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PEDIATRICS Vol. 106 No. 1 July 2000, pp. 86-91
From the Hospital for Children and Adolescents, Helsinki University Hospital, Helsinki, Finland.
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ABSTRACT |
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Top
Abstract
Methods
Results
Discussion
Conclusion
References
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Objectives. Few data are available in the literature regarding the long-term outcome of newborns with congenital complete heart block (CHB). The aims of this retrospective study were to assess neonatal morbidity and mortality, incidences of dilated cardiomyopathy (DCM), and associated heart defects, and to establish prenatal and postnatal factors that might predict adverse outcome in children with CHB.
Design and Setting. The cohort includes 91 infants with CHB diagnosed in 5 tertiary centers in Finland between 1950 and 1998.
Patients. Maternal connective tissue disease was evident in 89% of the patients. At birth, the median gestational age was 37.1 weeks, and the median weight was 2969 g. Of the 91 infants, 60 (66%) were girls and 7 (8%) were twins.
Results. Incidences of perinatal morbidity and mortality were 58% and 7%, respectively. The total mortality of CHB was 16%; 11 of 15 (73%) died during the first 12 months. Cumulative probability of survival at 10 years old was 82%. Pacing as a newborn was indicated in 48 of 90 cases (53%), and 36 received pacemakers at older ages. Cardiac defects not causally related to CHB were found in 38 of 90 patients (42%), of whom 22 were operated on. DCM was found in 21 (23%), of whom 13 died. During the follow-up, among 75 survivors with a median age of 9 years, 54 (72%) are free from symptoms. Poor outcome defined as clinically or pathologically evident congestive DCM was associated with intrauterine hydrops, low fetal and neonatal heart rate, low birth weight, male sex, and neonatal problems attributable to prematurity or neonatal lupus.
Conclusions. Despite early pacing, CHB carries high mortality during the first 12 months of life. High incidences of DCM and associated heart defects indicate close echocardiographic monitoring of all children with CHB. Key words: heart block, pediatrics, cardiomyopathy, heart defects, follow-up studies.
Congenital complete heart block (CHB) without intracardiac
structural abnormality is a potentially lethal disease affecting fetuses and newborns.1-3 In previous studies, it has been
estimated that 1 of every 15 000 to 20 000 live births results in an
infant with CHB.4 In a recent study, Siren et
al5 found that the incidence during the last decades in
Finland has increased from 1:25 000 to 1:11 000. It may be attributable
to the better diagnostic methods and more effective antenatal and
neonatal care of the children with CHB. It is also possible that the
actual incidence has increased because of the increasing number of
successful pregnancies in women with connective tissue disease.
CHB is associated with a maternal autoimmune disorder with
autoantibodies against SS-A/Ro and/or SS-B/La antigens,6 which may subsequently elicit an immune-mediated tissue
injury.1,7 Histologically, there is fibrous replacement of
the conducting tissue,7 which is best interpreted as
resulting from apoptosis.8 Transplacentally mediated
maternal antibodies may cause immunomyocarditis and severe prenatal or
postnatal dilated cardiomyopathy (DCM).9,10
Few data are available regarding the long-term outcome of newborns with
CHB. Asymptomatic neonates do not have absolute indications for pacing,
but low heart rate combined with long QT interval has a remarkably poor
outcome.10 In previous reports, the mortality rates of CHB
varied from 8% to 19%11,12 and were mostly attributable
to cardiac failure in the neonatal period.12 Accordingly,
the objective of the present study was to assess neonatal morbidity and
mortality, causes of death, indications for pacemaker treatment, and
incidences of DCM and anatomic heart defects of the patients with CHB.
The secondary objective was to establish prenatal and postnatal factors
that might predict adverse outcome in children with CHB.
We undertook a retrospective follow-up study of 91 children who
have CHB without major structural abnormality diagnosed in utero or
immediately after birth in 5 tertiary referral centers in Finland
between 1950 and 1998. Of them, 64 fetuses and children have been
diagnosed and followed at the Hospital for Children and Adolescents in
Helsinki, and 27 have been followed by pediatric cardiologists in other
university hospitals. This study was approved by an institutional
review board. In 1998, 22 patients are >15 years old and are
followed by an adult cardiologist at 5 university hospitals. The median
follow-up age is 9.0 years (range: .5-47.5 years).
