peter schielen | RIVM - Academia.edu (original) (raw)

Papers by peter schielen

PLOS One, 2011

Background: As a first step to identify novel potential biomarkers for prenatal Down Syndrome scr... more Background: As a first step to identify novel potential biomarkers for prenatal Down Syndrome screening, we analyzed gene expression in embryos of wild type mice and the Down Syndrome model Ts1Cje. Since current Down Syndrome screening markers are derived from placenta and fetal liver, these tissues were chosen as target.

Community Genetics, 2008

To evaluate prenatal screening methods for Down syndrome and neural tube defects (NTD) with regar... more To evaluate prenatal screening methods for Down syndrome and neural tube defects (NTD) with regard to costs per detected case and the number of screening-related miscarriages. The screening methods compared were risk assessment tests, i.e. serum tests and nuchal translucency measurement (NT), and invasive testing through chorionic villus sampling (CVS) or amniocentesis. Costs, the number of cases detected and screening-related miscarriages were calculated using a decision tree model. The costs per detected case of Down syndrome ranged from EUR 98,000 for the first-trimester (serum) double test to EUR 191,000 for invasive testing. If NTD detection was included, the (serum) triple test had the lowest costs, EUR 73,000, per detected case of Down syndrome or NTD. The number of screening-related miscarriages due to invasive diagnostic tests varied from 13 per 100,000 women for the (serum) first- and second-trimester combined test to 914 per 100,000 women for invasive testing. Considering screening for both Down syndrome and NTD favors the triple test in terms of costs per detected case. Compared to invasive testing, risk assessment tests in general substantially lower screening-related miscarriages, which raises the question of whether invasive testing should still be offered in a screening program for Down syndrome.

Clinical Chemistry and Laboratory Medicine, 2009

The VU University Medical Center (VUmc) was the first hospital in the Netherlands to introduce th... more The VU University Medical Center (VUmc) was the first hospital in the Netherlands to introduce the Delfia Xpress for the analysis of free beta-human chorionic gonadotrophin (beta-hCG) and pregnancy associated plasma protein-A (PAPP-A) in the first trimester screening program for Down syndrome. Since then, others have implemented this system. In this study, we tested the equality of measurements for free beta-hCG and PAPP-A between Delfia Xpress systems and one AutoDelfia system. A total of 40 serum samples were aliquoted and stored at -20 degrees C. Samples were analyzed by six Delfia Xpress systems and one AutoDelfia system over a time period of 2 years. The relationships between free beta-hCG and PAPP-A were excellent for the different Delfia Xpress systems (r&amp;amp;amp;amp;amp;amp;amp;gt;0.99, p&amp;amp;amp;amp;amp;amp;amp;lt;0.0001). For PAPP-A, the agreement between the main system at VUmc and five other systems was linear with slopes between 0.99 and 1.06. Similarly, agreement for free beta-hCG was linear with slopes between 0.99 and 1.09. Likewise, agreement for PAPP-A and free beta-hCG was excellent for the AutoDelfia vs. the main Delfia Xpress at the VUmc (r&amp;amp;amp;amp;amp;amp;amp;gt;0.99, p&amp;amp;amp;amp;amp;amp;amp;lt;0.0001). For both PAPP-A and free beta-hCG, the relationships were linear with slopes of 1.08 and 1.07. We demonstrate an excellent agreement for the analysis of PAPP-A and free beta-hCG between Delfia Xpress systems and one AutoDelfia system.

