Beyond diagnostic yield: prenatal exome sequencing results in maternal, neonatal, and familial clinical management changes

Tolusso, Leandra; Hazelton, Paige; Wong, Beatrix Ling Ling; Swarr, Daniel T.

doi:10.1038/s41436-020-01067-9

Cited by 28 publications

(33 citation statements)

References 41 publications

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“…14,32,[41][42][43][44][45][46][47][48][33][34][35][36][37][38][39][40] Eight studies targeted ES analysis more tightly using phenotypespecific gene panels, 7,12,15,[49][50][51][52][53] while the remainder took a whole ES approach. 8,13,[62][63][64][65][66][67][68][69][70][71]54,[72][73][74][75][76][77][78][79][80][81]55,[82][83]…”

Section: Study Characteristicsmentioning

confidence: 99%

“…Studies examining other aspects of clinical utility such as impact on clinical management and parental decision-making will be an important complement to this, 90 however we found only six to include in our review. 8,26,52,62,73,74,82 Three of these studies found that negative as well as diagnostic results impacted upon parental and clinical decision-making, 73,74,82…”

Section: Mellis Et Almentioning

confidence: 99%

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Diagnostic yield of exome sequencing for prenatal diagnosis of fetal structural anomalies: A systematic review and meta‐analysis

et al. 2022

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Objectives: We conducted a systematic review and meta-analysis to determine the diagnostic yield of exome sequencing (ES) for prenatal diagnosis of fetal structural anomalies, where karyotype/chromosomal microarray (CMA) is normal.Methods: Following electronic searches of four databases, we included studies with ≥10 structurally abnormal fetuses undergoing ES or whole genome sequencing. The incremental diagnostic yield of ES over CMA/karyotype was calculated and pooled in a meta-analysis. Sub-group analyses investigated effects of case selection and fetal phenotype on diagnostic yield. Results:We identified 72 reports from 66 studies, representing 4350 fetuses. The pooled incremental yield of ES was 31% (95% confidence interval (CI) 26%-36%, p < 0.0001). Diagnostic yield was significantly higher for cases pre-selected for likelihood of monogenic aetiology compared to unselected cases (42% vs. 15%, p < 0.0001). Diagnostic yield differed significantly between phenotypic sub-groups, ranging from 53% (95% CI 42%-63%, p < 0.0001) for isolated skeletal abnormalities, to 2% (95% CI 0%-5%, p = 0.04) for isolated increased nuchal translucency. Conclusion:Prenatal ES provides a diagnosis in an additional 31% of structurally abnormal fetuses when CMA/karyotype is non-diagnostic. The expected diagnostic yield depends on the body system(s) affected and can be optimised by pre-selection of cases following multi-disciplinary review to determine that a monogenic cause is likely. Key pointsWhat's already known about this topic? � Prenatal exome sequencing (ES) increases genetic diagnoses in fetuses with structural abnormalities and a normal karyotype and chromosomal microarray.� Published diagnostic yields from ES are varied and may be influenced by study size, case selection and fetal phenotype.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Section: Study Characteristicsmentioning

confidence: 99%

Section: Mellis Et Almentioning

confidence: 99%

Diagnostic yield of exome sequencing for prenatal diagnosis of fetal structural anomalies: A systematic review and meta‐analysis

et al. 2022

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“…The 2019 survey has highlighted interest by several of the participating laboratories to evaluate prenatal/ perinatal WES or WGS testing over the next 1-5 years. There is increasing evidence that WES and WGS can provide improved diagnostic yield in both the prenatal [26][27][28][29] and postnatal [30][31][32] periods. Despite this, guidelines for use of these technologies in the prenatal/perinatal setting are not yet available from the relevant Canadian professional bodies, namely the CCMG and SOGC, though a CCMG working group to examine fetal exome testing has been established (personal communication).…”

Section: Discussionmentioning

confidence: 99%

Practice patterns of prenatal and perinatal testing in Canadian cytogenetics laboratories

