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1. Prenatal cell-free DNA testing of women with pregnancy-associated cancer: a retrospective cross-sectional study

Author

Sistermans, E.A., Henneman, L., Polstra, A., Voorhoeve, E., Zelderen-Bohla, S.L., Boon, E.M.J., Lombardi, M.P.R., Louwerens-Zintel, C., Smit, M., van Maarle, M.C., Tan-Sindhunata, M.B., van der Meij, K., Meij, H., Bax, C., Pajkrt, E., Linskens, I.H., Martin, L., Gitsels-van der Wal, J.T., Galjaard, R.J.H., Van Opstal, D., Srebniak, M.I., Jehee, F.M. Sarquis, Hollink, I.H.I.M., Sleutels, F., de Valk, W., Deelen, W.H., Joosten, A.M.S., Diderich, K.E.M., Redeker, M.E., Go, A.T.J.I., Knapen, M.F.C.M., Galjaard, S., Prinsen, A.K.E., Braat, A.P.G., Macville, M.V.E., Stevens, S.J.C., van der Wijngaard, A., Houben, L.H., van Esch-Lennarts, M.A.A., Hamers, L., Jetten, A.G.P., Ghesquiere, S.A.I., Koning, B. de, ZamaniEsteki, M., Heesterbeek, C.J., de Die-Smulders, C.E.M., Brunner, H., Pieters, M.J., Coumans, A.B.C., Smeets, D.F.C.M., Faas, B.H.W., Westra, D., Weiss, M.M., Derks-Prinsen, I., Feenstra, I., van Rij, M., Sikkel, E., Hoffer, M.J.V., Hollander, N.S. den, Verweij, E.J.T., Haak, M.C., Suijkerbuijk, R.F., Sikkema-Raddatz, B., van Langen, I.M., Bouman, K., Duin, L.K., Schuring-Blom, G.H., Lichtenbelt, K.D., Bekker, M.N., van der Ven, A.J.E.M., van Vliet-Lachotzki, E., Pot, J., van ‘t Padje, S., Bakker, I.M.C., Bradley, E.J., Heesterbeek, Catharina J., Tjan-Heijnen, Vivianne C.G., Heimovaara, Joosje H., Lenaerts, Liesbeth, Lok, Christianne, Vriens, Ingeborg J.H., Van Opstal, Diane, Boon, Elles M.J., Sie, Daoud, de Die-Smulders, Christine E.M., Amant, Frédéric, and Macville, Merryn V.E.

Published
2024
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3. Do Preferred Risk Formats Lead to Better Understanding? A Multicenter Controlled Trial on Communicating Familial Breast Cancer Risks Using Different Risk Formats

Author

Henneman L, van Asperen CJ, Oosterwijk JC, Menko FH, Claassen L, and Timmermans DRM

Subjects
risk communication, breast cancer, genetic counseling, patient preference, understanding, risk accuracy, Medicine (General), R5-920
Abstract

Lidewij Henneman,1 Christi J van Asperen,2 Jan C Oosterwijk,3 Fred H Menko,4 Liesbeth Claassen,5 Daniëlle RM Timmermans5 1Department of Clinical Genetics, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands; 2Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands; 3Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; 4Family Cancer Clinic, Netherlands Cancer Institute, Amsterdam, the Netherlands; 5Department of Public and Occupational Health, Amsterdam UMC, Vrije Universiteit, Amsterdam, the NetherlandsCorrespondence: Lidewij HennemanDepartment of Clinical Genetics, Amsterdam UMC, Vrije Universiteit, PO Box 7057, 1007 MB, Amsterdam, the NetherlandsTel +31 20-4449815Email l.henneman@amsterdamumc.nlPurpose: Counselees’ preferences are considered important for the choice of risk communication format and for improving patient-centered care. We here report on counselees’ preferences for how risks are presented in familial breast cancer counseling and the impact of this preferred format on their understanding of risk.Patients and Methods: As part of a practice-based randomized controlled trial, 326 unaffected women with a family history of breast cancer received their lifetime risk in one of five presentation formats after standard genetic counseling in three Dutch familial cancer clinics: 1) in percentages, 2) in frequencies (“X out of 100”), 3) in frequencies plus graphical format (10× 10 human icons), 4) in frequencies and 10-year age-related risk and 5) in frequencies and 10-year age-related risk plus graphical format. Format preferences and risk understanding (accuracy) were assessed at 2-week follow-up by a questionnaire, completed by 279/326 women.Results: The most preferred risk communication formats were numbers combined with verbal descriptions (37%) and numbers only (26%). Of the numerical formats, most (55%) women preferred percentages. The majority (73%) preferred to be informed about both lifetime and 10-year age-related risk. Women who had received a graphical display were more likely to choose a graphical display as their preferred format. There was no significant effect between the intervention groups with regard to risk accuracy. Overall, women given risk estimates in their preferred format had a slightly better understanding of risk.Conclusion: The results suggest that the accuracy of breast cancer risk estimation is slightly better for women who had received this information in their preferred format, but the risk format used had no effect on women’s risk accuracy. To meet the most frequent preference, counselors should consider providing a time frame of reference (eg, risk in the next 10 years) in a numerical format, in addition to lifetime risk.Keywords: risk communication, breast cancer, genetic counseling, patient preference, understanding, risk accuracy

Published
2020

5. Clinical impact of additional findings detected by genome-wide non-invasive prenatal testing

Author

Schuurman, L.V., Sistermans, E.A., Opstal, D. van, Henneman, L., Bekker, M.N., Bax, C.J., Pieters, M.J., Bouman, K., Munnik, S. de, Hollander, N.S. den, Diderich, K.E.M., Faas, B.H.W., Feenstra, I., Go, A.T.J.I., Hoffer, M.J.V., Joosten, M., Komdeur, F.L., Lichtenbelt, K.D., Lombardi, M.P., Polak, M.G., Jehee, F.S., Schuring-Blom, H., Stevens, S.J.C., Srebniak, M.I., Suijkerbuijk, R.F., Tan-Sindhunata, G.M., Meij, K.R.M. van der, Maarle, M.C. van, Vernimmen, V., Zelderen-Bhola, S.L. van, Ravesteyn, N.T. van, Knapen, M.F.C.M., Macville, M.V.E., Galjaard, R.J.H., Dutch NIPT Consortium, Human genetics, Amsterdam Reproduction & Development (AR&D), Obstetrics and gynaecology, Pathology, Rehabilitation medicine, APH - Quality of Care, Obstetrics and Gynaecology, Human Genetics, ACS - Pulmonary hypertension & thrombosis, ARD - Amsterdam Reproduction and Development, Public Health, Clinical Genetics, Obstetrics & Gynecology, Department of Psychology, Education and Child Studies, Clinical genetics, Amsterdam Reproduction & Development, Emergency Medicine, Research Methods and Techniques, RS: GROW - R4 - Reproductive and Perinatal Medicine, Obstetrie & Gynaecologie, MUMC+: MA Medische Staf Obstetrie Gynaecologie (9), MUMC+: DA KG Lab Specialisten (9), MUMC+: DA KG Lab Centraal Lab (9), MUMC+: DA KG Polikliniek (9), and MUMC+: DA KG AIOS (9)

