1
ORIGINAL ARTICLE Epidemiology of Congenital Heart Disease in India Ritu Bhardwaj, MSc,* Sunil Kumar Rai, MSc,* Abhishek Kumar Yadav, MSc,* Siddharth Lakhotia, MCh,† Damyanti Agrawal, MCh,† Ashok Kumar, MD,‡ and Bhagyalaxmi Mohapatra, PhD* *Cytogenetics Laboratory, Department of Zoology, and Departments of †Cardiovascular and Thoracic Surgery and ‡ Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India ABSTRACT
Objective. Congenital heart defects (CHDs) affect a large number of newborns and account for a high proportion of infant mortality worldwide. There are regional differences in the prevalence and distribution pattern of CHDs. The aim of this study is to estimate the distribution pattern and prevalence of CHDs among the population of north-central India and to compare the results with studies in other regions of the country to get an overview of prevalence of CHDs in India. Design. We carried out a prospective study in the outpatient department of a tertiary care referral center in north-central India. This study was carried out from January 2011 to April 2014, with 34 517 individuals being recruited for the study. All patients were examined by chest x-ray, electrocardiogram, and 2D echocardiography. Prevalence rate per 1000 individuals examined was calculated. Relative frequencies of individual CHD types as a proportion of total CHDs were also calculated. Results. Out of 34 517 individuals examined, 661 were diagnosed with CHDs, giving a prevalence of 19.14 per 1000 individuals. The most common defect was ventricular septal defect (33%), followed by atrial septal defect (19%) and tetralogy of Fallot (16%). The majority of CHD cases (58%) diagnosed were between 0 and 5 years of age. The prevalence of CHDs in adults was 2.4 per 1000 individuals in this cohort, with atrial septal defect (44.5%) being the most frequent defect. Conclusion. The prevalence of CHDs in our cohort was high, possibly because of the power of the diagnostic methods we used and the inclusion of all age groups. Adults with CHDs may significantly contribute to the prevalence of CHDs in the next generation, and this needs to be considered when estimating prevalence rates. Although several small regional studies have been carried out in India, there is an urgent need to establish a nationwide registry/database for congenital heart defects. Key Words. Congenital Heart Disease; India; Prevalence
Introduction
C
ongenital heart defects (CHD) are defined as abnormal cardiocirculatory structure or function present at birth, although they are often not detected until later in life. CHDs are the most frequent lethal malformation, affecting about 1% of newborns and causing significant morbidity and mortality in infants. These account for 30% of total congenital abnormalities, with a birth prevalence of 4–50 per 1000.1 With the advancement of diagnostic techniques and corrective therapies for CHDs, the percentage of individuals surviving to © 2014 Wiley Periodicals, Inc.
adulthood has increased over past few decades. Now CHD patients are more likely to reproduce, leading to an increase in incidence rate.2 The birth prevalence of CHD varies over time depending on the population being studied and whether it is community- or hospital-based. Birth prevalence worldwide has increased between 1930 and 2009 and has arrived at a steady state of 9 per 1000 live births over the last 10–15 years. Prevalence is high in developing countries because of their high birth rate.2 The frequency of various CHDs also varies in different populations. A population-based study from Atlanta, Georgia, USA, reported the prevaCongenit Heart Dis. 2014;••:••–••
2 lence of CHD as 8.1 per 1000 live births from 1998 to 2005.3 A 20-year study (1985–2004) from England estimated a frequency of 6.4 per 1000 live births.4 Similarly, in a comprehensive study by EUROCAT (European Surveillance of Congenital Anomalies) that included the live birth registries of 22 countries, prevalence of CHD (without chromosomal abnormality) was 6.5 per 1000 births.5 Higher frequencies of CHD have also been reported in population-based studies from Denmark (1977–2005) and Taiwan (2000–2006), with prevalences of 10.3 and 13.1, respectively, per 1000 live births.6,7 Although there are birth defect registries in several countries, such structured studies are lacking in India. Crude birth rate (CBR) in India is 21.8 per 1000, according to 2011 census data.8 At this CBR, total live births per year are approximately 26 382 216. If birth prevalence is taken to be 8 per 1000 live births, presumably nearly 211 058 children are born with CHD every year. This number becomes much higher if spontaneously aborted pregnancies and neonatal deaths are taken into account. An autopsy study has shown that fetal coarctation of the aorta, transposition of the great arteries (TGA), and aortic atresia are the three major cardiac anomalies responsible for death in neonates.9 Nearly 27.5% of stillbirths are due to CHDs.10 Ten percent of infant mortality in India is due to CHDs alone.11 In a developing country like India, this is a major