Ashfield¹,

McCready

Shago

et al. 2021

Prenatal Diagnosis

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Objective: To survey patterns of practice in Canadian cytogenetics laboratories and evaluate whether newer technologies have influenced testing algorithms for the detection of common aneuploidies and other genomic imbalances in the prenatal and perinatal settings.Methods: Cytogenetics laboratories across Canada were invited to participate in two patterns-of-practice surveys: one in 2016 and one in 2019. They were asked to identify the prenatal and perinatal specimen types tested at their facility and which testing methods were used for initial testing and for follow-up.Results: All clinical laboratories performing prenatal testing offer rapid aneuploidy detection (RAD). Most laboratories also offer microarray analysis. A positive result is either followed up by karyotyping or no further testing is performed. For prenatal samples, a negative result may be followed up by microarray or karyotyping and is dependent on the reason for referral. For perinatal samples, availability of microarray to follow up a negative result is increasing.Conclusions: Since 2016, the availability of RAD as a first-line test in Canadian cytogenetics laboratories remains consistent, while microarray has become the preferred follow-up testing method over traditional karyotyping following a normal RAD result. Despite a universal healthcare system, disparities in prenatal and perinatal cytogenetic testing algorithms are apparent. Key pointsWhat's already known about this topic? � Chromosome abnormalities are recognized as a common cause of miscarriage and congenital anomalies � Until recently, karyotype assessment of G-banded metaphases has been the gold standard for detection of chromosome abnormalities in the prenatal and perinatal period � Development of molecular cytogenetic tools has allowed for direct testing of tissues, reduced turnaround times and increased sensitivity for small, potentially clinically significant copy number changes TA and EM should be considered joint first author

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“…Beyond aneuploidy, genomic testing can be helpful in diagnosing conditions that may influence obstetric and neonatal management, especially when an ultrasound has revealed fetal anomalies [17,[98][99][100][101]. In addition, if prenatal genomic testing yields a positive diagnosis, neonatal management decisions could be made immediately at birth, rather than having to wait for test results after delivery, which could take several weeks.…”

Section: Medical and Emotional Preparationmentioning

confidence: 99%

“…Hospitals and care providers may have different policies about what they consider appropriate care in these situations. Prenatal knowledge of a condition could allow a family to choose a delivery location and care providers who will respect the family's wishes as much as is legally possible [99].…”

Section: Medical and Emotional Preparationmentioning

confidence: 99%

Prenatal Testing – What Is It Good For? A Review and Critique

Resta¹

2021

obm genet

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The goals of prenatal testing remain controversial and reflect competing interests of public health, patient rights, disability activists, scholars, feminist critics, commercial laboratories, judiciary/legislative trends, and medical science. This paper reviews and critiques the most common justifications of prenatal testing for fetal aneuploidy that have been put forth over the half century of its existence: reducing the medical and economic burden to society of genetic disease through selective abortion, allowing parents to avoid raising a child with disabilities, preventing the suffering associated with chromosomal and genetic disorders, emotional reassurance about the health of the baby, and medical and emotional preparation for the birth of a baby with a disability. Each of these goals has problematic aspects, as do some of the criticisms of these goals. The most striking shortcoming of the justifications for prenatal testing is a dearth of research about potential medical, psychological, or adaptational benefits of prenatal testing, especially for aneuploidy, for babies and families, beyond the option of pregnancy termination.

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Beyond diagnostic yield: prenatal exome sequencing results in maternal, neonatal, and familial clinical management changes

Cited by 28 publications

References 41 publications

Diagnostic yield of exome sequencing for prenatal diagnosis of fetal structural anomalies: A systematic review and meta‐analysis

Diagnostic yield of exome sequencing for prenatal diagnosis of fetal structural anomalies: A systematic review and meta‐analysis

Practice patterns of prenatal and perinatal testing in Canadian cytogenetics laboratories

Prenatal Testing – What Is It Good For? A Review and Critique

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