Subjects
Placenta, Trisomy, first tier test, Cohort Studies, genome-wide, Pregnancy, Prenatal Diagnosis/methods, Prenatal Diagnosis, Genetics, Humans, cfDNA, Genetics (clinical), confined placental mosaicism, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Mosaicism, Other Research Radboud Institute for Health Sciences [Radboudumc 0], NIPS, fetal trisomy, PREECLAMPSIA, common trisomies, prenatal screening, CELL-FREE DNA, Female, NIPT, Follow-Up Studies, rare autosomal trisomies
Abstract

Contains fulltext : 251979.pdf (Publisher’s version ) (Open Access) In the TRIDENT-2 study, all pregnant women in the Netherlands are offered genome-wide non-invasive prenatal testing (GW-NIPT) with a choice of receiving either full screening or screening solely for common trisomies. Previous data showed that GW-NIPT can reliably detect common trisomies in the general obstetric population and that this test can also detect other chromosomal abnormalities (additional findings). However, evidence regarding the clinical impact of screening for additional findings is lacking. Therefore, we present follow-up results of the TRIDENT-2 study to determine this clinical impact based on the laboratory and perinatal outcomes of cases with additional findings. Between April 2017 and April 2019, additional findings were detected in 402/110,739 pregnancies (0.36%). For 358 cases, the origin was proven to be either fetal (n = 79; 22.1%), (assumed) confined placental mosaicism (CPM) (n = 189; 52.8%), or maternal (n = 90; 25.1%). For the remaining 44 (10.9%), the origin of the aberration could not be determined. Most fetal chromosomal aberrations were pathogenic and associated with severe clinical phenotypes (61/79; 77.2%). For CPM cases, occurrence of pre-eclampsia (8.5% [16/189] vs 0.5% [754/159,924]; RR 18.5), and birth weight

Published
2022

6. Experiences of pregnant women with genome-wide non-invasive prenatal testing in a national screening program.

Author

Meij, K.R.M. van der, Pol, Q.Y.F. van de, Bekker, M.N., Martin, L., Gitsels-van der Wal, J.T., Vliet-Lachotzki, E.H. van, Weiss, J., Galjaard, R.H., Sistermans, E.A., Macville, M.V.E., Henneman, L., Meij, K.R.M. van der, Pol, Q.Y.F. van de, Bekker, M.N., Martin, L., Gitsels-van der Wal, J.T., Vliet-Lachotzki, E.H. van, Weiss, J., Galjaard, R.H., Sistermans, E.A., Macville, M.V.E., and Henneman, L.

Abstract

Item does not contain fulltext, Pregnant women's perspectives should be included in the dialogue surrounding the expanding offers of non-invasive prenatal testing (NIPT), especially now that technological possibilities are rapidly increasing. This study evaluated women's experiences with the offer of genome-wide (GW) first-tier NIPT in a national screening program. A nationwide pre-and post-test questionnaire was completed by 473 pregnant women choosing between targeted NIPT (trisomies 21, 18 and 13 only) and GW-NIPT (also other findings) within the Dutch TRIDENT-2 study. Measures included satisfaction, reasons for or against choosing GW-NIPT, anxiety, and opinion on the future scope of NIPT. Most respondents (90.4%) were glad to have been offered the choice between GW-NIPT and targeted NIPT; 76.5% chose GW-NIPT. Main reasons to choose GW-NIPT were 'wanting as much information as possible regarding the child's health' (38.6%) and 'to be prepared for everything' (23.8%). Main reasons to choose targeted NIPT were 'avoiding uncertain results/outcomes' (33.7%) and 'not wanting to unnecessarily worry' (32.6%). Nearly all respondents received a low-risk NIPT result (98.7%). No differences were found in anxiety between women choosing GW-NIPT and targeted NIPT. Most respondents were favorable toward future prenatal screening for a range of conditions, including life-threatening disorders, mental disabilities, disorders treatable in pregnancy and severe physical disabilities, regardless of their choice for GW-NIPT or targeted NIPT. In conclusion, women who chose first-tier NIPT were satisfied with the choice between GW-NIPT and targeted NIPT, and most women were favorable toward a broader future screening offer. Our results contribute to the debate concerning the expansion of NIPT.

Published
2023

7. Rapid exome sequencing as a first-tier test in neonates with suspected genetic disorder: results of a prospective multicenter clinical utility study in the Netherlands.

Author

Olde Keizer, R.A.C.M., Marouane, A., Kerstjens-Frederikse, W.S., Deden, A.C., Lichtenbelt, K.D., Jonckers, T., Vervoorn, M., Vreeburg, M., Henneman, L., Vries, L.S. de, Sinke, R.J., Pfundt, R.P., Stevens, S.J.C., Andriessen, P., Lingen, R.A. van, Nelen, M.R., Scheffer, H., Stemkens, D., Oosterwijk, C., Ploos van Amstel, H.K., Boode, W.P. de, Zelst-Stams, W.A.G. van, Frederix, G.W., Vissers, L.E.L.M., Olde Keizer, R.A.C.M., Marouane, A., Kerstjens-Frederikse, W.S., Deden, A.C., Lichtenbelt, K.D., Jonckers, T., Vervoorn, M., Vreeburg, M., Henneman, L., Vries, L.S. de, Sinke, R.J., Pfundt, R.P., Stevens, S.J.C., Andriessen, P., Lingen, R.A. van, Nelen, M.R., Scheffer, H., Stemkens, D., Oosterwijk, C., Ploos van Amstel, H.K., Boode, W.P. de, Zelst-Stams, W.A.G. van, Frederix, G.W., and Vissers, L.E.L.M.

