**1. Introduction**

Congenital heart disease (CHD), the most common type of birth defect, is an abnormal cardiocirculatory structure or function present at birth, although the disease is often discovered later in life. During prenatal life, the incidence of cardiac defect is higher due to affected fetuses that are aborted. CHD stems from an alteration in the embryonic development from a normal structure, or a failure of a structure to properly develop beyond an early stage of embryonic and fetal development. The non-typical patterns of cardio-circulatory flow owning to an anatomical defect may significantly influence the structural and functional development of the remainder of the circulatory system. Additionally, postnatal events have a marked impact on the clinical presentation of a specific isolated malformation.

As CHD accounts for the most frequent cause of lethal malformation among infants, CHD is also considered a major problem affecting public health worldwide (Bernier et al., 2010). Despite the continuing progress in non-surgical and surgical treatments that allow for the survival of the majority of patients, some complex heart diseases are still associated with substantial morbidity and mortality. According to a report, 45% of infant deaths owing to congenital anomalies were caused by CHD in Western Europe. In Latin America, North America, Eastern Europe and the South Pacific region (including Japan) this proportion has been reported to be 35%, 37%, 42% and 48%, respectively (Botto, 2003). 20% of spontaneous abortions and 10% of stillbirths are attributed to CHD (Botto, 2001). CHD causes high morbidity and mortality among infants, and affects the quality of life during childhood and adulthood, depending on the progression of the disease (Majnener et al., 2008). It also affects social interactions and the quality of life for parents of children with CHD.

While newborns with the cardiac disorder are symptomatic and identified soon after birth, many others are not diagnosed until the disease progresses into a severe stage. Data from the Northern Region Pediatric Cardiology database suggest around 1 in 4 cases of congenital heart disease in the UK are diagnosed later in childhood (Petersen et al., 2003). The signs and symptoms of heart disease depend on the type and severity of the disease. Children with critical cardiac lesion generally exhibit high morbidity and mortality because the risk of morbidity and mortality increases as treatment and diagnosis is delayed.

The screening process is very important to detect congenital heart malformations. One of the major contributors to increased mortality and morbidity is clinical deterioration and heart

diagnosis of life-threatening CHD ranges from £4,900 for pulse oximetry to £4.5 million for screening echocardiography (Knowles et al., 2005). Hence, the public health officers need to

Although, there have been many studies to find the etiology of CHD, the cause of most CHDs continues to be unknown. Some reports suggested the cause to be a combination between genetic and environmental factors. Heart disease symptoms in a child are generally simple when compared with an adult, and have widely different pathology and physiology. Heart disease in an adult is a disease that often happens later in life (acquired heart disease) in the blood vessels (coronary artery disease) and heart valves. In this chapter, we will

The first corrective surgery with cardiopulmonary bypass for intra-cardiac malformations began at the Mayo Clinic and the University of Minnesota Hospital in the 1950s (Lillehei, 1956). Through the past half century, the diagnosis and treatment of CHDs have markedly improved. The rapid evolution of diagnosis, medical and surgical therapies has reduced the morbidity and mortality rate. The surgical mortality has decreased from an average of 15% in 1990 to an average of 5% in 2000 (Kenny, 2008, as cited in Gibbs et al., 2004). The majority of infants with CHD are now expected to survive into adolescence and adulthood. Currently, the number of adults diagnosed with CHD exceeds the number of children diagnosed with CHD. Hence, the objectives of this chapter are to describe epidemiology and etiology of CHD, including preventative guidelines for pregnant mothers. The authors hope this will provide essential overview to not only physicians and public health officers but also pregnant women, interested readers and societal awareness for the possibility of CHD in newborns. We also hope to provide appropriate strategies for managing the problem. This would lead

to an appropriate health care budget and plan for diseased children in the future.

MR = mitral regurgitation, (MVP = mitral valve prolapse)

T/PAPVR = total/partial anomalous pulmonary venous return

consider appropriate methods of CHD detections for their countries.

describe the possible causes and risk factors of CHD.

