Jane McCredie: Unexpected results

WHEN a woman has prenatal testing to check the genetic health of her fetus, she’s unlikely to expect the test to instead reveal concerns about her own health.

 

But the more we succeed in pulling pull apart the human genome, the more it presents us with unexpected clinical and ethical challenges.

 

Among them is the vexed issue of incidental findings, abnormalities that show up during a test for something entirely different, and that may or may not indicate a problem requiring investigation.

 

Newer prenatal screening techniques are putting a novel spin on this, throwing up results that are not only for a different condition, but also a different person — the mother, rather than the fetus.

 

Questions about how to interpret and communicate such findings are becoming increasingly urgent, as non-invasive tests based on analysis of genetic fragments found in maternal blood become more popular, writes medical geneticist Professor Diana Bianchi in Nature.

 

Professor Bianchi describes, for example, cases where irregularities revealed by cell-free DNA (cfDNA) testing of a maternal blood sample turned out to result from previously unsuspected chromosomal abnormalities in the mother.

 

Even more confronting were cases where the test results revealed the presence of a maternal tumour. 

 

Obstetricians and other health care providers are often ill-equipped to deal with these kinds of situations, Professor Bianchi writes, adding that “few are familiar with genome sequencing or trained to discuss the management of a pregnancy that has been complicated by the discovery of a maternal health problem”.

 

Lack of understanding of the test results might also lead some women to terminate a pregnancy unnecessarily, Professor Bianchi suggests. She cited a 2014 study that found 6% of women chose termination after an abnormal cfDNA test, without first having the findings confirmed by chorionic villus sampling or amniocentesis, although guidelines recommend this.

 

“Women might weigh options differently if they understood that a result could signal a genetic anomaly in themselves, rather than in their baby”, she writes.

 

Compounding the problem is the fact that medical guidelines often struggle to keep up with technological change, and consent processes rarely deal adequately with the issue of incidental findings, she suggests.

 

The clinical dilemmas are destined to become more complex and more common. Since their introduction in 2011, cfDNA tests have grown rapidly in popularity, thanks to their non-invasive nature and low false-positive rate, increasing from around 200 000 tests globally in 2012 to more than 800 000 in 2014. 

 

In Australia, the tests have been available for just over 2 years, although only for patients who can afford a fee of up to $1000, with no Medicare or private health insurance rebate. 

 

The Royal Australian and New Zealand College of Obstetricians and Gynaecologists raised concerns in a recent statement (C-Obs 59) about the potential ethical challenges posed by this financial barrier, while also suggesting the cost is likely to drop in the near future, which would presumably lead to a greater uptake. 

 

For Professor Bianchi, the clinical and ethical dilemmas posed by this kind of testing raise questions about how we deal with the potential challenges and benefits of unexpected genetic information more generally.

 

“Handled properly, the incidental findings emerging from prenatal tests could accelerate treatments and save lives — rather than just increase the anxiety of thousands of pregnant women”, she writes.

 

But proper handling of such complex and sensitive information isn’t always easy. 

 

Professor Bianchi’s conclusion sums up the dilemmas ahead: “The speed at which these blood tests have taken off in mainstream health care has brought focus and urgency to issues long debated in genetic circles — particularly, when and how to report to patients secondary findings from genomic sequencing.”