Abstract

01 juni 2023, Contains fulltext : 293809.pdf (Publisher’s version ) (Open Access), The introduction of rapid exome sequencing (rES) for critically ill neonates admitted to the neonatal intensive care unit has made it possible to impact clinical decision-making. Unbiased prospective studies to quantify the impact of rES over routine genetic testing are, however, scarce. We performed a clinical utility study to compare rES to conventional genetic diagnostic workup for critically ill neonates with suspected genetic disorders. In a multicenter prospective parallel cohort study involving five Dutch NICUs, we performed rES in parallel to routine genetic testing for 60 neonates with a suspected genetic disorder and monitored diagnostic yield and the time to diagnosis. To assess the economic impact of rES, healthcare resource use was collected for all neonates. rES detected more conclusive genetic diagnoses than routine genetic testing (20% vs. 10%, respectively), in a significantly shorter time to diagnosis (15 days (95% CI 10-20) vs. 59 days (95% CI 23-98, p < 0.001)). Moreover, rES reduced genetic diagnostic costs by 1.5% (€85 per neonate). CONCLUSION: Our findings demonstrate the clinical utility of rES for critically ill neonates based on increased diagnostic yield, shorter time to diagnosis, and net healthcare savings. Our observations warrant the widespread implementation of rES as first-tier genetic test in critically ill neonates with disorders of suspected genetic origin. WHAT IS KNOWN: • Rapid exome sequencing (rES) enables diagnosing rare genetic disorders in a fast and reliable manner, but retrospective studies with neonates admitted to the neonatal intensive care unit (NICU) indicated that genetic disorders are likely underdiagnosed as rES is not routinely used. • Scenario modeling for implementation of rES for neonates with presumed genetic disorders indicated an expected increase in costs associated with genetic testing. WHAT IS NEW: • This unique prospective national clinical utility study of rES in a NICU setting shows that rES obtained

Published
2023

8. Current practice of first-trimester ultrasound screening for structural fetal anomalies in developed countries.

Author

Bronsgeest, K., Lust, E.E.R., Henneman, L., Crombag, N., Bilardo, C.M., Stemkens, D., Galjaard, R.H., Sikkel, E., Hout, S.H. van der, Bekker, M.N., Haak, M.C., Bronsgeest, K., Lust, E.E.R., Henneman, L., Crombag, N., Bilardo, C.M., Stemkens, D., Galjaard, R.H., Sikkel, E., Hout, S.H. van der, Bekker, M.N., and Haak, M.C.

Abstract

01 juni 2023, Contains fulltext : 294339.pdf (Publisher’s version ) (Open Access), OBJECTIVES: First-trimester ultrasound screening is increasingly performed to detect fetal anomalies early in pregnancy, aiming to enhance reproductive autonomy for future parents. This study aims to display the current practice of first-trimester ultrasound screening in developed countries. METHOD: An online survey among 47 prenatal screening experts in developed countries. RESULTS: First-trimester structural anomaly screening is available in 30 of the 33 countries and is mostly offered to all women with generally high uptakes. National protocols are available in 23/30 (76.7%) countries, but the extent of anatomy assessment varies. Monitoring of scan quality occurs in 43.3% of the countries. 23/43 (53.5%) of the respondents considered the quality of first-trimester ultrasound screening unequal in different regions of their country. CONCLUSIONS: First-trimester screening for structural fetal anomalies is widely offered in developed countries, but large differences are reported in availability and use of screening protocols, the extent of anatomy assessment, training and experience of sonographers and quality monitoring systems. Consequently, this results in an unequal offer to parents in developed countries, sometimes even within the same country. Furthermore, as offer and execution differ widely, this has to be taken into account when results of screening policies are scientifically published or compared.

Published
2023

9. Informed choice and routinization of the second-trimester anomaly scan: a national cohort study in the Netherlands.

Author

Lust, E.E.R., Bronsgeest, K., Henneman, L., Crombag, N., Bilardo, C.M., Vliet-Lachotzki, E.H. van, Galjaard, R.H., Sikkel, E., Haak, M.C., Bekker, M.N., Lust, E.E.R., Bronsgeest, K., Henneman, L., Crombag, N., Bilardo, C.M., Vliet-Lachotzki, E.H. van, Galjaard, R.H., Sikkel, E., Haak, M.C., and Bekker, M.N.

Abstract

Contains fulltext : 296945.pdf (Publisher’s version ) (Open Access), BACKGROUND: Since 2007 all pregnant women in the Netherlands are offered the second-trimester anomaly scan (SAS) in a nationwide prenatal screening program. This study aims to assess the level of informed choice of women opting for the SAS and to evaluate the presence of routinization 16 years after its implementation. It further explores decisional conflict and women's decision making. METHODS: This prospective national survey study consisted of an online questionnaire which was completed after prenatal counseling and before undergoing the SAS. Informed choice was measured by the adapted multidimensional measure of informed choice (MMIC) and was defined in case women were classified as value-consistent, if their decision for the SAS was deliberated and made with sufficient knowledge. RESULTS: A total of 894/1167 (76.6%) women completed the questionnaire. Overall, 54.8% made an informed choice, 89.6% had good knowledge, 59.8% had deliberated their choice and 92.7% held a positive attitude towards the SAS. Women with low educational attainment (p=0.004) or respondents of non-Western descent (p=0.038) were less likely to make an informed choice. Decisional conflict was low, with a significantly lower decisional conflict score in women that made an informed choice (p<0.001). Most respondents (97.9%) did not perceive pressure to undergo the SAS. CONCLUSIONS: Our study showed a relatively low rate of informed choice for the SAS, due to absence of deliberation. Therefore, some routinization seem to be present in the Netherlands. However, most women had sufficient knowledge, did not perceive pressure and experienced low decisional conflict.

