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Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology
03, 2023;61 (3): 339-345.

Prenatal exome sequencing and impact on perinatal outcome: cohort study.

B Poljak, U Agarwal, Z Alfirevic, S Allen, N Canham, J Higgs, A Kaelin Agten, A Khalil, D Roberts, F Mone, K Navaratnam
Author Information
  1. B Poljak: Fetal Medicine Unit, Liverpool Women's Hospital NHS Foundation Trust, Liverpool, UK.
  2. U Agarwal: Fetal Medicine Unit, Liverpool Women's Hospital NHS Foundation Trust, Liverpool, UK. ORCID
  3. Z Alfirevic: Fetal Medicine Unit, Liverpool Women's Hospital NHS Foundation Trust, Liverpool, UK. ORCID
  4. S Allen: West Midlands Regional Genetics Laboratory and Clinical Genetics Service, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK.
  5. N Canham: Clinical Genetics Department, Liverpool Women's Hospital NHS Foundation Trust, Liverpool, UK.
  6. J Higgs: Clinical Genetics Department, Liverpool Women's Hospital NHS Foundation Trust, Liverpool, UK.
  7. A Kaelin Agten: Fetal Medicine Unit, Liverpool Women's Hospital NHS Foundation Trust, Liverpool, UK. ORCID
  8. A Khalil: Fetal Medicine Unit, St George's University Hospitals NHS Foundation Trust, University of London, London, UK. ORCID
  9. D Roberts: Fetal Medicine Unit, Liverpool Women's Hospital NHS Foundation Trust, Liverpool, UK.
  10. F Mone: Centre for Public Health, Queen's University Belfast, Belfast, UK. ORCID
  11. K Navaratnam: Fetal Medicine Unit, Liverpool Women's Hospital NHS Foundation Trust, Liverpool, UK. ORCID
PMID: 36508432 DOI: 10.1002/uog.26141

Abstract

OBJECTIVES: First, to determine the uptake of prenatal exome sequencing (pES) and the diagnostic yield of pathogenic (causative) variants in a UK tertiary fetal medicine unit following the introduction of the NHS England Rapid Exome Sequencing Service for fetal anomalies testing (R21 pathway). Second, to identify how the decision to proceed with pES and identification of a causative variant affect perinatal outcomes, specifically late termination of pregnancy (TOP) at or beyond 22 weeks' gestation.
METHODS: This was a retrospective cohort study of anomalous fetuses referred to the Liverpool Women's Hospital Fetal Medicine Unit between 1 March 2021 and 28 February 2022. pES was performed as part of the R21 pathway. Trio exome sequencing was performed using an Illumina next-generation sequencing platform assessing coding and splice regions of a panel of 974 prenatally relevant genes and 231 expert reviewed genes. Data on demographics, phenotype, pES result and perinatal outcome were extracted and compared. Descriptive statistics and the χ-square or Fisher's exact test were performed using IBM SPSS version 28.0.1.0.
RESULTS: In total, 72 cases were identified and two-thirds of eligible women (n = 48) consented to trio pES. pES was not feasible in one case owing to a low DNA yield and, therefore, was performed in 47 cases. In one-third of cases (n = 24), pES was not proposed or agreed. In 58.3% (14/24) of these cases, this was because invasive testing was declined and, in 41.7% (10/24) of cases, women opted for testing and underwent chromosomal microarray analysis only. The diagnostic yield of pES was 23.4% (11/47). There was no overall difference in the proportion of women who decided to have late TOP in the group in which pES was agreed compared with the group in which pES was not proposed or agreed (25.0% (12/48) vs 25.0% (6/24); P = 1.0). However, the decision to have late TOP was significantly more frequent when a causative variant was detected compared with when pES was uninformative (63.6% (7/11) vs 13.9% (5/36); P < 0.0009). The median turnaround time for results was longer in cases in which a causative variant was identified than in those in which pES was uninformative (22 days (interquartile range (IQR), 19-34) days vs 14 days (IQR, 10-15 days); P < 0.0001).
CONCLUSIONS: This study demonstrates the potential impact of identification of a causative variant by pES on decision to have late TOP. As the R21 pathway continues to evolve, we urge clinicians and policymakers to consider introducing earlier screening for anomalies, developing robust guidance for late TOP and ensuring optimized support for couples. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Keywords

R21 exome sequencing prenatal termination of pregnancy

References

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MeSH Term

Pregnancy
Female
Humans
Cohort Studies
Ultrasonography, Prenatal
Retrospective Studies
Exome Sequencing
Fetus
Prenatal Diagnosis
Journal Article
Article has an altmetric score of 5

Word Cloud

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