Nuchal translucency screening (NTS) is a relatively new test that combines blood test results with special ultrasound results. It has been found to be highly accurate and an excellent noninvasive alternative to amniocentesis. NTS is generally recommended for all women (previously this was only recommended for women over age 35, but guidelines have now changed and this test is offered to all women) and is usually performed between the gestational age period of ten weeks, three days, and thirteen weeks, six days. Some women are referred for an amniocentesis or chorionic villus sampling based on the results, but many women decide not to have further testing after receiving reassuring results on this test.

The NTS uses a special ultrasound called a nuchal translucency test, in which space at the back of the baby's neck is measured. This measurement is used in conjunction with a triple or quad screen (and sometimes first-trimester blood work) to evaluate the risk for Down syndrome. When the ultrasound is done in conjunction with a second-trimester blood test, it identifies 95 percent of babies with Down syndrome. The test positive rate is approximately 5 percent; for every 100 women tested, five will have a positive result. The false positive rate is only slightly lower than the test positive rate, so most positive tests end up being false positives that ultimately show a normal baby. If the test is positive, you will be given the option of having a chorionic villus sampling or an amniocentesis later in the pregnancy, which will confirm or deny the presence of Down syndrome. If the baby has an increased nuchal translucency, but is found to have normal chromosomes, there may still be a risk of problems such as other genetic syndromes or congenital heart disease and further testing may be needed.

Some sonographers include assessment of the baby's nasal bone (some Down babies have poorly ossified nasal bones) as well as the baby's heart to detect tricuspid regurgitation (a leaky heart valve). The test screens for trisomy 13, 18, and 21 and is especially accurate for the detection of trisomy 21.

Some women 35 and over opt to go directly to chorionic villus sampling or genetic amniocentesis without having noninvasive screening first. Except in very rare cases, this will detect any chromosome problem. It has the advantage of certainty, but that comes with the disadvantage of the discomfort of an invasive procedure and a small risk of pregnancy loss. The risk of pregnancy loss may be particularly bothersome in the case of fertility patients who have tried so hard to become pregnant.

There is some debate about combining first- and second-trimester testing. Sequential screening employs NTS first. If that is negative, then a second-trimester quad screen is performed. If either the NTS or the quad screen is positive, then invasive testing is offered. Integrated screening, the other option, involves both NTS and quad screening. After the quad screen result is known, both test results are integrated into a final risk. This differs from sequential screening in that the individual NTS and quad screen results are not individually interpreted. Instead, the results are put together after quad results return. The patient is not made aware of results until the integrated risk result is available. There is presently no consensus on which test method is better.