburg. Gothenburg; -'National Board of Health and Welfare, Bureau FAP 3, Stockholm; and 3Department of Embryology, University of Lund, Lund, Sweden

SUMMARY. An effort was made to identify all infants born with a congenital cardiac defect in 1981 in Sweden by using four different registries: the Swedish Registry of Congenital Malformations, the Medical Birth Registry, the Registry of Death Certificates, and a specially designed Child Cardiology Registry. All infants diagnosed before the age of one year at one of the five child cardiology clinics in Sweden were reported to the latter registry. This registry, together with the Congenital Malformation Registry, can be used for surveillance as they together cover 85%-90% of all severe cases identified. The data quality in the Medical Birth Registry is too low to permit meaningful surveillance. A total of 853 infants with a diagnosis of a congenital cardiac defect were identified. This represents 9 per 1000 newborns. Many of the cases were dubious, but the diagnosis was stated as probable in 708 (7.6 per 1000); 146 infants died. Cardiac diagnoses were stored in the Child Cardiology Registry and in the Registry of Congenital Malformations as ISC codes. A Monitor Code is described that can be used for grouping and monitoring of diagnoses. Using these codes, data in the Child Cardiology Registry for 1981-1983 were analyzed and epidemiologic information on maternal age and parity, sex rate, and birth weight distribution is given. KEY WORDS: Congenital heart defects - - Registry - - Monitoring

Since the middle of the 1960s, many countries or areas within countries have set up surveillance registries for congenital malformations with the primary aim of detecting and analyzing changes in the prevalence at birth of specific types of malformations. This is a difficult problem [7], even when easily diagnosed and externally visible malformations are monitored. The problem gets still larger with internal malformations that are sometimes difficult to diagnose and that may not produce symptoms until some time after birth, e.g., congenital heart defects. They are relatively frequent, representing a multitude of different morphologic types with difAbbreviations: ASD, atrial septal defect; CoA, coarctatio aortae; CR, Child Cardiology Registry; ECD, endocardial cushion defect; HLHS, hypoplastic left heart syndrome; ICD, International Classification of Diseases, Injuries, and Causes of Death; ISC, International Society for Cardiology; MBR, Medical Birth Registry; PDA, patent ductus arteriosus; RCM, Registry of Congenital Malformations; TGV, transposition of great vessels; and VSD ventricular septum defect. Address reprint requests to: Prof. Bengt Khllrn, Department of Embryology, Biskopsgatan 7, S-22362 Lund, Sweden.

ferent morphogeneses and with different pathophysiologic effects. Even serious cardiac defects may not produce symptoms until after the first week of life. Furthermore, the diagnosis of a cardiac defect in a living infant to a large extent depends on the available diagnostic technology and surgical fac i l i t i e s - a n d in the dead infant on the use of autopsy. The causes of congenital heart defects are complex. Although genetics play a role, exogenous factors have sometimes been shown to increase the risk for a cardiac defect to develop; examples are maternal rubella, maternal alcoholism, and maternal use of lithium, thalidomide, or some anticonvulsant drugs. This further strengthens the case for a good surveillance of cardiac defects in order to detect new teratogens. In Sweden, a Registry of Congenital Malformations was started in 1964 [6] and became compulsory in 1965. Even before this registry was set up, the difficulties of diagnosing cardiac defects in the newborn had been realized and registration was limited to infants who were judged to have a clinically

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Pediatric Cardiology Vol. 8, No. 4, 1987

Per L000 births 2-

Materials and Methods

Registry of Congenital Malformations

The function of this registry has been described [6]. With respect to cardiac defects, the following conditions should be noted: (a) Only infants with cyanosis or cardiac failure or that died during the first week of life whose symptoms are reasonably thought to be caused by a cardiac defect are registered. (b) Infants with a known syndrome and a cardiac defect (e.g., Down's syndrome) are registered based on the syndrome, not on the cardiac defect. (c) Infants are registered only when reported within six months after their birth. Reports to the registry may come directly from the delivery unit or from the pediatric unit that cares for the infant. If a report is obtained from the children's cardiology clinics (see below) that fulfills the criteria for inclusion in the Registry of Congenital Malformations, the case is included even though it has not (yet) been reported by the delivery hospital. Coding of the heart defect is made by one of us (B.K.) using the ISC code list used in the Child Cardiology Registry (see below).

