BACKGROUND Chromosomal microarray analysis (CMA) improves the detection of genetic anomalies over standard karyotype and is thus recommended in many prenatal indications. However, evidence is still lacking on the clinical… Click to show full abstract
BACKGROUND Chromosomal microarray analysis (CMA) improves the detection of genetic anomalies over standard karyotype and is thus recommended in many prenatal indications. However, evidence is still lacking on the clinical utility of CMA in cases of isolated fetal growth restriction (FGR). OBJECTIVE To estimate the proportion of copy number variants (CNVs) detected by CMA and the incremental yield of CMA over karyotype in the detection of genetic abnormalities in fetuses with isolated FGR. STUDY DESIGN This retrospective study included all singleton fetuses diagnosed with FGR and no structural ultrasound anomalies and referred to 13 French fetal medicine centers over a one-year period in 2016. FGR was defined as an estimated fetal weight <10th percentile for gestational age identified in ultrasound reports. For this analysis, we selected fetuses who underwent invasive genetic testing with karyotype and CMA results. Data were obtained from medical records and ultrasound databases as well as post-mortem and placental examination reports in case of spontaneous stillbirths and terminations of pregnancy. Following the American College of Medical Genetics and Genomics guidelines, CNVs were classified into 5 groups as following: pathogenic, likely pathogenic, variant of unknown significance (VOUS), likely benign and benign. RESULTS Of 682 referred fetuses diagnosed with isolated FGR, both karyotype and CMA were performed in 146 fetuses. Overall, the detection rate of genetic anomalies found by CMA was estimated to be 7.5% (11/146, CI95%: 3.3,11.8) including 10 CNVs classified as pathogenic and one as likely pathogenic. Among the 139 fetuses with normal karyotype, 5 fetuses were detected with pathogenic and likely pathogenic CNVs resulting in an incremental yield of 3.6% (CI95%: 0.5-6.6) of CMA over karyotype. All fetuses detected with pathogenic or likely pathogenic CNVs resulted in terminations of pregnancy. In addition, 3 fetuses with normal karyotype were detected with VOUS (2.1%). Of the 7 fetuses with abnormal karyotype, CMA did not detect one fetus with trisomy 18 mosaicism. CONCLUSION Our study found that CMA improves the detection of genetic anomalies over karyotype in fetuses diagnosed with isolated FGR. These results support the use of CMA in addition to karyotype for isolated FGR.
               
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