AR = aortic regurgitation AS = aortic stenosis ASD = atrial septal defect

BAV = bicuspid aortic valve CHD = congenital heart disease Coarc = coarctation of the aorta DORV = double outlet right ventricle HLH = hypoplastic left heart HRH = hypoplastic right heart IAA = interrupted aortic arch

PA = pulmonary atresia PDA = patent ductus arteriosus PS = pulmonary stenosis SV = single ventricle TA = tricuspid atresia

TOF = tetralogy of Fallot VSD = ventricular septal defect

AVSD = atrioventricular septal defect

TGA = transposition of great arteries

**Abbreviations** 

failure prior to diagnosis and treatment. Early detection of CHD in the fetus or in the asymptomatic period immediately after birth will reduce clinical deterioration by instigation of appropriate management of the disease. Technical improvements in sonographic systems during the past two decades have helped the obstetric sonographers detect congenital heart anomalies, especially in experienced hands. A fetal cardiac screening with fetal echocardiography allows for early detection of CHD allowing for the option of pregnancy termination in cases of complicated defects. In areas where termination of pregnancy is a realistic and supported option, a universal sonographic screening of all pregnancies with an average reported sensitivity of 35% and a termination rate of 43% following prenatal diagnosis, would result in a 15% overall reduction of the prevalence of most severe forms of CHD (Germanakis & Sifakis, 2006). The information from 20 registries of congenital malformation in 12 European countries demonstrated the overall prenatal detection rate of CHD was 25% (Garne et al, 2001). Echocardiography can be used for screening in live birth infants. Newborn echocardiographic screening enables pediatricians to detect abnormal cardiac characteristics early and accurately, especially heart diseases without murmur such as coarctation of the aorta (Coarc), atrial septal defect (ASD), atrioventricular septal defect (AVSD), hypertrophic cardiomyopathy and cardiac tumor. In addition, cardiopulmonary information obtained from the echocardiographic examination can be useful for neonatal care providers (Wang et al., 2007).

The echocardiographic screening in developing countries may be difficult due to lack of echocardiographic machines and sonographers. Fortunately, most of patients with CHDs can be detected by clinical presentations and physical examinations. Approximately 90% of patients with CHDs were referred for cardiovascular evaluation with cardiac murmur, arrhythmia, cyanosis, palpitation and chest pain. False positives occurred 22.3% of the time with innocent (functional) murmur, and non organic chest pain or other non cardiac diagnosis (Borzouee & Jannati, 2008). In a Toronto study, 0.28% of the school-age children were found to have innocent murmurs (Rose et al., 1964). Currently, infants are screened to detect CHD by clinical and physical examination after birth and another examination at 6-8 weeks. However, this screening program can detect only 50% of congenital defects (Knowles et al., 2005). Thailand has a lack of pediatric doctors and cardiologists, and, therefore, there has been training available for qualified nurses and health officers to screen patients for CHD using clinical and physical examinations. These screenings are not only for infants, but also for school-age children and adults too. Although we detected a lot of false positives from innocent murmurs and abnormal clinical presentations, we recognized many undiagnosed CHD patients and have found many CHD patients who choose to undergo proper treatment (Sayasathid et al., 2009, 2010). Another tool to recognize CHD is pulse oximetry. It can detect cyanotic CHD which are not detected by routine examination with high specificity (99.8%) and very low false positive rate (2%) although the sensitivity was only 63%. Either functional or fractional oxygen saturation was measured by pulse oximetry with oxygen saturation below 95% as the cut-off level in most studies (Thangaratinam et al., 2007). Children who are suspected of having CHD should be referred to a pediatric cardiologist for definitive diagnosis, suitable treatment and follow up.

Nonetheless, the cost-effectiveness remains a concern, especially in developing countries. Costs are very different between screening using echocardiography versus clinical examination. A cost-effectiveness analysis study for screening 100,000 newborns in the UK showed the total program cost £300,000 for clinical examination, £480,000 for pulse oximetry and £3.54 million for screening echocardiography. The addition cost per additional timely diagnosis of life-threatening CHD ranges from £4,900 for pulse oximetry to £4.5 million for screening echocardiography (Knowles et al., 2005). Hence, the public health officers need to consider appropriate methods of CHD detections for their countries.

