Nationwide, Couple-Based Genetic Carrier Screening
Authors: Edwin P Kirk, Martin B Delatycki, Alison D Archibald, Erin Tutty, Jade Caruana, Jane L Halliday, Sharon Lewis, Belinda J McClaren, Ainsley J Newson, Lisa Dive, Stephanie Best, Janet C Long, Jeffrey Braithwaite, Martin J Downes, Paul A Scuffham, John Massie, Kristine Barlow-Stewart, Abhi Kulkarni, Amy Ruscigno, Anaita Kanga-Parabia, Bianca Rodrigues, Bruce H Bennetts, Camron Ebzery, Clare Hunt, Corrina C Cliffe, Crystle Lee, Dimitar Azmanov, Emily A King, Evanthia O Madelli, Futao Zhang, Gladys Ho, Isabelle Danos, Jan Liebelt, Janice Fletcher, Jillian Kennedy, John Beilby, Jon D Emery, Julie McGaughran, Justine E Marum, Katrina Scarff, Katrina Fisk, Katrina Harrison, Kirsten Boggs, Lana Giameos, Lara Fitzgerald, Lauren Thomas, Leslie Burnett, Lucinda Freeman, Madeleine Harris, Marina Berbic, Mark R Davis, Marta Cifuentes Ochoa, Mathew Wallis, Meaghan Wall, Melissa T M Chow, Monica M Ferrie, Nicholas Pachter, Nila Quayum, Nitzan Lang, Praveena Kasi Pandy, Rachael Casella, Richard J N Allcock, Royston Ong, Samantha Edwards, Samantha Sundercombe, Sarah Jelenich, Sarah Righetti, Sebastian Lunke, Sharanbeer Kaur, Sharyn Stock-Myer, Stefanie Eggers, Susan P Walker, Tahlia Theodorou, Tara Catchpool, Tenielle Clinch, Tony Roscioli, Tristan Hardy, Ying Zhu, Zoe Fehlberg, Tiffany F Boughtwood, Nigel G Laing
Journal: New England Journal of Medicine (2024)

BackgroundGenomic sequencing technology allows for identification of reproductive couples with an increased chance, as compared with that in the general population, of having a child with an autosomal recessive or X-linked genetic condition.MethodsWe investigated the feasibility, acceptability, and outcomes of a nationwide, couple-based genetic carrier screening program in Australia as part of the Mackenzie's Mission project. Health care providers offered screening to persons before pregnancy or early in pregnancy. The results obtained from testing at least 1281 genes were provided to the reproductive couples. We aimed to ascertain the psychosocial effects on participants, the acceptability of screening to all participants, and the reproductive choices of persons identified as having an increased chance of having a child with a condition for which we screened.ResultsAmong 10,038 reproductive couples enrolled in the study, 9107 (90.7%) completed screening, and 175 (1.9%) were newly identified as having an increased chance of having a child with a genetic condition for which we screened. These conditions involved pathogenic variants in 90 different genes; 74.3% of the conditions were autosomal recessive. Three months after receiving the results, 76.6% of the couples with a newly identified increased chance had used or planned to use reproductive interventions to avoid having an affected child. Those newly identified as having an increased chance had greater anxiety than those with a low chance. The median level of decisional regret was low in all result groups, and 98.9% of participants perceived screening to be acceptable.ConclusionsCouple-based reproductive genetic carrier screening was largely acceptable to participants and was used to inform reproductive decision making. The delivery of screening to a diverse and geographically dispersed population was feasible. (Funded by the Medical Research Future Fund of the Australian government; ClinicalTrials.gov number, NCT04157595.)