Journal of Perinatal Medicine, 2006

To call attention to differences in first trimester risk estimates for trisomy 21, as calculated ... more To call attention to differences in first trimester risk estimates for trisomy 21, as calculated by two different software packages. Methods: A total of ninety-four pregnant women who had a first trimester risk assessment for trisomy 21 that was based on maternal age, biochemical analysis and a nuchal translucency (NT) measurement. Two commonly used software packages were used for the estimation of individual risks (i.e. Wallac-Perkin-Elmer ᮋ software and Fetal Medicine Foundation ᮋ software). Results: Risk estimates derived from each software programme were strikingly different. In each case the discrepancy in reported magnitude of risk resulted from disparities between the two calculation methods for the assessment of the individual risk for trisomy 21. The disparities in risk estimates can be explained by significant differences in reported likelihood ratios for biochemical analyses (Ps0.01), NT measurements (P-0.0001) and both screening parameters combined Ps0.003). Conclusion: It is illustrated that the lack of agreement between these risk calculation methods could give rise to major counselling problems. In order to avoid confusion, there is a need for estimating individual risks of trisomy 21 in a standardized way. It is proposed to select a set of parameters that have a proven track record as judged by detection and false positive rates and then use that set exclusively, while simultaneously monitoring its performance.

Expert Review of Molecular Diagnostics, 2010

Prenatal screening for Down syndrome (DS) is performed by risk calculation based on biochemical a... more Prenatal screening for Down syndrome (DS) is performed by risk calculation based on biochemical and biometric parameters. This way, approximately 75-85% of all DS cases can be detected. A way to improve detection rates is to search for new screening markers. Since the majority of biomarkers used in current DS screening are predominantly produced by the placenta, and the presence of an extra chromosome (as in DS) complicates placental development and function, it is plausible to assume that new potential screening markers may also originate from the placenta. Any alterations in these markers can be attributed to abnormal placental development and function. This article focuses on normal early placental development and function compared with that in DS pregnancies. Using this knowledge, we reason towards candidate biomarkers that may be useful in screening for DS.

Journal of Immunological Methods, 1995

We describe here a new type of solid support for the ELISPOT assay, the PVDF membrane. In paralle... more We describe here a new type of solid support for the ELISPOT assay, the PVDF membrane. In parallel tests, spot yields on this membrane were superior to those obtained with the frequently used nitrocellulose (NC) membrane, coated with the same rat anti-IgM and anti-IgG antibodies, incubated with the same rat spleen cell suspensions, and developed with the same combination of AP-labeled conjugates and substrate.We therefore used the PVDF membrane, coated with anti-rat IgM and IgG antibodies, ssDNA or bromelain-treated mouse erythrocytes (BrMRBC) (exposing phosphatidylcholine (PC) as major autoantigen) to develop ELISPOT assays for the quantification of isotype-specific natural antibody secreting cells (ASC) in rats. We confirmed the isotype specificity of the binding of the anti-rat IgM and anti-rat IgG coating antibodies and conjugates with the secreted rat antibodies in this assay, and, by inhibition of spot formation with soluble antigen, their specificity for ssDNA and BrMRBC.An in-house 18-well culture device for the easy manufacture of PVDF-lined culture wells greatly facilitated coating, blocking, and washing procedures, as compared to the original method in 24 well culture plates. This simple, fast, specific and sensitive ELISPOT assay was used to make an inventory of the numbers of natural splenic ASC in Wistar and Fischer rats.

