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

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. Key points: What's already known about this topic? Bilateral echogenic kidneys (BEKs) have a recognized association with monogenetic conditions and are an indication for prenatal exome sequencing (PES) in many healthcare systems. What does this study add? For urinary tract malformations other than BEKs, there is a modest incremental yield from PES over chromosome microarray and G‐banding karyotype. [ABSTRACT FROM AUTHOR]