health burden. Accurate estimation of the prevalence and distribution pattern of various CHDs in this population will help us to gauge the severity of the burden and take effective steps for the better management of the disease. There are no comprehensive prevalence data on CHDs in Indian populations. The few, small, scattered studies, either school- or hospital-based, are from different regions and are mostly confined to northern India (8 studies; region I in Figure 1). There are only 2 studies from southern India (region II), 2 from north-central India (region IV), and 1 from western India (region III). However, no study has been undertaken in the south-central region (region V) or northeastern region (region VI). These independent regional studies show a prevalence range of 0.8–26.4 (mean = 7.10, 95% CI 2.94–11.27) per 1000 individuals.12–24 (Summaries of these studies are given in Tables 1 and 2.) The purpose of our study is to determine the as yet unknown prevalence and profile of CHDs in north-central India, including eastern Uttar Pradesh and adjoining Bihar, Jharkhand, and Chhattisgarh. This study estimates the prevalence Congenit Heart Dis. 2014;••:••–••
Bhardwaj et al. of different CHD types in this cohort and compares it with other cohorts from India in order to perform a comprehensive analysis of available existing information to estimate the overall CHD burden of the country and try to establish regional differences. Methods
Our study is a prospective cohort study, conducted from January 2011 through April 2014 as a collaboration between the Department of Zoology of Banaras Hindu University (BHU), Varanasi, and the Department of Pediatrics and Department of Cardiovascular and Thoracic Surgery of the Institute of Medical Sciences at the same university. The Institute of Medical Sciences at BHU is one of the largest tertiary care referral centers in north-central India, catering to the medical needs of the populations of the states of Uttar Pradesh, Bihar, Jharkhand, Madhya Pradesh, and Chhattisgarh. A good number of patients from West Bengal and the neighboring countries of Nepal and Bangladesh also visit the hospital. A total of 34 517 patients were examined in the outpatient departments of both the pediatric and cardiovascular clinics, of whom 661 cases were diagnosed with confirmed CHD and registered for this study after giving their informed consent. The ethical committee of the university approved the study. All cases were thoroughly examined by chest x-ray, electrocardiogram, and 2D echocardiography. Family history of any heart abnormality, history of multiple abortions, nutrition and drug intake, any other pathophysiological conditions, and parity status of mother were also considered for analysis. All age groups were included in this study. Cases with possible chromosomal abnormalities (Down syndrome, Turner syndrome, and Klinefelter syndrome) as well as cases with congenital cardiomyopathy or rheumatic heart disease were excluded from this study. Classification of CHDs was based on the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) and the work of Reller et al.3 CHDs can be broadly divided into 3 classes: left-to-right shunts, right/left heart obstructive defects, and cyanotic CHDs. Left-to-right shunts, or acyanotic CHDs, include ventricular septal defect (VSD), atrial septal defect (ASD), Eisenmenger complex, Gerbode defect, atrioventricular (AV) canal defect, and patent ductus arteriosus (PDA). All PDA and patent foramen ovale (PFO) cases below 3 months of age were excluded. Cya-
3
Congenital Heart Disease in India
Figure 1. Prevalence rates per 1000 population of congenital heart disease across different regions of India. Region I, northern India; region II, southern India; region III, western India; region IV, north-central India; region V, south-central India; region VI, eastern India.
notic CHDs include tetralogy of Fallot (TOF), truncus arteriosus (TA), tricuspid atresia, Ebstein anomaly, dextrocardia, TGA, total/partial anomalous pulmonary venous connection (T/PAPVC), situs inversus totalis, double-outlet right ventricle (DORV), and double-chambered right ventricle. Right/left heart obstructive defects include coarctation of the aorta (CoA), bicuspid aortic valve (BAV), aortic stenosis (AS), and pulmonary stenosis (PS). Prevalence rates were calculated by dividing the number of cases of a CHD by the total number of patients examined during the study period. The CHD prevalence pattern was also compared with studies from different regions of
India and other neighboring Asian countries (Pakistan, Bangladesh, Nepal, China, and Taiwan). All statistical tests were performed using SPSS software (SPSS Inc., Chicago, IL, USA). Results
During this study, out of 34 517 patients examined in the outpatient department (OPD), 661 individuals (422 males and 239 females) were diagnosed with CHD, giving a prevalence of 19.14 per 1000 individuals. Relative frequencies of different CHDs and total numbers of males and females affected in individual groups are shown in Table 3. Congenit Heart Dis. 2014;••:••–••
