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

Background: Application of chromosomal microarray analysis (CMA) to investigate the genetic characteristics of fetal growth restriction (FGR) without ultrasonic structural anomalies at 18-32 weeks.

Methods: This 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.

Results: CMA 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.

Conclusions: When 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.