Chromosomal Microarray Analysis in Fetuses with Growth Restriction and Normal Karyotype: A Systematic Review and Meta-Analysis

Abstract

Objective: To perform a systematic review of the literature and a meta-analysis to estimate the incremental yield of chromosomal microarray analysis (CMA) over karyotyping in fetal growth restriction (FGR).

Methods: This was a systematic review conducted in accordance with the PRISMA criteria. All articles identified in PubMed, Ovid Medline, and ISI Web of Knowledge (Web of Science) from January 2009 to November 2016 describing pathogenic copy number variants (CNVs) in fetuses with growth restriction were included. Case reports were excluded. Risk differences were pooled to estimate the overall and stratified CMA incremental yield.

Results: Ten studies with full data available met the inclusion criteria for analysis. Combined data from these studies revealed a 4% (95% confidence interval [CI] 1-6%) incremental yield of CMA over karyotyping in nonmalformed growth-restricted fetuses, and a 10% (95% CI 6-14%) incremental yield in FGR when associated with fetal malformations. The most frequently found pathogenic CNVs were 22q11.2 duplication, Xp22.3 deletion, and 7q11.23 deletion (Williams-Beuren syndrome), particularly in isolated FGR.

Conclusion: The use of genomic CMA provides a 4% incremental yield of detecting pathogenic CNVs in fetuses with isolated growth restriction and normal karyotype.

Keywords: Chromosomal microarray analysis; Copy number variants; Fetal growth restriction; Incremental yield; Prenatal diagnosis.