0
Year

Fig. 1, Incidence of infants registered in the Registry of Congenital Malformations with diagnosis of a cardiac defect. s e v e r e h e a r t d e f e c t , r e s u l t i n g in d e a t h , c y a n o s i s , or c a r d i a c d e c o m p e n s a t i o n . U s i n g this c r i t e r i o n m d i s r e g a r d i n g the t y p e o f c a r d i a c d e f e c t - - a s t e a d y inc r e a s e in the registered rate was s e e n d u r i n g the o b s e r v a t i o n p e r i o d (Fig. 1). I n 1973, the M e d i c a l Birth R e g i s t r y - - a c o m p u t erized r e g i s t r y o f all d e l i v e r y r e c o r d s in the c o u n t r y - w a s e s t a b l i s h e d , listing, a m o n g o t h e r things, d i a g n o s e s for the i n f a n t , i n c l u d i n g c a r d i a c defects. T h e n u m b e r o f i n f a n t s r e g i s t e r e d with such d i a g n o ses w a s , of c o u r s e , m u c h higher t h a n the n u m b e r r e g i s t e r e d in the R e g i s t r y o f C o n g e n i t a l M a l f o r m a t i o n s , b u t t h e r e w e r e n o specific c a r d i a c d i a g n o s e s in the m a j o r i t y o f c a s e s (Fig. 2A). W h e n the m o s t c o m m o n a m o n g the specified d i a g n o s e s w e r e studied (Fig. 2B), the o n l y o n e with a definitely i n c r e a s ing t r e n d was p a t e n t d u c t u s , b u t the large g r o u p o f s u s p e c t e d or u n s p e c i f i e d d i a g n o s e s m a k e s studies o n the specified d i a g n o s e s v e r y u n c e r t a i n . F r o m 1977 o n w a r d , efforts w e r e m a d e to inc r e a s e the q u a l i t y a n d a c c u r a c y o f the r e p o r t s on i n f a n t s with c a r d i a c d e f e c t s b y r e q u e s t i n g r e p o r t s also f r o m the child c a r d i o l o g y clinics in the c o u n t r y . T h e e a r l y efforts w e r e n o t v e r y effective, so a n e w r e p o r t i n g s y s t e m , the Child C a r d i o l o g y R e g i s t r y , w a s e s t a b l i s h e d in 1980. T h i s registry w a s i n t e n d e d n o t o n l y to i n c r e a s e the p o s s i b i l i t i e s o f s u r v e i l l a n c e o f c a r d i a c d e f e c t s , b u t also to s u p p l y v a l u a b l e feedb a c k i n f o r m a t i o n to the r e p o r t i n g c l i n i c i a n s . T h e first c o m p l e t e b i r t h c o h o r t i n c l u d e d in this registry was that b o r n in 1981. W e here d e s c r i b e the i d e n t i f i c a t i o n o f i n f a n t s with c a r d i a c d e f e c t s b o r n in S w e d e n in 1981, as r e p o r t e d to the t h r e e a b o v e - m e n t i o n e d registries. I n f o r m a t i o n f r o m d e a t h certificates o f i n f a n t s that died w i t h i n o n e y e a r o f birth are i n c l u d e d . D a t a f r o m the Child C a r d i o l o g y R e g i s t r y for 1982-1983 w e r e a n a l y z e d u s i n g its 1981 b a s e l i n e data.

Medical Birth Registry

In this registry, each infant can have four diagnoses, coded according to the ICD code (Swedish modification [8]), These include malformation diagnoses. The cardiac defect codes (746747) in the Swedish ICD version used do not quite correspond to the international one, but enable some further specification (Table l). If an infant with, for example, Down's syndrome, also has a cardiac defect, both diagnoses can be given, Diagnoses can be added as long as the inthnt is in hospital care, at the delivery unit or in a pediatric ward for instance, and there is thus no fixed seven-day limit. Similarly, reports can be entered more than six months after the birth of an infant--the finalization of the registry usually takes place more than one year after the calendar year studied.

