A measurement done at transvaginal ultrasound of tissue in the neck of the fetus; if excessive, it implies a substantially increased risk that the fetus is affected by Down syndrome and Turner syndrome.

Due to trisomy 21. Chromosome 21 is the smallest of the "autosomes" (the non-sex chromosomes): trisomies of the other autosomes tend to be lethal at an earlier stage of embryonic or fetal development, and so are seen much more rarely. Diagnosis of Down's syndrome requires a karyotype, obtainable from pregnancy tissue by chorionic villus sampling (CVS) or amniocentesis. Screening for increased risk in pregnancy can be performed by triple screen or by looking for nuchal translucency at transvaginal ultrasound.

A screen for congenital abnormalities of the fetus done on the mother's blood serum during pregnancy to look for fetal trisomy, including Down syndrome. The original test comprised measurements of (1) serum alpha fetoprotein (decreased in the trisomies), (2) serum hCG (increased in trisomy 21, decreased in trisomy 18), and (3) serum estriol (decreased in trisomy 21, increased in trisomy 18). Note that only 60% of pregnancies with Down syndrome will be revealed by a triple test. Refinements have taken place, with 'free beta' (part of the hCG molecule) replacing hCG itself, and with the addition of PAPP-A replacing estriol, increasing the sensitivity and specificity of the test. Further gains in sensitivity and specificity comes from adding an ultrasound test for nuchal translucency. Even so, false positive tests are possible, which will be resolved only by performing CVS or amniocentesis, and so also are false negative tests, which means that CVS and amniocentesis should still be considered in otherwise high-risk situations.