NEW YORK (GenomeWeb) – Obstetric health professionals in the Netherlands would like to have noninvasive prenatal testing serve as a first-tier screening method for all pregnant women, regardless of their risk, according to a study published in Prenatal Diagnosis last month.
The country is in the midst of considering how to implement NIPT and researchers studying the issue expect to publish a number of other studies looking at test performance, clinical outcomes in high and average risk pregnancies, patients' and health providers' preferences, and economics. Researchers have also applied for a license from the ministry of health to extend a national study that examined NIPT in high-risk pregnancies to the average risk population.
In the most recent study, researchers from the VU Medical Center in Amsterdam and colleagues surveyed 240 midwives, gynecologists, and sonographers working in two regions in the Netherlands about their opinions on NIPT as a first-tier screening method and its potential to replace other first-tier screening procedures like the first trimester combined test, which includes nuchal translucency measurement.
Currently, in the Netherlands, more than 80 percent of pregnant women receive counseling for prenatal screening from primary care midwives, and the overall uptake for the first-trimester combined test (FCT) for trisomies 21, 13, and 18 is around 27 percent.
The study evaluated health professionals' opinions on NIPT, whether it should replace FCT, and how it would affect genetic counseling. In addition, the researchers asked professionals how broad such tests should be, and when and to whom broader tests versus more narrow tests that screen just for the aneuploidies of chromosomes 21, 18, and 13 should be offered.
Overall, the team found that 72 percent of respondents thought NIPT should replace FCT. However, 43 percent said that nuchal translucency measurement should still be done, while 28 percent thought NIPT should fully replace both FCT and the nuchal translucency measurement.
Saskia Tamminga, lead author of the study and a clinical geneticist in training at the VU University Medical Center, said that she was at first surprised by how many health professionals wanted to keep the nuchal translucency measurement. Looking a bit deeper into the data, though, she said that the health professionals that favored keeping nuchal translucency measurements were primarily sonographers, who perform the ultrasound for such testing.
"Their practice comprises nuchal translucency measurements that they see additional value in," she said. "There may be concerns about important fetal conditions other than trisomies 21, 18, and 13 that might not be detected without the nuchal translucency measurement."
Just 22 percent of participants thought NIPT should remain as a follow-up test for women whose FCT indicated a high risk of fetal aneuploidy.
In addition, more survey respondents said that replacing the FCT with NIPT had only advantages, would simplify the counseling, and would lead to more women getting the test but also to more women getting to the test without thinking through their decision.
Only 25 percent believed that counseling and the blood sampling should be done on the same day, with the vast majority in favor of not shortening the amount of time taken for counseling and decision making.
Health professionals were also asked to rank the importance of six different features of NIPT: accuracy, safety, background information about the disorders, time to results, costs and reimbursement, and the procedure of blood sampling.
Accuracy was rated as most important, followed by safety, while the testing procedure was ranked as the least important.
The question of how broad to make noninvasive prenatal testing has begun to be debated by professionals, and in this study, the Dutch health professionals overwhelming agreed that NIPT should be used for disorders that cause neonatal death or death in the first year of life. They also thought that NIPT should be offered for disorders for which children would need significant medical attention throughout their lives.
About half of health professionals favored using NIPT for a broader range of conditions, like preeclampsia and pre-term birth. Tamminga said she was somewhat surprised that this number was not higher, especially considering that a higher percentage of women want this type of testing available to them.
There were other differences between health professionals' opinions and those of pregnant women. In a previous study published in Prenatal Diagnosis, researchers found that pregnant women thought they should have a choice over which additional disorders to screen for, while health professionals were more likely to think that a set panel of additional disorders should be offered.
The survey is one of a number of studies researchers in the Netherlands are conducting to evaluate NIPT's suitability as a first-tier screening method.
Last year, as part of a national implementation study called TRIDENT, NIPT was offered as a second-tier test for pregnant women whose FCT indicated that they were at a high risk for fetal trisomies.
Results from that study were presented earlier this year at the European Society of Human Genetics meeting in Glasgow, Scotland.
Currently, NIPT is available to all Dutch women who are found to be at high risk based on the results of the FCT, which is defined as greater than a 1 in 200 risk, or who have a medical indication that puts them at higher risk, such as an earlier child with Down syndrome, Tamminga said. Testing for the first year of TRIDENT was paid for by the government, but now, health insurance reimburses for the test after patients reach their €375 ($400) "excess," she said. The excess is akin to a deductible in the US.
In addition, researchers have applied for a license from the Netherlands ministry of health to conduct a follow-up study called TRIDENT 2, which would allow all pregnant women to undergo NIPT along with the FCT, in order to study the test's performance in average risk pregnancies, Erik Sistermans, head of genome diagnostics at VU University Medical, told GenomeWeb.
The health council will likely review the study in December, he said, after which it may have additional questions before giving a final recommendation to the health minister. The health minister will make the final decision about TRIDENT 2, which Sistermans said is expected next summer.
Sistermans was not part of the study surveying health professionals' attitudes about NIPT, but he is working on a different facet of NIPT implementation — evaluating the tests' performance in high-risk pregnancies.
"We're doing a full follow up of clinical outcomes, so we know the true false positive and false negative rates," he said.
There are now five medical centers that are part of the NIPT consortium, which will be part of the TRIDENT 2 study if it is approved, Sistermans said. The tests offered have all been developed in house, he said, and none of the labs are using tests from commercial providers. The methods are slightly different — they use different algorithms, and run on different sequencing platforms — but are all based on whole-genome shotgun sequencing rather than targeted sequencing, he said.
For instance, Radboud University Medical Center runs its test on the Illumina NextSeq 500, while the University Medical Center Utrecht developed its NIPT on Thermo Fisher's SOLiD 5500xl Wildfire platform.
Sistermans said that the Netherlands is moving more slowly than other countries on allowing NIPT. "It took us longer to have a test on the market, which is maybe a drawback," he said, "but we also thought about it really well before starting, which is also not a bad thing to do."
However, one impact of moving slowly, he said, is that some women with average-risk pregnancies who have the financial means and desire for NIPT often go to Belgium or Germany for testing.
In Germany, NIPT prices range from around €400 ($425) to €900 ($957), depending on the test provider, testing method, turnaround time, and conditions screened.