Published
2023

11. Rapid exome sequencing as a first-tier test in neonates with suspected genetic disorder: results of a prospective multicenter clinical utility study in the Netherlands

Author

Olde Keizer, Richelle A.C.M., Marouane, Abderrahim, Kerstjens-Frederikse, Wilhelmina S., Deden, A. Chantal, Lichtenbelt, Klaske D., Jonckers, Tinneke, Vervoorn, Marieke, Vreeburg, M., Henneman, Lidewij, de Vries, Linda S., Sinke, Richard J., Pfundt, Rolph, Stevens, Servi J.C., Andriessen, Peter, van Lingen, Richard A., Nelen, Marcel, Scheffer, Hans, Stemkens, Daphne, Oosterwijk, Cor, van Amstel, Hans Kristian Ploos, de Boode, W. P., van Zelst-Stams, W., Frederix, Geert W.J., Vissers, L. E.L.M., Henneman, L., van Haelst, M. M., Sistermans, E. A., Cornel, M. C., Misra-Isrie, M., Mannens, M. M.A.M., Waisfisz, Q., van Hagen, J. M., Brooks, A. S., Barakat, T. S., Hoefsloot, E. H., van Lingen, R. A., Ruivenkamp, C. A.L., Koene, S., Rutten, J. W., de Koning, B., Stevens, S. J.C., van den Wijngaard, A., Stegmann, A. P.A., Deden, A. C., Rodenburg, W., Sinke, R. J., van der Velde, K. J., de Vries, L. S., Frederix, G. W.J., Oegema, R., Clinical Genetics, Pediatric Surgery, Radiology & Nuclear Medicine, Internal Medicine, Department of Finance, Cell biology, Cardiothoracic Surgery, Molecular Genetics, Pathology, Erasmus School of Law, and Health Economics (HE)

Abstract

The introduction of rapid exome sequencing (rES) for critically ill neonates admitted to the neonatal intensive care unit has made it possible to impact clinical decision-making. Unbiased prospective studies to quantify the impact of rES over routine genetic testing are, however, scarce. We performed a clinical utility study to compare rES to conventional genetic diagnostic workup for critically ill neonates with suspected genetic disorders. In a multicenter prospective parallel cohort study involving five Dutch NICUs, we performed rES in parallel to routine genetic testing for 60 neonates with a suspected genetic disorder and monitored diagnostic yield and the time to diagnosis. To assess the economic impact of rES, healthcare resource use was collected for all neonates. rES detected more conclusive genetic diagnoses than routine genetic testing (20% vs. 10%, respectively), in a significantly shorter time to diagnosis (15 days (95% CI 10–20) vs. 59 days (95% CI 23–98, p < 0.001)). Moreover, rES reduced genetic diagnostic costs by 1.5% (€85 per neonate). Conclusion: Our findings demonstrate the clinical utility of rES for critically ill neonates based on increased diagnostic yield, shorter time to diagnosis, and net healthcare savings. Our observations warrant the widespread implementation of rES as first-tier genetic test in critically ill neonates with disorders of suspected genetic origin.What is Known:• Rapid exome sequencing (rES) enables diagnosing rare genetic disorders in a fast and reliable manner, but retrospective studies with neonates admitted to the neonatal intensive care unit (NICU) indicated that genetic disorders are likely underdiagnosed as rES is not routinely used.• Scenario modeling for implementation of rES for neonates with presumed genetic disorders indicated an expected increase in costs associated with genetic testing.What is New:• This unique prospective national clinical utility study of rES in a NICU setting shows that rES obtained more and faster diagnoses than conventional genetic tests.• Implementation of rES as replacement for all other genetic tests does not increase healthcare costs but in fact leads to a reduction in healthcare costs.

Published
2023

13. Noninvasive Prenatal Test Results Indicative of Maternal Malignancies: A Nationwide Genetic and Clinical Follow-Up Study

Author

Heesterbeek, C.J., Aukema, S.M., Galjaard, R.J.H., Boon, E.M.J., Srebniak, M.I., Bouman, K., Faas, B.H.W., Govaerts, L.C.P., Hoffer, M.J.V., Hollander, N.S. den, Lichtenbelt, K.D., Maarle, M.C. van, Schuurman, L.V., Rij, M.C. van, Schuring-Blom, G.H., Stevens, S.J.C., Tan-Sindhunata, G., Esteki, M.Z., Die-Smulders, C.E.M. de, Tjan-Heijnen, V.C.G., Henneman, L., Sistermans, E.A., Macville, M.V.E., Dutch NIPT Consortium, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Interne Geneeskunde, MUMC+: DA KG AIOS (9), MUMC+: DA KG Lab Specialisten (9), Klinische Genetica, MUMC+: DA KG Lab Centraal Lab (9), RS: GROW - R4 - Reproductive and Perinatal Medicine, Genetica & Celbiologie, MUMC+: DA KG Polikliniek (9), MUMC+: MA Medische Oncologie (9), Human genetics, Amsterdam Reproduction & Development (AR&D), Pathology, APH - Quality of Care, Clinical Genetics, and Public Health

Subjects
Chromosome Aberrations, Cancer Research, Other Research Radboud Institute for Health Sciences [Radboudumc 0], Aneuploidy, All institutes and research themes of the Radboud University Medical Center, Oncology, SDG 3 - Good Health and Well-being, Pregnancy, Neoplasms, Prenatal Diagnosis, Humans, Female, Follow-Up Studies, Retrospective Studies
Abstract

PURPOSE: Noninvasive prenatal testing (NIPT) for fetal aneuploidy screening using cell-free DNA derived from maternal plasma can incidentally raise suspicion for cancer. Diagnostic routing after malignancy suspicious–NIPT faces many challenges. Here, we detail malignancy suspicious–NIPT cases, and describe the clinical characteristics, chromosomal aberrations, and diagnostic routing of the patients with a confirmed malignancy. Clinical lessons can be learned from our experience. METHODS: Patients with NIPT results indicative of a malignancy referred for tumor screening between April 2017 and April 2020 were retrospectively included from a Dutch nationwide NIPT implementation study, TRIDENT-2. NIPT profiles from patients with confirmed malignancies were reviewed, and the pattern of chromosomal aberrations related to tumor type was analyzed. We evaluated the diagnostic contribution of clinical and genetic examinations. RESULTS: Malignancy suspicious–NIPT results were reported in 0.03% after genome-wide NIPT, and malignancies confirmed in 16 patients (16/48, 33.3%). Multiple chromosomal aberrations were seen in 23 of 48 patients with genome-wide NIPT, and a malignancy was confirmed in 16 patients (16/23, 69.6%). After targeted NIPT, 0.005% malignancy suspicious–NIPT results were reported, in 2/3 patients a malignancy was confirmed. Different tumor types and stages were diagnosed, predominantly hematologic malignancies (12/18). NIPT data showed recurrent gains and losses in primary mediastinal B-cell lymphomas and classic Hodgkin lymphomas. Magnetic resonance imaging and computed tomography were most informative in diagnosing the malignancy. CONCLUSION: In 231,896 pregnant women, a low percentage (0.02%) of NIPT results were assessed as indicative of a maternal malignancy. However, when multiple chromosomal aberrations were found, the risk of a confirmed malignancy was considerably high. Referral for extensive oncologic examination is recommended, and may be guided by tumor-specific hallmarks in the NIPT profile.

