Clinical:First-trimester aneuploidy risk assessment

First-trimester Down Syndrome Risk Assessment

Why First-trimester Down Syndrome Risk Assessment Is Done

In the early 1990s in London, Kypros Nicolaides first recognized that a combination of neck thickness measurements and blood tests could be used to provide personalized Down syndrome risks to women early in pregnancy. ^[1] The first method of screening for Down syndrome was the mother’s age, which is not completely effective because most babies are born to young women and, depending on the population, only 15 to 25 percent of Down syndrome occurs in babies born to women age 35 or older.

Second trimester serum screening for Down syndrome risk started with alphafetoprotein (AFP) testing, because AFP tends to be low in women carrying fetuses with Down syndrome. Later, additional serum analytes were described that raised the detection rate for Down syndrome to 80 to 85 percent at a 5 percent screen positive rate (i.e. 5 percent of normal women were told that they had an increased risk of Down syndrome, usually set at a risk greater that 1:270). The statistical method that is used for the blood test is to calculate “likelihood” ratios, and as long as different analytes are statistically independent of each other, multiple likelihood ratios can be used together.

Nicolaides recognized that the distribution of the size of a small fluid collection normally found in the back of the fetal neck differed between normal and Down syndrome fetuses, and that allowed the calculation of likelihood ratios just like those created for blood tests. This measurement requires much greater precision than all the other measurements we take in prenatal ultrasound. And just like any other lab test, regular monitoring of results must occur to ensure consistency over time. This has also been validated in several large studies in the U.S. ^{[2] [3]}

Physicians and sonographers who perform this measurement must undergo very specific training and their results need to be monitored statistically over time. Several programs are available to do this. When properly performed, first-trimester risk assessment can detect 85 to 90 percent of Down syndrome fetuses at the same 5 percent screen positive rate.

There are several benefits to first-trimester risk assessment compared to second-trimester blood tests alone. We often change the dating based on first-trimester scans. One study showed that 40 percent of pregnancies were redated by a first-trimester scan. ^[4]. Multiple gestations are detected accurately and early. Over time, we’ve also learned that increased neck thickness can be a sign of more than just chromosome abnormalities. There are a number of structural abnormalities, such as congenital heart disease, that can also be identified by an increased neck thickness in the first-trimester. ^{[5] [6]} The normal range is usually between 1.0 and 3.0 millimeters (at 11 to 14 weeks gestation).

One in 800 babies is born with Down syndrome. First-trimester Down syndrome risk assessment gives information early when it is more private for the patient, and if she chooses to terminate, abortion is safer early in pregnancy. The patient can opt for chorionic villus sampling (CVS) if she wants to have definitive testing.

Preparation

Women having this test will usually need to have a full bladder prior to the sonogram. There is also a blood test which might be performed either a few days before or the same day as the ultrasound.

Benefits

The benefit of this test is that women can get personal risks of their fetuses having either Down syndrome or another chromosome abnormality, trisomy 18, also known as Edward syndrome.

Risks

There are no risks to the ultrasound or the blood draw. About 5% of women carrying normal fetuses will be told they are at increased risk of having an abnormal fetus. The usual threshold for saying risk is increased is about 1:270, but some programs use other thresholds. Another approach is to tell the woman her risk number without having an arbitrary level that is considered high or low.

Side Effects

Effectiveness

About 85-90% of Down syndrome pregnancies are identified with this test.

Recovery

Expected Outcomes

Women who have concerns after finding out their risks can have definitive testing by either chorionic villus sampling or amniocentesis.

Statistics

Alternatives

The alternative test is a second trimester "Quad screen," which combines 4 blood tests to provide a risk assessment. The detection rate of Down syndrome is slightly lower with a Quad test.

Experts on Down Syndrome Risk Assessment

Nuchal Translucency Quality Review <www.ntqr.org>

Research

Future alternatives may include detection of fetal cells, RNA or DNA in the maternal circulation.

Clinical Trials

Controversy

Interesting Facts

References

1. ↑ Nicolaides KH, Azar G, Byrne D et al. Fetal nuchal translucency: ultrasound screening for chromosomal defects in first-trimester of pregnancy. BMJ 1992;304:867-869
2. ↑ Wapner R, Thom E, Simpson JL et al. First-trimester screening for trisomies 21 and 18. N Engl J Med. 2003;349:1405-13.
3. ↑ Malone FD, Canick JA, Ball RH, et al. First-trimester or second-trimester screening, or both, for Down's syndrome. N Engl J Med 2005;353:2001-11.
4. ↑ Bennett KA, Crane JM, O'Shea P, et al. First-trimester ultrasound screening is effective in reducing postterm labor induction rates: a randomized controlled trial. Am J Obstet Gynecol. 2004;190:1077-81
5. ↑ Bahado-Singh RO, Wapner R, et al. Elevated first-trimester nuchal translucency increases the risk of congenital heart defects. Am J Obstet Gynecol 2005;192:1357-61.
6. ↑ Souka AP, Von Kaisenberg CS, Hyett JA, et al. Increased nuchal translucency with normal karyotype. Am J Obstet Gynecol. 2005;192:1005-21. Erratum in: Am J Obstet Gynecol. 2005;192:2096.