4 November 2019

Trisomies NIPT in the bud

Genetics Women

Non-invasive prenatal testing, or NIPT, is a highly accurate aneuploidy screening test that should be offered to all pregnant women, but cost is a significant barrier in Australia.

Genetic pathologist Dr Melody Caramins told an audience at the GP19 conference in Adelaide that “genomics is something that’s coming to general practice”, hopefully to change it for the better.

Dr Caramins, chair of the Royal College of Pathologists of Australasia’s genetics advisory committee and national director of genomics in Healius’ pathology division, said the simple blood test was extremely sensitive and specific – barely less so than the invasive tests that pose a risk to the fetus.

But the $400 to $500 non-rebated cost in Australia made some patients (and their GPs) reluctant.

NIPT analyses cell-free DNA from the placenta that circulates in the mother’s blood, known as fetal fraction, for slight increases in the volume of chromosomes 21 (where a triple chromosome or trisomy causes Downs syndrome), 18 (Edwards) and 13 (Patau) and generally is effective from 10 weeks.

High maternal BMI, which means a reduced proportion of placental DNA, makes it harder to get a reliable result.

Some NIPT techniques don’t work with twins and none of them work with more than two fetuses, so NIPT should always be preceded by a dating scan.

Dr Caramins emphasised that NIPT was a screening test, not a diagnostic one. This had nothing to do with a lack of accuracy, though she said that was a common misconception among practitioners. The difference is in the population to which it is offered: a screening test is for asymptomatic patients (a low-prevalence population), while a diagnostic test is for those already at risk of carrying the condition (high prevalence).

And like chorionic villus sampling, NIPT uses placental DNA as a proxy for fetal DNA, whereas amniocentesis analyses fetal cells directly. Because of this, occasionally two prenatal tests will produce discordant results. This can be due to an organ transplant, a demised twin or placental or fetal mosaicism.

Another important distinction was that a diagnostic test forms the basis for action, whereas a screen such as NIPT should always be followed by a confirmatory test.

NIPT can also be used on other chromosomes or to detect sub-chromosomal abnormalities known as microdeletions. But Dr Caramins said this was not recommended except in cases of family history or an ultrasound result suggesting a particular condition, and should only be offered by physicians who were confident to deliver the appropriate counselling.

Dr Caramins told The Medical Republic that were it not for the cost, everyone should have the test.

“It is the most sensitive and specific screening test,” she said.

“If you see a woman who’s had a combined first trimester screen and she returns a very high-risk result for an aneuploidy, like a one in 10 result, you may want to go straight to invasive testing rather than waiting another week and doing an NIPT.

“But in my honest opinion, if cost were not an issue, absolutely I would think everybody probably should have it.”

A paper in the Journal of Medical Ethics in September by Dutch medical ethicists argued that making women pay anything for NIPT limited reproductive autonomy.

Dr Eline Bunnik, an assistant professor in at Rotterdam’s Erasmus Medical Centre, and colleagues wrote that there were two rationales for charging a co-payment or the full cost of the test: to discourage uptake – implicitly, to prevent more abortions – and to promote considered decision-making.

They argued that the first was inconsistent with the aims of any screening, and cited evidence that a significant minority of women (15%) chose not to terminate a fetus with Downs syndrome.

As to the second, the cost meant many women would make a choice out of financial constraint and therefore actually reduced their ability to make a considered decision.