Child Cardiology Registry

The five pediatric cardiology units in Sweden (Karolinska and St, GcSran Hospitals in Stockholm, Uppsala, Lund, Gothenburg) have agreed to report infants in whom a cardiac defect has been diagnosed during the first year of life at that clinic. A special form is used, Only infants with a defect diagnosed by echocardiography, cardiac catheterization, at operation, or at autopsy are included, and isolated patent ductus under the age of three months should not be reported. The report form contains some basic information on patient identity including mother's identity, delivery hospital, birth weight, sex, time of first symptoms (-<7 days, >7 days, unknown), possible time of death, and place of autopsy. Furthermore, all cardiac defects diagnosed are described verbally, dates for echocardiography, catheterization, and operation are given, and all operations performed are stated. Presence of possible extracardiac malformations or severe diseases is stated. Cardiac malformations are coded after a slightly modified ISC code [5] that consists of 3-digit codes with a high specificity. Up to eight such codes can be used for each infant. Coding is done by one of us (L.E.C.).

Carlgren et at.: Heart Defect Monitoring

249

A Per 1,000 births

1098-

Per 1,000 births 1.5-

7.
6.

5432l. 0

All
~ ~ 7~3 "7/~ 7'5 7'6 77
Year

VSO unspecified

lc

. VSD PDA

0.s ,,TGV ' ~ iz;,c..... "~.HLHS ............ ~"~:uASD 9 "CoA 78 ")9 8'0 81

~ " . . . . . 718 719

"'-~"-~ 76 47 Year

80 81

7'3

";~

?'5

Fig. 2. Frequency of cardiac defect diagnoses (746-747 excluding 747.70) per 1000 infants registered in the Medical Birth Registry. (A) The frequency of all diagnoses and the proportions made up of suspected or unspecified cases and of ventricular septal defects. (B) Corresponding graphs for the six most-frequent specified diagnoses.

Death Certificates
All death certificates of infants born and dead before the age of one year were scrutinized and a list of infants with diagnoses 746 or 747 was prepared. In the death certificates, the international ICD code Ili] is used (cf. Table 1). The four registries are briefly summarized in Table 2. Those infants surviving the immediate postnatal period that were not reported to the Child Cardiology Registry were followed up as well as possible. A number of diagnostic mistakes in the other registries could then be identified. The infants recorded in these four registries were compared individually, using the mother's personal identification number (a unique number that every Swedish citizen has), and the infant's birth date or identification number. Sometimes, obvious mistakes had been made in these numbers and dates, and when identified they were corrected. A common file was prepared of these infants containing information on delivery hospital, mother's and infant's identification numbers, number and outcome of previous pregnancies, infant's birth date (and possibly identification number), length of pregnancy, sex, birth weight, possible death date, and the codes listed in the different registries. From this file, the various tables and graphs were prepared.

only with an ICD code in the Medical Birth Registry, and 75 of these had only the code 746.90 or 747.90, i.e., a suspected cardiac or circulatory organ malformation; two infants had only the diagnosis of cardiac malposition; and 68 infants had a diagnosis of PDA and a birth weight below 2500 g. If these 145 dubious cases are removed, the remaining 708 represent a prevalence at birth of 7.6 per 1000. The Child Cardiology Registry and the Registry of Congenital Malformations together register 256 infants, 225 of whom were recorded in the former registry. Another 35 infants with cardiac diagnoses were not included in those registries, but were identified from death certificates (20 of them also had cardiac diagnoses in the Medical Birth Registry); 17 dead infants had a cardiac diagnosis in that registry, but did not appear in other registries. The total number of dead infants registered with cardiac diagnoses was 146, but nine of them had merely a PDA at a birth weight below 2500 g.

Results

Diagnoses in Registries Other than the Child Cardiology Registry and the Registry of Congenital Malformations
Table 3 presents the distribution of diagnoses among infants registered only in the Medical Birth Registry or identified from death certificates (599 infants). Scrutiny of the original records showed that at least seven (two from the Medical Birth Registry, four from death certificates, and one from both sources) actually had no cardiac defect in spite of their diagnoses. At least some of the others appear to fulfill the criteria for inclusion in the Child Cardiology Registry.