4 Table 1.
Bhardwaj et al. Prevalence of Congenital Heart Defects from 1980 to 2014 in Different Regions of India
Region
City
Age Group
Sample Size
Cases
Study Setting
Prevalence per 1000
Reference
Northern India
Delhi Shimla Agra Delhi Shimla Delhi Kashmir Dehradun Kanpur Gorakhpur Mumbai Mysore Karimnagar
0–5 years 6–16 years 5–15 years LBs 5–16 years
ORIGINAL ARTICLE Epidemiology of Congenital Heart Disease in India Ritu Bhardwaj, MSc,* Sunil Kumar Rai, MSc,* Abhishek Kumar Yadav, MSc,* Siddharth Lakhotia, MCh,† Damyanti Agrawal, MCh,† Ashok Kumar, MD,‡ and Bhagyalaxmi Mohapatra, PhD* *Cytogenetics Laboratory, Department of Zoology, and Departments of †Cardiovascular and Thoracic Surgery and ‡ Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India ABSTRACT
Objective. Congenital heart defects (CHDs) affect a large number of newborns and account for a high proportion of infant mortality worldwide. There are regional differences in the prevalence and distribution pattern of CHDs. The aim of this study is to estimate the distribution pattern and prevalence of CHDs among the population of north-central India and to compare the results with studies in other regions of the country to get an overview of prevalence of CHDs in India. Design. We carried out a prospective study in the outpatient department of a tertiary care referral center in north-central India. This study was carried out from January 2011 to April 2014, with 34 517 individuals being recruited for the study. All patients were examined by chest x-ray, electrocardiogram, and 2D echocardiography. Prevalence rate per 1000 individuals examined was calculated. Relative frequencies of individual CHD types as a proportion of total CHDs were also calculated. Results. Out of 34 517 individuals examined, 661 were diagnosed with CHDs, giving a prevalence of 19.14 per 1000 individuals. The most common defect was ventricular septal defect (33%), followed by atrial septal defect (19%) and tetralogy of Fallot (16%). The majority of CHD cases (58%) diagnosed were between 0 and 5 years of age. The prevalence of CHDs in adults was 2.4 per 1000 individuals in this cohort, with atrial septal defect (44.5%) being the most frequent defect. Conclusion. The prevalence of CHDs in our cohort was high, possibly because of the power of the diagnostic methods we used and the inclusion of all age groups. Adults with CHDs may significantly contribute to the prevalence of CHDs in the next generation, and this needs to be considered when estimating prevalence rates. Although several small regional studies have been carried out in India, there is an urgent need to establish a nationwide registry/database for congenital heart defects. Key Words. Congenital Heart Disease; India; Prevalence
Introduction
C
ongenital heart defects (CHD) are defined as abnormal cardiocirculatory structure or function present at birth, although they are often not detected until later in life. CHDs are the most frequent lethal malformation, affecting about 1% of newborns and causing significant morbidity and mortality in infants. These account for 30% of total congenital abnormalities, with a birth prevalence of 4–50 per 1000.1 With the advancement of diagnostic techniques and corrective therapies for CHDs, the percentage of individuals surviving to © 2014 Wiley Periodicals, Inc.
adulthood has increased over past few decades. Now CHD patients are more likely to reproduce, leading to an increase in incidence rate.2 The birth prevalence of CHD varies over time depending on the population being studied and whether it is community- or hospital-based. Birth prevalence worldwide has increased between 1930 and 2009 and has arrived at a steady state of 9 per 1000 live births over the last 10–15 years. Prevalence is high in developing countries because of their high birth rate.2 The frequency of various CHDs also varies in different populations. A population-based study from Atlanta, Georgia, USA, reported the prevaCongenit Heart Dis. 2014;••:••–••
2 lence of CHD as 8.1 per 1000 live births from 1998 to 2005.3 A 20-year study (1985–2004) from England estimated a frequency of 6.4 per 1000 live births.4 Similarly, in a comprehensive study by EUROCAT (European Surveillance of Congenital Anomalies) that included the live birth registries of 22 countries, prevalence of CHD (without chromosomal abnormality) was 6.5 per 1000 births.5 Higher frequencies of CHD have also been reported in population-based studies from Denmark (1977–2005) and Taiwan (2000–2006), with prevalences of 10.3 and 13.1, respectively, per 1000 live births.6,7 Although there are birth defect registries in several countries, such structured studies are lacking in India. Crude birth rate (CBR) in India is 21.8 per 1000, according to 2011 census data.8 At this CBR, total live births per year are approximately 26 382 216. If birth prevalence is taken to be 8 per 1000 live births, presumably nearly 211 058 children are born with CHD every year. This number becomes much higher if spontaneously aborted pregnancies and neonatal deaths are taken into account. An autopsy study has shown that fetal coarctation of the aorta, transposition of the great arteries (TGA), and aortic atresia are the three major cardiac anomalies responsible for death in neonates.9 Nearly 27.5% of stillbirths are due to CHDs.10 Ten percent of infant mortality in India is due to CHDs alone.11 In a developing country like India, this is a major health