11:00-11:03 P1-92 Fetal interventions for left atrium decompression, Lucas Otaño, Hospital Italiano de Buenos Aires
11:05-11:08 P1-77 Prenatal diagnosis of corpus callosum anomalies, Annigje Nellie Stam, University Hospitals Leuven
11:10-11:13 P2-50 Knowledge of perinatal palliative care following a fatal fetal anomaly diagnosis, Stacey Power, Cork University Maternity Hospital
11:15-11:18 P1-69 The ultrasound elastography in placenta might predict high risk pregnancies, Tomoya Hasegawa, Tokyo Medical University
11:20-11:23 P1-87 In utero treatment of a large symptomatic rhabdomyoma with sirolimus, Han-Shin Lee, King Edward Memorial Hospital
11:25-11:28 P1-79 The added value of the first-trimester scan in the prenatal detection of isolated severe congenital heart defects, Elvire Verbaarschot, Academic Medical Center
11:30-11:33 P2-41 Development and pilot study of the PRENID-scale: A measure for informed-decision making in first trimester prenatal screening, Iris Bakkeren, Erasmus Medical Center
ISPD aims to build global partnerships in genetics and fetal care. We have global outreach programs to promulgate knowledge in prenatal genetics and fetal care around the world. For example, ISPD courses have been held in Shanghai during the 7th Chinese Congress of Fetal Medicine in May 2017. This year, courses will be held in collaboration with the Taiwan Maternal Fetal Medicine Society in Taipei in October 2018 and with the Asociacion Mexicana de Genetica Humana in Aguascalientes, Mexico, in November 2018.
If you are interested in running an ISPD course closer to home or want to propose other global educational activities for ISPD to consider, please come to the Global Outreach meeting during our 22nd International Conference in Antwerp, Belgium. Everyone is welcome!
The BElgian PREnatal MicroArray consortium: towards relating prenatally detected CNVs, prenatal phenotype and postnatal clinical data.
Joke Muys1, Bettina Blaumeiser2, Yves Jacquemyn3, Koenraad Devriendt4, Sandra Janssens5, Kathelijn Keymolen6, Sonia Rombout7, Jean-Stéphane Gatot8, Julie Desir7, Yves Sznajer9, Marije Meuwissen10, Joris Vermeesch4, Bjorn Menten5, Annelies Fieuw11, Benoit Parmentier12, Saskia Bulk13, Bruno Pichon14, Claude Bandelier9, Erik Fransen15, Kris Van Den Bogaert4, Annelies Dheedene5, Marjan De Rademaeker6, Anne Destree7, Winnie Courtens, Anne Deleener, Nathalie Brison, Olivier Vanakker5, Ann Van Den Bogaert6, Mauricette Jamar, patrizia chiarappa, Damien Lederer12, - The Belgian Microarray Prenatal Consortium (BEMAPRE), Katrien Janssens
1University Hospital Antwerp, Edegem, Belgium, Belgium
2Center for Medical genetics, Universiteit Antwerpen, Antwerp, Belgium
3University Hospital Antwerp, Edegem, Belgium
4Center for Medical genetics, Katholieke Universiteit Leuven, Leuven, Belgium
5Center for Medical genetics, Universiteit Gent, Ghent, Belgium
6Center for Medical genetics, Vrije Universiteit Brussel, Brussels, Belgium
7Center for Medical genetics, IPG, Charleroi Gosselies, Charleroi Gosselies, Belgium
8Center for Medical Genetics, Université de Liège, Belgium, Liège, Belgium
9Center for Medical genetics, Université Catholique de Louvain, Louvain, Belgium
10Center for Medical Genetics, Universiteit Antwerpen, Edegem, Belgium
11Center for Medical Genetics, Vrije Universiteit Brussel, Brussel, Belgium
12Center for Medical Genetics, IPG, Charleroi Gosselies, Gosselies, Belgium
13Center for Medical genetics, Université de Liège, Liège, Belgium
14Center for Medical genetics, Université Libre de Bruxelles, Brussels, Belgium
15University of Antwerp, Edegem, Belgium Center for Medical Genetics, Université Catholique Louvain, Sint Lambrechts Woluwe, Belgium Center for Human Genetics, University Hospital Leuven, Leuven, Belgium Center for Medical Genetics, Université Catholique de Louvain, Brussel, Belgium Belgian Society for Human Genetics (http://www.beshg.be), Edegem, Belgium Center for Medical genetics, Universiteit Antwerpen, Antwerpen, Belgium
Objectives
The uncertainty concerning the significance and clinical implications of some prenatally identified CNVs detected using microarray (CMA) underscores the urgency and importance of the development of an appropriate database relating prenatal genetic and ultrasound findings with postnatal clinical and neurodevelopmental data. The unique BElgian PREnatal MicroArray (BEMAPRE) collection allows us to identify the most frequent pathogenic CNVs, susceptibility CNVs and VOUS in the Belgian prenatal population and to calculate added values for the use of CMA versus karyotyping. Moreover, this database is the basis for longitudinal studies on the developmental effect of CNVs.
