When should we offer antenatal sequencing for urinary tract malformations? A systematic review, cohort study and meta-analysis

Sarah Sonner; Kelly Reilly; Adrian S. Woolf; Natalie Chandler; Mark D. Kilby; Eamonn R. Maher; Cheryl Flanagan; Amy Jayne McKnight; Fionnuala Mone

doi:10.1002/pd.6479

When should we offer antenatal sequencing for urinary tract malformations? A systematic review, cohort study and meta-analysis

Sarah Sonner
, Kelly Reilly
, Adrian S. Woolf
, Natalie Chandler
, Mark D. Kilby
, Eamonn R. Maher
, Cheryl Flanagan
, Amy Jayne McKnight
, Fionnuala Mone

Aston Medical School

Queens University Belfast
University of Manchester
Great Ormond Street Hospital NHS Foundation Trust
Fetal Medicine Centre, Birmingham Women’s NHS Foundation Trust, Birmingham B15 2TT, UK
Catholic University of Sacred Heart, Institute of General Pathology Gemelli Hospital, 00168 Roma, Italy

Research output: Contribution to journal › Review article › peer-review

10 Citations (Scopus)

12 Downloads (Pure)

Abstract

OBJECTIVE: Determine the incremental yield of prenatal exome sequencing (PES) over chromosome microarray (CMA) and/or karyotype for urinary tract malformations (UTMs).

METHOD: A prospective cohort study encompassing data from the English Genomic Medicine Service North Thames Laboratory Hub for fetuses with bilateral echogenic kidneys (BEKs) was combined with data from a systematic review. MEDLINE, EMBASE, Web of Science, MedRxiv and GreyLit were searched from 01/2010-02/2023 for studies reporting on the yield of PES over CMA or karyotype in fetuses with UTMs. Pooled incremental yield was determined using a random effects model. PROSPERO CRD42023364544.

RESULTS: Fourteen studies (410 cases) were included. The incremental yield for multisystem UTMs, any isolated UTMs, and BEKs was 31% [95% CI, 18%-46%; I2 = 78%], 16% [95% CI, 6%-26%; I2 = 80%] and 51% [95% CI, 27%-75%; I2 = 34%]. The most common clinical diseases and syndromes identified, based on the variant genes detected, were Bardet-Biedl syndrome (BBS genes), dominant and recessive polycystic kidney diseases (PKD1, PKD2 and PKHD1) and renal cysts and diabetes syndrome (HNF1B).

CONCLUSION: There was a notable incremental genetic diagnostic yield when PES was applied to multisystem UTMs and BEKs. There was a modest incremental yield when this technique was used for UTMs other than BEKs.

Original language	English
Pages (from-to)	187-195
Number of pages	9
Journal	Prenatal diagnosis
Volume	44
Issue number	2
Early online date	6 Dec 2023
DOIs	https://doi.org/10.1002/pd.6479
Publication status	Published - Feb 2024

Bibliographical note

Copyright © 2023 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Funding

The authors thank the Rapid fetal exomes sequencing, Bioinformatics team and the Translational research teams at North Thames Genomic Laboratory Hub. The work described here was partially funded by the NIHR Biomedical Research Centre at the Great Ormond Street Hospital. ASW acknowledges support from the MCR‐NIHR UK Rare Disease Research Platform MR/Y008340/1. ERM acknowledges support from the NIHR Cambridge Biomedical Research Centre (NIHR203312). SS and FM acknowledge the funding provided by the Department for the Economy, Northern Ireland.

Funders	Funder number
MCR‐NIHR UK Rare Disease Research Platform	MR/Y008340/1
Manchester Biomedical Research Centre
Department for the Economy
NIHR Cambridge Biomedical Research Centre	NIHR203312

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Cohort Studies
Female
Humans
Karyotyping
Kidney/diagnostic imaging
Polycystic Kidney Diseases
Pregnancy
Prospective Studies

Access to Document

10.1002/pd.6479

Prenatal Diagnosis - 2023 - Sonner - When should we offer antenatal sequencing for urinary tract malformations A
Copyright © 2023 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Final published version, 527 KBLicence: CC BY-NC 4.0

Cite this

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title = "When should we offer antenatal sequencing for urinary tract malformations? A systematic review, cohort study and meta-analysis",

abstract = "OBJECTIVE: Determine the incremental yield of prenatal exome sequencing (PES) over chromosome microarray (CMA) and/or karyotype for urinary tract malformations (UTMs).METHOD: A prospective cohort study encompassing data from the English Genomic Medicine Service North Thames Laboratory Hub for fetuses with bilateral echogenic kidneys (BEKs) was combined with data from a systematic review. MEDLINE, EMBASE, Web of Science, MedRxiv and GreyLit were searched from 01/2010-02/2023 for studies reporting on the yield of PES over CMA or karyotype in fetuses with UTMs. Pooled incremental yield was determined using a random effects model. PROSPERO CRD42023364544.RESULTS: Fourteen studies (410 cases) were included. The incremental yield for multisystem UTMs, any isolated UTMs, and BEKs was 31\% [95\% CI, 18\%-46\%; I2 = 78\%], 16\% [95\% CI, 6\%-26\%; I2 = 80\%] and 51\% [95\% CI, 27\%-75\%; I2 = 34\%]. The most common clinical diseases and syndromes identified, based on the variant genes detected, were Bardet-Biedl syndrome (BBS genes), dominant and recessive polycystic kidney diseases (PKD1, PKD2 and PKHD1) and renal cysts and diabetes syndrome (HNF1B).CONCLUSION: There was a notable incremental genetic diagnostic yield when PES was applied to multisystem UTMs and BEKs. There was a modest incremental yield when this technique was used for UTMs other than BEKs.",

