Nationwide, couple-based genetic carrier screening

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; Mackenzie’s Mission Investigators

doi:10.1056/NEJMoa2314768

Nationwide, couple-based genetic carrier screening

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-ParabiaBianca 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, Mackenzie’s Mission Investigators

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

BACKGROUND: Genomic 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.

METHODS: We 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.

RESULTS: Among 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.

CONCLUSIONS: Couple-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.).

Original language	English
Pages (from-to)	1877-1889
Number of pages	13
Journal	New England Journal of Medicine
Volume	391
Issue number	20
DOIs	https://doi.org/10.1056/NEJMoa2314768
Publication status	Published - 21 Nov 2024

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10.1056/NEJMoa2314768

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Kirk, E. P., Delatycki, M. B., Archibald, A. D., Tutty, E., Caruana, J., Halliday, J. L., Lewis, S., McClaren, B. J., Newson, A. J., Dive, L., Best, S., Long, J. C., Braithwaite, J., Downes, M. J., Scuffham, P. A., Massie, J., Barlow-Stewart, K., Kulkarni, A., Ruscigno, A., ... Mackenzie’s Mission Investigators (2024). Nationwide, couple-based genetic carrier screening. New England Journal of Medicine, 391(20), 1877-1889. https://doi.org/10.1056/NEJMoa2314768

@article{2b2fa81ba7f645e7aebafa3cdc26f977,

title = "Nationwide, couple-based genetic carrier screening",

abstract = "BACKGROUND: Genomic 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.METHODS: We 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.RESULTS: Among 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.CONCLUSIONS: Couple-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.).",

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

year = "2024",

month = nov,

day = "21",

doi = "10.1056/NEJMoa2314768",

language = "English",

volume = "391",

pages = "1877--1889",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachussetts Medical Society",

number = "20",

}

Kirk, EP, Delatycki, MB, Archibald, AD, Tutty, E, Caruana, J, Halliday, JL, Lewis, S, McClaren, BJ, Newson, AJ, Dive, L, Best, S , Long, JC , Braithwaite, J, Downes, MJ, Scuffham, PA, Massie, J, Barlow-Stewart, K, Kulkarni, A, Ruscigno, A, Kanga-Parabia, A, Rodrigues, B, Bennetts, BH, Ebzery, C, Hunt, C, Cliffe, CC, Lee, C, Azmanov, D, King, EA, Madelli, EO, Zhang, F, Ho, G, Danos, I, Liebelt, J, Fletcher, J, Kennedy, J, Beilby, J, Emery, JD, McGaughran, J, Marum, JE, Scarff, K, Fisk, K, Harrison, K, Boggs, K, Giameos, L, Fitzgerald, L, Thomas, L, Burnett, L, Freeman, L, Harris, M, Berbic, M, Davis, MR, Cifuentes Ochoa, M, Wallis, M, Wall, M, Chow, MTM, Ferrie, MM, Pachter, N, Quayum, N, Lang, N, Kasi Pandy, P, Casella, R, Allcock, RJN, Ong, R, Edwards, S, Sundercombe, S, Jelenich, S, Righetti, S, Lunke, S, Kaur, S, Stock-Myer, S, Eggers, S, Walker, SP, Theodorou, T, Catchpool, T, Clinch, T, Roscioli, T, Hardy, T, Zhu, Y, Fehlberg, Z, Boughtwood, TF, Laing, NG & Mackenzie’s Mission Investigators 2024, 'Nationwide, couple-based genetic carrier screening', New England Journal of Medicine, vol. 391, no. 20, pp. 1877-1889. https://doi.org/10.1056/NEJMoa2314768

TY - JOUR

T1 - Nationwide, couple-based genetic carrier screening

AU - Kirk, Edwin P.

AU - Delatycki, Martin B.

AU - Archibald, Alison D.

AU - Tutty, Erin

AU - Caruana, Jade

AU - Halliday, Jane L.

AU - Lewis, Sharon

AU - McClaren, Belinda J.

AU - Newson, Ainsley J.

AU - Dive, Lisa

AU - Best, Stephanie

AU - Long, Janet C.

AU - Braithwaite, Jeffrey

AU - Downes, Martin J.

AU - Scuffham, Paul A.

AU - Massie, John

AU - Barlow-Stewart, Kristine

AU - Kulkarni, Abhi

AU - Ruscigno, Amy

AU - Kanga-Parabia, Anaita

AU - Rodrigues, Bianca

AU - Bennetts, Bruce H.

AU - Ebzery, Camron

AU - Hunt, Clare

AU - Cliffe, Corrina C.

AU - Lee, Crystle

AU - Azmanov, Dimitar

AU - King, Emily A.

AU - Madelli, Evanthia O.

AU - Zhang, Futao

AU - Ho, Gladys

AU - Danos, Isabelle

AU - Liebelt, Jan

AU - Fletcher, Janice

AU - Kennedy, Jillian

AU - Beilby, John

AU - Emery, Jon D.

AU - McGaughran, Julie

AU - Marum, Justine E.

AU - Scarff, Katrina

AU - Fisk, Katrina

AU - Harrison, Katrina

AU - Boggs, Kirsten

AU - Giameos, Lana

AU - Fitzgerald, Lara

AU - Thomas, Lauren

AU - Burnett, Leslie

AU - Freeman, Lucinda

AU - Harris, Madeleine

AU - Berbic, Marina

AU - Davis, Mark R.

AU - Cifuentes Ochoa, Marta

AU - Wallis, Mathew

AU - Wall, Meaghan

AU - Chow, Melissa T. M.

AU - Ferrie, Monica M.

AU - Pachter, Nicholas

AU - Quayum, Nila

AU - Lang, Nitzan

AU - Kasi Pandy, Praveena

AU - Casella, Rachael

AU - Allcock, Richard J. N.

AU - Ong, Royston

AU - Edwards, Samantha

AU - Sundercombe, Samantha

AU - Jelenich, Sarah

AU - Righetti, Sarah

AU - Lunke, Sebastian

AU - Kaur, Sharanbeer

AU - Stock-Myer, Sharyn

AU - Eggers, Stefanie

AU - Walker, Susan P.

AU - Theodorou, Tahlia

AU - Catchpool, Tara

AU - Clinch, Tenielle

AU - Roscioli, Tony

AU - Hardy, Tristan

AU - Zhu, Ying

AU - Fehlberg, Zoe

AU - Boughtwood, Tiffany F.

AU - Laing, Nigel G.

AU - Mackenzie’s Mission Investigators

PY - 2024/11/21

Y1 - 2024/11/21

N2 - BACKGROUND: Genomic 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.METHODS: We 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.RESULTS: Among 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.CONCLUSIONS: Couple-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.).

AB - BACKGROUND: Genomic 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.METHODS: We 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.RESULTS: Among 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.CONCLUSIONS: Couple-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.).

UR - http://www.scopus.com/inward/record.url?scp=85210340620&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa2314768

DO - 10.1056/NEJMoa2314768

M3 - Article

C2 - 39565987

SN - 0028-4793

VL - 391

SP - 1877

EP - 1889

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 20

ER -

Nationwide, couple-based genetic carrier screening

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