Wednesday, 21 December 2011 00:03

Prenatal Testing and Diagnosis

There are two types of tests for Down syndrome that can be performed before your baby is born: screening tests and diagnostic tests. Prenatal screenings estimate the chance of the fetus having Down syndrome. These tests do not tell you for sure whether your fetus has Down syndrome; they only provide a probability. Diagnostic tests, on the other hand, can provide a definitive diagnosis with almost 100 percent accuracy.

There is an extensive menu of prenatal screening tests now available for pregnant women. Most of these screening tests involve a blood test and an ultrasound (sonogram). The blood tests (or serum screening tests) measure quantities of various substances in the blood of the mother, including alpha-fetoprotein, inhibin A, plasma protein A, estriol, and human chorionic gonadotropin. Together with a woman's age, these are used to estimate her chance of having a child with Down syndrome. Typically offered in the first and second trimesters, maternal serum screening tests are only able to predict about 80 percent of fetuses with Down syndrome. It is important to note that none of these prenatal screens will be able to definitively diagnose Down syndrome. Instead, mothers should expect results such as, “You have a 1 in 240 chance of having a child with Down syndrome” or “You have a 1 in 872 chance of having a child with Down syndrome.”

These blood tests are often performed in conjunction with a detailed sonogram (ultrasound) to check for "markers" (characteristics that some researchers feel may have a significant association with Down syndrome). Recently, researchers have developed a maternal serum/ultrasound/age combination that can yield a much higher accuracy rate at an earlier stage in the pregnancy. Still even with the ultrasound, however, the screen will not definitively diagnose Down syndrome.

As of October 2011, a prenatal screening test, named “MaterniT21,” was made available by the company, Sequenom.  This test, which can only be ordered through a physician, involves blood being taken from the expectant mother, as early as 10 weeks of gestation, and relies on the detection of cell-free DNA that circulates between the fetus and the expectant mother.  According to the latest research, this blood test can detect up to 98.6% of fetuses with trisomy 21.  A “positive” result on the test means that there is a 98.6% chance that the fetus has trisomy 21; a “negative” result on the test means that there is a 99.8% chance that the fetus does not have trisomy 21.   The turn-around time for the test is about 8-10 days, and approximately 0.8% of patients do not receive a result due to technical standards. While the initial clinical trials were conducted just on cases with trisomy 21, one form of Down syndrome, a “positive” result cannot distinguish between trisomy 21, translocation Down syndrome, and high- percentage mosaic Down syndrome.  Put another way, a “positive” result will pick up all forms of Down syndrome, except mosaic Down syndrome that is 33% or lower.  All mothers who receive a “positive” result on this test are encouraged to confirm the diagnosis with one of the diagnostic procedures described below.

Prenatal screening tests are now routinely offered to women of all ages. If the chance of having a child with Down syndrome is high from prenatal screening, doctors will often advise a mother to undergo diagnostic testing.

The diagnostic procedures available for prenatal diagnosis of Down syndrome are chorionic villus sampling (CVS) and amniocentesis. These procedures, which carry up to a 1 percent risk of causing a spontaneous termination (miscarriage), are nearly percent accurate in diagnosing Down syndrome. Amniocentesis is usually performed in the second trimester between 15 and 22 weeks of gestation, CVS in the first trimester between 9 and 14 weeks. Amniocentesis and CVS are also able to distinguish between these genetic types of Down syndrome: trisomy 21, translocation Down syndrome, and mosaic Down syndrome. 

Why Should I Get a Prenatal Test?

Some mothers choose to forgo all diagnostic testing, knowing that they would continue their pregnancy no matter what and do not want to expose their pregnancy to even the small risk of miscarriage that come with CVS and amniocentesis. Some start with a prenatal screen and then proceed to a definitive diagnostic test. Other mothers simply bypass the prenatal screen and start with a definitive diagnostic test. Whether or not to undergo a prenatal screening or diagnostic test is a personal decision, and expectant parents must make the choice that is best for them.

Some reasons for choosing a prenatal test include:

Advanced Awareness: Some parents would like to know as soon as possible if their fetus has Down syndrome so that they could make preparations (like informing other family members and doing research on Down syndrome) prior to the birth. Families who have chosen this option have reported in research studies that the birth of their child with Down syndrome is as much of a celebratory process as any other birth because they have had time to adjust to the new diagnosis.