keywords = "Cohort Studies, Female, Humans, Karyotyping, Kidney/diagnostic imaging, Polycystic Kidney Diseases, Pregnancy, Prospective Studies",

author = "Sarah Sonner and Kelly Reilly and Woolf, \{Adrian S.\} and Natalie Chandler and Kilby, \{Mark D.\} and Maher, \{Eamonn R.\} and Cheryl Flanagan and McKnight, \{Amy Jayne\} and Fionnuala Mone",

note = "Copyright {\textcopyright} 2023 The Authors. Prenatal Diagnosis published by John Wiley \& Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.",

year = "2024",

month = feb,

doi = "10.1002/pd.6479",

language = "English",

volume = "44",

pages = "187--195",

journal = "Prenatal diagnosis",

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T1 - When should we offer antenatal sequencing for urinary tract malformations? A systematic review, cohort study and meta-analysis

AU - Sonner, Sarah

AU - Reilly, Kelly

AU - Woolf, Adrian S.

AU - Chandler, Natalie

AU - Kilby, Mark D.

AU - Maher, Eamonn R.

AU - Flanagan, Cheryl

AU - McKnight, Amy Jayne

AU - Mone, Fionnuala

N1 - Copyright © 2023 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

PY - 2024/2

Y1 - 2024/2

N2 - OBJECTIVE: Determine the incremental yield of prenatal exome sequencing (PES) over chromosome microarray (CMA) and/or karyotype for urinary tract malformations (UTMs).METHOD: A prospective cohort study encompassing data from the English Genomic Medicine Service North Thames Laboratory Hub for fetuses with bilateral echogenic kidneys (BEKs) was combined with data from a systematic review. MEDLINE, EMBASE, Web of Science, MedRxiv and GreyLit were searched from 01/2010-02/2023 for studies reporting on the yield of PES over CMA or karyotype in fetuses with UTMs. Pooled incremental yield was determined using a random effects model. PROSPERO CRD42023364544.RESULTS: Fourteen studies (410 cases) were included. The incremental yield for multisystem UTMs, any isolated UTMs, and BEKs was 31% [95% CI, 18%-46%; I2 = 78%], 16% [95% CI, 6%-26%; I2 = 80%] and 51% [95% CI, 27%-75%; I2 = 34%]. The most common clinical diseases and syndromes identified, based on the variant genes detected, were Bardet-Biedl syndrome (BBS genes), dominant and recessive polycystic kidney diseases (PKD1, PKD2 and PKHD1) and renal cysts and diabetes syndrome (HNF1B).CONCLUSION: There was a notable incremental genetic diagnostic yield when PES was applied to multisystem UTMs and BEKs. There was a modest incremental yield when this technique was used for UTMs other than BEKs.

AB - OBJECTIVE: Determine the incremental yield of prenatal exome sequencing (PES) over chromosome microarray (CMA) and/or karyotype for urinary tract malformations (UTMs).METHOD: A prospective cohort study encompassing data from the English Genomic Medicine Service North Thames Laboratory Hub for fetuses with bilateral echogenic kidneys (BEKs) was combined with data from a systematic review. MEDLINE, EMBASE, Web of Science, MedRxiv and GreyLit were searched from 01/2010-02/2023 for studies reporting on the yield of PES over CMA or karyotype in fetuses with UTMs. Pooled incremental yield was determined using a random effects model. PROSPERO CRD42023364544.RESULTS: Fourteen studies (410 cases) were included. The incremental yield for multisystem UTMs, any isolated UTMs, and BEKs was 31% [95% CI, 18%-46%; I2 = 78%], 16% [95% CI, 6%-26%; I2 = 80%] and 51% [95% CI, 27%-75%; I2 = 34%]. The most common clinical diseases and syndromes identified, based on the variant genes detected, were Bardet-Biedl syndrome (BBS genes), dominant and recessive polycystic kidney diseases (PKD1, PKD2 and PKHD1) and renal cysts and diabetes syndrome (HNF1B).CONCLUSION: There was a notable incremental genetic diagnostic yield when PES was applied to multisystem UTMs and BEKs. There was a modest incremental yield when this technique was used for UTMs other than BEKs.

KW - Cohort Studies

KW - Female

KW - Humans

KW - Karyotyping

KW - Kidney/diagnostic imaging

KW - Polycystic Kidney Diseases

KW - Pregnancy

KW - Prospective Studies

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U2 - 10.1002/pd.6479

DO - 10.1002/pd.6479

M3 - Review article

C2 - 38056891

SN - 0197-3851

VL - 44

SP - 187

EP - 195

JO - Prenatal diagnosis

JF - Prenatal diagnosis

IS - 2

ER -

When should we offer antenatal sequencing for urinary tract malformations? A systematic review, cohort study and meta-analysis

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

Access to Document

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