‘Something that helped the whole picture’: Experiences of parents offered rapid prenatal exome sequencing in routine clinical care in the English National Health Service

Objectives: In October 2020, rapid prenatal exome sequencing (pES) was introduced into routine National Health Service (NHS) care in England. This study aimed to explore parent experiences and their information and support needs from the perspective of parents offered pES and of health professionals involved in its delivery. Methods: In this qualitative study, semi-structured interviews were conducted with 42 women and 6 male partners and 63 fetal medicine and genetic health professionals. Interviews were transcribed verbatim and analysed using thematic analysis. Results: Overall views about pES were positive and parents were grateful to be offered the test. Highlighted benefits of pES included the value of the additional information for pregnancy management and planning for future pregnancies. An anxious wait for results was common, often associated with the need to make decisions near to 24 weeks in pregnancy when there are legal restrictions for late termination. Descriptions of dealing with uncertainty were also common, even when results had been returned. Many parents described pES results as informing decision-making around whether or not to terminate pregnancy. Some professionals were concerned that a non-informative result could be overly reassuring and highlighted that careful counselling was needed to ensure parents have a good understanding of what the result means for their pregnancy. Emotional support from professionals was valued; however, some parents felt that post-test support was lacking. Conclusion: Parents and professionals welcomed the introduction of pES. Results inform parents' decision-making around the termination of pregnancy. When there are no diagnostic findings or uncertain findings from pES, personalised counselling that considers scans and other tests are crucial. Directing parents to reliable online sources of information and providing emotional support throughout could improve their experiences of care

Incremental yield of whole genome sequencing over chromosome microarray and exome sequencing for congenital anomalies in prenatal period and infancy: systematic review and meta-analysis.

Publication status: PublishedOBJECTIVE: Primarily to determine the incremental yield of Whole Genome Sequencing (WGS) over Chromosome Microarray Assessment (CMA) and/or Exome Sequencing (ES) in fetuses and infants with a congenital anomaly that was or could have been detectable on ultrasound prenatally. Secondly, to evaluate the turnaround time (TAT) and quantity of DNA required for testing using these pathways. METHODS: OVID MEDLINE(R), EMBASE, Medline (Web of Science), Cochrane Library, and ClinicalTrials.gov databases were searched electronically (January 2010 to December 2022). Inclusion criteria were cohort studies including fetuses/infants with ≥n=3 cases of: (i) one or more congenital anomalies; (ii) an anomaly which was or would have been detectable on prenatal ultrasound and; (iii) exclusion of aneuploidy and pathogenic Copy Number Variants >50kb. Pooled incremental yield was determined using a random-effects model and heterogeneity was assessed statistically using Higgins' I2 . Sub-analyses were performed based on pre- or postnatal presentation, multi-system anomalies and classification based upon NHS England prenatal (R21) ES inclusion criteria. PROSPERO 2022 CRD42022380483 RESULTS: Eighteen studies incorporating n=1284 cases were included, of which n=8 (44.4%) incorporating n=754 (58.7%) cases were prenatal cohorts and the remainder representing postmortem (postnatal evaluation), neonatal or infants with congenital structural anomalies. The incremental yield of WGS over QF-PCR/CMA was 26% (95% CI 18-36%, I2 =86%), 16% (9-24%, I2 =85%) and 39% (95%CI 27-51%, I2 =53%) for all, prenatal and postnatal cases. The incremental yields were optimal where sequencing was performed in line with NHS England prenatal ES criteria; 32% (22%-42%, I2 =70%). The incremental yield of Variants of Uncertain Significance (VUS) was 18% (95% CI 7-33%, I2 =74%). The yield of WGS over ES was non-significant at 1% (95% CI 0%-4%, I2 =47%). The pooled median TAT for WGS was 18 days (range: 1-912 days) and the quantity of DNA required for WGS versus CMA and ES was 100ng (±0) and 350ng (±50) p=0.03 respectively. CONCLUSION: Whilst WGS investigation for congenital anomaly holds great promise, for the future, its' incremental yield over ES is yet to be demonstrated. However, the laboratory pathway for WGS (compared to sequential QF-PCR/CMA/ES) requires less DNA with a potentially faster TAT. There was a relatively high rate of VUS. This article is protected by copyright. All rights reserved

Something that helped the whole picture': Experiences of parents offered rapid prenatal exome sequencing in routine clinical care in the English National Health Service

OBJECTIVES: In October 2020, rapid prenatal exome sequencing (pES) was introduced into routine National Health Service (NHS) care in England. This study aimed to explore parent experiences and their information and support needs from the perspective of parents offered pES and of health professionals involved in its delivery. METHODS: In this qualitative study, semi-structured interviews were conducted with 42 women and 6 male partners and 63 fetal medicine and genetic health professionals. Interviews were transcribed verbatim and analysed using thematic analysis. RESULTS: Overall views about pES were positive and parents were grateful to be offered the test. Highlighted benefits of pES included the value of the additional information for pregnancy management and planning for future pregnancies. An anxious wait for results was common, often associated with the need to make decisions near to 24 weeks in pregnancy when there are legal restrictions for late termination. Descriptions of dealing with uncertainty were also common, even when results had been returned. Many parents described pES results as informing decision-making around whether or not to terminate pregnancy. Some professionals were concerned that a non-informative result could be overly reassuring and highlighted that careful counselling was needed to ensure parents have a good understanding of what the result means for their pregnancy. Emotional support from professionals was valued; however, some parents felt that post-test support was lacking. CONCLUSION: Parents and professionals welcomed the introduction of pES. Results inform parents' decision-making around the termination of pregnancy. When there are no diagnostic findings or uncertain findings from pES, personalised counselling that considers scans and other tests are crucial. Directing parents to reliable online sources of information and providing emotional support throughout could improve their experiences of care.Published version, accepted version (12 month embargo)RD&E staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted