Application Of Chromosome Microarray Analysis In The Prenatal Diagnosis Of Abnormal Ultrasound Fetus

PurposeTo explore and evaluate the value of chromosomal microarray analysis（chromosomal microarray analysis,CMA）in fetal prenatal diagnosis of ultrasound abnormalities.Method1.Cases of voluntary interventional prenatal diagnosis from January 2020 and from January 2020 to December 2021 were collected,and those with fetal ultrasound abnormalities were examined in a retrospective study.The mean age of the pregnant women was 29.06±5.27 years old（18-44 years old）,of which the advanced age（35 years old）accounted for 12.5%,and the mean gestational age was 24±4.2 weeks(12⁺²-36⁺¹circumference).2.A total of 428 fetal ultrasound abnormalities were included in this study,divided into 2 groups:175（40.9%）in the ultrasound soft index group and 253（59.1%）in the group of ultrasound structural abnormality group.Ultrasound soft indicators include:NT thickening,nasal bone dysplasia/absence,intestinal echogenicity,mild renal pelvis expansion,mild lateral ventricle widening,NF thickening,choroid plexus cyst,single umbilical artery,mild long bone short,etc.Structural abnormalities include:cardiovascular,nervous system,facial surface and neck,chest,abdominal wall and abdominal cavity,urogenital,bone and limbs and other system development abnormalities,as well as fetal edema,fetal growth restriction,abnormal amniotic fluid volume,etc.According to the single or multiple ultrasonic structural abnormalities,196（77.5%）and 57（22.5%）in the group of multiple structural abnormalities.3.According to different gestational age,villi,amniotic fluid and umbilical cord blood were used as fetal specimens,and G band chromosome karyotyping and CMA（gene chip Affymetrix Cytoscan 750K）were performed.Observed data rows were statistically analyzed using SPSS 22.0 statistical software.Counting data were expressed as cases and rates,measurement data were expressed as X±S,group comparisons using the 2 test,P<0.05 was considered statistically significant??.Results1.In this study,11 cases of chromosomal abnormalities were detected in the single structural abnormality group,with a detection rate of 5.61%（11/196）,and 15 cases in the group of multiple structural abnormalities,with a detection rate of 26.32%（15/57）.The detection rate of chromosome karyotype analysis was significantly higher in multiple ultrasound structural abnormalities than in a single ultrasound structural abnormality（P<0.01）.CMA detected 14 pathogenic copy number variants（copy number variations;CNVs）in the single structural abnormalities group with a detection rate of 7.14%（14/196）;pathogenic CNVs 20 was detected in the group with multiple structural abnormalities of 35.09%（20/57）.The detection rate of the latter was significantly higher than the former（P<0.01）.2.The detection rate of CMA pathogenic CNVs was 13.44%（34/253）,the detection rate of chromosome karyotype was 10.28%（26/253）,and the additional diagnosis rate of CMA was 3.16%.In the group with single ultrasound abnormalities,the additional detection rate of CMA was 1.53%;in the group with multiple ultrasound abnormalities,CMA was 8.77%.3.For ultrasound structural abnormalities,14 additional abnormal copy number variants were detected by CMA,including 6 cases with pathogenic CNVs 8 and of unknown significance（variants of unknown significance;V O US）.Pathogenic CNVs were mainly deletion types（7 deletion types,1 duplication type）with fragment size<10Mb（1.2-6.9Mb）,including:Wolf-Hirschhorn syndrome,1q21.1 microduplication syndrome,RCAD（renal cyst and diabetes）syndrome（2 cases）,aortic valve disease type1,X-linked ichthyosis,Di George syndrome,and SRY gene deletion.All cases of pathogenic CNVs terminated the pregnancy.4.In this study,25cases（14.29%）were detected by chromosome karyotyping and 26cases（14.86%）were detected by CMA.There was no statistical difference in the detection rate between the two groups（P>0.05）,which was related to the small sample size.CMA detected one more case of pathogenic CNVs compared with chromosome karyotype analysis.The case was 1q21.1 microduplication syndrome with a fragment size of 1.3 Mb.Because the syndrome could be manifested as mental retardation,learning disability,autism,macrocephaly,ocular abnormalities and heart defects,the pregnant woman and her family requested to terminate the pregnancy.Conclusion1.The incidence of chromosomal aberrations in the fetus with multiple structural aberrations is higher than that in a single structural abnormality.2.Chromosome microarray analysis（CMA）of fetal ultrasound structural abnormalities detected about 3.16%more pathogenic CNVs compared with chromosome karyotype.CMA technology can detect more pathogenic CNVs,and more comprehensively detect abnormal chromosomes.Its application in fetal structural abnormalities,especially multiple structural abnormalities,is necessary.3.CMA in ultrasound soft index cases can detect all abnormal chromosomes detected by chromosome karyotyping,and can detect additional pathogenic CNVs.4.CMA can detect most chromosomal abnormalities during fetal ultrasonographic abnormalities,and can detect pathogenic CNVs,especially deletions and duplications less than 5 Mb.5.Chromosome karyotype analysis and chromosomal microarray analysis have different advantages in the etiology diagnosis of fetal ultrasound abnormalities,and the combined use improves the diagnostic efficiency.