Number of Infants with Diagnoses of Cardiac Defects and Distribution between Sources
A total of 853 infants born to 848 women (in four twin pairs both infants had a cardiac diagnosis and two infants in a set of triplets also both had a cardiac diagnosis) in 1981 have been identified, along with some information on cardiac defects. This represents a prevalence at birth of 9.1 per 1000, because 93,678 infants were born in Sweden in 1981 (liveborn and stillborn): 564 of them were identified

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Table 6. Monitor Codes used Code 10 11 12 13 20 21 30 Content Cor bi/triloculare, includes common truncus, transposition, or valvular malformations when also present ASD with no other defect than possibly PDA VSD with no other defect than possibly PDA ASD + VSD with no other defect than possibly PDA Common truncus if not cor bi/triloculare Transposition, double-outlet, includes VSD, ASD, PDA, and malf. of aortic or pulmonary valves Aortic valve malformations if no transposition or cor bi/triloculare, includes VSD, ASD, PDA, and mitral malf. Pulmonary artery malformations if no transposition or cor bi/triloculare, includes VSD, ASD, PDA, and tricuspidal malformations except tricuspid atresia Endocardial cushion defects, includes malformations in tricuspid or mitral valves Mitral valve anomalies if no ECD and without aortic atresia or stenosis Pulmonary valve anomalies if no ECD and without pulmonary artery atresia or stenosis Ductus arteriosus malformations if no other cardiac defect Aorta malformations includes HLHS and interrupted arch Coronary artery malformations without aortic atresia/ stenosis Pulmonary artery malformations Other systemic artery malformations Venous anomalies, including cor triatriatum Other anomalies

R 2.0-

,J ~ / - . . .

,/tt
'. ",

/"

..."

-dead

all

1.o
..

.,..,~
/ ./
/

.~"

0.~

. in '.CR/RCM

35

15

2'0

25 :'

30 ' Maternal

35 acle

40

/,'5

Fig.

40 41 42 50 51 54 55 56 60 7O

3. Effect of maternal age on registration frequency, expressed as relative risks (R): all, all infants identified from any one of the four sources; all dead, all dead infants with a cardiac diagnosis in any one of the four sources; and CR/RCM, all infants in the Child Cardiology Registry or the Registry of Congenital Malformations.

fled" (746.99) heart defect: 90 had the former diagnosis; 75 of them did not appear in other registries, two still had an unspecified heart defect as a death certificate diagnosis, and 13 (17%) had a final diagnosis (12 in the Child Cardiology Registry and one on the death certificate). The "unspecified" diagnosis was given to 368 infants in the Medical Birth Registry: 308 of them did not appear in other registries, two remained on the death certificate as unspecified heart defects, and 58 (16%) had a specific diagnosis (five on the death certificate, 53 in the Child Cardiology Registry).

infant with a cardiac defect. If all are included, a marked increase in the risk is present in higher age groups. A Cochran-Armitage test for linear trend gives chi-square = 6.0 at 1 df, p = 0.025 > p > 0.01. If the study is restricted to definite cases, an underrisk is indicated at a maternal age below 20 or above 40 years, but is based on low numbers and no statistical significance exists (chi-square = 1.7). If the study is restricted to only dead infants with heart defects--irrespective of s o u r c e - - a steady increase with age is seen with the exception of the highest age group, and the trend is again significant (chisquare = 6.6, p = 0.01).

Parity. As seen from Fig. 4, no definite parity effect

is seen for registered heart defects until the highest parity group, 4 + , where an increased risk is for a dead infant with a heart defect, but it is of marginal statistical significance (chi-square = 3.6, p = 0.05).

Sex Ratio. Among all infants born in Sweden in

1981,51.2% were boys (excluding 13 with unknown sex). Among all infants registered with a cardiac defect, the percentage of males in only 49.0%, but this difference is not statistically significant (chisquare = 1.7 at 1 df). For infants registered in the Child Cardiology Registry or the Registry of Congenital Malformations or for dead infants, the percentage is even slightly higher than the value for the country, 54.5%, but again not significantly so (chisquare = 1.2 at 1 df).

Some Epidemiologic Characteristics

Table 10 presents information on maternal age and parity distribution, sex distribution, and birth weight distribution of the material and of all births registered in Sweden in 1981.