Published
2022

14. Prenatale screening: verleden, heden, toekomst

Author

Gitsels-van der Wal, JT, Henneman, L, Sistermans, EA, Haak, MC, Martin, L., Midwifery Science, Human genetics, Amsterdam Reproduction & Development (AR&D), and APH - Quality of Care

Published
2022

15. Prenatale screening op cytomegalovirus: tijd voor herevaluatie?

Author

Reuss, A., Meij, K.R.M. van der, Vossen, A.C.T.M., Leeuwen, E. van, Henneman, L., Sistermans, E.A., Cornel, M.C, Faas, B.H.W., Reuss, A., Meij, K.R.M. van der, Vossen, A.C.T.M., Leeuwen, E. van, Henneman, L., Sistermans, E.A., Cornel, M.C, and Faas, B.H.W.

Abstract

Item does not contain fulltext

Published
2022

16. Clinical impact of additional findings detected by genome-wide non-invasive prenatal testing: Follow-up results of the TRIDENT-2 study

Author

Prooyen Schuurman, L. van, Sistermans, E.A., Opstal, D. Van, Henneman, L., Bekker, M.N., Bax, C.J., Pieters, M.J., Bouman, Katelijne, Munnik, S.A. de, Hollander, N.S. den, Diderich, K.E.M., Faas, B.H.W., Feenstra, I., Go, A., Hoffer, M.J.V., Joosten, Marieke, Komdeur, F.L., Lichtenbelt, K.D., Lombardi, M.P., Polak, M.G., Jehee, F.S., Schuring-Blom, H., Stevens, S.J.C., Srebniak, M.I., Suijkerbuijk, R.F., Tan-Sindhunata, G.M., Meij, K.R.M. van der, Maarle, M.C. van, Vernimmen, V., Zelderen-Bhola, S.L. van, Ravesteyn, N.T. van, Knapen, M., Macville, M.V.E., Galjaard, R.H., Prooyen Schuurman, L. van, Sistermans, E.A., Opstal, D. Van, Henneman, L., Bekker, M.N., Bax, C.J., Pieters, M.J., Bouman, Katelijne, Munnik, S.A. de, Hollander, N.S. den, Diderich, K.E.M., Faas, B.H.W., Feenstra, I., Go, A., Hoffer, M.J.V., Joosten, Marieke, Komdeur, F.L., Lichtenbelt, K.D., Lombardi, M.P., Polak, M.G., Jehee, F.S., Schuring-Blom, H., Stevens, S.J.C., Srebniak, M.I., Suijkerbuijk, R.F., Tan-Sindhunata, G.M., Meij, K.R.M. van der, Maarle, M.C. van, Vernimmen, V., Zelderen-Bhola, S.L. van, Ravesteyn, N.T. van, Knapen, M., Macville, M.V.E., and Galjaard, R.H.

Abstract

Item does not contain fulltext, In the TRIDENT-2 study, all pregnant women in the Netherlands are offered genome-wide non-invasive prenatal testing (GW-NIPT) with a choice of receiving either full screening or screening solely for common trisomies. Previous data showed that GW-NIPT can reliably detect common trisomies in the general obstetric population and that this test can also detect other chromosomal abnormalities (additional findings). However, evidence regarding the clinical impact of screening for additional findings is lacking. Therefore, we present follow-up results of the TRIDENT-2 study to determine this clinical impact based on the laboratory and perinatal outcomes of cases with additional findings. Between April 2017 and April 2019, additional findings were detected in 402/110,739 pregnancies (0.36%). For 358 cases, the origin was proven to be either fetal (n = 79; 22.1%), (assumed) confined placental mosaicism (CPM) (n = 189; 52.8%), or maternal (n = 90; 25.1%). For the remaining 44 (10.9%), the origin of the aberration could not be determined. Most fetal chromosomal aberrations were pathogenic and associated with severe clinical phenotypes (61/79; 77.2%). For CPM cases, occurrence of pre-eclampsia (8.5% [16/189] vs 0.5% [754/159,924]; RR 18.5), and birth weight <2.3rd percentile (13.6% [24/177] vs 2.5% [3,892/155,491]; RR 5.5) were significantly increased compared to the general obstetric population. Of the 90 maternal findings, 12 (13.3%) were malignancies and 32 (35.6%) (mosaic) pathogenic copy number variants, mostly associated with mild or no clinical phenotypes. Data from this large cohort study provide crucial information for deciding if and how to implement GW-NIPT in screening programs. Additionally, these data can inform the challenging interpretation, counseling, and follow-up of additional findings.

Published
2022

18. Prenatale screening op cytomegalovirus: tijd voor herevaluatie?

Author

Reuss, A, van der Meij, KRM, Vossen, A C T M, van Leeuwen, E, Henneman, L, Sistermans, EA, Cornel, MC, Faas, Brigitte H.W., Human genetics, Amsterdam Reproduction & Development (AR&D), APH - Quality of Care, and APH - Personalized Medicine

Subjects
Other Research Radboud Institute for Health Sciences [Radboudumc 0]
Abstract

Item does not contain fulltext

Published
2022

19. Factsheet hielprik PANDA studie:De hielprik nu en in de toekomst

Author

Kater-Kuipers, A, van Dijk, T, Wins, Sophie, van der Pal, Sylvia M., and Henneman, L

Abstract

Met de hielprik wordt het bloed onderzocht op een aantal ziektes. Dit zijn ziektes die niet veel baby’s hebben, maar die wel ernstig zijn. Als deze ziektes tijdig worden ontdekt, kan de behandeling snel starten. De gevolgen van de ziekte zijn dan minder erg. De ZonMw PANDA-studie heeft onderzocht wat ouders en professionals van de huidige hielprik en de uitbreiding vinden. De resultaten worden in deze Factsheet samengevat.Project samen met RIVM en patiëntenorganisaties: Vereniging Volwassenen, Kinderen en Stofwisselingsziekten (VKS), Stichting Kind en Ziekenhuis en VSOP patiëntenkoepel voor zeldzame en genetische aandoeningen.

