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

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

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
Journal	Prenatal diagnosis
Early online date	6 Dec 2023
DOIs	https://doi.org/10.1002/pd.6479
Publication status	E-pub ahead of print - 6 Dec 2023

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.

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

@article{f98385156d88496c96ecf789f827b22d,

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.",

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 = "2023",

month = dec,

day = "6",

doi = "10.1002/pd.6479",

language = "English",

}

TY - JOUR

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 - 2023/12/6

Y1 - 2023/12/6

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.

UR - http://www.scopus.com/inward/record.url?scp=85178966770&partnerID=8YFLogxK

UR - https://obgyn.onlinelibrary.wiley.com/doi/10.1002/pd.6479

U2 - 10.1002/pd.6479

DO - 10.1002/pd.6479

M3 - Review article

C2 - 38056891

SN - 0197-3851

JO - Prenatal diagnosis

JF - Prenatal diagnosis

ER -

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

Abstract

Bibliographical note

Access to Document

Other files and links

Fingerprint

Cite this