What would you do if you were pregnant with a fetus affected by a severe disorder? If you keep up with the brilliant Twitter musings of Richard Dawkins, you’re probably aware of his recent stance on the morality of bringing Down syndrome children into this world. Dawkins blurted this less-than 140 character gem last month:
I won’t dwell on Dawkins’ misogynistic presumption to morally-police a woman’s body and decisions based on her fetus’ trisomy status and the impact of his statement in undermining individuals with this condition. As Tabitha Powledge reported for Genetic Literacy Project, abortion is often the choice women make after receiving a Down syndrome diagnosis. As many people would agree, choice is paramount.
What are the testing methods that enable diagnosis for trisomies and other fetal chromosomal abnormalities?
To this day, only CVS (Chorionic Villus Sampling) or amniocentesis testing are considered “diagnostic” for trisomies, meaning only these tests can provide a definite yes or no diagnosis for Down syndrome and other aneuploidies. CVS testing samples cells from the chorionic villi, small portions of placental tissue sharing the same genomic profile as the fetus. The prefix “amnio” refers to the amniotic sac, while “centesis” refers to a procedure in which fluid is collected through a puncture. As is commonly known, these invasive procedures carry up to about a 1 percent risk of miscarriage.
In addition to miscarriage risk, another hitch with these diagnostic tests is that they’re typically only advised for women at significantly increased risk of fetal abnormalities. These include women at advanced maternal age, with family history or with worrisome screening test results. Women judged to be at normal risk are offered the option to take “screening tests” in the first or second trimester. Screening tests are useful for informed clinical decision-making, and/or peace of mind for the mother.
At today’s cusp of technology, all prenatal screening tests are not created equal. Why?
The most common screening tests offered are the first trimester screening test, and the triple or quad screen in the second trimester. The first trimester screening test is performed between the 11th and 14th weeks, and measures levels of substances called PAPP-A and hCG from a maternal blood draw. Combined with specific measurements on an ultrasound and maternal age, these data predict the risk that the fetus has either Down syndrome (trisomy 21), or the lesser-known trisomies 13 and 18.
The triple or quad screen is offered between the 15th and 20th weeks. As the names suggest they each measure levels of three or four substances, also from maternal blood: AFP, hCG, estriol, and inhibin-A. Based on comparative levels of these substances and maternal age, these tests also predict the risk of Down syndrome and other trisomies, as well as neural tube defects. Results are delivered in a “risk score” format (like 1 in 4,000, or 1 in 70.)
So what’s the problem? Compared to the next screening test I’ll describe, the first trimester and triple/quad screens are offered relatively late, and have relatively low detection rates and high false positive rates. They only detect anywhere from 80-87 percent of Down syndrome cases. This means that up to 20 percent of babies with Down syndrome will not be identified! Furthermore, an up to 5 percent false-positive rate means that most women with positive results will not be carrying an affected fetus. How can women be in a position to make the choice Dawkins encourages with these fuzzy numbers?
Compare these hazy results to what we might learn from new tests like Sequenom’s Maternit21 and Illumina’s Verifi. While these tests are not currently routinely offered, it’s likely they will be in the near future. These tests also use maternal blood, but rather than measuring analyte levels, they use cell-free fetal DNA.
Cell-free fetal DNA are short fragments of placental DNA (remember, the placenta is technically fetal tissue.) Because the fetal fragments are shorter than maternal DNA fragments, they can be isolated, aligned, and sequenced. What are the benefits of this technique?
- It allows positive or negative test results rather than a risk profile.
- Testing can occur as early as 10 weeks into pregnancy
- Detection rate is high: For example, more than 99 percent of Down syndrome cases were detected by Maternit21 in a clinical validation study.
- False positives are far less likely than with non-DNA screening methods. (If a patient receives positive results, she will receive counseling, likely followed by an invasive testing method like amniocentesis.)
- Tests for additional conditions, including less common aneuploidies.
- Can be offered in lieu of invasive testing as a follow-up to worrisome results from the integrated, triple, or quad screens.
- By detecting presence or absence of Y chromosome, mothers can definitively know their child’s gender with higher accuracy than from an ultrasound. (This also brings up ethical considerations, like sex-selective abortion.)
It’s important to note that at this time, cell-free fetal DNA methods are still considered “screening” tests. While very unlikely, false positives and negatives occur. Still, they can be excellent tools to enable decisions. Contrary to Richard Dawkins overreaching declaration, morality when it comes to continuing an affected pregnancy is subjective. Still, most women knowingly carrying an affected fetus will choose to terminate. The ability to make an informed decision is essential, and part of women’s right to bodily autonomy. Advancements in fetal diagnostics are a remarkable piece in the dynamic puzzle of genomic medicine.
Note: Sometimes the risk profile from a quad screen can seem confusing and unsettling. Normal results also allow something precious and rare in pregnancy: peace of mind. Read about the author’s personal experience with Quad Screen and Maternit21 here.
Kavin Senapathy is a contributor at Genetic Literacy Project and other sites. She works for a genomics/bioinformatics R&D in Madison, WI. She is not a scientist, but loves all things genetics, genomics, and bioinformatics. Her interests span the human and agricultural realms. Opinions expressed are her own and do not reflect her employer. Follow Kavin on twitter @ksenapathy and Google +