Although, there have been many studies to find the etiology of CHD, the cause of most CHDs continues to be unknown. Some reports suggested the cause to be a combination between genetic and environmental factors. Heart disease symptoms in a child are generally simple when compared with an adult, and have widely different pathology and physiology. Heart disease in an adult is a disease that often happens later in life (acquired heart disease) in the blood vessels (coronary artery disease) and heart valves. In this chapter, we will describe the possible causes and risk factors of CHD.

The first corrective surgery with cardiopulmonary bypass for intra-cardiac malformations began at the Mayo Clinic and the University of Minnesota Hospital in the 1950s (Lillehei, 1956). Through the past half century, the diagnosis and treatment of CHDs have markedly improved. The rapid evolution of diagnosis, medical and surgical therapies has reduced the morbidity and mortality rate. The surgical mortality has decreased from an average of 15% in 1990 to an average of 5% in 2000 (Kenny, 2008, as cited in Gibbs et al., 2004). The majority of infants with CHD are now expected to survive into adolescence and adulthood. Currently, the number of adults diagnosed with CHD exceeds the number of children diagnosed with CHD.

Hence, the objectives of this chapter are to describe epidemiology and etiology of CHD, including preventative guidelines for pregnant mothers. The authors hope this will provide essential overview to not only physicians and public health officers but also pregnant women, interested readers and societal awareness for the possibility of CHD in newborns. We also hope to provide appropriate strategies for managing the problem. This would lead to an appropriate health care budget and plan for diseased children in the future.

#### **Abbreviations**

48 Congenital Heart Disease – Selected Aspects

failure prior to diagnosis and treatment. Early detection of CHD in the fetus or in the asymptomatic period immediately after birth will reduce clinical deterioration by instigation of appropriate management of the disease. Technical improvements in sonographic systems during the past two decades have helped the obstetric sonographers detect congenital heart anomalies, especially in experienced hands. A fetal cardiac screening with fetal echocardiography allows for early detection of CHD allowing for the option of pregnancy termination in cases of complicated defects. In areas where termination of pregnancy is a realistic and supported option, a universal sonographic screening of all pregnancies with an average reported sensitivity of 35% and a termination rate of 43% following prenatal diagnosis, would result in a 15% overall reduction of the prevalence of most severe forms of CHD (Germanakis & Sifakis, 2006). The information from 20 registries of congenital malformation in 12 European countries demonstrated the overall prenatal detection rate of CHD was 25% (Garne et al, 2001). Echocardiography can be used for screening in live birth infants. Newborn echocardiographic screening enables pediatricians to detect abnormal cardiac characteristics early and accurately, especially heart diseases without murmur such as coarctation of the aorta (Coarc), atrial septal defect (ASD), atrioventricular septal defect (AVSD), hypertrophic cardiomyopathy and cardiac tumor. In addition, cardiopulmonary information obtained from the echocardiographic examination can be useful for neonatal

The echocardiographic screening in developing countries may be difficult due to lack of echocardiographic machines and sonographers. Fortunately, most of patients with CHDs can be detected by clinical presentations and physical examinations. Approximately 90% of patients with CHDs were referred for cardiovascular evaluation with cardiac murmur, arrhythmia, cyanosis, palpitation and chest pain. False positives occurred 22.3% of the time with innocent (functional) murmur, and non organic chest pain or other non cardiac diagnosis (Borzouee & Jannati, 2008). In a Toronto study, 0.28% of the school-age children were found to have innocent murmurs (Rose et al., 1964). Currently, infants are screened to detect CHD by clinical and physical examination after birth and another examination at 6-8 weeks. However, this screening program can detect only 50% of congenital defects (Knowles et al., 2005). Thailand has a lack of pediatric doctors and cardiologists, and, therefore, there has been training available for qualified nurses and health officers to screen patients for CHD using clinical and physical examinations. These screenings are not only for infants, but also for school-age children and adults too. Although we detected a lot of false positives from innocent murmurs and abnormal clinical presentations, we recognized many undiagnosed CHD patients and have found many CHD patients who choose to undergo proper treatment (Sayasathid et al., 2009, 2010). Another tool to recognize CHD is pulse oximetry. It can detect cyanotic CHD which are not detected by routine examination with high specificity (99.8%) and very low false positive rate (2%) although the sensitivity was only 63%. Either functional or fractional oxygen saturation was measured by pulse oximetry with oxygen saturation below 95% as the cut-off level in most studies (Thangaratinam et al., 2007). Children who are suspected of having CHD should be referred to a pediatric

