Prenatal detection of chromosome abnormalities has been available for over 40 years. Amniocentesis started in the early 1970s and then chorionic villus sampling (CVS) in the 1980s. Given that increasing maternal age is associated with a higher risk of genetic abnormalities such as trisomy, the main use for testing used to be for testing offered to pregnant women 35 and older. But, according to the American Congress of Obstetricians and Gynecologists, all pregnant women should be offered prenatal testing for chromosome abnormalities.
What is a trisomy? Humans have 23 pairs of chromosomes, which are strands of DNA and proteins that carry genetic information. A trisomy is a chromosomal condition that occurs when there are 3 copies of a particular chromosome instead of the expected 2.
Trisomy 21 is due to an extra copy of chromosome 21 and is the most common trisomy at the time of birth. It causes Down syndrome, which is associated with mild to moderate intellectual disabilities and may lead to digestive issues and congenital heart defects. Down syndrome is present in 1 out of every 740 newborns.
Trisomy 18 is due to an extra copy of chromosome 18. Trisomy 18 causes Edwards syndrome and is associated with a high rate of miscarriage. Infants born with Edwards syndrome may have multiple medical problems and a shortened life. It affects 1 out of every 5000 newborns.
Trisomy 13 is due to an extra copy of chromosome 13 and causes Patau syndrome, which is associated with a high rate of miscarriage. Infants born with it have congenital heart defects and rarely live more than a year.
Sex chromosome conditions involve the X and Y-chromosomes, which make us male or female. Testing can determine the presence of an extra copy of one of the sex chromosomes (Klinefelter syndrome) or the absence of one copy (Turner syndrome).
Although young women have a low risk of conceiving a child with Down syndrome (trisomy 21), the majority of pregnant women are in their teens, twenties and early thirties. For these women having an invasive test (amniocentesis and CVS) is not a good option as the risk of complications from the procedure is greater than the chance of finding a genetic abnormality.
For this reason, a number of non-invasive prenatal tests (NIPT) have been developed, including first trimester genetic screening (NT test), maternal blood testing (AFP test) and ultrasound evaluation at 18-22 weeks. All of these tests have limitations in their accuracy and their need for follow-up confirmation by additional testing.
For years scientists have been looking for a more powerful test, safe, accurate and specific. It appears it may now have been discovered in the test called cell-free DNA. Direct analysis of fetal cells in maternal circulation is limited by their scarcity; only about 1 in a million cells in maternal circulation are fetal in origin. But the fetal DNA has been found in much greater amount. There are now many confirmed reports of the successful analysis of cell-free DNA for non-invasive prenatal testing for chromosomal abnormalities such as Down syndrome.
Fetal DNA accounts for 3-13% of the total cell free maternal DNA. The test can be performed as early as 10 weeks gestation. The sensitivity for trisomy 21 (Down Syndrome) is high, about 99% with a low false positive rate, less than 1%.
Cell Free DNA is a screening test with the advantages of early detection, high sensitivity and low false positive rates. The disadvantages of it include that it does not test for other abnormalities such as Neural tube defects and only screens for trisomy 13, 18, 21 and sex chromosomes. There is only limited experience with the analysis of twin pregnancies and in very overweight women. The main disadvantage is that it can cost between $795 and $2762.
Currently cell free DNA testing is recommended for women of advanced maternal age (35 or older), women who had a prior child with trisomy, and those with abnormal prenatal screening results. In the future, as the test gathers more experience and if the cost becomes less, cell free DNA may be offered for genetic screening of all pregnant women.