Congenital Heart diseases : Causes and Risk Factors / Early Diagnosis and Role of MTP

 

What are the causes of congenital heart diseases ?

Congenital heart disease (CHD) results from abnormal development of the heart or great vessels during fetal life, particularly during the first 3–8 weeks after conception. In most affected children, there is no single identifiable cause; CHD usually reflects a combination of genetic susceptibility and environmental influences.

Major causes and risk factors

1. Genetic and chromosomal abnormalities
• Down syndrome (trisomy 21) — commonly AV septal defects, VSD
• Turner syndrome — coarctation of the aorta, bicuspid aortic valve
• Trisomy 18 and 13
• 22q11.2 deletion/DiGeorge syndrome — conotruncal defects such as TOF and interrupted aortic arch
• Noonan syndrome — pulmonary stenosis, hypertrophic cardiomyopathy
• Single-gene mutations, including genes involved in cardiac development such as NKX2-5, GATA4 and NOTCH1
2. Maternal illnesses during pregnancy
• Pre-existing diabetes mellitus, especially if poorly controlled around conception
• Maternal phenylketonuria if inadequately controlled
• Certain autoimmune diseases, particularly maternal anti-Ro/SSA or anti-La/SSB antibodies, which can cause congenital heart block
• Maternal obesity is associated with a modestly increased risk
3. Infections during early pregnancy
• Rubella is the classic example and may cause PDA and pulmonary artery stenosis.
4. Drugs and teratogenic exposures
• Retinoids such as isotretinoin
• Lithium has historically been associated with Ebstein anomaly, although the absolute risk is smaller than once thought
• Some anti-epileptic medications
• Certain other medications with known teratogenic potential
• Alcohol, particularly heavy exposure
• Smoking is associated with a modest increase in risk
5. Family history
• Having a parent or sibling with CHD increases the risk.
• The recurrence risk varies considerably according to the specific defect and whether an identifiable genetic syndrome is present.
6. Multifactorial/unknown causes
   This is the most important category. Most congenital heart defects occur without a clearly identifiable cause. They probably arise from complex interactions among multiple genes, developmental processes and environmental factors.

An important point for parents

CHD usually cannot be attributed to something the mother did or did not do during pregnancy. Even with excellent antenatal care, congenital heart defects can occur. Importantly, having a risk factor increases probability but does not mean the baby will develop CHD.

Also, the term congenital means present at birth, not necessarily hereditary. Only a proportion of congenital heart diseases have a clearly inherited genetic basis.

 

Risk factor	Examples / association
Family history of CHD	CHD in a parent, sibling, or previous child
Chromosomal abnormalities	Down syndrome, trisomy 13/18, Turner syndrome
Genetic syndromes/mutations	22q11.2 deletion, Noonan syndrome and other pathogenic variants
Maternal pregestational diabetes	Particularly when glucose control is poor around conception/early pregnancy
Maternal phenylketonuria	Especially if phenylalanine is poorly controlled
Maternal obesity	Associated with a modest increase in CHD risk
Maternal rubella infection	Particularly during early pregnancy
Maternal autoimmune antibodies	Anti-Ro/SSA and anti-La/SSB → particularly congenital heart block
Alcohol exposure	Heavy maternal alcohol use increases risk of congenital anomalies including CHD
Maternal smoking	Associated with a modestly increased risk of some CHDs
Teratogenic medications	Retinoids/isotretinoin, some antiseizure drugs and certain other teratogens
Lithium exposure	Small increased risk of cardiac malformations; historically associated with Ebstein anomaly
Assisted reproductive technology	IVF/ICSI pregnancies show a small increased association with CHD, partly related to underlying parental factors and multiple pregnancy
Multiple pregnancy	Particularly monochorionic twins; risk of CHD is higher than in singleton pregnancies
Advanced maternal age	Mainly increases CHD risk indirectly through increased frequency of chromosomal abnormalities

 

Who should receive detailed fetal cardiac assessment/fetal echocardiography ?

Some of the strongest indications include suspected fetal cardiac abnormality on screening ultrasound, abnormal fetal genetic/chromosomal testing, first-degree family history of significant CHD, pregestational maternal diabetes, maternal anti-Ro/SSA antibodies, certain teratogenic exposures, and monochorionic twinning.

One useful distinction is that risk factors explain only a minority of CHD cases. Most babies born with CHD have no recognized maternal or familial risk factor, which is why routine antenatal cardiac screening is important for all pregnancies.

How is routine antenatal cardiac screening done ?

Routine antenatal cardiac screening is mainly done during the second-trimester anomaly ultrasound, rather than by performing a formal fetal echocardiogram in every pregnancy.

How it is usually done

The key examination is the fetal anomaly scan at about 18–22 weeks of pregnancy. During this scan, the fetal heart is systematically assessed.

