Non-Invasive Prenatal Testing


Chromosomally derived anomalies have been with us for millenia –maintaining structural and functional integrity is obviously difficult when you think about it. We humans have 46 chromosomes that must continually divide and reproduce unerring copies of themselves as they issue unique and contextual instructions for cell development or maintenance.

The functional components of chromosomes are called genes and we have around 20,000-30,000 of them, each one built from smaller base pairs like words in a sentence. And depending on the chromosome, each strand of DNA has well over a hundred million base pairs to supervise. It doesn’t take too much imagination to realize that rearranging words in such a sentence, or letters in each word, can alter its meaning. Jumble its information – or even destroy its function…

Throughout recorded history, there has been a recognition that some individuals lacked the same intellectual or emotional attributes as the rest of the community, and yet these people still had a role in the society. They were tolerated and often cherished members of the group and contributed to the weft and warp of the social fabric. Every town had its Village Idiot, to use the ancient (and non-revisionist) term; every village had its special people…

It would seem we live in different times, however, and social values have shifted; there is an expectation of normalcy, if not perfection, in our offspring. The current thrust is early –prenatal– diagnosis of suspected anomalies so that the expectant parents can choose whether the issue lies within their comfort and capability zones.

Prenatal testing has undergone many sea-changes over the years as technology and attitudes have goaded each other. Early tests sought to detect only the most frequent genetic anomaly: Down syndrome –or trisomy 21. As time and ability progressed, more genetic abnormalities have received similar surveillance.

But accuracy of prediction has come under scrutiny of late. It is no longer acceptable merely to arouse suspicion of an abnormality. False positives (thinking the anomaly is present when it is not) and false negatives (not detecting the anomaly) each have their own consequences. Risk of error, in other words, needed to be minimized if decisions were to be reliably dependent on the results.

In Canada, there are currently three (and now four –the subject of this essay) options for prenatal screening of genetic abnormalities –still largely for trisomy 21 because it is by far the largest component of the pool of abnormalities:

  • First trimester screening –done between 11 and 14 weeks gestational age with a detection rate of 87-90% and a false +ve rate of 5%
  • Integrated prenatal screening– consisting of two parts: the first one the same as with first trimester screening and the second between 15 and 20 weeks gestational age. This has a detection rate of 87%-95% and a false +ve rate of 2 to 5%
  • Quad screening– done between 15-20 weeks but with a detection rate of only 81% and a false +ve rate of between 5 and 7%

These results are pretty good and statistically acceptable –unless, that is, a mother has to make an irrevocable decision based on them. There was a need for even more accuracy –less risk- and so technology again rose to the challenge: the Non-Invasive Prenatal Test (NIPT). This is a blood test taken from the mother that measures her baby’s DNA that is floating free in the part of her blood called plasma. It is being continually released into the maternal circulation (with a half-life of around 16 minutes), so it’s an up to date survey of the foetus. There is maternal DNA there though, and the fetal fraction of it is usually about 10% so, to be sure the result is representative, the fetal fraction measured has to be at least 4%… Confused? Well, just remember that it is most reliably measured after 10 weeks gestation and with no upper limit of gestational age; that it has a detection rate of over 98% and a false +ve rate of less than 0.3% (I’ve taken these figures from the June 2014 edition of JOGC).

There are some caveats, of course –there always are- and seemingly a variety of iterations of what can be measured. But by and large it seems close to ideal: high accuracy with minimal if any risk to mother or baby. It is still recommended that a result indicating a chromosomal anomaly be confirmed with an amniocentesis (taking a sample of fluid from around the baby in the uterus) for confirmation, however.

So why don’t we fully embrace NIPT and relegate the other tests to history –tests that were helpful in their time, but indirectly naïve on sober reflection? Well, apart from the current high cost which might preclude its equal availability to all strata of society, there are other ethical considerations. And although these same considerations obtain with any prenatal genetic test, with NIPT these are largely attributable to its accuracy; one could foresee a time when the recommendation for a corroborative amniocentesis to obviate any risk of false positivity might be rescinded, further decreasing the time available for thoughtful and reflective parental decision-making.

Autonomy is the right of an individual to make informed choices for herself. But the key word here is ‘informed’. This implies that the information that informs her is both relevant and appropriate information. And yet, by necessity, it is provided and constructed by others; it is drawn from social and political contexts that she may not share and the options it provides may reflect this. Relational autonomy is an ethical theory that considers the ramifications of those choices that are made available to her. More traditional views have tended to treat the person making decisions as an isolated unit; but in fact, she is embedded in her own -perhaps differing- culture that influences both the context and the situation in which she has to make her decision.

We do not all react the same to identical information, nor is the ability to make an informed choice simply a function of the amount of information available. Women and doctors have different data priorities. Even different message priorities. We all need time to sift through the context; we need time for processing our feelings. Our needs. Our connection to the simmering culture in which we swim.

And then there is the issue of what we want NIPT to detect. Access to fetal DNA offers boundless opportunities in the future for singling out other aspects of the chromosomes we wish to interrogate –whether with serious concerns: hereditary conditions like cystic fibrosis, for example, or with more broad-based anxieties such as concern about random mutations

Other, more frivolous concerns such as sex selection or, in the forseeable future, even searches for –and hence management of- certain genetic traits, present a growing tension between individual autonomy and societal values. For that matter, even detection of the trisomies has engendered much controversy, let alone the prospect of finding and perhaps eliminating other abnormalities not shared by the majority. What is the expectation –perceived or otherwise- after an ‘abnormal’ test? And what is abnormal? What should we accept?

I suppose, ultimately, it is for each of us to decide. Of course Shakespeare offered his opinion long ago: Love looks not with the eyes, but with the mind. But are we still that wise? Or have time and circumstance changed that as well?

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