Fetal genetics & the NIPT Tango

Having stumbled into a rabbit hole of genetic research, I find myself gasping for air amid the choppy seas of pseudogenes (more to come on that particular monster). Thus, I would like to take a moment to address something closer to home for me. I work in women’s health and obstetrics, and spend quite a bit of time caring for high-risk pregnancies. As such, I have a lot of conversations about the available options for prenatal testing. Now, to those of you who are not actively engaged in childbearing, you may find yourselves backing away rapidly from this topic to go refill your birth control…and I understand. But bear with me, because this information has implications for society as a whole.

Until recently, the best option for early prenatal testing that we could offer was a first-trimester screen (FTS), which involves a sonogram and a maternal blood draw, and is completed exclusively between 11-13 weeks gestation. The sonogram is for the purpose of measuring nuchal translucency (the thickness of the area at the back of the fetal neck). This information is combined with the maternal labs to kick out a report that details overall risk of Trisomy 18 and Trisomy 21 (Down Syndrome). If the FTS indicated increased risk, the parents could opt for an amniocentesis or chorionic villus sampling. Now, these procedures, the removal of some amniotic fluid or placental tissue, respectively, with a long needle under guidance from ultrasound, do carry a small risk of inducing miscarriage. But both do offer definitive diagnostic results about aneuploidy.

Suffice it to say, discussion of these options typically causes some raised eyebrows among parents-to-be, no matter how delicately the topic is addressed. I find myself having to preface the conversation with the reassurance:

We’re not implying that you would choose to do anything different with this pregnancy, necessarily. But this information will allow us to set up the most effective plan of care for you and your child. If the testing does indicate a problem, you’ll be able to learn about it, to investigate resources, and to make a good decision for your family. The delivery of a child with a known genetic issue looks different than a typical birth, and we can ensure that the appropriate providers are available to ensure the best outcome.

That said, I also assure them, we have no vested interest in this testing. If the parents choose to do NO prenatal screening, that’s just fine. We’re just happy if they attend their prenatal visits and heed medical advice about healthy pregnancy lifestyle choices. *cough* Quit smoking. *cough*

But I digress. In 2012, a new form of genetic testing hit the market to screen for fetal aneuploidy. This method, which is known as NIPT (non-invasive prenatal testing), uses cell-free DNA to determine if a genetic abnormality exists. What is cell-free DNA, you ask? Well so do all my moms. There is always some amount of fetal genetic information circulating in the maternal bloodstream. This is referred to as the fetal fraction. If this value falls within normal parameters, chances are that the baby has typical chromosomal makeup. However, if it is noted that there is excess genetic material, this sends up a red flag that there may have been an issue with nondisjunction, giving the fetus extra copies of chromosome 16, 18, or 21. In human genetics, small errors translate into big problems. It only takes a couple stray pieces of DNA to throw development into disarray. I would like to delve further into the science of this. However, in the name of brevity I will refrain for now. My intention for this piece is to cover the societal aspect of this topic.

Cell-free DNA screening, which is known by different “brand names” depending on the lab that is administering the test, is able to detect these issues with far greater accuracy than the FTS alone. It can be completed as early as 10 weeks gestation, and can be done at any time for the rest of the pregnancy, and it’s as simple as a single maternal blood-draw.

Why do physicians and parents like this option? It is highly accurate. NIPT can detect aneuploidy in 98/100 babies, and the false-positive rate is only about 0.3%. This is compared to the FTS, which has an 85% accuracy rate, with a false positive occurrence of 5%. Additionally, the expanded window of testing is a benefit, as not all mothers seek prenatal care in time to have a FTS performed. It may also eliminate the need for unnecessary invasive procedures. The OTHER benefit, the one that has parents clamoring for this testing, is the fact that it incidentally detects fetal gender as early as 10 weeks gestation. At times, this seems to be the only value that our patients are interested in, much to our chagrin.

Ms. Smith? I’m calling to let you know about the results of your genetic testing. What’s that? You want to know the gender? Oh. Well, can we discuss the health of your child first? Yes, right after you put the entire family on speakerphone…

Which brings me to societal implications.

As genetic testing advances, we will presumably be able to determine not only chromosomal integrity, but other information about a developing fetus. Along with that information comes the potential for people making decisions about a pregnancy based on the attributes of the child. Sound jaded? Perhaps. However, I have run across the occasional circumstance where a patient was on the fence about continuing a pregnancy based on the gender of the child. It sounds abhorrent, of course, and I’m certainly not advocating in favor of this behavior. But it happens. (Of note, I do not work for an organization that provides abortion. Also of note, I’m pro-choice. But these are ALSO topics for further posts.)

From there, it is merely a short jump to the oft-discussed concept of “designer babies,” or embryos selected based on the expression of specific traits. We’re not talking about disease or developmental defects in this case, but rather attributes like eye color, stature, or intelligence. As with any scientific advancement, there is the potential for great benefit and also for abuse. We, as a society, need to reflect carefully on the implications of genetic testing and manipulation, at a pace that keeps up with the ever-changing landscape of the field.

I’m afraid that I’ve dredged up for myself, and hopefully for you, more questions than I’ve answered. Questions about where we need to draw the line. There is no inherent morality here. It is up to us, as a society, to determine a point at which our responsibility needs to supersede our capability. What constitutes a perfect society, and would we even want to see the reality of that? Who makes decisions about what constitutes the “ideal” human form?

What makes us human?

Ponder, dear reader.

To be continued…

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