NEW YORK (GenomeWeb) – One year after the Netherlands made noninvasive prenatal aneuploidy screening available to all pregnant women as part of a nationwide implementation study, the uptake of the test has been 42 percent, according to a presentation at the American Society of Human Genetics annual meeting in San Diego last week.
The test yielded few false-positive and false-negative results for trisomy 21 and trisomy 18 during its first year and reported incidental findings — rare trisomies, subchromosomal alterations, or complex or chaotic chromosome profiles — in just 0.28 percent of cases, according to Erik Sistermans, head of genome diagnostics at the VU University Medical Center Amsterdam and leader of the TRIDENT-2 (Trial by Dutch Laboratories for Evaluation of Noninvasive Prenatal Testing) study.
TRIDENT-2 started in April of 2017, funded with €26 million ($29.8 million) from the Dutch Ministry of Health, and followed an earlier study called TRIDENT that had been testing NIPT in Dutch women with high-risk pregnancies since 2014. Under TRIDENT-2, NIPT became available to all women in the Netherlands for a fee of €175 ($200). Alternatively, they can choose the conventional first-trimester combined test (FCT) for €170, or they can forego prenatal aneuploidy screening altogether.
Women have their blood taken at one of 170 sampling labs across the Netherlands and testing is performed at one of three centers: the VU University Medical Center Amsterdam, the Erasmus Medical Center in Rotterdam, or the Maastricht University Medical Center.
Initially, those centers ran in-house-developed tests that used Illumina sequencing platforms and an analysis algorithm called Wisecondor. However, following a European tender, the centers started deploying Illumina's VeriSeq NIPT Solution in May.
Over the first year of TRIDENT-2, 173,000 women were approached about prenatal aneuploidy screening, and 74,000, or 42 percent, chose NIPT. Another 3 percent opted for FCT, Sistermans said, primarily those who were excluded from NIPT for reasons such as a twin pregnancy. This is a higher aneuploidy screening uptake rate than in 2016 when 34 percent of women chose FCT, he said. However at that time, some Dutch women went to Belgium or Germany for NIPT since it was not widely available in the Netherlands back then.
Women who opt for NIPT can choose between receiving results only for trisomies 21, 18, or 13 or results for all autosomes, and 78 percent chose the latter. Testing of sex chromosomes is not permitted in the Netherlands, Sistermans explained.
Overall, NIPT reported 237 trisomy 21 results in the first year, of which 96 percent were confirmed by invasive testing; 49 trisomy 18 results, of which 98 percent were confirmed; and 55 trisomy 13 results, of which just 52 percent were confirmed, largely because of placental mosaicism that did not affect the fetus, Sistermans said.
In terms of incidental findings, the tests reported 100 cases of other trisomies, 91 cases of subchromosomal alterations, and 14 cases of complex or chaotic chromosome profiles, for a total rate of 0.28 percent. Of the other trisomies, only 11 percent were confirmed by invasive testing — again, often because of confined placental mosaicism that was not present in the fetus. In addition, 41 percent of the subchromosomal alterations were confirmed by invasive testing.
Many of the 14 cases of complex or chaotic chromosome profiles resulted from maternal DNA, including seven maternal hematological disorders or malignancies, two maternal solid tumors, and two cases of maternal non-malignant fibroids. They included two cases of chromosome 5q syndrome, a hematological disorder that may lead to myelodysplastic syndrome or acute myelogenous leukemia in the mother.
NIPT also missed a small number of trisomies — six cases of trisomy 21 and five cases of trisomy 18 — likely because of low fetal DNA fraction or because of confined mosaicism in the fetus.
Sistermans said that the TRIDENT-2 sequencing centers have performed 25,000 tests since they switched to the Illumina VeriSeq NIPT Solution in May of this year, but not all results from these tests have been analyzed yet. He noted that there have been some issues, in particular concerning samples with low fetal DNA fraction and certain rare trisomies. For now, the centers do not report on samples with a fetal fraction below 1 percent, he said, adding that Illumina is aware of the issues and is working on resolving them.