TY - JOUR
T1 - How to deal with uncertainty in prenatal genomics
T2 - A systematic review of guidelines and policies
AU - Klapwijk, Jasmijn E.
AU - Srebniak, Malgorzata I.
AU - Go, Attie T.J.I.
AU - Govaerts, Lutgarde C.P.
AU - Lewis, Celine
AU - Hammond, Jennifer
AU - Hill, Melissa
AU - Lou, Stina
AU - Vogel, Ida
AU - Ormond, Kelly E.
AU - Diderich, Karin E.M.
AU - Brüggenwirth, Hennie T.
AU - Riedijk, Sam R.
N1 - Funding Information: We would like to thank the biomedical information specialists, Wichor Bramer, Maarten F.M. Engel, Sabrina Gunput, and Elise Krabbendam from the Erasmus Medical Centres' Medical Library for their professional assistance in compiling the search terms, conducting the systematic search and removing the duplicates. This work was supported by a Wellcome Trust Small Grant in Humanities and Social Science [211288/Z/18/Z]. In loving memory of prof. Robert Hofstra. Funding Information: We would like to thank the biomedical information specialists, Wichor Bramer, Maarten F.M. Engel, Sabrina Gunput, and Elise Krabbendam from the Erasmus Medical Centres' Medical Library for their professional assistance in compiling the search terms, conducting the systematic search and removing the duplicates. This work was supported by a Wellcome Trust Small Grant in Humanities and Social Science [211288/Z/18/Z]. In loving memory of prof. Robert Hofstra. Publisher Copyright: © 2021 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.
PY - 2021/12
Y1 - 2021/12
N2 - Exome sequencing (ES) enhanced the diagnostic yield of genetic testing, but has also increased the possibility of uncertain findings. Prenatal ES is increasingly being offered after a fetal abnormality is detected through ultrasound. It is important to know how to handle uncertainty in this particularly stressful period. This systematic review aimed to provide a comprehensive overview of guidelines available for addressing uncertainty related to prenatal chromosomal microarray (CMA) and ES. Ten uncertainty types associated with prenatal ES and CMA were identified and defined by an international multidisciplinary team. Medline (all) and Embase were systematically searched. Laboratory scientists, clinical geneticists, psychologists, and a fetal medicine specialist screened the papers and performed the data extraction. Nineteen papers were included. Recommendations generally emphasized the importance of trio analysis, clinical information, data sharing, validation and re-analysis, protocols, multidisciplinary teams, genetic counselling, whether to limit the possible scope of results, and when to report particular findings. This systematic review helps provide a vocabulary for uncertainties, and a compass to navigate uncertainties. Prenatal CMA and ES guidelines provide a strong starting point for determining how to handle uncertainty. Gaps in guidelines and recommendations were identified and discussed to provide direction for future research and policy making.
AB - Exome sequencing (ES) enhanced the diagnostic yield of genetic testing, but has also increased the possibility of uncertain findings. Prenatal ES is increasingly being offered after a fetal abnormality is detected through ultrasound. It is important to know how to handle uncertainty in this particularly stressful period. This systematic review aimed to provide a comprehensive overview of guidelines available for addressing uncertainty related to prenatal chromosomal microarray (CMA) and ES. Ten uncertainty types associated with prenatal ES and CMA were identified and defined by an international multidisciplinary team. Medline (all) and Embase were systematically searched. Laboratory scientists, clinical geneticists, psychologists, and a fetal medicine specialist screened the papers and performed the data extraction. Nineteen papers were included. Recommendations generally emphasized the importance of trio analysis, clinical information, data sharing, validation and re-analysis, protocols, multidisciplinary teams, genetic counselling, whether to limit the possible scope of results, and when to report particular findings. This systematic review helps provide a vocabulary for uncertainties, and a compass to navigate uncertainties. Prenatal CMA and ES guidelines provide a strong starting point for determining how to handle uncertainty. Gaps in guidelines and recommendations were identified and discussed to provide direction for future research and policy making.
KW - chromosomal microarray
KW - health planning guidelines
KW - health policy
KW - practice guidelines
KW - prenatal diagnosis
KW - uncertainty
KW - whole exome sequencing
UR - http://www.scopus.com/inward/record.url?scp=85108970933&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/cge.14010
DO - https://doi.org/10.1111/cge.14010
M3 - Review article
C2 - 34155632
SN - 0009-9163
VL - 100
SP - 647
EP - 658
JO - Clinical Genetics
JF - Clinical Genetics
IS - 6
ER -