burden. Accurate estimation of the prevalence and distribution pattern of various CHDs in this population will help us to gauge the severity of the burden and take effective steps for the better management of the disease. There are no comprehensive prevalence data on CHDs in Indian populations. The few, small, scattered studies, either school- or hospital-based, are from different regions and are mostly confined to northern India (8 studies; region I in Figure 1). There are only 2 studies from southern India (region II), 2 from north-central India (region IV), and 1 from western India (region III). However, no study has been undertaken in the south-central region (region V) or northeastern region (region VI). These independent regional studies show a prevalence range of 0.8–26.4 (mean = 7.10, 95% CI 2.94–11.27) per 1000 individuals.12–24 (Summaries of these studies are given in Tables 1 and 2.) The purpose of our study is to determine the as yet unknown prevalence and profile of CHDs in north-central India, including eastern Uttar Pradesh and adjoining Bihar, Jharkhand, and Chhattisgarh. This study estimates the prevalence Congenit Heart Dis. 2014;••:••–••
Bhardwaj et al. of different CHD types in this cohort and compares it with other cohorts from India in order to perform a comprehensive analysis of available existing information to estimate the overall CHD burden of the country and try to establish regional differences. Methods
Our study is a prospective cohort study, conducted from January 2011 through April 2014 as a collaboration between the Department of Zoology of Banaras Hindu University (BHU), Varanasi, and the Department of Pediatrics and Department of Cardiovascular and Thoracic Surgery of the Institute of Medical Sciences at the same university. The Institute of Medical Sciences at BHU is one of the largest tertiary care referral centers in north-central India, catering to the medical needs of the populations of the states of Uttar Pradesh, Bihar, Jharkhand, Madhya Pradesh, and Chhattisgarh. A good number of patients from West Bengal and the neighboring countries of Nepal and Bangladesh also visit the hospital. A total of 34 517 patients were examined in the outpatient departments of both the pediatric and cardiovascular clinics, of whom 661 cases were diagnosed with confirmed CHD and registered for this study after giving their informed consent. The ethical committee of the university approved the study. All cases were thoroughly examined by chest x-ray, electrocardiogram, and 2D echocardiography. Family history of any heart abnormality, history of multiple abortions, nutrition and drug intake, any other pathophysiological conditions, and parity status of mother were also considered for analysis. All age groups were included in this study. Cases with possible chromosomal abnormalities (Down syndrome, Turner syndrome, and Klinefelter syndrome) as well as cases with congenital cardiomyopathy or rheumatic heart disease were excluded from this study. Classification of CHDs was based on the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) and the work of Reller et al.3 CHDs can be broadly divided into 3 classes: left-to-right shunts, right/left heart obstructive defects, and cyanotic CHDs. Left-to-right shunts, or acyanotic CHDs, include ventricular septal defect (VSD), atrial septal defect (ASD), Eisenmenger complex, Gerbode defect, atrioventricular (AV) canal defect, and patent ductus arteriosus (PDA). All PDA and patent foramen ovale (PFO) cases below 3 months of age were excluded. Cya-
3
Congenital Heart Disease in India
Figure 1. Prevalence rates per 1000 population of congenital heart disease across different regions of India. Region I, northern India; region II, southern India; region III, western India; region IV, north-central India; region V, south-central India; region VI, eastern India.
notic CHDs include tetralogy of Fallot (TOF), truncus arteriosus (TA), tricuspid atresia, Ebstein anomaly, dextrocardia, TGA, total/partial anomalous pulmonary venous connection (T/PAPVC), situs inversus totalis, double-outlet right ventricle (DORV), and double-chambered right ventricle. Right/left heart obstructive defects include coarctation of the aorta (CoA), bicuspid aortic valve (BAV), aortic stenosis (AS), and pulmonary stenosis (PS). Prevalence rates were calculated by dividing the number of cases of a CHD by the total number of patients examined during the study period. The CHD prevalence pattern was also compared with studies from different regions of
India and other neighboring Asian countries (Pakistan, Bangladesh, Nepal, China, and Taiwan). All statistical tests were performed using SPSS software (SPSS Inc., Chicago, IL, USA). Results
During this study, out of 34 517 patients examined in the outpatient department (OPD), 661 individuals (422 males and 239 females) were diagnosed with CHD, giving a prevalence of 19.14 per 1000 individuals. Relative frequencies of different CHDs and total numbers of males and females affected in individual groups are shown in Table 3. Congenit Heart Dis. 2014;••:••–••
4 Table 1.
Bhardwaj et al. Prevalence of Congenital Heart Defects from 1980 to 2014 in Different Regions of India
Region
City
Age Group
Sample Size
Cases
Study Setting
Prevalence per 1000
Reference
Northern India
Delhi Shimla Agra Delhi Shimla Delhi Kashmir Dehradun Kanpur Gorakhpur Mumbai Mysore Karimnagar
0–5 years 6–16 years 5–15 years LBs 5–16 years
