Dealing with uncertain results from chromosomal microarray and exome sequencing in the prenatal setting: An international cross‐sectional study with healthcare professionals

Objectives To conduct qualitative interviews with healthcare providers working in different countries to understand their experiences of dealing with uncertain results from prenatal chromosome microarray analysis (CMA) and exome sequencing (ES). Methods Semi‐structured interviews with 31 healthcare providers who report or return prenatal CMA and/or ES results (clinicians, genetic counsellors and clinical scientists) in six countries with differing healthcare systems; Australia (4), Denmark (5), Netherlands (6), Singapore (4), Sweden (6) and United Kingdom (6). The topic guide explored the main sources of uncertainty and their management. Results There was variation in reporting practices both between and across countries for variants of uncertain significance, however, there was broad agreement on reporting practices for incidental findings. There was also variation in who decides what results are reported (clinical scientists or clinicians). Technical limitations and lack of knowledge (to classify variants and of prenatal phenotypes) were significant challenges, as were turnaround times and lack of guidelines. Conclusion Health professionals around the globe are dealing with similar sources of uncertainty, but managing them in different ways, Continued dialogue with international colleagues on ways of managing uncertain results is important to compare and contrast the benefits and limitations of the different approaches. Key points What's already known about this topic? Chromosome microarray analysis and exome sequencing have increased diagnostic yield over karyotyping but have increased the incidence of uncertain results. What does this study add? Our findings highlight variation in reporting practices both between and across countries for variants of uncertain significance, although there is broad agreement on reporting practices for incidental findings. International guidelines may help to standardise how we define and categorise variants, however, global uniformity on the management of uncertain results may not be a realistic or desirable goal.