Spotlight on Test Utilization: Prenatal Diagnosis in the Genomic Microarray Era

hello my name is Allen lamb and I'm a member of the cytogenetics laboratory here at ARUP laboratories and in the department of pathology at the University of Utah I would like to talk to you about various testing options for prenatal chromosome diagnosis the options include traditional chromosome analysis fish or fluorescence in situ hybridization and genomic microarray analysis based on the general increase in the use of genomic microarray analysis in prenatal cases especially based on the large study by Ron Wapner and colleagues published in the New England Journal of Medicine in December of 2012 the American College of Obstetricians and Gynaecologists and the society for maternal fetal medicine made recommendations for the use of chromosomal microarray analysis in prenatal diagnosis in December of 2013 their recommendations were as follows first in patients with a fetus with one or more major structural abnormalities identified by ultrasound and who are undergoing invasive prenatal diagnosis chromosomal microarray analysis is recommended this replaces the traditional fetal karyotype which may be viewed as a low resolution whole genome analysis two in patients with a structurally normal fetus undergoing invasive prenatal diagnostic testing either traditional chromosome analysis or chromosome microarray analysis may be performed three as most copy number mutations identified by chromosomal microarray analysis are not associated with increasing maternal age the use of microarray analysis for prenatal diagnosis should not be restricted to women aged 35 and older Four in cases of intrauterine fetal demise or stillbirth when further cytogenetic analysis is desired microarray analysis on fetal tissue is recommended this increases the likelihood of obtaining results and improves the detection of causative abnormalities there are several testing options available depending on the specific circumstances of each of your cases some clinicians are choosing to perform prenatal interface fish analysis and if normal reflex to genomic microarray analysis alternatively if fish results are abnormal then the reflex is to traditional chromosome analysis to confirm the abnormality and determine the meditational mechanism that is a free-standing additional chromosome or translocation involving chromosomes 21 or 13 genomic microarray results may be obtained more quickly on uncultured cells both for amniotic fluid and for CVS however to obtain results on uncultured samples depends on the specimen volume and on the quality of the sample if the sample volume of the amniotic fluid or villi is limited then fish may not be performed in culturing of cells may be required to provide sufficient cells for extraction of DNA for the microarray a bloody amniotic fluid cell pellet and we observe this after the lab centrifuges the sample may prevent us from performing fish analysis or microarray analysis on uncultured cells and then this requires culturing of the cells to obtain sufficient material if blood contamination is heavy this can even result in the cells growing more slowly further delaying the turnaround time most laboratories like to perform maternal cell contamination studies we also refer to these as MCC studies on prenatal samples so providing a maternal blood sample for use in comparing genetic markers is important this becomes more critical for amniotic fluid samples with some blood contamination in the need for a quick turnaround time and for samples that have been in culture for two to three weeks as your specific circumstance may vary don't hesitate to contact your cytogenetics laboratory to discuss your needs and options many of the larger laboratories including ours have genetic counselors available to assist you based on the sample and the specific needs for your case for NIPT or cell free DNA screening there is the need for confirmatory testing often there is a desire for a rapid confirmation of the abnormal screening results please consider carefully the best sample for confirmatory studies although CVS is available for testing earlier in the pregnancy confirmation by fish alone is not adequate as this may confirm a false positive case in rare situations culturing and traditional cytogenetic analysis on villus mesenchymal cora cells is more reliable as these cells more closely represent the true fetal genotype genetic microarray analysis on uncultured villi is also an option as is microarray analysis on uncultured Amniocytes Amniocytes in general are more representative of the true fetal genotype in summary I have tried to present various testing options that use fish traditional cytogenetic analysis and genomic microarray analysis these options take in consideration the 2013 recommendations of the ACOG and the Society for MFM as your needs and options may vary for a specific case depending on the gestational age indication for study likelihood of a common trisomy sample volume and sample condition please do not hesitate to call your lab for help in determining your best testing options thank you


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