**3.2. Postnatal**

the least amount of physical and emotional trauma for the mother and family [90, 96, 104]. In one center experience, over 2000 sets of parents were counseled, half of them chose termination and the other half continued with pregnancy. Those who accepted termination of pregnancy recovered from it and with time ended up as normal healthy family. However, many of those who continued with the pregnancy, eventually lost the affected child, which was associated with increase grief and agony. In addition, break- down of the whole family unit

Outcomes in terms of rate of termination, after prenatal diagnosis of heart defects vary between countries and even between centers within the same country [105, 106]. The reason for this may be due to differences in social/religious elements and in the local laws and practices. Termination rates are greatly influenced by the gestational age at the time of diagnosis [107], by the presence of the chromosomal abnormalities and other extracardiac malformations [25]. Severity of the cardiac malformation also influences the termination rate like hypo-

Intrauterine interventions may be available for some cardiac malformations like Balloon aortic and pulmonary valvuloplasty. Currently there is a conflict between American College of Obstetricians and Gynecologists and the American Academy of Pediatrics (AAP) regarding the issue of fetal interventions [108]. The AAP favors fetal intervention if available, and puts less weight in maternal decision that is recommended for fetal benefits. This approach may place the mother at greater risks and decrease autonomy [96, 109]. If the intervention considered are questionable and carry a high risks to the mother, it is prudent to respect the mothers autonomy and giving her priority [96], until further research and consensuses are definitive in this regards. In case of multiple pregnancies with one fetus with a serious congenital anomaly need to be highlighted in this step of the counseling. These risks and benefits of continuing or terminating the pregnancy of affected twin needs to be considered and balanced. The expectant parents need to understand that the death of the normal twin can occur if the twin pregnancy is continued. This is particularly true when there is a monochorionic twin pregnancy [96, 110]. The prenatal counseling should discuss the anticipated postnatal course, intervention and outcome/survival. In most cases, the infant born with cardiac malformation will require immediate medical and/or surgical intervention. Medical intervention to ensure patency of the ductus arteriosus will include starting Prostaglandin for duct-dependent lesions for either pulmonary blood flow (e.g., severe TOF or pulmonary atresia) or systemic blood flow (e.g., HLHS, interrupted aortic arch). Once these patients are stable medically, they may require cardiac catheterization and/or surgical repair. Parents should be counseled on what to expect in the delivery room. Management will vary, depending on the severity of the cardiac defect. Decision such as, where the baby will be admitted and how much time they will have the baby, will be decided prior to the delivery date. Parent should be made aware that the postnatal cardiac diagnosis might be modified after birth. Emphasis on the possibility of modification of the postnatal course, including change in the interventions and length of stay needs to be discussed. Helping the parents understand and deal with changes that may occur and be

The outcomes and long-term survival (20 years) are profoundly dependent on the type of defect in babies born with CHD. Majority of these babies, approximately 85% are expected

after many years was reported [90].

422 Congenital Anomalies - From the Embryo to the Neonate

plastic left heart syndrome [81, 105].

contrary to what they might have been told [98].

The advancement of cardiac diagnostic and therapeutic techniques in the past decade, with relatively low morbidity and mortality, has led to more and more children with congenital heart disease living to adulthood. Therefore, the role of genetic counseling becomes even more paramount as there is a higher likelihood of these patients living to reproduce and that they may have families of their own [22]. It is very important to help elucidate the genetic basis for patients' congenital cardiac malformation for the reason mentioned, as there may be important reproductive risks that the families need to know about [22, 115, 116]. Recent analysis indicate that adults now constitute roughly two-thirds of the congenital heart disease population, representing a nearly 60% increase in congenital heart disease among adult patients since the year 2000 [115, 116]. The greatest increase in congenital heart disease survival has occurred among the 18-year old to 40-year-old demographic, which has clear implications for heritability [116].

One of the obstacles, in performing genetic testing in patients with congenital heart disease is that there are no standardized recommendations or protocols incorporating, newer genetic testing technologies at present. The literature is sparse with guidelines, and there is evidence that there is under use even of those modalities of testing that are available [22, 115]. However, there has been an emphasis from the American Heart Association in the recent past, in obtaining genetic testing in these patients [117].

#### *3.2.1. Genetics in congenital heart disease*

Cardiac malformation present at birth are an important component of pediatric cardiovascular disease. Defects can range from simple ventricular septal defects to complicated cyanotic lesions, requiring complex interventions shortly after birth. With the possibility of myriad of presentations, it begets one to ask, what is the percentage of pediatric cardiac defects are a result of a genetic anomaly. CHD is estimated that the prevalence of cardiac malformation at birth ranges from 4 to 10 live born infants per 1000. The true incidence, perhaps maybe higher as there are silent cardiac malformations that are only found later on in life [115]. As most calculations do not include bicuspid aortic valves, mitral valve prolapse and conduction problems, such as prolonged QT syndrome and complete atrioventricular block [115, 116]. The care of the pediatric patient with cardiac malformation is multifaceted, ranging from simple reassurance and observation to advanced surgeries and interventional techniques shortly after birth. The primary focus of treatment of the patient with cardiac malformation is diagnosis and best course of treatment. However an important and integral part of the care of these patients is to have genetic counseling with their parents in regards to possible etiologies of the congenital heart disease. In the past, it was believed that the recurrence of congenital cardiovascular malformations in the same family was low, with expert quoting recurrence rate of only 3–5%. However currently it is known that for a family with autosomal-dominant 22q 11 deletion syndrome, the risk is up to 50% with a variable phenotypic expression [117, 118].

