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Screening for Down Syndrome – What does the future hold?
Down syndrome is the most common chromosomal abnormality in newborns. As this risk is clearly increased with advancing maternal age, initial screening is focused on older pregnant women (>35 years). Amniocentesis is the only test available to definitively make the diagnosis. It is therefore a diagnostic test, not a screening test, is invasive and hence not without risk.
In the 1980’s, with the discovery that pregnancies complicated by Down syndrome had abnormally low AFP levels, the era of antenatal screening began. This allowed assignment of an estimated risk of Down’s in an individual pregnancy. A woman of any age could then use this estimated risk to help make a decision whether to have the diagnostic test (amniocentesis) with its known risk performed.
Over the next several years the test was expanded and its accuracy improved with the measurement of other markers in maternal blood. Addition of estriol and HCG levels to the AFP resulted in the “Triple Screen.” Following this, inhibin levels led to the “Quad Screen,” the test we’ve been offering for several years.
While this test offers us the ability to detect 70-80% of Down’s fetuses, it has the drawback of being performed in the mid-second trimester. Blood screening is during the 16th week of pregnancy. While abnormal results are generally available within one week, making arrangements for an amniocentesis and awaiting diagnostic results takes another 2-3 weeks. This leaves couples who do not want to continue with the pregnancy faced with a late pregnancy termination.
The development of an accurate first trimester screening tool has therefore been of interest for some time. While a diagnostic test (chorionic villus sampling or CVS) has been available, it is invasive and carries a risk of pregnancy loss analogous to that of amniocentesis. In addition, it is a technically more difficult procedure to perform and the availability of skilled physicians has remained quite limited.
A true screening tool does now appear to be on the horizon and is indeed being offered in some medical centers. It combines serum markers (in this case HCG and a protein called PAPP-A) with a specific fetal ultrasound measurement referred to as the nuchal translucency (NT). Work pioneered in England has recently been confirmed in this country that demonstrates the accuracy of this test. The study called the FASTER Trial compared this screening technique to the Quad Screen. They demonstrated comparable detection rates (83% vs. 79% respectively) for Down syndrome. The NT screen however is performed much earlier in pregnancy, between approximately 10 ½ weeks and 14 weeks, thus allowing the potential for much earlier diagnosis. In addition, the study found that women who went ahead and had both tests done improved their chances of detecting Down syndrome to 90%. In other words, if both tests returned as normal, a woman can be told that her risk is now 90% lower than her age specific risk. This allows many women to be highly reassured without running the risk of an invasive diagnostic test. Other women might use the new estimated risk to help them decide that the risk of the diagnostic test is warranted.
Problems remain however. While the first trimester blood test is readily available now, the NT procedure is not. It is technically difficult to obtain and is presently performed at only a few medical centers. Also, evidence from the FASTER Trial suggests that individual practices that want to offer this testing should develop their own population specific measurements and need to monitor their accuracy very carefully. On top of this is the problem noted above that CVS (the diagnostic test used in the first trimester) remains quite limited in its accessibility. Could women with abnormal screening results be left without the option of CVS and have to await amniocentesis thus defeating the whole purpose of early screening? While these factors will certainly inhibit the rapid, widespread availability of this screening protocol, it has become generally accepted that this will become the standard of care over the next several years.
Mark Chag MD
Harbour Women’s Health