Prenatal Diagnosis and Management of Congenital Heart Disease (CHD) in Down Syndrome
By: Prema Ramaswamy, MD
Director, Pediatric Cardiology
Maimonides Children’s Hospital
What is Down syndrome?
Down syndrome is a genetic disorder which affects the 21st chromosome (out of the 23 pairs present in every cell). It is caused when abnormal cell division results in an extra full or partial copy of chromosome 21; hence it is also called Trisomy 21. This extra genetic material causes the birth defects, learning challenges and physical features of Down syndrome. It was first described by John Langdon Down, a British physician, in 1866 but the genetic abnormality was only confirmed in 1959. Of note, Dr. Down’s grandson was born with Down syndrome.
What causes Down syndrome?
There are 3 different causes
- The most common cause is Trisomy 21 (tri meaning three) where there are three copies of the 21st chromosome instead of two. This is the cause in 95% of all cases.
- Rarely (in ~4% cases), either a full or partial copy of chromosome 21 attaches to another chromosome. This is called translocation and this is the only form of Down syndrome that may be inherited.
- Very rarely (in 1-2% cases), a child may have some normal cells (with 2 copies of chromosome 21) and some abnormal cells (with 3 copies of chromosome 21). This is called mosaicism and in this condition, there may be fewer symptoms of Down syndrome since some of the cells are normal.
Is it inherited?
In the majority of cases (95%), it is not inherited. However, in roughly 4% of cases there may be a risk of inheriting it either from the father or the mother due to the presence of a genetic translocation in either of them – a condition where part of chromosome 21 has been transferred to another chromosome. A genetic evaluation can confirm its presence.
How often does it occur?
Each year, in the US, about 6,000 babies are born with Down syndrome, which is about 1 in every 700 babies born.
Which women are considered at high risk for having a baby with Down syndrome?
Women who are above the age of 35 years, women whose babies have an abnormal ultrasound test and women who have had a previous baby or a close family member with Down syndrome.
Are most children with Down syndrome born to women above 35 years of age?
Actually, most children with Down syndrome are born to women under the age of 35 years since many more babies are born to younger women.
Why are women above 35 years at higher risk of having a baby with Down syndrome?
As the natural aging of a woman’s eggs results in more chromosomal abnormalities, the average 40-year-old woman will have as many as 60% of chromosomally abnormal eggs.
Are women who have had a previous baby with Down syndrome at higher risk of having another baby with Down syndrome?
Yes. This is related to the advancing age of the mother. In addition, if there is a translocation, that may increase the chances of recurrence.
Can Down syndrome be diagnosed before birth?
Yes. Generally, there are two types of tests you can have when you are pregnant- screening and diagnostic. A screening test is suggestive and tells you what your chances are of the baby having a chromosomal condition. The diagnostic test is confirmatory and can tell for sure.
What are the screening tests?
These are blood tests performed on the mother and are of two main types. The first (also called the triple test or quad screening) measures the proteins in the serum. This is usually combined with measuring the amount of fluid at the back of the baby’s neck (also called nuchal translucency) and is performed between 11 and 14 weeks. The other test (also called cell free or cfDNA) measures small fragments of fetal genetic material. This test can be done after 10 weeks of pregnancy and is considered to be very accurate in diagnosing Down syndrome.
What are the diagnostic tests?
There are two. An amniocentesis (or amnio for short) is a procedure where a needle is inserted into the uterus to remove some of the fluid surrounding the baby to study the baby’s skin cell DNA. This is usually performed between 15 – 18 weeks. The second is called CVS (chorionic villus sampling) and is performed between the 10th and 13th weeks. There is a very small risk of miscarriage with these tests (usually quoted as 0.1-0.3%)
Are babies with Down syndrome at risk of CHD?
Yes. Almost half of all babies with Down syndrome have congenital heart disease.
Can heart disease in Down syndrome be diagnosed before birth?
Yes. This is done by a fetal echocardiogram. This is a sonogram of the heart but different from the one performed by your obstetrician. It is very detailed in its scope and looks at the fetal heart and the arteries and veins that enter it in multiple views. It can tell the position, size, structure, function and rhythm of the unborn baby’s heart.
Is a fetal echo the same as an ultrasound that my obstetrician performs and if not, who performs it?
A fetal echo is not the same as a sonogram performed by an obstetrician. It is a higher quality test that is capable of picking up more of the baby’s heart structure. It is usually performed by pediatric cardiologists as well as some perinatologists.