The sonologist looks at:

• Situs and position — stomach and heart position, cardiac axis
• Four-chamber view — atria, ventricles, AV valves, septa and relative chamber sizes
• Left ventricular outflow tract (LVOT) — LV → aorta
• Right ventricular outflow tract (RVOT) — RV → pulmonary artery
• Three-vessel view (3VV)
• Three-vessel-and-trachea view (3VT) — particularly useful for detecting abnormalities of the great arteries and aortic arch
• Heart rate and rhythm
• Where indicated, additional views of the aortic and ductal arches and systemic/pulmonary venous connections

These views detect a substantial proportion of major structural congenital heart defects, especially when performed by trained personnel.

What happens if something is abnormal?

If the screening scan shows a suspected cardiac abnormality, or if the pregnancy has an important risk factor for CHD, the mother is referred for a detailed fetal echocardiogram, generally performed by a fetal cardiologist/pediatric cardiologist or another appropriately trained specialist.

A fetal echo is much more detailed and uses:

2-D imaging + colour Doppler + pulsed-wave Doppler, with M-mode or other modalities, when necessary, to evaluate cardiac anatomy, blood flow and rhythm.

An important limitation

A normal anomaly scan does not completely exclude CHD. Small VSDs, mild valve lesions, some venous abnormalities, coarctation of the aorta and lesions that evolve later in gestation may not be apparent at the routine scan.

Hence :

Every pregnancy → 18–22-week anomaly scan with cardiac views → abnormal/suspicious findings or significant risk factors as mentioned earlier → specialist fetal echocardiography.

This approach is important because many babies with serious CHD are born to mothers with no identifiable risk factors.

So, at what time of gestation fetal echocardiography is done?

A fetal echocardiogram is usually performed at 18–22 weeks of gestation. This is generally the optimal period because the fetal heart is large enough for detailed anatomical assessment while allowing sufficient time for further evaluation and counselling if an abnormality is detected. 

What are the CHD in which Medical Termination of Pregnancy MTP is advised ?

MTP may be offered/considered after multidisciplinary counselling for severe CHD with a poor or highly burdensome prognosis. The decision depends on the exact anatomy, associated genetic/extracardiac abnormalities, expected surgical pathway and outcomes, gestational age, and the parents’ informed choice.

CHDs in which MTP may particularly be considered

1. Functionally univentricular hearts
These are among the most important lesions for prenatal counselling because treatment is generally staged palliation rather than restoration of a normal two-ventricle circulation.

Examples include:

• Hypoplastic left heart syndrome (HLHS)
• Double-inlet left ventricle
• Severe unbalanced AV septal defect
• Tricuspid atresia with severe associated abnormalities
• Pulmonary atresia with intact ventricular septum with severely hypoplastic RV
• Other complex lesions in which biventricular repair is not feasible

For HLHS, for example, postnatal management typically requires multiple staged operations and lifelong specialist care.

2. Severe complex CHD with very poor anticipated outcome
Examples can include:

• Severe forms of heterotaxy with complex CHD
• Complex single-ventricle anatomy with significant AV-valve regurgitation or ventricular dysfunction
• Severe Ebstein anomaly with massive cardiomegaly/hydrops
• Critical valvar disease associated with progressive ventricular hypoplasia/dysfunction
• Complex CHD associated with fetal heart failure or hydrops

The prognosis within these diagnoses varies considerably, so the diagnosis alone isn't sufficient to recommend termination.

3. CHD associated with major chromosomal/genetic abnormalities

This is particularly important because prognosis may be determined more by the associated syndrome than by the cardiac lesion itself.

Examples include:

• Trisomy 18
• Trisomy 13
• Severe chromosomal/genomic abnormalities
• Some syndromic CHDs associated with major extracardiac abnormalities

Therefore, after diagnosing major fetal CHD, detailed fetal anatomical assessment and appropriate genetic testing/counselling become important before parents make decision.

What about TOF, TGA, VSD, AVSD etc.?

Isolated, surgically correctable CHD with a good expected outcome would generally not by itself be a reason to advise MTP.

For example, many cases of:

• Tetralogy of Fallot
• Transposition of the great arteries
• Coarctation
• Complete AVSD

can have good outcomes with appropriate treatment. However, the counselling changes substantially when there is severe anatomy, ventricular dysfunction, additional malformations or a genetic/chromosomal disorder.

A useful approach for fetal CHD counselling

Hence the protocol can be

Major CHD on anomaly scan → expert fetal echocardiography → define whether biventricular repair is possible → look for extracardiac anomalies → genetic testing/counselling where appropriate → pediatric cardiac surgeon/cardiologist + fetal medicine counselling → discuss continuation versus MTP according to prognosis and parental preference.