# The Incremental Yield of CMA Over Karyotype in Fetal Growth Restriction—A Systematic Review and Meta‐Analysis

## TL;DR

This study finds that chromosomal microarray analysis (CMA) detects more chromosomal abnormalities than karyotyping in fetuses with growth restriction, especially in those with structural abnormalities.

## Contribution

The study quantifies the incremental diagnostic yield of CMA over karyotyping in different fetal growth restriction subtypes.

## Key findings

- CMA has a 3% higher yield than karyotyping in isolated fetal growth restriction cases.
- CMA shows a 4% higher yield in nonmalformed fetal growth restriction cases.
- CMA provides a 10% higher yield in malformed fetal growth restriction cases.

## Abstract

The main objective of our study was to conduct a systematic literature review and a meta‐analysis to evaluate the incremental yield of chromosomal microarray analysis compared with karyotyping in cases of fetal growth restriction. Our review was designed according to the PRISMA guidelines. It included all observational studies that reported the results of CMA testing in fetuses diagnosed with growth restriction without additional findings (isolated FGR), with structural abnormalities (malformed FGR) and with the presence of additional findings that would not qualify as structural abnormalities (nonmalformed FGR). The study included 22 studies with a total of 2275 cases of affected fetuses that met the inclusion criteria for analysis. Combined data from these studies revealed an overall 3% incremental yield of CMA over karyotyping (95% CI 2%–5%) in isolated cases, an overall 4% incremental yield of CMA over karyotyping (95% CI 3%–5%) in nonmalformed FGR cases and an overall 10% incremental yield (95% CI –13%) in malformed FGR cases. Our findings may be useful in clinical practice to guide management options and the counseling of the couples to individualize patient care and facilitate clinicians when they come across such a common clinical entity.

What is already known about this topic?◦Underlying chromosomal abnormalities represent one of the most common causes of FGR and while karyotyping has demonstrated efficacy in identifying significant structural mutations, its inability to detect copy number variants restricts the potential identification of pathological submicroscopic DNA gains or losses.What does this review add?◦CMA demonstrated an overall 3% incremental yield over karyotyping in FGR cases without any additional findings, an overall 4% incremental yield in nonmalformed FGR cases and an overall 10% incremental yield in malformed FGR cases.

What is already known about this topic?

Underlying chromosomal abnormalities represent one of the most common causes of FGR and while karyotyping has demonstrated efficacy in identifying significant structural mutations, its inability to detect copy number variants restricts the potential identification of pathological submicroscopic DNA gains or losses.

What does this review add?

CMA demonstrated an overall 3% incremental yield over karyotyping in FGR cases without any additional findings, an overall 4% incremental yield in nonmalformed FGR cases and an overall 10% incremental yield in malformed FGR cases.