Her risk is high, but how high? Is invasive testing the only answer?
Mrs. S, a 37-year-old primigravida, has an age-related risk of having a baby with Down syndrome of 1 in 250. Before deciding whether to undergo an invasive diagnostic procedure based on her age alone, she wants to learn more about her risk by having a prenatal screening test. The 2 safest and most informative options: first-trimester combined screening and fully integrated screening. About 5% of women who have the first test are found to be high-risk, and the test identifies about 85% of all cases of Down syndrome. As for fully integrated screening, it identifies about 85% of all Down syndrome cases at a 1% screen-positive rate. Since it offers a faster result, Mrs. S opts for first-trimester screening.
At 11 weeks, 0 days (according to crown-rump length), she undergoes nuchal translucency imaging and has a blood sample drawn to measure pregnancy-associated plasma protein A (PAPP-A) and human chorionic gonadotropin (hCG). Her test results are reported in multiples of the median (MoM):
|Nuchal translucency||2.3 mm||1.62 MoM|
|PAPP-A||0.5 mIU/mL||0.79 MoM|
|hCG||45 IU/mL||1.25 MoM|
These values suggest that Mrs. S has a risk of having a pregnancy affected by Down syndrome of 1 in 170. In other words, her results are screen-positive.
Can her risk be more precisely quantified without invasive testing?
Had Mrs. S chosen fully integrated screening, the answer to that question would be yes, but it would have meant waiting until the second trimester for the result.
This article describes the 2 screening approaches—first-trimester combined screening and fully integrated screening—as well as the serum-only variant of the integrated test and the established quad marker test. Also discussed are the findings of recent studies, including 2 key trials:
- the First and Second Trimester Evaluation of Risk (FASTER) of aneuploidy trial, published in November1
- the Serum, Urine, and Ultrasound Screening Study (SURUSS), published in 2003 in the United Kingdom2
These 2 trials are the only ones to compare screening markers at different times during pregnancy in the same women—the only way to fairly assess the quality of various marker combinations within and across gestational weeks.
How good is current practice?
In 1995, about 2.5 million of the approximately 4 million gravidas in the United States had maternal serum screening for Down syndrome and open neural tube defects.3 Today, this practice usually involves a serum sample drawn early during the second trimester (15–20 weeks), measurement of 3 or 4 serum markers (the triple or quad test), and calculation and reporting of risk.
Second-trimester serum screening is a relatively easy procedure involving a single blood sample and established risk-calculation methods. Further, the follow-up when a woman is screen-positive—ie, at increased risk—is clear: amniocentesis in the case of Down syndrome risk and targeted ultrasound in the case of open neural tube defects (with amniocentesis backup). For the triple test, we can expect a detection rate of about 70%, and for the quad test, 80%, by identifying 5% of screened women with the highest calculated risk (the effective screen-positive rate).1,2,4
Why the newer options are better
Optimally, prenatal screening should minimize the number of women identified as screen-positive (ie, women at sufficient risk to be offered amniocentesis or comparable procedures) while maximizing the overall detection rate. This point is important because screen-positive status leads to follow-up diagnostic procedures that are necessarily invasive and risky.
First-trimester screening slightly better than the quad test
The option Mrs. S selected entails measuring 3 markers during the late first trimester (11–13 gestational weeks): nuchal translucency, PAPP-A, and hCG or its free βsubunit. These markers constitute a screening test that performs as well as, or slightly better than, the second-trimester quad test. The best estimate of first-trimester screening is an 85% detection rate at a 5% screen-positive rate (compared with about 80% detection rate at a 5% screen-positive rate for the quad test).1,2,5,6