Objective: To critically review the literature and synthesize evidence on the incremental yield of prenatal exome sequencing (PES) in fetuses with an apparently normal phenotype with a normal G-banded karyotype or chromosomal microarray (CMA).
Methods: This systematic review and meta-analysis was conducted using a predetermined protocol and registered with PROSPERO (ID: CRD42024593349). We included observational cohort studies reporting on the incremental yield of PES in fetuses with an apparently normal phenotype and a previously normal G-banded karyotype/CMA. The risk of bias of the included studies was assessed using the Newcastle-Ottawa Scale. The pooled proportion of events was calculated using generalized linear mixed models, using the metaprop function in R version 2.15.1.
Results: Four studies (1916 fetuses) were included in this systematic review and meta-analysis, of which 32 cases had a pathogenic or likely pathogenic variant. The pooled incremental yield of PES in fetuses with an apparently normal phenotype was 1.6% (95% CI, 1.0-2.6%); the majority of variants were de novo within genes associated with autosomal dominant inherited conditions (pooled incremental yield, 0.9% (95% CI, 0.5-1.7%)). Based on the expected severity of the associated disease, the pooled incremental yield was 0.5% (95% CI, 0.1-1.5%) for severe disease and 0.5% (95% CI, 0.2-1.5%) for moderate disease. There were insufficient data to conduct the predefined secondary analyses according to normality of phenotype at birth, variants of uncertain significance and expected age of disease onset.
期刊介绍:
Ultrasound in Obstetrics & Gynecology (UOG) is the official journal of the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) and is considered the foremost international peer-reviewed journal in the field. It publishes cutting-edge research that is highly relevant to clinical practice, which includes guidelines, expert commentaries, consensus statements, original articles, and systematic reviews. UOG is widely recognized and included in prominent abstract and indexing databases such as Index Medicus and Current Contents.