Review Question - QID 106976

The only way to confirm a diagnosis is to extract cells that originate from the fetus and perform a chromosomal analysis. An amniocentesis can be performed to extract amniotic fluid, which has cells from the fetus in it.

Prenatal screening typically begins between 15-18 weeks of gestation to determine whether the fetus has any abnormalities. The maternal serum triple marker screen (hCG, estriol, and AFP) can be performed, but the quadruple marker screen looks at inhibin A as well. The quadruple marker screen increases the likelihood of detecting at risk pregnancies for Down syndrome, plus it has a lower false positive rate. The serum test can be combined with an ultrasound of the fetus, which is termed an "integrated test." If an abnormal result is obtained from any of these tests, an amniocentesis can be performed with a chromosomal analysis to confirm the result.

Newberger discusses the screening for Down syndrome in women of different ages. Women < 35 years old should be offered a triple marker screening test if they are between 15-18 weeks of gestation. He recommends the use of ultrasound to determine the age of the fetus, as this will increase the sensitivity and specificity of the triple test. For women who are 35 years and older, he advises chorionic villus sampling or second-trimester amniocentesis.

Benn et al. discuss the current and future prospects of non-invasive prenatal testing (NIPT) which is changing the field of prenatal screening. The current methods that are available for NIPT are the following: whole-genome sequencing, targeted sequencing, and single nucleotide polymorphism detection between mother and fetus. NIPT has been tested in clinical trials for the detection of Down, Patau, and Edward syndromes and has shown to be effective in high-risk women. However, the test is not cost effective and positive results need to be confirmed with amniocentesis. The detection range for NIPT is still rather small compared to more invasive procedures, but in time the method will be improved and should be able to detect other chromosomal abnormalities.

Illustration A demonstrates an ultrasound of a fetus with increased nuchal translucency (white arrow). Increased nuchal translucency is related to a dilated lymphatic system, which suggests that there may be an abnormality in the pregnancy. Illustration B demonstrates a Down syndrome karyotype showing trisomy 21.


Incorrect Answers:
Answers 1-4: These tests can be performed to screen for Down syndrome. If an abnormal result is obtained from these, a confirmatory test such as amniocentesis or chorionic villus sampling with chromosomal analysis needs to be performed to confirm the diagnosis.