Toxicology and Applied Pharmacology, 1995

Toxicology and Applied Pharmacology, 1993

We investigated whether autoimmune disregulation underlies the formerly reported induction of IgM... more We investigated whether autoimmune disregulation underlies the formerly reported induction of IgM hypergammaglobulinemia and lymphoid organ enlargement by hexachlorobenzene (HCB) in rats. To this end blood, liver, and lymphoid organs were collected from male Wistar rats after feeding a semisynthetic diet containing 0, 500, or 1000 mg HCB/kg for 3 weeks. Sera prepared from the blood were analyzed for total and (auto)antigen-specific antibody levels by ELISA, organs were weighed, and spleens were further investigated morphogically using immunohistochemically stained cryosections. Present experiments confirmed the ability of HCB to increase total IgM, but not IgG, levels and to increase relative spleen, lymph node, and liver weights. HCB treatment elevated IgM, but not IgG, levels against single-stranded DNA, native DNA, rat IgG (representing rheumatoid factor), and bromelain-treated mouse erythrocytes that expose phosphatidylcholine as a major autoantigen. Antibody levels against the foreign antigens sheep erythrocytes, tetanus toxoid, and bovine serum albumin remained unaffected. The IgM autoantibodies proved to be polyreactive. Morphometric analysis of spleen sections showed that HCB caused a proportionally equal expansion of all splenic compartments, but when individual spleen weights were taken into account a significantly larger expansion of the predominantly B cell-containing marginal zones could be noted. The latter compartment also contained an increased number of macrophages that can be recognized by the monoclonal antibody ED3. The ability of HCB to elevate serum antibody levels against autoantigens, but not foreign antigens, indicates that HCB probably does not act by polyclonal B cell activation. The IgM isotype, the repertoire, and the polyreactivity of the serum autoantibodies suggest that HCB activates a recently described B cell subset shown to be committed to the production of these autoantibodies and associated with various systemic autoimmune diseases. Since the marginal zone is considered to be the splenic lodging site of this B cell subset and since increases of ED3+ macrophages have been associated with autoimmune diseases in the rat, the observed changes of the marginal zones in HCB-treated rats is in line with this notion.

Tsg, 2010

In 2004 heeft de overheid besloten dat elke zwangere in Nederland moet worden geïnformeerd over p... more In 2004 heeft de overheid besloten dat elke zwangere in Nederland moet worden geïnformeerd over prenatale screening op Downsyndroom. In de afgelopen jaren is hard gewerkt aan een uitvoeringsorganisatie die de kwaliteit van het aanbod moet garanderen. Daarmee lijkt een einde te zijn gekomen aan een decennia lange discussie over de mogelijkheden en betekenis van deze vorm van prenatale screening. Waarom bleek het in al die jaren zo moeilijk om tot overeenstemming te komen? Vaak wordt gewezen op de overheid die als besluitvormende partij prenatale screening jarenlang heeft tegengehouden. Maar als we terugkijken naar de geschiedenis van het debat, dan ontstaat een ander en complexer beeld. Prenatale screening verschijnt daarin als een probleem dat eerst ‘getemd’ moest worden, alvorens daarover maatschappelijk en politiek overeenstemming kon worden bereikt. In dat proces is het aanbod van prenatale screening steeds meer in het teken komen te staan van geïnformeerde besluitvorming als het primaire doel. Goede voorlichting en uitgebreide counseling zijn daarmee de middelen bij uitstek geworden die de maatschappelijke aanvaardbaarheid van prenatale screening moeten waarborgen. Maar of die middelen voldoen is op dit moment nog allerminst duidelijk. In dit opzicht heeft de praktijk van prenatale screening nog steeds een ongetemd karakter. Deze conclusie is niet alleen van belang voor de huidige praktijk, maar zeker ook voor de toekomst van prenatale screening. Prenatal screening: a (not yet) fully tamed problem? In 2004 the Dutch government decided that prenatal screening should be available in the Netherlands for all pregnant women. In the past few years an organisation has been created for the implementation and quality control of a nation-wide screening programme. Thus, after several decades, a long debate about the possibilities and implications of prenatal screening came to a close. Why did prenatal screening remain controversial for so many years? Often, the reluctant attitude of the Dutch government towards prenatal screening is mentioned in this context. However, a detailed study of the history of the debate suggests a different and more complex story. Prenatal screening emerges in this history as a wicked problem that first had to be ‘tamed’ in a process of societal learning before a societal and political consensus could be reached. In this process, informed choice increasingly became the major goal for offering prenatal screening. Consequently, education and counselling are emphasized as vital means to guarantee the societal acceptability of prenatal screening. However, it is far from clear whether these means really do achieve their stated goals. In this respect, prenatal screening should be considered a not yet fully tamed problem. This conclusion is not only relevant for current practice, but even more for the future of prenatal screening.