The rise of noninvasive prenatal testing (NIPT) has been one of the biggest success stories in laboratory medicine in recent decades. For many pregnant patients, a simple blood test targeting cell-free placental DNA can significantly reduce the need for invasive alternatives such as amniocentesis or chorionic villus sampling (CVS) that introduce a small but real risk of miscarriage.

If pregnant women are part of the patient population served by your clinical laboratory, NIPT is an important capability to add to your test menu if it has not yet been implemented. Recent updates to guidelines for prenatal screening from the American College of Medical Genetics and Genomics (ACMG) are likely to increase demand for NIPT around the world, including in Asia Pacific.

According to those guidelines, published late last year, ACMG makes a “strong recommendation” that all pregnant women carrying single babies or twins should be tested with NIPT instead of traditional prenatal screening methods. Specifically, ACMG recommends NIPT as the preferred method to screen for:

• Trisomy 21 (Down syndrome)
• Trisomy 18 (Edwards syndrome)
• Trisomy 13 (Patau syndrome)
• Sex chromosome abnormalities/aneuploidy

For each of these conditions, ACMG relied on evidence showing that detection rates are excellent — better than 98% for trisomies 18 and 21 and sex chromosome abnormalities, with the detection rate for trisomy 13 around 93%.

While the guidelines indicate that additional screening targets, such as microdeletions and rare autosomal trisomies, are future areas of interest, the ACMG has not issued a recommendation for using NIPT for this purpose across all pregnant women.

NIPT uptake in South Korea and Singapore

In laboratories offering targeted NIPT products for prenatal screening, these tests have been welcomed by physicians and patients. At Seoul Clinical Laboratories in Korea, for example, Dr Mikyeong Lee and Dr Bryan Lee saw so much demand for NIPT results that in 2021 they shifted to a system that allows them to perform screening in their own lab without the need for extensive informatics support or expensive sequencing instruments.

In Korea, the average age of pregnant women has been steadily rising; today, at least a third of all expecting mothers are considered high risk. That makes NIPT a critical alternative to invasive tests that could add to the risk.

“Literally every baby is precious,” says Dr Mikyeong Lee. “While NIPT is not a diagnostic test, it screens out low-risk pregnancies, so physicians can provide a rationale when performing invasive testing for chromosomal abnormalities. Having a low-risk result at screening will greatly reduce any stress a pregnant woman will have about her baby’s health.”

Dr Bryan Lee notes the value of selecting a test limited to the targets recommended by ACMG or other professional guidelines. “When only abnormalities included in practical guidelines such as the recent ACMG guidelines are tested, there is no need for lengthy consideration on whether the test is appropriate,” he says. “On the other hand, NIPT tests that utilise other less proven technologies or are not as widely used will inevitably incur higher costs and require more effort.”

Meanwhile, in Singapore, physicians at Singapore General Hospital have offered NIPT capabilities since 2017 and their patients have responded well. A local study published in 2022 showed that patients appreciated the higher detection rates and lower false-positive rates of this kind of testing [1]. Physicians have also been happy, especially because NIPT has fewer timing restrictions compared to conventional tests that have to be done at very specific points in gestation.

“NIPT is a test with increasing demand and laboratories should consider if they can help with fulfilling this demand,” says Dr Tan Lay Kok    at Singapore General Hospital. “Key factors to consider would be laboratory expertise, commercial viability, and clinical need in the patient pool.”

Addressing concerns from patients and clinicians

Even in the early years of NIPT availability, the technique rapidly replaced traditional invasive tests that had been used for decades. But NIPT is still based on a relatively young technology, and as such, it has encountered growing pains among clinical audiences and the general public [2].

Concerns about the use of NIPT are often based on a misunderstanding about the purpose of this kind of testing [3]. NIPT is intended as a screening tool rather than as a diagnostic test; any positive findings should be followed up with traditional methods such as amniocentesis or CVS for confirmation. While this is common knowledge within the clinical lab community, many obstetricians and general practitioners are not fully aware of this or may fail to explain it adequately to patients prior to testing. Without that valuable context, false positives can be seen as catastrophic by patients.

Those false positives tend to come from areas of testing that go beyond ACMG guidelines, such as microdeletions. Even though NIPT products that promise to test a much larger number of targets may be enticing to patients and physicians alike, choosing a test that only screens for the current ACMG targets — trisomies 21, 18, and 13 along with sex chromosome abnormalities — allows clinical laboratory teams to report the most relevant and reliable results without getting into problematic areas of lower accuracy and the possible onslaught of follow-up testing that ensues.

References:
[1] Sim, W.S. et al. (2022) ‘Preferences for a non‐invasive prenatal test as first‐line screening for Down Syndrome: A discrete choice experiment’, Prenatal Diagnosis, 42(11), pp. 1368–1376. doi:10.1002/pd.6239.

[2] Baldus, M. (2023) ‘overestimated technology – underestimated consequences’ – reflections on risks, ethical conflicts, and social disparities in the handling of non-invasive prenatal tests (nipts) – medicine, health care and philosophy, SpringerLink. Available at: https://link.springer.com/article/10.1007/s11019-023-10143-1.

[3] Matloff, E. (2022) What the NYTimes got wrong on prenatal screening, Forbes. Available at: https://www.forbes.com/sites/ellenmatloff/2022/01/06/what-the-nytimes-got-wrong-on-prenatal-screening/?sh=418f1e8537a7.