Maternal Age. Figure 3 shows the maternal agespecific risk ratio (R) of a woman to give birth to an

Birth Weight. As shown in Fig. 5, the birth weight

distribution of these infants is markedly abnormal

Carlgren et al.: Heart Defect Monitoring

253

Table 7. Number o f Monitor Codes registered in 1981 among 256 infants in the Child Cardiology Registry or the Registry o f Congenital Malformations (CR/RCM): as single or as multiple (that is, with also other Monitor Code); also such infants in only the Child
Cardiology Registry (CR) registered 1981-1983

Monitor
Code

Diagnoses (abbreviated)

CR/RCM 1981
Single Multiple 9 4 13 4 2 9 11 12 9 0 2 0 29 1 5 4 21 10

CR 1981
Single 3 9 39 6 2 23 19 33 5 4 4 5 8 2 1 0 3 4 Multiple 6 3 11 2 2 9 10 11 9 0 2 0 24 ! 3 4 17 8

CR 1982
Single 6 7 29 7 0 21 9 32 10 0 1 10 11 i 0 1 2 6 Multiple 3 8 16 6 5 5 13 19 11 0 2 0 40 3 5 5 21 21

CR 1983
Single 2 6 21 4 3 30 20 20 24 1 3 8 10 2 0 1 4 2 Multiple 5 6 13 2 1 10 t2 11 7 3 3 0 40 0 5 1 8 9

10 11 12 13 20 21 30 35 40 41 42 50 51 54 55 56 60 70

Cor bi/triloculare ASD VSD A S D + VSD Common truncus Transpositions Aortic valve mall, Pulmonary valve malf. Endocardial cushion def. Mitral valve malt'. Tricuspidal valve malf. Ductus arteriosus malf. Aortic arch malf. Coronary vessel malf. Pulmonary artery mall. Other systemic art. malf. Vein malformations Other specified malf.

6 10 40 6 4 24 25 35 5 6 5 5 9 2 1 0 3 4

R 2.0-

25-

20
dead/" / . " in CR / RCM I.o
10
0'.

\~ dead all
\

all

'

0
Parity
Fig. 4. Effect of parity on registration frequency. Calculations and designations as in Fig. 3.

1.0

1.5 2.0

2.5 3.0 3.5 4.0 4.5 5~ 5.s Birth weight, kg

Fig. 5. Effect o f birth weight on registration frequency. Calculations and designations as in Fig, 3.

with an increased risk at low birth weight (partly explainable by the inclusion of PDA in low birth weight infants). Also for the group registered in the Child Cardiology Registry and the Registry of Congenital Malformations, an increased risk for heart defects is seen in infants with a birth weight below 2.5 kg (chi-square = 451, p < 0.001).

Syndromes. In 61 infants, the cardiac defect was

associated with a syndrome where a high incidence of cardiac defects is well known. Down's syndrome was present in 39 of the cases (19 were only re-

corded in the Medical Birth Registry) and trisomy 18 in 13 eases (one only in the Medical Birth Registry). In 17 of the Down's syndrome infants, unspecified diagnoses were given, nine had ECD, possibly with other defects, nine had septal defects (ASD, VSD, or both), and the remaining four had VSD + CoA, VSD + pulmonary artery stenosis, Fallot, and an unspecified heart valve defect, respectively. The total number of infants with Down's syndrome born in Sweden in 1981 was 129 and cardiac defects diagnosed before the age of one year were thus recorded in 30% of them.

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Pediatric Cardiology Vol. 8, No. 4, 1987

