I Found the 'Holy Grail' of Prenatal Testing

The real draw of NIPT is its potential as an alternative to invasive testing, a way to replace a needle in the belly with one in the arm, to get information without putting pregnancies in harm's way. The draw of NIPT is that it is non-invasive. That's what makes it exciting.
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I've been pregnant twice in my 40s and am expecting my fifth child in November. Like most women my age, I was offered -- indeed encouraged to have -- an amniocentesis or chorionic villous sampling (CVS). While I crave reassurance, I've never been able to bring myself to do either. I know my risks of genetic problems are high (about 1 in 30, given my age). But I also know there is one thing that I don't want to live with: even a whisper of a sense I had something to do with ending the life of my child-to-be.

My worry is always about procedure-related miscarriage -- the small chance that an invasive test (involving a needle in the uterus) could cause the loss of an otherwise healthy child. As a doctor who has run a miscarriage clinic, I've seen how harrowing it can be, especially for women riveted by the fact that but for their "informed choice" to test, they'd still be pregnant. I get it.

Perhaps that's why I felt such gratitude when I was offered a new test that can reassure without the devil's bargain of invasive testing. With non-invasive prenatal testing (NIPT), it is now possible through a single blood sample to determine with accuracy whether a fetus carries the genes for one of three major chromosome abnormalities. NIPT is new, commercially available for just over a year, rapidly appearing in doctors' offices around the country. I've never been more eager to roll up my sleeve.

To look at my work schedule this spring, you might think otherwise. It was packed with meetings of ethicists and others to discuss the several issues raised by NIPT: worries about the distorting influence of commercial interests; about routine use without adequate consent; about misinterpretation of test results; about use for dubious purposes, like sex selection. Worries we are edging on a brave new world.

Yet none muted my enthusiasm to get NIPT, nor my sense that what is most powerful about it is its potential to transform the experience of pregnancy -- and for the better. As my colleague (and my obstetrician) Diana offered candidly, "You know, Annie, this the Holy Grail. It's what we've been waiting for all these years." It felt that way to me.

Early on, I'd kept my pregnancy news a secret, held it at bay. I knew well that a pair of red lines on a pregnancy test held no guarantee of a baby to hold in nine months. My husband and I didn't tell a soul, spent weeks not knowing whether to imagine our fifth, think about how he or she would reshape our lives, our family, our selves. "It is love that takes courage," the eloquent Forrest Church has offered, "because the people we love most may die before we do." No wonder many of us hold onto our news until we have some assurance -- the passage of a particular week, a heartbeat heard in clinic, a test result. Something that gives us courage.

Here is where NIPT comes in. The test can be done as early as 10 weeks gestation with results returned by 11 weeks -- when even a mother of four can hide a protruding belly. The timing is similar to CVS, but the key difference is that NIPT is physically "non-invasive," meaning blood is taken from a woman's arm. There is no needle in the uterus, no chance that efforts to garner information might cause the unthinkable. When I asked one colleague how NIPT has changed her practice, she answered "two things: less angst, and fewer invasive tests."

So, why the worry?

For one, there are "false positives" -- results indicating a fetus has a chromosome problem when in fact the chromosomes are normal. One colleague tells the story of a patient who had a positive NIPT, passed up the amniocentesis and engaged the Down syndrome community during pregnancy, attended several meetings and events. Then, lo and behold, gave birth to a completely normal baby. More massive adjustment than tragedy, but the events will no doubt leave an enduring mark.

What most worries genetic counselors and ethicists though are false positives that could result in unnecessary abortions of healthy fetuses. One group of investigators estimated that if the test were incorrectly understood to be absolutely predictive of Down syndrome, it could result in abortions of nearly 2,500 unaffected fetuses in one year. There is a simple way to avoid this. Nobody should do -- or get -- an abortion for a chromosome problem unless the diagnosis is confirmed by invasive testing. The same investigators estimated that if amniocentesis were used to confirm positive NIPT tests, the number of test-related losses would be reduced to 29.

Indeed, the worry about the misuse of NIPT seems over-wrought, emerging from deep questions about whether society can trust doctors open to abortion or women themselves to make ethically responsible decisions about their reproductive health. The American College of Medical Genetics was concerned enough that they proposed a new acronym -- "NIPS" (non-invasive prenatal screening) since the word "screening" implies that further testing is needed to confirm a diagnosis -- that NIPS (or NIPT) is better understood as a first step.

This would surely be a disappointment. The real draw of NIPT is its potential as an alternative to invasive testing, a way to replace a needle in the belly with one in the arm, to get information without putting pregnancies in harm's way. The draw of NIPT is that it is non-invasive. That's what makes it exciting. That's what makes it a gift. That's what makes it a Holy Grail. If just the first step, it would better be understood as improvement.

But it is not false positives that worry many of us who've gotten the test. Rather, it is false negatives -- getting a normal result when we are carrying an affected child. Here the news is better. NIPT seems to detect almost all cases of Down syndrome, and most Trisomy 13 or 18; those it misses will usually be detected by ultrasound. The bottom line: If we understand that no test will guarantee a "perfect" baby, a normal finding is pretty darn reassuring. With a normal NIPT and a normal second trimester ultrasound, invasive testing to detect the three major trisomies could be called unwarranted, a search for a needle in a haystack at best.

It's important to know that NIPT won't find everything; for a woman my age, it will miss a considerable proportion of other problems detectable by amniocentesis. A few centers have started offering "microarray" testing with amniocentesis, which can detect errors in chromosome number but also tiny deletions and duplications of genes associated with birth defects and cognitive problems in children. But microarray also detects genetic variations whose clinical significance is unknown. Studies suggest that many who get this information wish they didn't have it -- experience it as "toxic" rather than reassuring, a source of enduring uncertainty for those who terminate pregnancies, of enduring worry for those who do not. It is another devil's bargain -- and another I am glad to avoid.

A week after I rolled up my sleeve, my results were back: "This specimen showed an expected representation of chromosome 21, 18, and 13. No Y chromosomal material detected." With that news, I settled in to the fact that I was going to have a baby, tentativeness pressed firmly aside, heart opening at last.

I was still, if barely, in my regular jeans, nobody knew anything. But now, at 11 weeks gestation, I was ready to tell. I let out a sigh of relief and perhaps, just a bit, the belly I was unconsciously holding in. That night, as we sat down to dinner, I said to our four boys, "I have some big news for you. You're getting a sister."

Disclosure: Anne Drapkin Lyerly is currently part of study that will examine the relationship between intellectual property disputes about NIPT and access to testing.