Adoption: Some parents would like to receive a prenatal diagnosis so that they could make arrangements for adoption if their fetus were to have Down syndrome. There is a long waiting list of families in the United States ready to adopt a child with Down syndrome. For more information, visit

Termination: Some parents want to have a prenatal diagnosis so that they can discontinue their pregnancy. Parents should discuss this option with their obstetrician.

One of the best ways to begin to consider these choices is to speak to family members of individuals with Down syndrome through a local Down syndrome organization. In addition, there are many books and articles written by family members about their personal experiences. A message from families that is echoed again and again is that the positive impacts of having a member with Down syndrome far outweigh any difficulties or challenges that may come up.

If you have any questions about these procedures, do not hesitate to ask your doctor. It is important that you receive accurate information and understand all your options.

Diagnosing Down syndrome

Since many expectant parents choose to forgo prenatal tests, most cases of Down syndrome are diagnosed after the baby is born. Doctors will usually suspect Down syndrome if certain physical characteristics are present. Some of the traits common to babies with Down syndrome include: low muscle tone, a flat facial profile, a small nose, an upward slant to the eyes, a single deep crease across the center of the palm, an excessive ability to extend the joints, small skin folds on the inner corner of the eyes, and excessive space between large and second toe.

Not all babies with Down syndrome have all these characteristics, and many of these features can be found, to some extent, in individuals who do not have the condition. Therefore, doctors must perform a special test called a karyotype before making a definitive diagnosis.

To obtain a karyotype, doctors draw a blood sample to examine your baby's cells. They use special tools to photograph the chromosomes and then group them by size, number and shape. By examining the karyotype, they can determine accurately whether or not your baby has Down syndrome.

NDSS establishes criteria to evaluate companies with non-invasive prenatal diagnostic tests for Down syndrome

The National Down Syndrome Society (NDSS) recognizes that many companies, both within the United States and abroad, are developing new non-invasive blood tests that might be able to detect Down syndrome prenatally.  NDSS appreciates that these tests are likely to be safer for pregnant women than the current invasive options of chorionic villus sampling and amniocentesis.  However, before these new tests are made commercially available, companies should first meet all of the following criteria:

The noninvasive prenatal diagnostic (NIPD) tests should first undergo rigorous double- blind, case-controlled trials, and the sensitivity, specificity, positive and negative predictive values should be published in a respected peer-reviewed medical journal.  The company performing the NIPD test should clearly list these values in its marketing and informational materials to healthcare professionals and the general public.

After publication(s) in peer-reviewed medical journals, the NIPD should be clearly marketed for only the form of Down syndrome that is being detected.  For a test to be called a “Down syndrome test,” all forms of Down syndrome—trisomy 21, translocation Down syndrome, and mosaic Down syndrome—must be evaluated.

The decision whether to have NIPD performed must be that of the pregnant woman and her significant other, as desired and as appropriate.   The decision should remain strictly confidential and voluntary.

All pregnant women should be fully informed as to the purpose, limitations, and expense of the NIPD.  They should be told how the test is performed, when such a result will be available, and how that result will be delivered.  Each pregnant woman opting to proceed with NIPD should sign an informed consent, which should include, at minimum, this understanding.  The company performing the test should not accept or process any samples without first receiving a signed informed consent.

If a NIPD result suggests, but does not confirm with near 100% accuracy, the diagnosis of Down syndrome, the company should emphasize in the reported results that the pregnant woman should be offered an invasive diagnostic test, such as chorionic villus sampling or amniocentesis, if she desires to confirm the result and her physician feels such a procedure is safe given her medical history.

If a NIPD result suggests or confirms a form of Down syndrome, the company performing the test must ensure that the pregnant woman’s ordering healthcare provider receive, no later than 24 hours after receiving the results, up to date, balanced and medically reviewed information on Down syndrome. The ordering healthcare provider should be encouraged to share the material with the pregnant woman after delivering the results.

In its marketing and informational materials, the company performing the test must make clear that all women have the absolute right to continue a pregnancy after a definitive prenatal diagnosis.  Women should never be subjected to unwanted pressure from healthcare professionals or others concerning this decision.

The company should demonstrate a commitment to educating healthcare professionals on how to best communicate a prenatal diagnosis of Down syndrome to expectant parents using available evidence-based materials. Healthcare professionals should be trained to deliver the diagnosis in a nondirective manner so that women can make informed decisions about their pregnancies.

Click here to view the Sequinom report card. Courtesy: National Down Syndrome Society (NDSS)