Application of chromosomal microarray to investigate genetic causes of isolated fetal growth restriction

Gang An,Si Ping Liu,Yan Hong Yu,Liang Pu Xu,Yuan Lin,Fang Yang,Hai Long Huang

doi:10.1186/s13039-018-0382-4

Abstract

BackgroundApplication of chromosomal microarray analysis (CMA) to investigate the genetic characteristics of fetal growth restriction (FGR) without ultrasonic structural anomalies at 18–32 weeks.MethodsThis study includes singleton fetuses with the estimated fetal weight (EFW) using the formula of Hadlock C below the 10th percentile for gestational age. FGRs without structural anomalies were selected, and the ones at high risk of noninvasive prenatal testing for trisomy 13, 18 and 21 would be excluded. The cases were divided into two groups: early-onset group (< 24+ 0 weeks) and late-onset group (24–33 weeks). All patients were offered invasive prenatal testing with CMA and karyotype analysis.ResultsCMA detected 10 pathogenic copy number variants and 2 variant of uncertain significance case. CMA has a 5.5% (7/127) incremental yield of pathogenic chromosomal abnormalities over karyotyping. The positive detected rate was 9.6% (5/52) in early-onset group and 9.3% (7/75) in late-onset group respectively.ConclusionsWhen FGR without structural anomaly is diagnosed before 33 weeks, an invasive prenatal procedure is strongly recommended. CMA can identify a 5.5% (7/127) incremental detection rate of pathogenic chromosomal abnormalities, which would impact clinical management for FGR.

Highlights

Application of chromosomal microarray analysis (CMA) to investigate the genetic characteristics of fetal growth restriction (FGR) without ultrasonic structural anomalies at 18–32 weeks
CMA can detect a potentially pathogenic copy-number variants (CNV) in an additional 6–7% of cases with fetal structural abnormalities detected by ultrasound [7].The American Congress of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-fetal Medicine (SMFM) recommend that CMA as a first-line test is recommended when genetic analysis is performed in cases with fetal structural anomalies [8]
A total of 155 cases with isolate FGR met the inclusion criteria. 28 cases refused to accept an invasive procedure and 127 cases were consented to participate in the study. 52 prenatal samples were obtained by amniocentesis and 75 were obtained by cordocentesis

Summary

Introduction

Application of chromosomal microarray analysis (CMA) to investigate the genetic characteristics of fetal growth restriction (FGR) without ultrasonic structural anomalies at 18–32 weeks. Conventional karyotyping is the current gold standard for prenatal cytogenetic analysis for several decades, chromosomal microarray analysis (CMA) has CMA can detect a potentially pathogenic CNV in an additional 6–7% of cases with fetal structural abnormalities detected by ultrasound [7].The American Congress of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-fetal Medicine (SMFM) recommend that CMA as a first-line test is recommended when genetic analysis is performed in cases with fetal structural anomalies [8] For those FGR fetuses without ultrasonic structural anomaly, defined as isolated FGR, An et al Molecular Cytogenetics (2018) 11:33 whether to implement CMA is still under consideration. We sought to investigate the genetic causes of isolate FGR by SNP array and karyotype

Methods

Results

Conclusion