The field of genetics is rapidly expanding. There is no place this is truer than in the area of prenatal screening for genetic conditions.
So what exactly is prenatal screening?
Prenatal screening refers to any test that assess the risk for a baby to have specific genetic conditions such as Down syndrome. It differs from prenatal
diagnosis in that in cannot say yes or no, but can only give an estimate on how likely it is for a child to be affected with a particular condition.
Women are typically offered prenatal screening starting at 10 weeks in pregnancy.
As recently as last year women who were considered low risk for these conditions were offered something called the first trimester screen. This test pairs
the analysis of levels of proteins in mom’s blood with an ultrasound to give a risk for Down syndrome and another genetic condition called trisomy
18. However, a newer technology has recently taken over as the recommended screening test for all women.
This new technology is called NIPS (non-invasive prenatal screening). For those of you that google, NIPT (non-invasive
prenatal testing) and cell-free fetal DNA (cfDNA or cffDNA for short) are other names for the exact same test.
How does NIPS work exactly?
NIPS differs from its older counterparts in that it actually looks at chromosome material in the mom’s blood stream, as opposed to proteins made by the
For a refresher, we have 23 pairs of chromosomes. The first 22 pairs are numbered 1-22, and are the same in men and women. The last pair are the sex
chromosomes and are typically XY for males and XX for females.
A trisomy is when there are three copies of one chromosome instead of the expected two, and a monosomy is when there is one copy.
The standard NIPS test screens for Down syndrome (also known as trisomy 21), trisomy 18, trisomy 13, trisomy X, Klinefelter syndrome (XXY), and Turner
syndrome (monosomy X).
Incidentally, NIPS can predict the sex of the baby. The screening test looks at small pieces of chromosomes that have been shed by the placenta and entered
mom’s blood stream. The most common type of technology sorts these small pieces based on sequencing data. That is essentially just a way to say the
test reads each piece to try and understand which chromosome it is coming from. If too many pieces of one chromosome are seen, the test will trigger
a “positive” result for a specific condition.
Let’s stop here.
We mentioned earlier that this test cannot diagnosis a baby with any condition. Then why does the test read POSITIVE in big letters across the top? Confusing
In reality the risk will be based on the mother’s age and the specific condition involved, something known as the positive predictive value (PPV).
The PPV tells us what the odds are that the child is actually affected. This is due to the fact that some conditions are more common than
others, and a woman’s risk for a child with a trisomy increases very slightly each year she gets older.
Many NIPS tests boast a 99% sensitivity and specificity. This may sound like your risk is 99% if your test is positive, but it is typically much less.
For example, a 21 year old woman who screens “positive” for trisomy 13, actually only has a PPV of 6%, or a 6% chance that her child actually has trisomy
13. That means there is still a 93% chance her child is completely unaffected! Conversely, a 35 year old woman who screens positive for Down syndrome
has a 79% chance her child is actually affected.
There are a variety of factors that can cause a false positive.
- While the placenta and the baby are typically genetically identical, they may differ due to a process called confined placental mosaicism.
If this occurs there is a chance the placenta could be affected with a trisomy but not the baby. Since this NIPS is screening placental material,
it would detect this trisomy and give a positive result, even though the baby is unaffected.
- The other most common possibility is that the technology incorrectly identified pieces of chromosome during analysis, for example assigning some pieces
to 13 that were not actually pieces of 13.
While getting a false positive is terrifying, it fortunately only happens to an estimated 0.2% of women who take the test. This is compared with 5% of
all women who get a first trimester screen. Additionally, NIPS detects 99.2% of cases of Down syndrome (and slightly less for the other conditions), compared to an 85% detection rate for the first trimester screen. The best part of this screening is
that it can reduce your risk for these conditions to less than 1 in 10,000. While that is NOT zero, it certainly can be very reassuring. A
false negative, while possible, is very rare. The only way to know if a baby is affected definitively would be through a diagnostic test such as amniocentesis or CVS (chorionic villus sampling).
I wish I could say that I have explained everything you need to know, but there is always more to learn! For instance, some NIPS tests now look for conditions
known as microdeletions or single gene conditions like neurofibromatosis, while some have uncovered maternal genetic
conditions. Additionally, women who have cancer currently or have had an organ transplant are not candidates for NIPS.
Well that’s a whole different can of worms!
Prenatal screening is not right for everyone, and discussing with your OB or a genetic counselor can help you decide if this is something you want to pursue. You can find a genetic counselor near you through the National Society of Genetic Counselors website.
Liz Francisco, MS, CGC
Clinical Genetic Counselor in GGC’s Greenville office