Methods
The BEMAPRE consortium is a collaboration of all eight genetic centers in Belgium. We collected data from invasive prenatal procedures performed between May 2013 and July 2016. In this period, 13266 prenatal CMAs were performed in Belgium. For each invasive prenatal procedure, centers provided the indication for the invasive test and the obtained CMA results. Descriptive statistics were used to describe population, patient and CNV characteristics. SPSS 24 was applied to analyze data. Frequency tables describing the association between indication and mutation type were visualized using correspondence analysis.
Results
Invasive prenatal procedures were performed in on average 3.6% of pregnancies per year. There was a gradual decline of 61.3% since 2007. Added values for using CMA versus conventional karyotyping were 1.8% in the general invasive population; 2.7% in cases with an ultrasound anomaly. The 22q11.2 duplication and the 15q11.2 duplication are respectively the most frequently reported and unreported susceptibility CNVs. Correspondence analysis did not detect an association between indication of the test and finding a susceptibility CNV. Up to 22.1% of reported diagnoses would have remained undetected with ‘genome-wide NIPT’ as the first-tier test. Postnatal follow-up is currently ongoing.
Conclusions
Our prenatal strategy is unique, as Belgium is currently the only country with a nationwide uniform approach of prenatal CMA analysis, reporting and communal CNV data storage. Only a limited number of susceptibility CNVs and none of the VOUS are reported. No association between the indication of the test and finding a susceptibility CNV was detected. With the implementation of NIPT, invasive prenatal testing increasingly becomes restricted to pregnancies with ultrasound anomalies and those with a familial genetic disorder. Subchromosomal pathogenic CNVs will be missed.
Improving uptake of perinatal autopsy: Lessons learned from parents and key stakeholders
Celine Lewis1, Megan Riddington2, Melissa Hill3, Zahira Latif4, Monica Lakhanpaul5, Owen Arthurs6, John Hutchinson7, Neil Sebire8, Lyn Chitty9
1North East Thames Regional Genetics Service; Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom
2Genetics and Genomic Medicine, Great Ormond Street Hospital and UCL Institute of Child Health, London, United Kingdom
3NE Thames Regional Genetics Laboratory, Great Ormond Street Hospital NHS Foundation Trust & UCL Great Ormond Street Institute for Child Health, London, London, United Kingdom
4College of Medical and Dental Sciences, Birmingham, United Kingdom
5Faculty of Population Health Sciences, London, United Kingdom
6Department of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom
7Department of Histopathology, London, United Kingdom
8Department of Histopathology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom
9Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health and North-East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK, London, london, United Kingdom
Objectives
Autopsy examination is the single most useful investigation in providing information to parents about why their baby or child died. Nevertheless, uptake rates have declined globally due to dislike of the invasive procedure, poor communication and religious objections. A number of less invasive techniques have been developed in recent years including MRI based imaging techniques with/without laparoscopic examination and organ biopsy. Here we aim to:
1) understand current barriers to parental consent to autopsy,
2) explore parental views towards less invasive autopsy,
3) examine attitudes of Muslim and Jewish communities towards less invasive techniques.