Published
2021

20. Factsheet hielprik PANDA studie: De hielprik nu en in de toekomst

Author

Kater-Kuipers, A, van Dijk, T, Wins, Sophie, van der Pal, Sylvia M., Henneman, L, Amsterdam Reproduction & Development (AR&D), Human genetics, and APH - Quality of Care

Abstract

Met de hielprik wordt het bloed onderzocht op een aantal ziektes. Dit zijn ziektes die niet veel baby’s hebben, maar die wel ernstig zijn. Als deze ziektes tijdig worden ontdekt, kan de behandeling snel starten. De gevolgen van de ziekte zijn dan minder erg. De ZonMw PANDA-studie heeft onderzocht wat ouders en professionals van de huidige hielprik en de uitbreiding vinden. De resultaten worden in deze Factsheet samengevat. Project samen met RIVM en patiëntenorganisaties: Vereniging Volwassenen, Kinderen en Stofwisselingsziekten (VKS), Stichting Kind en Ziekenhuis en VSOP patiëntenkoepel voor zeldzame en genetische aandoeningen.

Published
2021

26. Medical Costs of Children Admitted to the Neonatal Intensive Care Unit: the Role and Possible Economic Impact of WES in Early Diagnosis

Author

Frederix G, Amstel JPv, Marouane A, Vissers L, de Boode W, Zelst-Stams Wv, Keizer Ro, Keusters W, Henneman L, and Deden A

Subjects
medicine.medical_specialty, Neonatal intensive care unit, business.industry, medicine, Economic impact analysis, Intensive care medicine, business, Medical costs
Abstract

Objective: The objective of this study is to provide an overview of average healthcare costs for patients admitted to the Neonatal Intensive Care Unit (NICU) and to assess possible impact of implementing Whole Exome Sequencing (WES) on these total healthcare costs.Methods: We retrospectively collected postnatal healthcare data of all patients admitted to the level IV NICU at the Radboudumc (October 2013-October 2015) and linked unit costs to these healthcare consumptions. Average healthcare costs were calculated and a distinction between patients was made based on performance of genetic tests and the presence of congenital anomalies (CAs).Results: Overall, €26,627 was spend per patient. Genetic costs accounted for 2.3% of all costs. Healthcare costs were higher for patients with CAs compared to patients without CAs. Patients with genetic diagnostics were also more expensive then patients without genetic diagnostics. When performing trio-WES for all patients instead of current diagnostics, overall healthcare costs will increase with 22.2%. In case only patients with CAs receive trio-WES, average per patient healthcare costs will increase with 5.3%. Performing trio-WES only for patients with multiple CAs did not result in any cost changes.Conclusions: Genetic diagnostic testing accounted for a small fraction of total costs. By implementing trio-WES as genetic diagnostic test for all patients with CAs there is a limited increase in overall healthcare budget. Not only the diagnostic yield of this cohort will increase, but implementing trio-WES for all patients with CAs may also allow for improved personalized treatments options guided by the diagnoses made.

Published
2021

28. Parents' Perspectives and Societal Acceptance of Implementation of Newborn Screening for SCID in the Netherlands

Author

Blom, M, Bredius, R.G., Jansen, M.E., Weijman, G., Kemper, E.A., Vermont, C.L., Hollink, I., Dik, W.A., Montfrans, J.M., Gijn, M.E. van, Henriet, S.S., Aerde, K.J. van, Koole, W., Lankester, A.C., Dekkers, E., Schielen, P., Vries, M.C. de, Henneman, L., Burg, M. van der, Blom, M, Bredius, R.G., Jansen, M.E., Weijman, G., Kemper, E.A., Vermont, C.L., Hollink, I., Dik, W.A., Montfrans, J.M., Gijn, M.E. van, Henriet, S.S., Aerde, K.J. van, Koole, W., Lankester, A.C., Dekkers, E., Schielen, P., Vries, M.C. de, Henneman, L., and Burg, M. van der

Abstract

Contains fulltext : 231539.pdf (Publisher’s version ) (Open Access), PURPOSE: While neonatal bloodspot screening (NBS) for severe combined immunodeficiency (SCID) has been introduced more than a decade ago, implementation in NBS programs remains challenging in many countries. Even if high-quality test methods and follow-up care are available, public uptake and parental acceptance are not guaranteed. The aim of this study was to describe the parental perspective on NBS for SCID in the context of an implementation pilot. Psychosocial aspects have never been studied before for NBS for SCID and are important for societal acceptance, a major criterion when introducing new disorders in NBS programs. METHODS: To evaluate the perspective of parents, interviews were conducted with parents of newborns with abnormal SCID screening results (N = 17). In addition, questionnaires about NBS for SCID were sent to 2000 parents of healthy newborns who either participated or declined participation in the SONNET-study that screened 140,593 newborns for SCID. RESULTS: Support for NBS for SCID was expressed by the majority of parents in questionnaires from both a public health perspective and a personal perspective. Parents emphasized the emotional impact of an abnormal screening result in interviews. (Long-term) stress and anxiety can be experienced during and after referral indicating the importance of uniform follow-up protocols and adequate information provision. CONCLUSION: The perspective of parents has led to several recommendations for NBS programs that are considering screening for SCID or other disorders. A close partnership of NBS programs' stakeholders, immunologists, geneticists, and pediatricians-immunologists in different countries is required for moving towards universal SCID screening for all infants.