cardiologist for definitive diagnosis, suitable treatment and follow up.

Nonetheless, the cost-effectiveness remains a concern, especially in developing countries. Costs are very different between screening using echocardiography versus clinical examination. A cost-effectiveness analysis study for screening 100,000 newborns in the UK showed the total program cost £300,000 for clinical examination, £480,000 for pulse oximetry and £3.54 million for screening echocardiography. The addition cost per additional timely

care providers (Wang et al., 2007).


ordination of cardiac pediatricians between outpatient and private clinics, and absence of autopsy to determine the cause of certain fetal death in stillbirths. Nonetheless, the estimation for birth prevalence of CHD remains simpler and more precise compared with the estimation for incidence of CHD from the baby population. Hence, most epidemiological studies report the birth prevalence rather than the baby incidence of CHD. Table 1 compares the birth prevalence of all CHD subtypes from 4 recent studies by Hoffman & Kaplan, 2002 (review literatures); Reller et al., 2008 (Metropolian Atlanta Congenital Defects Program, MACDP); Dolk & Loane, 2009 (European Surveillance of Congenital Anomalies, Eurocat) and Wu et al., 2010 (Asian population, Taiwan). Table 2 shows different percent distribution

> **Dolk & Loane, 2009\*\* (Eurocat)**

**Wu, 2010\* (Asian population)** 

of CHD lesions in live births from various countries

**Reller, 2008\* (MACDP)** 

VSD 3.57 / 2.83 4.18 3.06 4.01 PDA 0.80 / 0.57 0.29 --- 2.01 ASD 0.94 / 0.56 1.31 2.05 3.23 AVSD 0.35 / 0.34 0.41 0.19 0.20 PA 0.13 / 0.08 0.04 0.09 --- PS 0.73 / 0.53 0.55 0.40 1.22 AS 0.40 / 0.26 0.11 0.14 0.16 Coarc 0.41 / 0.36 0.44 0.34 0.25 TOF 0.42 / 0.36 0.47 0.28 0.63 TGA 0.32 / 0.30 0.23 0.35 0.21 HRH 0.22 / 0.16 --- 0.04 --- HLH 0.27 / 0.27 0.23 0.26 0.06 TA 0.08 / 0.09 0.05 0.08 0.05 Ebstein's 0.11 / 0.04 0.06 0.05 0.05 Truncus 0.11 / 0.09 0.06 0.09 0.08 DORV 0.16 / 0.13 --- --- 0.15 SV 0.11 / 0.09 0.10 0.07 --- TAPVR 0.09 / 0.09 0.08 0.05 0.11 All CHD 9.60 / 7.67\*\*\* 8.14 7.05 13.08 BAV 13.56/9.24 --- --- ---

\*\*Non-chromosomal CHD prevalence (Includes: Live birth, Fetal death and Termination of pregnancy

Table 1. Prevalence of CHD based on CHD subtypes and per 1,000 births compared among

More importantly, the trend for birth prevalence of CHD was found to be increasing, highlighting three chief concerns. First, the increased number of CHD prevalence among the newborns could represent the greater number of adults with CHD and the likely increased number of CHD in their offspring in the future. This poses the concern about the overall

\*\*\*Excluding bicuspid non-stenosis aortic valves, isolated partial anomalous pulmonary venous

**Hoffman & Kaplan, 2002\* Mean/Median** 

**Cardiac Lesion** 

\*Live births

for fetal anomaly)

the four recent studies.

connection and silent ductus arteriosus