Methods
This was a qualitative study involving thematic analysis of: (1) free-text comments from 856 questionnaires from bereaved parents; (2) interviews with 20 questionnaire responders; (3) interviews with 16 religious and community leaders (6 Muslim, 6 Jewish and 4 from other dominant faiths in the UK as a comparator); and (4) ten focus groups with Muslim (n=60) and Jewish (n=16) parents. Bereaved parents were recruited through seven hospitals in England and four support groups in the UK (Antenatal Results and Choices, Sands, The Lullaby Trust and Child Bereavement UK). Muslim and Jewish parents were recruited through key informants from those communities.
Results
Regarding standard autopsy, for some parents the need for answers outweighed invasiveness concerns, however for others the child having “been through enough” was a barrier to consent. Non-invasive autopsy (NIA) enabled the child to “rest in peace” and put parents “at ease”. Minimally invasive autopsy (MIA) was a “good compromise” as it overcame limitations of NIA but enabled tissues samples to be taken. Muslim and Jewish participants agreed that whilst NIA was religiously permissible, MIA was less acceptable but where required by law was more acceptable than standard autopsy. The need to bury the body swiftly was a key priority.
Conclusions
The majority of parents are undecided about autopsy in the initial period after loss. Availability of less invasive options is likely to have a significant impact on uptake rates and decrease the burden of decision-making for many parents. Clear guidance around timing, communication and support are also likely to have a positive impact. Our research suggests that less invasive autopsy offers a viable alternative to many Muslim and Jewish parents who currently decline. These findings are relevant to healthcare providers involved in offering or conducting fetal, perinatal or paediatric autopsy, especially in countries with significant Muslim and/or Jewish communities.
The potential diagnostic yield of Whole Exome Sequencing in 391 pregnancies complicated by fetal ultrasound anomalies and with normal chromosomal microarray results
Kathleen Romijn1, Malgorzata Srebniak1, Marike Polak2, Alice Brooks1, Yolande van Bever1, Grazia Verheijen-Mancini1, Marieke Joosten1, Lutgarde Govaerts1, Joan Kromosoeto1, Maarten F.C.M. Knapen3, Attie Go4, Marjon van Slegtenhorst1, Hennie Bruggenwirth1, Diane Van Opstal4, Lies Hoefsloot1, Robert-Jan Galjaard1, Karin Diderich1
1Department of Clinical Genetics, Erasmus MC, Rotterdam, Netherlands
2Institute of Psychology, Erasmus University Rotterdam, Rotterdam, Netherlands
3Department of Obstetrics and Gynecology, Erasmus MC and Foundation Prenatal Screening Southwest Region of the Netherlands, Rotterdam, Netherlands
4Erasmus Medical Center, Rotterdam, Netherlands
Objectives
The aim of this retrospective cohort study is to determine the potential diagnostic yield of prenatal whole exome sequencing (WES) in fetuses with ultrasound abnormalities and with normal chromosomal microarray results. In cases of fetal abnormalities, it is now standard practice to perform chromosomal microarray, but whole genome testing for single-gene mutations is not yet routinely offered. Possibly, couples who have chosen for prenatal array testing would also choose for prenatal WES to discover the cause of the ultrasound anomaly found in their pregnancy.
Method
In the period January 1st, 2013- January 1st, 2017 845 pregnant women with fetal ultrasound anomalies who received normal microarray results were referred for additional genetic counselling. 391 couples wanted additional molecular testing to be performed. The couples were not selected based on the severity of ultrasound anomalies. Most of the couples received only targeted molecular testing and in only 131 cases WES (large panels or open exome) was performed (after birth). The results of these molecular tests were evaluated retrospectively, regardless of the time of the genetic diagnosis (before or after birth).