The records of the mothers were reviewed to assess gestational weeks of
detection of CHB, medications taken during the pregnancy, gestational
length of the pregnancy, mode of delivery, and the obstetric history of
all pregnancies before and after the affected pregnancy. If available,
perinatal echocardiographic reports were reviewed to note the presence
or absence of effusions or hydrops and the atrial and ventricular rate
of the fetus. The time of detection of CHB is taken as the earliest
documentation of a bradyarrhythmia in the prenatal medical record of
the mother. The information of maternal serum samples containing
antibodies to SSA/Ro or SSB/La was registered. Additional information
was obtained by sending a questionnaire to the mothers. Emphasis was
placed on organ system involvement characteristic of a rheumatic
disease.
Records of the affected neonates were reviewed to assess heart rate,
incidences of neonatal morbidity and mortality, and the age at
pacemaker implantation. Echocardiographic data and electrocardiograms (ECGs) were registered. The records of older patients were reviewed to
demonstrate associated structural abnormalities, left ventricular function during follow-up, the age and number of cardiac procedures, including pacemaker implantation and heart surgery, and chest radiographic and Holter monitor (ambulatory 24-hour ECG)
information. DCM was defined as clinically evident severe congestive
heart failure associated with cardiomegaly in radiograph and poor left ventricular function on echocardiography. Associated structural abnormalities included in this study were lesions not considered causally related to heart block, such as small ventricular septal defect (VSD), patent ductus arteriosus (PDA), secundum atrial septal
defect (ASD), pulmonary valve stenosis, and mild-to-moderate mitral
valve regurgitation. No child with chromosomal abnormality was
included. Clinical up-to-date information was collected from the
hospitals, parents, and adult patients. All the subjects gave informed
consent. The most recent echocardiographic or radiographic data and
ECGs were reviewed. Information of necropsy analysis of the cardiac
structure and histology were collected when available.
Data are presented as mean ± standard deviation or as median
(range). Poor outcome was defined as clinically or pathologically evident congestive DCM. The 2 groups (good or poor prognosis) were
compared. Dichotomous variables were contrasted using
The study population consists of 91 offspring of 89 pregnancies of
82 mothers. At the time of identification of CHB, symptoms of
connective tissue disease were evident in 55 mothers (67%), of whom 36 (65%) had Sjögren's syndrome, 9 (16%) had systemic lupus erythematosus, 8 (15%) had rheumatoid arthritis, and 2 (4%) had
undifferentiated autoimmune syndrome. The total incidence of connective
tissue disease was 89%, after the delivery diagnosis has been made in
17 mothers.
The time of detection of CHB was defined as the first prenatal record
of bradyarrhythmia. The median gestational age at diagnoses was 29.3 weeks (range: 17-40 weeks). Detection was most frequently (59%)
clustered between 25 and 34 weeks. However, 17 cases (20%) were first
identified after 35 weeks of gestation, 8 cases immediately after
birth. No cases were detected before 17 weeks of gestational age.
Antenatal medication was administered in a total of 20 pregnancies. In
every case, treatment was started after the identification of CHB. In
12 cases, glucocorticoid was started to improve neonatal pulmonary
outcome. Dexamethasone sodium (6 mg per dose) was started by
intramuscular injection every 12 hours for a total of 4 doses. Seven
mothers were taking prednisone (10-40 mg/day) and 2 acetosalicylic acid for underlying clinical disease activity.
Two mothers received The median gestational age at birth was 37.1 weeks (range: 29-41
weeks). Of the 53 deliveries by cesarean section, emergency section was
performed in 15 cases, 5 when gestational age was <37 weeks. The
median birth weight was 2969 g (range: 905- 4370 g). Of the
91 offspring, 60 (66%) were girls and 41 were boys. There were 5 sets
of twins; in 2 of these sets, both twins had CHB, and in 3 sets, only 1 twin had CHB. The recurrence rate in the same family was 10%; in 7 families, 71 of the mothers' next pregnancies resulted in a second
child with CHB.
Total perinatal morbidity was 58% and mortality 7% (Table
1). There was 1 stillbirth at 38 weeks of
gestation (CHB diagnosed by fetal echocardiogram 7 weeks before death).