**2.** Because not all chromosomal abnormalities result in a clinically recognizable syndrome, any infant or child with congenital heart disease combined with (a) dysmorphic features (b) growth retardation that cannot be explained by the heart defect (c) developmental de-

Congenital Heart Disease: Genetic Aspect and Prenatal and Postnatal Counseling

http://dx.doi.org/10.5772/intechopen.72486

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**3.** Infant or children with a family history of multiple miscarriage and/or sibling with birth

**4.** If major cardiac and/or other visceral organ malformations are documented by prenatal

Review of the literature shows that chromosome abnormalities were present in 12% of patients with TOF, 26% in tetralogy of Fallot/pulmonary atresia, 44% in interrupted aortic arch, 12% in truncus arteriosus, 5% in double outlet right ventricle, and 60% in absent pulmonary valve. With certain cardiac defect, chromosomal analysis should be considered. In patients with conotruncal defects or interrupted aortic arch, FISH should be used looking

Prior to the advent of advanced cytogenetic testing, the standard chromosomal analysis (i.e., karyotype) was widely used. Chromosome testing using standard metaphase karyotype is the traditional method and remains standard for the detection of aneuploidy (Trisomy 13, 18 and 21 and Turners 45 XO) and detecting gross changes such translocation and duplications [22, 117, 125]. A more sensitive karyotype is also available, which allows for the visualizations of greater number of bands. However, standard karyotype has an estimated 3% detection rate for pathogenic chromosome abnormalities. Conventional chromosome analysis detects wellknown chromosome aneuploidies in about 10% of cases of CHDs [126]. with the advent and

More advanced cytogenetic techniques such as FISH and chromosome microarray are required to diagnose more subtle structural abnormalities, such as microdeletions, tiny duplications and/or subtle translocations. This technology can be used to detect small deletions and duplications in chromosomes that cannot be detected with standard analysis as it looks specifically at the one area of the chromosome. A final FISH analysis will report on how many chromosomes of a certain type are present, in addition confirm suspected rearrangements. FISH technology uses probes of DNA that have been labeled with a fluorescent dye, that bind to complementary parts of a DNA, when it is heated. These probes are able to attach to their complementary DNA sequence [127]. The classic examples that uses this technology is the diagnosis of DiGeorge Syndrome with 22q11 deletion and William Syndrome with 7q11.23 deletion. The drawback of fluorescence in situ hybridization (FISH) lies in its targeted approach to detect chromosomal

for 22q11 deletion. Also analysis of the 8p region should be included [124].

feasibility of newer technology, karyotype maybe used less and become replaced.

defects, rather than a genome-wide screening method like microarrays [128].

lay or mental retardation or (d) multiple congenital anomalies.

ultrasound and/or fetal echocardiogram.

*3.2.3.2. Florescence in situ hybridization (FISH)*

defects

*3.2.3. Types of genetic testing*

*3.2.3.1. Karyotype*

Etiology of some cardiac malformation that are known to have genetic components, where they make up approximately 5–17% are part of a genetic syndrome. Environmental factors need to be considered and a detailed family history needs to be elicited [119]. The role of the primary care giver is paramount, in detecting possible associated cardiac genetic syndromes. When genetic syndromes are a possibility, intervention requires referral to a genetic counselor for accurate diagnosis and possible future pregnancy. Since approximately, 75% of currently known cardiac malformations have no identifiable cause or underlying condition, the necessity for genetic counseling may appear unwarranted. However with the advent of advanced genetic testing such as whole exome sequencing, once unrecognized features are now being associated with syndromes [120–123]. Postnatal, the purpose of the genetic evaluation is to help establish a diagnosis and educate the family about future risk recurrence and expected outcomes. Parents need to be counseled and educated on both the numeric risk and the variable expressivity that makes predicting severity difficult.

#### *3.2.2. Genetic evaluation of congenital heart disease*

The role of genetic evaluation in patients with cardiac malformations, as patients live longer is becoming increasingly important. In the past, where genetic testing was limited to research laboratories, in today clinical practice this is no longer the case. The current clinical practice allows for the physician to obtain chromosomal analysis and request FISH testing when looking for specific deletions [22, 121–123]. The yields of these testing becomes higher when a genetic counselor is consulted prior to obtaining specific test. However even with the advancement on genetic testing, not all patients with congenital heart disease will be identified to have a genetic cause. The recommend approach for newly diagnosed patients with cardiac malformations includes the routine evaluation of all available relatives for a potential genetic contribution [22], and obtaining an accurate and complete medical history and documenting and extended pedigree. If from the information a syndrome if recognized, then evaluation and counseling of other family members becomes extremely important. Depending on the suspected diagnosis or syndrome, other consultation will need to be obtained such neurology, ophthalmology, and others subspecialties.

Cytogenetic testing should be obtained in the following situations (from AHA Scientific Statement):

**1.** Any child or infant with the phenotype of a recognizable chromosomal syndrome (e.g., Trisomy 21 or 18)


Review of the literature shows that chromosome abnormalities were present in 12% of patients with TOF, 26% in tetralogy of Fallot/pulmonary atresia, 44% in interrupted aortic arch, 12% in truncus arteriosus, 5% in double outlet right ventricle, and 60% in absent pulmonary valve. With certain cardiac defect, chromosomal analysis should be considered. In patients with conotruncal defects or interrupted aortic arch, FISH should be used looking for 22q11 deletion. Also analysis of the 8p region should be included [124].