Results
In 81 (20.7%) of 391 fetuses molecular testing provided a genetic diagnosis with identification of (likely) pathogenic variants in 58 different candidate genes. In 84% of the abnormal cases (68/81) the variant was clearly pathogenic and would be reported prenatally regardless of the fetal phenotype. In the remaining cases, additional phenotypic data were necessary for the interpretation of the molecular results and clinical geneticists could finally conclude that these findings were (very likely) causal. In one diagnosed case an additional unexpected/incidental finding was detected, which concerned an early onset syndromic disorder.
Conclusions
Our retrospective cohort study shows that WES, if routinely offered to patients in a prenatal setting, would significantly increase the diagnostic yield in fetuses with ultrasound abnormalities. However because not all fetuses were tested with WES and some of the investigations were not yet completed at the time of the study, we presume that this yield of 20.7% could be an underestimation. Concluding, WES if performed prenatally would lead to an early diagnosis of a genetic disorder in a significant percentage of cases irrespective of the (incomplete) fetal phenotype.
A new era in aneuploidy screening for multifetal gestations: Clinical laboratory experience screening >30,000 cell-free DNA samples
Brittany Dyr, Integrated Genetics
Theresa Boomer, Sequenom Laboratories
Eyad Almasri, Sequenom Laboratories
Vanessa Nitibhon, Sequenom Laboratory
Jason Chibuk, Sequenom Inc., Integrated Genetics
Objectives
Traditional serum screening for twins demonstrates lower sensitivity and higher false positive rates, and pseudo aneuploidy risk calculations when compared to performance in singleton gestations.1 Clinical validation studies have established high sensitivity and specificity of cell-free DNA (cfDNA) screening for aneuploidy in singleton and multifetal pregnancy2-4, especially when compared to performance of traditional serum screening. Since introducing cfDNA screening in 2011, Sequenom Laboratories has analyzed over 750,000 clinical samples. More than 30,000 of these samples are from multifetal gestations (including twins, triplets and higher order multiples). The clinical laboratory experience with the first 30,000 multifetal samples will be discussed.
Method
More than 30,000 maternal plasma samples from multifetal gestations were subjected to DNA extraction and library preparation followed by massively parallel sequencing as described by Jensen et al.2 Sequencing data were analyzed to detect autosomal trisomies and other subchromosomal events as described by Zhao et al.3 Fetal fraction requirements were adjusted in proportion to fetal number. Outcome data were collected through provider solicitation.
Results
The predominant indication for testing in this large multifetal cohort was advanced maternal age (>60%). Compared with singletons, in which 6.1% of samples indicated abnormal serum screening, this was the indication for testing in multifetal gestations in 3.5% of samples. The positivity rate in multifetal samples for trisomy 21 was 1.50%, 0.47% for trisomy 18, and 0.21% for trisomy 13. The test had a total non-reportable rate of 5.95%. Average fetal fraction for all samples was 12.2%. Estimated performance based on ad hoc clinical outcome shows that sensitivity and specificity meet or exceed the original performance from clinical validation studies.
Conclusions
In over half a million samples submitted to one clinical laboratory, approximately 4% of samples are from multifetal gestations, which is greater than the rate of multiple births in the US5, suggesting that providers are turning to cfDNA for aneuploidy screening for multifetal gestations. CfDNA screening overcomes some disadvantages of traditional serum screening in multifetal gestations, including providing a result for trisomies 18 or 13 and the availability of screening in higher order multiples. MaterniT®21 PLUS offers patients with multifetal gestations accurate and reliable screening for fetal aneuploidy and has met or exceeded performance from the original clinical validation studies.
Illumina will be hosting a cocktail reception followed by a short discussion, where, Professor Rossa Chiu* from the Chinese University of Hong Kong will present unusual cell-free DNA (cfDNA) results from her practice - challenging you to find the best care path for the patient.
To register or to find out more details about the welcome reception, please click on the “Details and Registration” button above.
* A conflict-of-interest disclosure by Dr. Chiu is available at www.ispdhome.org/Board.