The fetus with weight of 2614 g had no hydrops. Postmortem
examination revealed enlarged heart without structural abnormality. All
neonates who died early had severe congestive heart failure; 1 death
resulted from multiorgan failure associated with cardiac perforation
after endocardial wire placement (Table
2). Hydrops was evident in 24 of 90 patients; of these, 6 (25%) died within 3 months of age. In utero,
heart rate was significantly lower in fetuses with hydrops than in
those without hydrops (50/minute vs 61/minute; P = .0001). Neonatal infection, defined as septicemia or infectious pneumonia, was evident in 17%, and symptoms of neonatal lupus were
evident in 18% of the patients (Table 1).
TABLE 1 TABLE 2
METHODS
Top
Abstract
Methods
Results
Discussion
Conclusion
References
2 analysis (1-tailed) or by Student's
t test (2-tailed). Ordered categoric variables and skewed
discrete variables were contrasted using the Mann-Whitney U
test. Continuous variables were analyzed by Student's
t test. We regarded P < .05 as significant.
RESULTS
Top
Abstract
Methods
Results
Discussion
Conclusion
References
-sympathomimetics (salbutamol) to increase
fetal heart rate. Digitalis was started in 2 mothers because of fetal
cardiac decompensation and hydrops.
Neonatal Morbidity (n = 90)
Clinical Details of Deaths (n = 16)
Forty-eight of the 90 children (53%) required pacemakers as newborns (Fig 1). Of these children, 8 (17%) died within the first year of life attributable to cardiac failure (Table 2). Thirty-six children have been paced later during the study. In these patients, heart rate decreased significantly during the follow-up (from 67 to 42 beats/minute; P = .0001). Only 6 patients of the whole study population have not been paced during the follow-up years. Indications for pacing are shown in Table 3.
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Thirty-eight (42%) children had miscellaneous structural lesions not known to be associated with the development of CHB. ASD secundum was evident in 19 patients (21%), of whom 13 were operated on. Three patients with ASD accompanied with DCM died, 1 after ASD operation. PDA was found in 12 (13%) patients, of whom surgical ligation was needed in 9 cases. Among them, 4 had DCM; 1 died and 1 underwent heart transplantation. Three patients had small muscular VSDs (3%) detected by cardiac ultrasound. During the follow-up, these have closed spontaneously. Two patients (2%) had mitral valve defects; 1 newborn with severe cardiac failure attributable to DCM already detected in utero died at 5 days of life (Table 2). Postmortem examination revealed dysplastic mitral valve. The other patient with floppy regurgitating mitral valve is doing well with a pacemaker. Two patients (2%) have pulmonary valve stenosis with a gradient <40 mm Hg. Both patients are paced and are doing well.
DCM was found in 21 of 91 offspring (23%), of whom 13 (62%) died. Sixteen of 21 cases (76%) were diagnosed before 1 year of age (Fig 1). DCM seemed to be the primary cause of death during the first 12 months of life (Table 2). Of the 8 surviving patients, 5 with CHB accompanied with DCM have been operated on because of minor cardiac defects. Two patients underwent heart transplantation, both at 3 years of age. During the follow-up, they are doing well. The occurrence of DCM was more common in patients with an associated heart defect than in those without a heart defect, but the difference was not statistically significant (57% vs 37%; P = .1).
The total mortality rate of CHB was 16%. Additionally, 1 male patient committed suicide at 16 years of age (Table 2). He had been paced since birth and had no DCM. Clinical and follow-up data of the patients with poor outcome were compared with the data of those with good outcome (Table 4). Poor outcome was associated with low fetal and neonatal heart rate, fetal hydrops, low birth weight, evidence of noncardiac neonatal problems, or symptoms of neonatal lupus. Further, male sex was significantly more common in patients with poor outcome than in those with good outcome (52% vs 28%). There was no significant difference in the outcome between the patients with associated minor heart defects to those without heart defects. In addition, long QT syndrome (QTc > .45 seconds) was not associated with poor outcome in this study.
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Those children who survive the first 4 years of life have a good
prognosis (Fig 2). The cumulative
probability of survival at 10 years old is 82%. The median follow-up
age of the 75 survivors is 9 years old (range: .5-47.5 years). Of the
75 survivors, only 3 (4%) do not have a pacemaker; 54 (72%) patients are free from symptoms. Two patients with DCM underwent mitral valve
replacement (at 26 and 35 years of age), and 2 with normal ventricular
function have moderate mitral valve regurgitation. In addition, 2 adult
patients with long QT syndrome are paced and treated with -blockers.
