Laboratory Techniques

The Laboratory Techniques SIG is dedicated to the advancement of the art and science of all aspects of the various laboratory techniques in use in fetal diagnosis, including validation and implementation of new techniques. The SIG wants to facilitate and encourage communication and education between SIG members. The SIG also participates in education and training activities of the ISPD. As there is an overlap with the interests of other SIGs, e.g. concerning ethical and psychosocial issues and screening aspects, the SIG closely operates with other SIGs.

SIG Topics of Discussion/Interest

  • Noninvasive prenatal testing
  • NIPD for monogenic disorders
  • PGD
  • Cytogenetics
  • Molecular genetics
  • Arrays
  • Quality control
  • Guidelines

Article submitted to Global Updates, June 2017

The Dutch TRIDENT studies: Implementing NIPT as part of the national prenatal screening program

Sistermans EA, Galjaard RJ, Scheffer H, Henneman L, on behalf of the NIPT Consortium

Non-Invasive Prenatal Testing (NIPT) has been rapidly introduced worldwide. In many countries this has been done by companies and/or (academic) medical centers, without any governmental guidance. This way of introducing NIPT was not possible in the Netherlands, because of the Population Screening Act (Wet op het bevolkingsonderzoek, WBO). The main goal of this act is to protect people against potentially harmful screening. A license from the Minister of Health must be obtained before offering some forms of screening, such as prenatal screening for Down syndrome. A WBO license for the introduction of a new screening method such as NIPT can only be obtained after approval by the Health Council of the Netherlands. In 2014 the Dutch NIPT Consortium obtained a license for the TRIDENT-1 study (Trial by Dutch Laboratories for Evaluation of Noninvasive Prenatal Testing), allowing NIPT for women with high-risk pregnancies based on first trimester combined test (FCT) results or medical history. TRIDENT-2, which aims at implementing NIPT for all pregnant women within the framework of the national prenatal screening program, started April 1st 2017.

Dutch Centre for population screening: Background information on the Dutch population screening program:

Commentary on unexpected prenatal test results:

Bianchi, D. Pregnancy: Prepare for unexpected prenatal test results. Nature 522, 29–30 (04 June 2015) doi:10.1038/522029a

TRIDENT-1 papers

Oepkes, D., et al. (2016) Trial by Dutch laboratories for evaluation of non-invasive prenatal testing. Part I—clinical impact. Prenat Diagn, 36: 1083–1090. doi: 10.1002/pd.4945.

van Schendel, R. V. et al. (2016) Trial by Dutch laboratories for evaluation of non-invasive prenatal testing. Part II—women's perspectives. Prenat Diagn, 36: 1091–1098. doi: 10.1002/pd.4941.

Background information (video): lecture on mosaicisms and cfdna implications.

Plenary Debate 2 - For Those Women Screened by NIPT Using Cell Free DNA Maternal Serum Biomarkers Are Obsolete.
Session number 3: Francesca Romana Grati (Italy), Mosaicism and its implications for prenatal diagnosis 

The Dutch NIPT Consortium, which designs and organizes the TRIDENT studies, includes all stakeholders that are involved in prenatal care (the eight Academic Medical centers that formally received the license, midwives, gynecologists, clinical geneticists, clinical laboratory geneticists, ethicists and patient organizations). The goal of the NIPT Consortium is not just to make NIPT available to all pregnant women in the Netherlands, but to integrate it in the existing national prenatal screening program. This will guarantee the chance that the patient receives proper pre- and post-test counseling about NIPT and appropriate follow up.  In the TRIDENT-2 study NIPT will become available for all pregnant women in the Netherlands (on average 180,000 pregnant women/year; FCT uptake rate ~30%). The NIPT Consortium received the license for the TRIDENT-2 study from the Minister of Health on September 20th 2016, with a starting date for testing of April 1st 2017. Women who want to have prenatal screening can now choose which test they prefer (NIPT or FCT). The minister decided to invest €26 million to ensure that the out-of-pocket cost of NIPT analysis (€175) would not exceed that of the FCT. As in TRIDENT-1, a whole genome sequencing approach is used, followed by analysis with the WISECONDOR analysis software developed at VU University Medical Center Amsterdam (Straver et al. Nucleic Acids Res. 2014 Mar;42(5):e31.). WISECONDOR allows the detection of all trisomies, as well as smaller deletions and amplifications with a minimum size of approximately 10 Mb. Women will have the choice between receiving results for chromosomes 21, 13 and 18 only, or for all autosomes. Sex chromosomal abnormalities will not be analyzed and reported.

Preparation of the study:
As the numbers of participants in TRIDENT-2 are much higher than for TRIDENT-1, the entire chain from counselor to laboratory and back needed to be revised. The main projects that needed to be taken care of were:

  • Training of ~3000 counselors for NIPT pretest counseling
  • Development of informational booklets and websites for pregnant women and professionals
  • Increase of the laboratory capacity at the three clinical genetic laboratory sites that will perform NIPT testing under TRIDENT-2, VU University Medical Center Amsterdam, Erasmus Medical Center Rotterdam and Maastricht University Medical Center
  • Contracting >160 organizations for blood withdrawal and setting up the logistics
  • Setting up a connection between the national prenatal screening database used by the midwives and the LIMS of the laboratories for ordering the NIPT test and reporting results
  • Writing a grant for performing the scientific part (study evaluation), including questionnaire and interview studies to study the women’s perspective.
All the preparation work was divided over several working groups, and a project manager was appointed. The set-up of the project was closely supervised by the Ministry of Health during monthly meetings. All working groups were ready in time for the starting date of April 1st 2017.

First results:
During the first month almost 6000 NIPT analyses were requested, and approximately 4000 reports were issued. The turnaround time is 5-6 working days for most of the samples, despite the fact that a large number of samples were received in the first week, as women were waiting for the study to start. No major problems were encountered during the first weeks. It is yet too early to give detailed information on the number of abnormalities found, or on the percentage of women that opt for whole genome analysis instead of analysis for trisomy 21, 13 and 18 only. We expect that this 3-year study will provide us with all the results needed for the final decision on the introduction of NIPT in the Dutch National prenatal screening program.

SIG Leadership 

Chair: Diane Van Opstal, PhD

Deputy Chair: Elaine Holgado


Board Liaison: Francesca Romana Grati

Meeting Minutes

12 July 2016 - Berlin, Germany
11 July 2016 - SIGs and Education Committee
15 July 2015 - Washington, DC USA
05 June 2013 - Lisbon, Portugal
06 June 2012 - Miami, Florida, USA
14 July 2010 - Amsterdam, Netherlands
04 June 2008 - Vancouver, Canada