Webinar Review: Genomics in Perinatal Medicine

The Royal College of Obstetricians and Gynaecologists (RCOG) hosted a free webinar on Genomics in Perinatal Medicine, which was a helpful walk-through of technical and practical aspects of whole exome sequencing in antenatal care, alongside ethical issues and parental perspectives. It functioned both as an introduction to those with little genomics experience, and as an update to those already involved.

The webinar was timely. A new NHS England service, known as 'R21', or whole exome sequencing for fetal anomalies, was introduced in October 2020. A basic understanding of genomics is key to helping patients who are navigating this test and its sequelae. This is not restricted to tertiary fetal medicine units; all patients are offered fetal anomaly screening which may open up the possibility of genomic testing. As emphasised by the chair of the webinar, Eddie Morris, president of the RCOG, genomics is now a part of everyday lives.

The webinar included four speakers with complementary roles. The first speaker, Dr Stephanie Allen, a consultant clinical scientist at Birmingham Women's and Children's Trust, described the scientific background to R21. She explained that three percent of fetuses are found to have anomalies, for which a genetic cause can be sought via invasive testing, with PCR testing uncovering 20-30 percent, microarray testing uncovering a further seven percent and exome sequencing making a substantial advance, uncovering around 35 percent. Dr Allen explained the difference between sequencing the genome (the entire genetic human material), versus the exome (the protein-coding DNA only), which makes up only one percent of the genome but contains 85 percent of disease-causing variants. The whole exome contains around 20-25,000 genes, with the 'R21' panel analysing only 1200 most clinically relevant genes. Dr Allen discussed trio testing, in which fetal information is interpreted alongside parental information, and how this and phenotypic information are combined using software that helps searching for the 'needle in the haystack'. She reported outcomes from the first seven months of the R21 service in England, which involved 120 pregnancies and identified a diagnosis in 40.8 percent of these. While she was humble about this finding, this represents a significant advance in fetal diagnostics.

The second speaker, Mark Kilby, professor of fetal medicine at the University of Birmingham, presented a similar story of the evolution of the test, focusing within the fetal medicine pathway. As one of the architects of the PAGE study, which demonstrated the potential of prenatal exome sequencing, he was able to explain the research development and contextualise it within evolving clinical practice.

The third speaker, Donna Kirwan, genomics midwifery lead for NHS England and NHS Improvement, described fetal medicine units as 'casualty for fetuses'. This surprising and visceral expression reframes fetal medicine, a unique service within obstetrics, and for most patients seen there, an anxiety-filled prospect. She raised interesting points about language. Renaming the terms 'risk', 'mutation' and 'abnormal' as 'chance', 'variant' and 'atypical' may help parents experience less stress when receiving difficult (not 'bad') news and be in a better place to make complex and life-changing decisions. For Kirwan, the genomics test is just one touchpoint in a multi-disciplinary pathway which healthcare professionals help women and families navigate.

The parental perspective was delivered with typical precision and insight by Jane Fisher, the director of the national charity Antenatal Results and Choices (ARC), based on her years of experience not only interacting with parents who contact ARC, but also as a patient advocate. While the other speakers alluded to challenging issues that can be raised by exome testing, Fisher brought some of these to life with vignettes. These issues included intense time pressures around testing before the 24-week gestational threshold in English termination law. She also raised the point that worries do not dissipate with results, quoting a grandmother who remains in contact with ARC several years after the testing of her granddaughter, as she has no other outlet for her worries.

A benefit of webinars over other teaching methods is the ability to respond to audience questions. A selection of insightful questions was answered. For example, why is the exome sequencing service provided in England different to other countries? This was answered with reference to reducing risk of difficult-to-interpret incidental findings but also futureproofing the processing pathway. Another question was about non-invasive approaches to genomics. As Professor Kilby said, this would be the holy grail – information without risk from invasive testing. Sadly, while this is possible for monogenic disorders, the combination of maternal and fetal DNA would make exome interpretation impossible.

The webinar, while hosted by the RCOG, aimed to speak not only to obstetricians but midwives and other maternity professionals, and achieved this, through the selection of speakers and the emphasis they delivered. It was made clear that genomics in perinatal medicine relies on skills of multiple different people, and that the woman and her family must be central to the process. It finished, unsurprisingly, with a call to arms, an emphasis on ongoing training and support for those working in the field, and an invitation to get involved with the work at an organisational level.