Published
2021

37. TRIDENT-2: National Implementation of Genome-Wide Non-Invasive Prenatal Testing as a First-Tier Screening Test in the Netherlands

Author

Meij, K.R.M. van der, Sistermans, E.A., Macville, M.V.E., Stevens, S.J.C., Bax, C.J., Bekker, M.N., Bilardo, C.M., Boon, E.M.J., Boter, M., Diderich, K.E.M., Die-Smulders, C.E.M. de, Duin, L.K., Faas, B.H.W., Feenstra, I., Haak, M.C., Hoffer, M.J.V., Hollander, N.S. den, Hollink, I.H.I.M., Jehee, F.S., Knapen, M.F.C.M., Kooper, A.J.A., Langen, I.M. van, Lichtenbelt, K.D., Linskens, I.H., Maarle, M.C. van, Oepkes, D., Pieters, M.J., Schuring-Blom, G.H., Sikkel, E., Sikkema-Raddatz, B., Smeets, D.F.C.M., Srebniak, M.I., Suijkerbuijk, R.F., Tan-Sindhunata, G.M., Ven, A.J.E.M. van der, Zelderen-Bhola, S.L. van, Henneman, L., Galjaard, R.J.H., Opstal, D. van, Weiss, M.M., Dutch NIPT Consortium, Health Psychology Research (HPR), Reproductive Origins of Adult Health and Disease (ROAHD), Obstetrics and Gynaecology, Human Genetics, Clinical Genetics, MUMC+: DA KG Lab Centraal Lab (9), RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Polikliniek (9), Klinische Genetica, Obstetrie & Gynaecologie, MUMC+: MA Medische Staf Obstetrie Gynaecologie (9), Human genetics, Amsterdam Reproduction & Development (AR&D), Amsterdam Neuroscience - Complex Trait Genetics, Obstetrics and gynaecology, and APH - Quality of Care

Subjects
0301 basic medicine, Trisomy 13 Syndrome, IMPACT, 030105 genetics & heredity, genome-wide, 0302 clinical medicine, Pregnancy, Prenatal Diagnosis/methods, Prenatal Diagnosis, Down Syndrome/diagnosis, Genetics(clinical), DOWN-SYNDROME, Young adult, cfDNA, First, Genetics (clinical), Netherlands, Trisomy 13 Syndrome/diagnosis, Genome, 030219 obstetrics & reproductive medicine, Obstetrics, implementation study, Middle Aged, Prognosis, fetal trisomy, common trisomies, Parental anxiety, CELL-FREE DNA, Christian ministry, Female, Pregnancy Trimester, HEALTH, Genetic Testing/methods, PREGNANT-WOMEN, Human, rare autosomal trisomies, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], Adult, medicine.medical_specialty, Screening test, Adolescent, first tier test, Netherlands/epidemiology, Prenatal care, ORGANIZATION, Article, 03 medical and health sciences, Young Adult, All institutes and research themes of the Radboud University Medical Center, medicine, Genetics, Journal Article, Humans, Genetic Testing, Trisomy 18 Syndrome/diagnosis, Chromosome Aberrations, business.industry, Genome, Human, Non invasive, Other Research Radboud Institute for Health Sciences [Radboudumc 0], Health Plan Implementation, medicine.disease, NIPS, Pregnancy Trimester, First, prenatal screening, EXPERIENCE, Down Syndrome, Trisomy, business, NIPT, Trisomy 18 Syndrome, Follow-Up Studies
Abstract

The Netherlands launched a nationwide implementation study on non-invasive prenatal testing (NIPT) as a first-tier test offered to all pregnant women. This started on April 1, 2017 as the TRIDENT-2 study, licensed by the Dutch Ministry of Health. In the first year, NIPT was performed in 73,239 pregnancies (42% of all pregnancies), 7,239 (4%) chose first-trimester combined testing, and 54% did not participate. The number of trisomies 21 (239, 0.33%), 18 (49, 0.07%), and 13 (55, 0.08%) found in this study is comparable to earlier studies, but the Positive Predictive Values (PPV)—96% for trisomy 21, 98% for trisomy 18, and 53% for trisomy 13—were higher than expected. Findings other than trisomy 21, 18, or 13 were reported on request of the pregnant women; 78% of women chose to have these reported. The number of additional findings was 207 (0.36%); these included other trisomies (101, 0.18%, PPV 6%, many of the remaining 94% of cases are likely confined placental mosaics and possibly clinically significant), structural chromosomal aberrations (95, 0.16%, PPV 32%,) and complex abnormal profiles indicative of maternal malignancies (11, 0.02%, PPV 64%). The implementation of genome-wide NIPT is under debate because the benefits of detecting other fetal chromosomal aberrations must be balanced against the risks of discordant positives, parental anxiety, and a potential increase in (invasive) diagnostic procedures. Our first-year data, including clinical data and laboratory follow-up data, will fuel this debate. Furthermore, we describe how NIPT can successfully be embedded into a national screening program with a single chain for prenatal care including counseling, testing, and follow-up.

Published
2019

38. Origin and clinical relevance of chromosomal aberrations other than the common trisomies detected by genome-wide NIPS: results of the TRIDENT study

Author

Opstal, D. van, Maarle, M.C. van, Lichtenbelt, K., Weiss, M.M., Schuring-Blom, H., Bhola, S.L., Hoffer, M.J.V., Huijsdens-van Amsterdam, K., Macville, M.V., Kooper, A.J.A., Faas, B.H.W., Govaerts, L., Tan-Sindhunata, G.M., Hollander, N. den, Feenstra, I., Galjaard, R.J.H., Oepkes, D., Ghesquiere, S., Brouwer, R.W.W., Beulen, L., Bollen, S., Elferink, M.G., Straver, R., Henneman, L., Page-Christiaens, G.C., Sistermans, E.A., Dutch NIPT Consortium, MUMC+: DA KG Lab Centraal Lab (9), RS: FHML non-thematic output, Human Genetics, Human genetics, Amsterdam Reproduction & Development (AR&D), APH - Quality of Care, Amsterdam Neuroscience - Complex Trait Genetics, Clinical Genetics, and Cell biology

