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

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

Genomic futures of prenatal screening: ethical reflection

The practice of prenatal screening is undergoing important changes as a result of the introduction of genomic testing technologies at different stages of the screening trajectory. It is expected that eventually it will become possible to routinely obtain a comprehensive genome scan' of all fetuses. Although this will still take several years, there are clear continuities between present developments and this future scenario. As this review shows, behind the still limited scope of screening for common aneuploidies, a rapid widening of the range of conditions tested for is already taking shape at the invasive testing stage. But the continuities are not just technical; they are also ethical. If screening for Down's syndrome is a matter of providing autonomous reproductive choice, then why would providing the choice to have a full fetal genome scan be something entirely different? There is a clear need for a sustainable normative framework that will have to answer three challenges: the indeterminateness of the autonomy paradigm, the need to acknowledge the future child as an interested stakeholder, and the prospect of broad-scope genomic prenatal screening with a double purpose: autonomy and prevention

[Genetic cancer syndromes and reproductive choice: dialogue between parents and politicians on preimplantation genetic diagnosis]

Genetic cancer syndromes have identical clinical severity, limited therapeutic options, reduced life expectancy, and risks of genetic transmission, as do other genetic or congenital diseases for which prenatal genetic diagnosis or preimplantation genetic diagnosis (PGD) is allowed in the Netherlands. That was implied in the certification of one Dutch PGD centre at Maastricht University Hospital by the Dutch Ministry of Health, Welfare and Sport in 2003. A report by the Health Council of the Netherlands in 2006 confirmed this view with scientific and ethical evaluation. However, in 2006 the State Secretary for Health strongly objected to PGD for cancer, and disease risks of 50-100% for gene carriers, i.e. for highly, but not always fully penetrant genes. In 2006, the Maastricht centre discontinued PGD for cancer and couples were referred to other countries; prenatal genetic diagnosis remained available, however. On 26 May 2008, the present State Secretary proposed to parliament that the Health Council of the Netherlands report from 2006 be followed. This once again clashed with the fears of some Christian parties for a slippery slope and embryo selection for 'only a risk and not certainty of disease'. Yet no firm evidence for the existence of such a slope has been found. The Dutch framework for handling the ethical and medical evaluation of new reproductive and genetic technologies by the Health Council of the Netherlands Advisory Committees, professional and patient organisations, and the Ministry, has functioned for over 30 years without leading to any wrongdoing. There is no actual need for a new government body to license genetic tests on a case-by-case or per disease basis

[207-POS]: Termination of pregnancy for hypertensive disorders prior to fetal viability in the Netherlands: A retrospective cohort study in 10 Dutch tertiary care centers

Item does not contain fulltextOBJECTIVES: To ascertain the incidence and demographic data of TOP for hypertensive disorders at the limits of fetal viability. METHODS: We conducted a retrospective cohort study. All terminations for hypertensive disorders between 2000 and 2009 in the ten Dutch tertiary care centers with a gestational age between 22 and 28weeks were included. In all cases the fetus was judged to be non-viable, either because of the low gestational age or because of the effects of the maternal condition on the fetus. There was no intention to intervene for fetal indications. RESULTS: During the study period TOP for hypertensive disorders occurred in 0.8promille (131/163.052) of all deliveries in these 10 centers, of which there were 126 singleton and five twin pregnancies. 94 women were nulliparous and 37 multiparous. The main indication for TOP was HELLP syndrome. General history revealed hypertension in 24 women (18.3%). History was unremarkable in 98 cases (75%). The mean gestational age at admission was 166days+/-9.6days (GA 23+5), and at delivery this was 173days+/-9.7days (GA 24+5weeks). The mean birth weight was 472+/-123g (70%<p10). The overall perinatal mortality was 99.3%. There were no maternal deaths. CONCLUSIONS: In 10 years there we identified 131 cases of TOP for hypertensive disorders prior to fetal viability in The Dutch tertiary care centers. Ninety-eight women (75%) had no preexisting maternal disease. DISCLOSURES: L. van Eerden: None

Trial by Dutch laboratories for evaluation of non-invasive prenatal testing. Part I-clinical impact

Contains fulltext : 171862.pdf (publisher's version ) (Open Access)OBJECTIVE: To evaluate the clinical impact of nationwide implementation of genome-wide non-invasive prenatal testing (NIPT) in pregnancies at increased risk for fetal trisomies 21, 18 and 13 (TRIDENT study). METHOD: Women with elevated risk based on first trimester combined testing (FCT >/= 1:200) or medical history, not advanced maternal age alone, were offered NIPT as contingent screening test, performed by Dutch University Medical laboratories. We analyzed uptake, test performance, redraw/failure rate, turn-around time and pregnancy outcome. RESULTS: Between 1 April and 1 September 2014, 1413/23 232 (6%) women received a high-risk FCT result. Of these, 1211 (85.7%) chose NIPT. One hundred seventy-nine women had NIPT based on medical history. In total, 1386/1390 (99.7%) women received a result, 6 (0.4%) after redraw. Mean turn-around time was 14 days. Follow-up was available in 1376 (99.0%) pregnancies. NIPT correctly predicted 37/38 (97.4%) trisomies 21, 18 or 13 (29/30, 4/4 and 4/4 respectively); 5/1376 (0.4%) cases proved to be false positives: trisomies 21 (n = 2), 18 (n = 1) and 13 (n = 2). Estimated reduction in invasive testing was 62%. CONCLUSION: Introduction of NIPT in the Dutch National healthcare-funded Prenatal Screening Program resulted in high uptake and a vast reduction of invasive testing. Our study supports offering NIPT to pregnant women at increased risk for fetal trisomy. (c) 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd. (c) 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd

Pregnancy outcome after previous termination of pregnancy for preeclampsia

Research into fetal development and medicin

Termination of pregnancy for maternal indications at the limits of fetal viability: a retrospective cohort study in the Dutch tertiary care centres

OBJECTIVE: Maternal morbidity, either pregnancy related or pre-existent, can become life threatening and of such severity as to warrant termination of pregnancy (TOP). In this situation, chances of fetal survival are usually poor, either because of low gestational age and/or because of the fetal effects of the maternal condition. Examples include severe growth restriction in pre-eclampsia and intrauterine infection due to the very early preterm prelabour rupture of membranes. There are very few reports on the prevalence of TOP for maternal indication at the limits of fetal viability. We investigated the prevalence of and indications for TOP on maternal indication in the 10 tertiary care centres in the Netherlands during the past decade. STUDY DESIGN: We conducted a retrospective review of the medical records of all women who underwent TOP for maternal indications between 22 and 27 completed weeks of gestation in all 10 tertiary care centres from 2000 to 2009. RESULTS: During the study period, there were 1 929 470 deliveries; 163 052 (8.4%) of these took place in one of the 10 tertiary care centres and 177 pregnancies were terminated for severe maternal disease, 131 for hypertensive disorders, 29 for intrauterine infection and 17 for other reasons. The mean gestational age at TOP was 171 days (24(3/7))+/-10 days. No maternal deaths were recorded. The overall perinatal mortality was 99.4%. CONCLUSIONS: Over a 10-year period, TOP for maternal indications was performed in 1 in 1000 deliveries in the 10 Dutch tertiary care centres. Hypertensive disorders comprised three-quarters of the cases