2.4 per 1000 when only cases confirmed by invasive methods were included. If the diagnoses recorded by Carlgren [1, 2] are selected that should, today, have resulted in catheterization, operation, or death of the individual, the corresponding figure would be approximately 3.3 per 1000 births. It therefore seems probable that we have had a rather good ascertainment with the use of the Child Cardiology Registry and the Registry of Congenital Malformations, supplemented with information from death certificates. Perhaps ten further cases, where a reasonable severe diagnosis was given in the Medical Birth Registry without the case appearing in the other registries, should be added. In order to obtain adequate monitoring, it is not necessary to have a complete ascertainment, and the ascertainment obtained by the Child Cardiology Registry combined with the Registry of Congenital Malformations is probably enough to permit monitoring. If we add approximately 30 of the cases listed in Table 2, which probably should have been ineluded in the Child Cardiology Registry and the Registry of Congenital Malformations but were not, these registries cover approximately 90% of all cases intended to be registered. This, however, presupposes that not a large number of "suspected" or "unspecified" cardiac defects in the Medical Birth Registry were not serious cases that were missed in reporting. It is hard to understand why this should be the case. It is perhaps more likely that the approximate 10% underascertainment is valid also for those cases, which would result in a final ascertainment of approximately 85% in the Child Cardiology Registry and the Registry of Congenital Malformations as a conservative estimate. This degree of underascertainment may be acceptable and the price to be paid to get such specific diagnoses that possible changes in one group of cardiac malformations are not hidden in fluctuations of the large group of VSDs and other common but less serious defects. Even using these data, changes in recorded rates may occur due to changes in medical routines. Table 8 shows that the number of infants with ECDs increases from 13 in 1981 to 36 in 1983. The probable explanation is the widespread and increasing use of echocardiography, which makes it easy to diagnose this malformation before the age of one year. A decline in the number of registered VSDs is also seen--diagnosis of this condition with invasive methods before the age of one may be affected by referral practice and access to diagnostic facilities. The fluctuation of the number of CoAs, if not random, is difficult to explain. The usefulness and efficiency of such an analy-

sis as that presented can be judged only after a longer period--perhaps 5-10 years. So far, only three consecutive years have been compared. Figures 1 and 2 show that time trends in crude diagnostic groups like cardiac defects without further specification are difficult or impossible to interpret, especially as this is a group of malformations for which ascertainment may well vary with time. A monitoring of cardiac defects with the aid of standard medical birth registries [I0, 13] or similar instruments is probably so uncertain that no conclusions should be drawn from them. Multiple-source ascertainment as that used may prove necessary for monitoring.

References
1. Carlgren L-E (1959) The incidence of congenital heart disease in children born in Gothenburg 1941-1950. Br Heart J 21:40-50 2. Carlgren L-E (1969) The incidence of congenital heart disease in Gothenburg. Proc Assoc Eur Paediatr Cardiol 5:2-8 3. Ferencz C, Rubin JD, McCarter, RJ, Brenner JI, Neill CA, Perry LW, Hepner SI, Downing JW (1985) Congenital heart disease: prevalence at livebirth: the Baltimore-Washington infant study. A m J Epidemiol 121:31-36 4. Fyler DC, Buckley LP, Hellenbrand WE, Cohn HE, Kirklin JW, Nadas AS, Cartier JM, Breibart MH (1980) Report of the New England Regional Infant Cardiac Program. Pediatrics 65 [Suppll:375-461 5. International Society of Cardiology (1970) Classification o f heart disease in childhood. VRB Offsetdrukkerij, Groningen, The Netherlands 6. K~illrn B, Winberg J (1968) A Swedish Register of Congenital Malformations: experience with continuous registration during 2 years with special reference to multiple malformations. Pediatrics 41:785-776 7. Kallrn B, Hay S, Klingberg M (1984) Birth defects monitoring systems: accomplishments and goals. In: Kalter H (ed) Issues and reoiews in teratology, vol 2. Plenum, New York, pp 1-22 8. Klassifikation at) sjukdomar 1968 (Classification o f diseases], 2nd edn. (1969) Swedish National Board of Health, Stockholm 9. Mitchell SC, Korones SB, Berendes HW (1971) Congenital heart disease in 56,109 births: incidence and natural history. Circulation 43:323-332 10. Windham GC, Bjerkedal T (1984) Malformations in twins and their siblings, Norway, 1967-1979. Acta Genet Med Gemellol 33:87-95 11. World Health Organization (1967) Manual o f the international statistical classification o f diseases, injuries, and causes o f death. World Health Organization, Geneva 12. World Health Organization Working Group on Congenital Heart Disease in Europe (Document EURO 8213), Copenhagen, 1972 13. Layde PM, Dooley K, Erickson JD, Edmonds LD (1980) Is there an epidemic of ventricular septal defects in the U.S.A.? Lancet 1:407-408.