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DISCUSSION |
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Top
Abstract
Methods
Results
Discussion
Conclusion
References
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In this series of 91 children with CHB diagnosed in utero or after delivery, poor outcome defined as death attributable to cardiac failure or diagnosed DCM was evident in 25% of cases. Neonatal morbidity of 58% and perinatal mortality of 7% were shown. Fetal hydrops was associated with poor outcome; 25% of fetuses with hydrops died within 3 months of age. Among them the median heart rate was 50 beats/minute. This finding is comparable with the previous study of Groves et al,10 who showed that heart rate <55 beats/minute is associated with greater likelihood of poor outcome. Buyon et al12 reported the total mortality of CHB to be 19%, of whom 27% died in utero and 45% died within the first 3 months after delivery. In our study, the total mortality of CHB was 16% and 11 of 15 children (73%) died during the first 12 months. Thus, according to these studies, early infancy is the time of greatest risk of death in CHB.
Neonatal carditis or late-onset DCM from maternal autoimmune disease is
becoming increasingly recognized as a serious outcome of
CHB.913-16 In this series, there was no controlled trial
in the management of fetuses with CHB. Because of severe hydrops and
bradycardia, 2 mothers received -sympathomimetics17 and
2 received digoxin.18,19
Late development of DCM several months after birth has been described.9 In a case report, McLeod et al14 described an infant with severe DCM despite a normal sinus rate. The cause of DCM is unclear but prolonged exposure to anti-Ro/SSa antibodies might be a major reason for the development of DCM in these children. Therapeutic options include treatment directed at depletion of anti-Ro/SSa antibodies from the child's circulation.20 In our study, 5 children developed severe DCM after infancy. None of them were treated with plasma exchange, 3 received systemic corticosteroids. Two children underwent heart transplantion.
The study by Buyon et al12 showed that 63% of live-born children required pacemakers, 33% within the first 9 days of life. In this study, permanent pacing was required in 53% of the children as a newborn. The primary indications for placement of pacemaker were congestive heart failure and low ventricular rate averaging <60 beats/minute. Despite pacing, 17% of them died within the first year of life because of severe DCM.9 Thus, early pacing is indicated in most children with CHB, but if cardiac muscle is affected by the immunologic disease process, the prognosis is poor.9,13
In this study, the occurrence of associated structural heart defects (42%) was more common than has been reported in previous articles. The incidence of 11% of heart defects was shown in the article by Buyon et al.12 Secundum type ASD was noted in 2.2% of the newborns of Chinese mothers with systemic lupus erythematosus disseminatus.21 In our study, ASD secundum was the most frequently presented defect, accounting for 50% of all defects found. At operation, ASD was most frequently found to be located close to foramen ovale. This finding might indicate that the asynchronic function between the atrias and the ventricles might prevent foramen ovale from closing. Whether an early application of a dual-chamber pacemaker is indicated in CHB remains to be answered.
PDA requiring surgical ligation was found in 10% of cases. Buyon et al12 described 3 (3%) of 107 live-born children with PDA ligation. Incidences of other associated cardiac defects (pulmonary stenosis and small VSD) were similar in both studies. The occurrence of a heart defect was not associated with DCM or death.
In adult studies,22,23 a prolonged QTc time associated
with CHB has been described as a separate disease entity, and
-blockers have been recommended together with pacemaker treatment.
Another speculation is that a prolonged QTc time is a sign of
myocardial damage, such as carditis rather than a separate syndrome.24 In this study, QTc of >.45 seconds was not associated with poor outcome. All these patients were paced, and in the
follow-up, they were treated with -blockers.
In a previous study, the relative risk for a female child compared with a male child to have CHB was 1.9, and the risk of the mother having another child with CHB was 12%.25 No gender-based differences in the frequency or prognosis of CHB was demonstrated in the study by Buyon et al.12 They found a recurrence rate of 16%. In our study, of the 91 offspring with CHB, 66% were girls. The risk of having a child with CHB after a previous birth of an affected child was 10% (7 of 71). Male sex was more frequently presented in the patients with poor outcome. Of the 31 males, 39% had poor prognosis. The reason remains unknown, but the influences of male hormones or antibody profiles might take part in the development of DCM.25 Although the recurrence rate of CHB was not very high in this series, close echocardiographic monitoring in all subsequent pregnancies is supported.
