Parental perceptions of prenatal whole exome sequencing (PPPWES) study

Wou, Karen; Weitz, Talia; McCormack, Clare; Wynn, Julia; Spiegel, Erica; Giordano, Jessica L.; Wapner, Ronald J.; Chung, Wendy K.

doi:10.1002/pd.5332

Cited by 33 publications

(97 citation statements)

References 25 publications

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“…It is also demonstrated in studies in the USA that parents are keen to receive as much information as possible regarding their child's health, even where results are uncertain (Kalynchuk et al, 2015;Wou et al, 2018). One study used hypothetical scenarios to determine the desire for uncertain results and found that while 86% would like to be told about these results, the proportion decreased as the level of uncertainty increased (Wou et al, 2018).…”

Section: Mmentioning

confidence: 99%

Update on the use of exome sequencing in the diagnosis of fetal abnormalities

Ferretti

Mellis

Chitty

2019

European Journal of Medical Genetics

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Unexpected fetal abnormalities detected through ultrasound scanning in pregnancy may have a monogenic aetiology but are difficult to diagnose. Next generation sequencing now enables us to sequence fetal exomes, providing increased resolution and broader diagnostic capability compared to traditional cytogenetic prenatal tests, improving the yield and accuracy of diagnoses and allowing better counselling for expectant parents. Here we review published studies of exome sequencing (ES) for prenatal diagnosis over the last 5 years and address important questions for its clinical implementation, including clinical utility, which groups benefit most, and practical and ethical challenges for interpreting and reporting results. We observe that fetal ES substantially improves diagnostic yield relative to cytogenetic techniques. However, diagnostic rates vary widely between studies, largely attributable to differences in case selection. Recently several large studies report variations in diagnostic yield between phenotypic groups, with fetuses with multisystem abnormalities most likely to receive a diagnosis from fetal ES. Challenges for prenatal ES include the limitations of ultrasound-based fetal phenotyping, the need for rapid return of results in pregnancy, and technical limitations compared to whole genome sequencing. We also consider ethical issues around potential secondary findings and variants of uncertain significance and the complex counselling needs these present. Prenatal ES is a valuable tool to diagnose fetal abnormalities and, as it is implemented in the clinic, more large-scale research will serve to further delineate its clinical utility, as well as

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Section: Mmentioning

confidence: 99%

Update on the use of exome sequencing in the diagnosis of fetal abnormalities

Ferretti

Mellis

Chitty

2019

European Journal of Medical Genetics

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“…Further, these advances allow for multi-disciplinary care planning, and they inform and improve neonatal care and health outcomes. 2 Prenatal trio exome sequencing (trio-ES) is one such advance. Evidence thus far suggests that trio-ES increases diagnostic yield when standard genetic testing (karyotype and microarray) is normal.…”

Section: Introductionmentioning

confidence: 99%

Impact of prenatal exome sequencing for fetal genetic diagnosis on maternal psychological outcomes and decisional conflict in a prospective cohort

Talati¹,

Gilmore²,

Hardisty³

et al. 2020

Preprint

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Objective: To evaluate associations between prenatal trio exome sequencing (trio-ES) and psychological outcomes among women with an anomalous pregnancy. Methods: Trio-ES study enrolling patients with major fetal anomaly and normal microarray. Women completed self-reported measures and free response interviews at two time points, pre- (1) and post- (2) sequencing. Pre-sequencing responses were compared to post-sequencing responses; post-sequencing responses were stratified by women who received trio-ES results that may explain fetal findings, secondary findings (medically actionable or carrier couple status), or negative results. Free responses were content analyzed. Results: 115 trios were enrolled. Of those, 41/115 (35.7%) received results from trio-ES, including 36 (31.3%) who received results that may explain the fetal phenotype. These women had greater post-sequencing distress compared to women who received negative results, including generalized distress (p=0.03) and test-related distress (p=0.2); they also had worse psychological adaptation to results (p=0.001). Genomic knowledge did not change from pre- to post-sequencing (p=0.51). Major themes from content analyses included closure, future pregnancy, altruism, anxiety, and gratitude. Conclusions: Women show more distress after receiving trio-ES results compared to those who do not.

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“…One study confirmed the range of challenges that existed, including the need for adequate counseling and informed consent, prenatal variant interpretation, inability to identify a genetic aetiology, and identifying secondary findings in the parents when offering trio testing . The other study clearly showed that parents wanted as much information as possible, including uncertain results that might be related to the diagnosis . These studies highlighted the need for clinicians to understand the power of sequencing, the ethical implications, and parental perceptions, as well as showing the need for specialized genetic counseling and health professional education.…”

Section: Introductionmentioning

confidence: 83%