The Non-Invasive Prenatal Test, commonly known as NIPT, can determine through a simple blood test whether an unborn child may have a chromosomal abnormality, such as Down syndrome. Erik Sistermans of Amsterdam UMC played a pivotal role in the development and implementation of this test, which is of great importance to all expectant parents in the Netherlands. Since April 1, 2023, NIPT has become the standard test for prenatal screening for congenital chromosomal abnormalities. Sistermans has now been nominated for the Huibregtsen Prize, which is awarded to innovative research projects with exceptional societal value.
The process is straightforward: with a simple blood test on the mother, starting from the tenth week of pregnancy, it is possible to determine whether the unborn fetus may have Down syndrome, Edwards syndrome, or Patau syndrome. "The test utilizes the fact that loose genetic material from the unborn child is present in the mother's blood. This has been known for over half a century, but initially, science couldn't do much with it," explains Erik Sistermans, Professor of Human Genetics and head of the Genome Analysis laboratory at Amsterdam UMC. He was also the project leader of the TRIDENT studies, conducted by the national NIPT consortium, in which the seven university medical centers and relevant professional associations collaborated to introduce the NIPT blood test in the Netherlands.
A breakthrough came around the turn of the century when Professor Dennis Lo of chemical pathology in Hong Kong, with the assistance of Professor Cees Oudejans from the Department of Clinical Chemistry at the former VUmc, found a way to analyze and interpret small fragments of fetal DNA in the mother's blood.
Significant Advantages of NIPT
At the initiative of Amsterdam UMC, the test was introduced in the Netherlands with great care, conducted as part of research, the so-called TRIDENT studies. Never before had there been such a large national study with complete clinical follow-up regarding NIPT. Additionally, research into the perspective of pregnant women themselves was novel. In 2014, NIPT was only offered to pregnant women who, based on the 'old' combination test, had an increased risk of having a child with conditions such as Down syndrome or if they had a previous child with Down, Edwards, or Patau syndrome. It quickly became clear that NIPT also had significant advantages as the first test compared to the combination test, which was still the norm at the time.
False Alarms
Both the combination test and NIPT require mothers with a 'positive' result to undergo either amniocentesis or chorionic villus sampling (CVS) to confirm the presence of Down syndrome. However, these latter tests carry a risk of approximately 2 in 1000 for a miscarriage, a daunting prospect for expectant parents. Sistermans states, "The evaluation of TRIDENT-1 revealed that the combination test often generates false alarms, whereas this occurs less than 1 in 1000 times with NIPT. Therefore, thanks to NIPT, the number of risky and unnecessary punctures after the combination test could be reduced by two-thirds."
In 2017, Amsterdam UMC initiated a follow-up study (TRIDENT-2) in which all pregnant women in the Netherlands who wished to do so could undergo NIPT. The TRIDENT studies were so successful that the combination test, the official screening test up to that point, was discontinued in 2021. Since April 2023, NIPT has been available free of charge to all pregnant women who desire it.
Preeclampsia and Viruses
As the chairman of the national NIPT consortium, which continues as a research consortium after the conclusion of the TRIDENT studies, Sistermans also looks beyond the current scope of NIPT. In a 2020 study involving 161 pregnant women, an adapted NIPT in the first trimester of pregnancy predicted the development of preeclampsia in the second or third trimester for four women. Furthermore, based on NIPT data, it was determined whether there was a viral infection. Some infections are dangerous for both the mother and the child, and early detection could facilitate timely treatment.
Sistermans expects a gradual expansion of the conditions that can be detected through NIPT. "Thanks to the multidisciplinary approach of the NIPT consortium and excellent cooperation with regional centers for prenatal diagnostics, RIVM, and VWS, I expect this to happen for expectant parents as carefully as before."
Huibregtsen Prize 2023
From 24 submissions for the Huibregtsen Prize 2023, the jury has nominated six scientific research projects. On the Evening of Science & Society, October 9, 2023, at the Pieterskerk in Leiden, jury chair Marileen Dogterom (president of KNAW) will announce this year's Huibregtsen Prize winner.
Source: Amsterdam UMC