Subjects
0301 basic medicine, CVS MOSAICISM, FETAL DNA, Placenta, DUTCH LABORATORIES, MATERNAL MALIGNANCIES, Aneuploidy, noninvasive testing, Chromosome Disorders, Trisomy, genome-wide NIPS, Bioinformatics, 0302 clinical medicine, Pregnancy, Prenatal Diagnosis/methods, Prenatal Diagnosis, TERM PLACENTAE, Original Research Article, Confined placental mosaicism, Genetics (clinical), confined placental mosaicism, 030219 obstetrics & reproductive medicine, ANEUPLOIDIES, Pregnancy Outcome, Genomics, ASSOCIATION, trisomy 21, CONFIRMATION, Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10], Cell-free fetal DNA, CELL-FREE DNA, Female, Genetic Testing/methods, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], medicine.medical_specialty, DNA Copy Number Variations, Prenatal diagnosis, Chromosome aberration, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, medicine, Placenta/metabolism, Humans, Genetic Testing, PRENATAL-DIAGNOSIS, Gynecology, Chromosome Aberrations, Autosome, Whole Genome Sequencing, business.industry, ANEUPLOIDY, Chromosome Disorders/diagnosis, Other Research Radboud Institute for Health Sciences [Radboudumc 0], Chromosome, medicine.disease, Genomics/methods, 030104 developmental biology, prenatal screening, business, FOLLOW-UP
Abstract

PurposeNoninvasive prenatal screening (NIPS) using cell-free DNA in maternal blood is highly sensitive for detecting fetal trisomies 21, 18, and 13. Using a genome-wide approach, other chromosome anomalies can also be detected. We report on the origin, frequency, and clinical significance of these other chromosome aberrations found in pregnancies at risk for trisomy 21, 18, or 13.MethodsWhole-genome shallow massively parallel sequencing was used and all autosomes were analyzed.ResultsIn 78 of 2,527 cases (3.1%) NIPS was indicative of trisomy 21, 18, or 13, and in 41 (1.6%) of other chromosome aberrations. The latter were of fetal (n = 10), placental (n = 22), maternal (n = 1) or unknown (n = 7). One case lacked cytogenetic follow-up. Nine of the 10 fetal cases were associated with an abnormal phenotype. Thirteen of the 22 (59%) placental aberrations were associated with fetal congenital anomalies and/or poor fetal growth (

Published
2018

45. Women’s Experience with Non-Invasive Prenatal Testing and Emotional Well-being and Satisfaction after Test-Results

Author

Schendel, R.V. van, Page-Christiaens, G.C.M.L., Beulen, L., Bilardo, C.M., Boer, M.A. de, Coumans, A.B.C., Faas, B.H.W., Langen, I.M. van, Lichtenbelt, K.D., Maarle, M.C. van, Macville, M.V.E., Oepkes, D., Pajkrt, E., Henneman, L., Dutch NIPT Consortium, Human genetics, Obstetrics and gynaecology, APH - Quality of Care, APH - Personalized Medicine, Amsterdam Reproduction & Development (AR&D), Other departments, Human Genetics, ARD - Amsterdam Reproduction and Development, Obstetrics and Gynaecology, Reproductive Origins of Adult Health and Disease (ROAHD), Health Psychology Research (HPR), MUMC+: MA Medische Staf Obstetrie Gynaecologie (9), RS: GROW - R4 - Reproductive and Perinatal Medicine, Obstetrie & Gynaecologie, and MUMC+: DA KG Lab Centraal Lab (9)

Subjects
DUTCH LABORATORIES, Satisfaction, Personal Satisfaction, Anxiety, 0302 clinical medicine, Pregnancy, Prenatal Diagnosis, Surveys and Questionnaires, Medicine, Genetics(clinical), 030212 general & internal medicine, Genetics (clinical), Original Research, Reassurance, media_common, 030219 obstetrics & reproductive medicine, Obstetrics, 3. Good health, Emotional well-being, Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10], Feeling, Female, TRIAL, Prenatal Screening, medicine.symptom, MATERNAL ANXIETY, PREGNANT-WOMEN, Adult, medicine.medical_specialty, Genetic counseling, media_common.quotation_subject, Health literacy, 03 medical and health sciences, AGE, Humans, Medical history, ATTITUDES, Gynecology, ANEUPLOIDY, business.industry, Public health, Other Research Radboud Institute for Health Sciences [Radboudumc 0], Patient Acceptance of Health Care, medicine.disease, Health Literacy, Pregnancy Trimester, First, PERSPECTIVES, Down Syndrome, business, Trisomy, NIPT, Non-invasive Prenatal Testing
Abstract

Increasingly, high-risk pregnant women opt for non-invasive prenatal testing (NIPT) instead of invasive diagnostic testing. Since NIPT is less accurate than invasive testing, a normal NIPT result might leave women less reassured. A questionnaire study was performed among pregnant women with elevated risk for fetal aneuploidy based on first-trimester combined test (risk ≥1:200) or medical history, who were offered NIPT in the nationwide Dutch TRIDENT study. Pre- and post-test questionnaires (n = 682) included measures on: experiences with NIPT procedure, feelings of reassurance, anxiety (State-Trait Anxiety Inventory, STAI), child-related anxiety (PRAQ-R), and satisfaction. The majority (96.1%) were glad to have been offered NIPT. Most (68.5%) perceived the waiting time for NIPT results (mean: 15 days, range 5–32) as (much) too long. Most women with a normal NIPT result felt reassured (80.9%) or somewhat reassured (15.7%). Levels of anxiety and child-related anxiety were significantly lower after receiving a normal NIPT result as compared to the moment of intake (p

Published
2017

46. National implementation of genome- wide non-invasive prenatal testing as a first-tier screening test in the Netherlands: evaluation of women's perspectives

Author

van der Meij, K. R. M., Bekker, M. N., Gitsels-van der Wal, J. T., Martin, L., van Vliet-Lachotzki, E. H., Timmermans, D. R. M., Galjaard, R. H., Sistermans, E. A., Henneman, L., Human genetics, Amsterdam Reproduction & Development (AR&D), Urology, Midwifery Science, Public and occupational health, APH - Quality of Care, Amsterdam Neuroscience - Complex Trait Genetics, and APH - Personalized Medicine

Published
2019

50. Informing relatives at risk of inherited cardiac conditions: experiences and attitudes of healthcare professionals and counselees.

Author

Heuvel, L.M. van den, Huisinga, M.J., Hoedemaekers, Y.M., Baas, A.F., Plantinga, M., Henneman, L., Tintelen, J.P. van, Smets, E.M.A., Christiaans, I., Heuvel, L.M. van den, Huisinga, M.J., Hoedemaekers, Y.M., Baas, A.F., Plantinga, M., Henneman, L., Tintelen, J.P. van, Smets, E.M.A., and Christiaans, I.

Abstract

Item does not contain fulltext

Published
2019

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