Abstract
Prenatal diagnoses of congenital malformations have increased significantly in recent years with use of high-resolution prenatal imaging. Despite more precise radiological diagnoses, discussions with expectant parents remain challenging because congenital malformations are associated with a wide spectrum of outcomes. Comprehensive prenatal genetic testing has become an essential tool that improves the accuracy of prognostication. Testing strategies include chromosomal microarray, exome sequencing, and genome sequencing. The diagnostic yield varies depending on the specific malformations, severity of the abnormalities, and multi-organ involvement. The utility of prenatal genetic diagnosis includes increased diagnostic clarity for clinicians and families, informed pregnancy decision-making, neonatal care planning, and reproductive planning. Turnaround time for results of comprehensive genetic testing remains a barrier, especially for parents that are decision-making, although this has improved over time. Uncertainty inherent to many genetic testing results is a challenge. Appropriate genetic counseling is essential for parents to understand the diagnosis and prognosis and to make informed decisions. Recent research has investigated the yield of exome or genome sequencing in structurally normal fetuses, both with non-invasive screening methods and invasive diagnostic testing; the prenatal diagnostic community must evaluate and analyze the significant ethical considerations associated with this practice prior to generalizing its use.
Impact
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Reviews available genetic testing options during the prenatal period in detail.
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Discusses the impact of prenatal genetic testing on care using case-based examples.
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Consolidates the current literature on the yield of genetic testing for prenatal diagnosis of congenital malformations.
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References
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Substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data: Olivier Fortin. Drafting the article or revising it critically for important intellectual content: Olivier Fortin, Sarah Mulkey, Jamie Fraser. Final approval of the version to be published: Olivier Fortin, Sarah Mulkey, Jamie Fraser.
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Fortin, O., Mulkey, S.B. & Fraser, J.L. Advancing fetal diagnosis and prognostication using comprehensive prenatal phenotyping and genetic testing. Pediatr Res (2024). https://doi.org/10.1038/s41390-024-03343-9
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DOI: https://doi.org/10.1038/s41390-024-03343-9
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