In the article about long-term outcome of CHB in adult life, Michaelsson et al26 described the high incidence of unpredictable Stokes-Adams disease with considerable mortality, a gradually decreasing ventricular rate, and a high incidence of acquired mitral insufficiency. In this study, of 75 surviving patients, only 4% are not paced during the follow-up. Although the follow-up age in the present study is shorter than in the previous study26 (9 years vs 38 years), the low incidence of mitral regurgitation (5%) in our study supports the practice to start pacemaker treatment early in life.
Limitations of the Study
Any retrospective study has inherent limitations. The study took place over multiple decades and the technology available to the caregivers has changed substantially over the study. In this study, pacemaker application for a neonate was first performed in 1965. In the subgroup of the children who did present from 1950 to 1980, the diagnosis of CHB was made using ECG because fetal echocardiography was not available. All these older patients were diagnosed and followed at the same hospital (the Hospital for Children and Adolescents). Any patient with insufficient records was excluded.
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CONCLUSION |
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Top
Abstract
Methods
Results
Discussion
Conclusion
References
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The present study demonstrates that CHB carries high neonatal morbidity, and high mortality during the first 12 months of life. Poor prognosis defined as death or severe DCM was associated with fetal hydrops, low fetal and neonatal heart rate, and neonatal problems attributable to prematurity or lupus erythematosus. Despite early pacing, prognosis was poor if the cardiac muscle was affected by an inflammatory process. However, early pacemaker treatment is indicated to prevent mitral valve regurgitation attributable to low ventricular rate and overdistension of the left ventricle and papillary muscles. Further, this study demonstrates that ASD and PDA are more frequently presented than has previously been reported. The high incidences of DCM and associated heart defects support the recommendation of close echocardiographic monitoring of all infants with CHB. In addition, in case of DCM, early cardiac transplantation should be taken into consideration. Whether early application of dual-chamber pacemaker is indicated to prevent DCM or clinically significant shunt through the atrial septum remains to be answered.
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ACKNOWLEDGMENT |
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This study was supported by grants from the Foundation for Pediatric Research.
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FOOTNOTES |
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Received for publication Aug 9, 1999; accepted Feb 8, 2000.
Reprint requests to (M.E.) Hospital for Children and Adolescents, Helsinki University Hospital, Stenbäckinkatu 11, 00290, Helsinki, Finland. E-mail: marianne.eronen{at}dlc.fi
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ABBREVIATIONS |
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CHB, complete/congenital heart block; DCM, dilated cardiomyopathy; ECG, electrocardiogram; VSD, ventricular septal defect; PDA, patent ductus arteriosus; ASD, atrial septal defect.
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REFERENCES |
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This article has been cited by other articles:
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  A. Skog, M. Wahren-Herlenius, B. Sundstrom, K. Bremme, and S.-E. Sonesson Outcome and Growth of Infants Fetally Exposed to Heart Block-Associated Maternal Anti-Ro52/SSA Autoantibodies Pediatrics, April 1, 2008; 121(4): e803 - e809. [Abstract] [Full Text] [PDF]
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 P.A. Gordon Review: Congenital heart block: clinical features and therapeutic approaches Lupus, August 1, 2007; 16(8): 642 - 646. [Abstract] [PDF]
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V. Vukomanovic, M. Stajevic, J. Kosutic, P. Stojanov, S. Rakic, M. Velinovic, I. Sehic, and V. Milovanovic Age-related role of ambulatory electrocardiographic monitoring in risk stratification of patients with complete congenital atrioventricular block Europace, February 1, 2007; 9(2): 88 - 93. [Abstract] [Full Text] [PDF]
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 M. S. Cohen, A. H. Schultz, Z.-Y. Tian, D. D. Donaghue, P. M. Weinberg, J. W. Gaynor, and J. Rychik Heterotaxy Syndrome with Functional Single Ventricle: Does Prenatal Diagnosis Improve Survival? Ann. Thorac. Surg., November 1, 2006; 82(5): 1629 - 1636. [Abstract] [Full Text] [PDF]
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