What is the meaning of the Down Syndrome risk evaluation result?
What are the limitations of the screening test?
(biochemical screening and nuchal translucency)
The result of the screening test is obtained as a weighted risk taking your age
and the results of the tests you have undergone into account. It predicts the statistical
risk: one out of a number of women of the same age having an identical result in
her screening test will give birth to a child with Down syndrome.
If a woman receives a result of a 1 in 100 risk, this means that if 100 women of
her age report with the same screening test values, and all of them undergo amniocentesis,
99 of them will be found to be carrying a fetus that does not have Down syndrome,
and one will be found to be carrying an affected fetus. In other words, there is
a 99% probability that the infant is normal as far as Down syndrome is concerned.
Moreover, a woman who receives a weighted Down syndrome risk of 1:500 has an even
lower risk - 499 women out of 500 with the same values will have infants without
Down syndrome and one will have an affected infant. Similarly, a woman who receives
a 1:1000 risk will have a 99.9% chance of her fetus not having Down syndrome.
When is the risk considered high according to medical definitions?
A weighted risk in excess of 1:386 is considered high (a result defined as "abnormal").
Women with a high weighted risk are invited to come for genetic counseling, where the results are explained
to them and they are advised to undergo invasive diagnostic testing (amniocentesis
or chorionic villus sampling, depending on the week of gestation).
Only this will give a precise, final result for whether the fetus has Down syndrome,
another chromosomal disorder, or has normal chromosomes.
See also the information sheet: "Why
is there no medical recommendation for amniocentesis in all cases?"
Does the recommendation for amniocentesis indicate that the mother has a serious
It is common for the mother to receive an "abnormal" result in the survey test (a
risk higher than 1:386 for Down Syndrome), with the fetus being found to be normal
in subsequent prenatal testing (e.g. chorionic villus sampling or amniocentesis).
In fact, about 98% of the women who receive an abnormal screening test result have
a healthy fetus. On the other hand, it can happen that the biochemical screening
test (or the nuchal translucency test) can erroneously indicate a relatively low
risk for a fetus to have Down syndrome, whereas in subsequent prenatal testing the
infant will be found to be affected.
Limitations of the screening test
Considering a risk of 1:386 as the borderline between high risk and lower risk means
that the predictive power of the screening test is not 100% absolute, and there
is a possibility that children with Down syndrome will be born to a certain percentage
of women despite the result of the screening test having been regarded as "normal".
Even in the case of a very low risk for Down syndrome, such as 1:5000, there is
still a small chance that the fetus will be affected. It appears that if only all
the women whose weighted risk for Down syndrome obtained from one screening test
(blood biochemical test or nuchal translucency test, separately) were to undergo
amniocentesis (or chorionic villus sampling), we would only be able to identify
66% of all the cases of Down syndrome in this country. In this situation, amniocentesis
would be performed on approximately 5% of pregnant women in the country. If, however,
the borderline for recommending amniocentesis or chorionic villus sampling is taken as
more than 1:1000, for example, the detection rate will be higher, but the percentage
of women undergoing amniocentesis will increase significantly.
Another limitation of screening tests is their limited ability to predict the statistical
risk for chromosomal syndromes other than
Down syndrome. Despite the fact that some of these cases (mainly severe
chromosomal disorders such as trisomy 18,
trisomy 13, etc.) are expressed
by an increased calculated statistical risk for Down syndrome, most go undetected.
Most of the cases that go undetected are chromosomal disorders of lesser severity
than Down syndrome, and descriptions of these can be found in the information sheets
titled "Turner syndrome,
etc." These chromosomal disorders can also be confirmed or ruled out completely
by amniocentesis. The frequency of chromosomal disorders other than Down syndrome
is about one in every 300 pregnancies on average - this risk is greater in older
women, and over the age of 35 the risk is more than 1 in 100 (more than 1%).
Despite these limitations, the "high risk group" for whom amniocentesis is offered
can be defined using the Down syndrome screening test (biochemical screening or
nuchal translucency, etc.). Using these tests, the invasive tests are directed to
a relatively small group of women, preventing the birth of many babies with chromosomal
disorders. It should be noted that these screening tests can also indicate risks
for problems other than Down syndrome - e.g. defects of closure of the spinal column,
kidney defects, and other chromosomal problems (as specified and subject to the
aforementioned limitations), etc.
The future of screening tests for detecting Down syndrome
Today it is possible to calculate the weighted risk taking into account all the
tests that the mother undergoes. Recent studies have shown that the statistical
data evaluating the risk for Down syndrome can be weighted to obtain a single combined
risk. This combined risk has been found to be more reliable than a risk calculated
based on a single test. Whereas a single screening test such as measurement of alpha-fetoprotein
performed in the second trimester can identify 66% of cases of Down syndrome in
the country, and amniocentesis is performed only on those women in the risk group
(who have a risk greater than 1:386), the combined risk assessment can result in
the detection of over 95% of all cases of Down syndrome without increasing the number
of women for whom amniocentesis is recommended. It must be emphasized that the combined
risk assessment method is still undergoing evaluation.
In the not so distant future, it should be possible to perform chromosome testing
of the fetus by examining the pregnant woman's blood. Between the 5th and the 8th
week of pregnancy a blood sample will be taken from the mother. At that stage of
gestation the mother's blood contains cells from the fetus that have passed through
the placenta into the maternal bloodstream. We already have today systems that can
"enhance" (increase the relative concentration of) the percentage of fetal cells
in the mother's bloodstream for the purpose of identifying fetal chromosomal problems.
The intention is that this test will join the current screening tests both in order
to reduce further the number of invasive interventions in pregnancy, and also to
identify a greater percentage of problems.
It is anticipated that by the end of the decade the test tube pregnancy (in vitro
fertilization) rate will have increased significantly. Then each fertilized embryo
will be examined before being returned to the uterus in order to ensure that the
embryos that are returned are chromosomally normal. Today at least two in vitro
fertilization centers in the USA are carrying out trials in which only embryos that
have undergone chromosomal testing are returned to the uterus. The risk of chromosomal
disorders in embryos returned to the uterus using this method is less than 1:50,000.
The purpose of the trials is to see whether the success rate of in vitro fertilization
treatments can be increased. As mentioned, these tests are currently expensive and
on an experimental basis only.
For further details, see the information sheet titled: How to reduce risk of Down syndrome.