How long does it take to perform a fetal echo?
It can take from 45 minutes to 120 minutes depending on the fetal position and complexity of the heart disease.
How accurate is a fetal echo and what are the limitations of a fetal echo?
Fetal echocardiography is highly accurate in determining the structure of the heart itself. However, there are a few abnormalities that could be missed, even by a detailed fetal echocardiogram, such as small holes in the heart or mild abnormalities in the veins and the great artery that arise from it.
When is the ideal time for performing a fetal echo?
It is typically done in the second trimester between 18 to 24 weeks.
Are there any side effects to a fetal echo?
There are no side effects from a fetal echo since it uses sound waves similar to those used in sonograms. It does not use radiation as is used in X- rays. So, this is a test that could be repeated multiple times, if needed.
Why is it important to diagnose congenital heart disease (CHD) prenatally?
It is important so that doctors can get ready for problems that may occur during pregnancy or during delivery. In some cases, early delivery may be scheduled; in others, a caesarian section may be planned if the baby needs a procedure immediately after birth. If the baby has problems with either too fast or too slow heart rates, then medicines can be given to treat that. Also importantly, it gives parents time to educate themselves about the heart condition and the treatment or surgeries that may be required after birth.
What are the most common CHD seen in Down syndrome?
The most common CHD noted in Down syndrome are AV canal defect (also called atrioventricular septal defect – AVSD) and ventricular septal defects (VSD). AVSDs account for 1/3 of all heart disease in Down syndrome. In an AVSD, the valves in between the upper and lower chambers of the heart do not develop normally and, in addition, there may be holes in the wall between the upper and lower chambers of the heart. A VSD is a hole in the wall between the two lower pumping chambers of the heart. The other defects that are common are an atrial septal defect (ASD – a hole in the wall between the upper chambers of the heart) and a patent ductus arteriosus (PDA – an artery that connects the two large arteries arising from the heart. This is present in all fetuses and typically closes within 2 weeks after birth).
Is there a CHD which may suggest the possibility of Down syndrome in a fetus?
Occasionally, a diagnosis of Down syndrome is made after the discovery of an AVSD on a fetal echo since this condition is commonly associated with Down syndrome. Interestingly, patients with Down syndrome tend to have a “complete” form of AV canal defect with a large VSD component, whereas babies with an AV canal but no Down syndrome tend to have more partial AV canal and more abnormalities of the left side of the heart.
If my baby has a CHD, what does that mean for the pregnancy and delivery?
That depends on what CHD the baby has. In the most commonly seen abnormalities such as AVSD, VSD and an atrial septal defect, there is usually no effect on pregnancy nor mode and timing of delivery. However, it is standard to evaluate the baby and perform a pediatric echocardiogram soon after birth to confirm or rule out any abnormality. If the baby indeed, has a significant narrowing, then an intravenous medication may be required to open up the artery connecting the two large arteries exiting the heart (the PDA) and these babies will need surgery soon after.
Are there any interventions that can be made in utero?
For the most commonly noted CHD in Down syndrome, no intervention is required in utero. However, rhythm problems (such as with a very fast heart rate) may be treated by giving the mother medications.
Does CHD in Down syndrome always need surgery?
No. A complete AVSD almost always needs surgery and this is typically done between 3-6 months of age. A large VSD also needs surgery by 3-6 months. However, with an ASD or a VSD where the lung pressures are normal, surgery may be delayed for a few years if the defect is moderate in size or not needed at all, if small.
What results can we expect with surgery?
In the current era, babies with Down syndrome have a similar survival to that seen in babies without Down syndrome for the most common heart defect surgeries. They may however, have a longer stay in the hospital. This may either be secondary to feeding issues in younger babies as well as post-operative infections and lung issues.
Can I continue to see my obstetrician and deliver my baby locally?
Yes, in the vast majority of cases. Most of the common heart defects in Down syndrome do not require surgery at birth and are best addressed in the first few months of life (and in some cases even later).
Can I have a vaginal delivery?
Yes, in most of the cases.
Should my baby have a postnatal echo even if I had a normal fetal echo?
Yes. Since the incidence of heart disease is very high (~50%) in Down syndrome, all babies with this condition should have an echocardiogram at birth (or definitely within 6 weeks) – even if they have had a normal fetal echocardiogram. This is since the fetal echo may miss some abnormalities of the pulmonary veins and the aorta. Moreover, there are some conditions (such as a PDA) which are normal in pregnancy and can only be diagnosed as abnormal if they have not closed after birth.