Diagnostic yield of exome sequencing in fetal growth restriction: Systematic review and meta-analysis

Abstract

To determine the diagnostic yield of exome sequencing (ES) above that of chromosomal microarray analysis (CMA) or karyotyping in fetuses with isolated fetal growth restriction (FGR) METHOD: This was a systematic review conducted in accordance with PRISMA guidelines. Selected studies included those with: (a) only fetuses with FGR in the absence of fetal structural anomalies and (b) negative CMA or karyotyping results. Only positive variants classified as likely pathogenic or pathogenic determined as causative of the fetal phenotype were considered. A negative CMA or karyotype result was treated as the reference standard. Incidence was used as the pooled effect size by single-proportion analysis using a generalized linear mixed model (by logit transformation).Eight studies with data on ES diagnostic yield, including 146 fetuses with isolated FGR, were identified. Overall, a pathogenic variant determined as potentially causative of the fetal phenotype was found in 17 cases, resulting in a 12% (95% CI: 7-18%) incremental performance pool of ES.A monogenic disorder was prenatally found in association with apparently isolated FGR in 12% of these fetuses. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.