Application Of Chromosomal Microarray Analysis In Fetuses With Ventriculomegaly

BackgroundVentriculomegaly（VM）is the most common fetal intracranial abnormality found by prenatal ultrasound in the second and third trimesters of pregnancy.The lateral ventricle width of a normal fetus is（7.6±0.6）mm during 14-38 weeks of gestation.A fetus with lateral ventricle width≥10 mm on ultrasound is diagnosed as VM.VM is closely related to fetal hereditary diseases.The detection methods,detection rate,pregnancy outcomes and prognosis of VM with different pathological characteristics need further analysis.Chromosomal microarray analysis（CMA）has been widely used in prenatal diagnosis,especially in the prenatal diagnosis of fetuses with abnormal ultrasound indicators.It can help to detect chromosomal microdeletions,microduplications and other subtle structural abnormalities.ObjectiveThe association of the diagnostic results of CMA for fetuses with VM with pregnancy outcome and intrauterine outcome was analyzed.MethodsThis study included 84 singleton pregnant women who were diagnosed with VM by ultrasound and admitted to the Department of Obstetrics and Gynecology,Jiaozuo Maternal and Child Health Hospital,Henan Province between January and December,2019.Conventional chromosome karyotype analysis was performed,and CMA was used to analyze fetal genome copy number variants（CNVs）.The pregnancy outcomes,neonatal development,neonatal behavioral neurological assessment scores,and intrauterine outcomes were statistically analyzed.According to the degree of VM,the subjects were divided into mild group（width of lateral ventricle between 1.00 cm and 1.20 cm）,moderate group（width of lateral ventricle between 1.21 cm and 1.50 cm）and severe group（width of lateral ventricle≥1.51 cm）.According to the presence or absence of other malformations,the subjects were divided into discrete group and non-discrete group.According to the location of VM lesions,the subjects were divided into unilateral group and bilateral group.The detection of pathogenic CNVs（p CNVs）,pregnancy outcomes,and intrauterine outcomes of different subgroups were compared.Spearman correlation analysis was performed to analyze the correlation between the degree of fetal VM and CMA copy number variation as well as pregnancy outcome.Results1.The detection rate of chromosome abnormality through karyotype analysis combined with CMA was 30.95%（26/84）,higher than 13.10%（11/84）of karyotype analysis alone and 28.57%（24/84）of CMA alone（χ~2=7.799,P<0.05,χ~2=0.114,P>0.05）.The abnormality detection rate of CMA was higher than that of karyotype analysis（χ~2=6.099,P<0.05）.17（70.84%）of the 24 cases with CMA abnormality had p CNVs,and the size was between198 kb and 8.71 Mb.5（20.83%）cases of fetuses had ambiguous and possibly pathogenic CNVs（pp CNVs）,and 2（8.33%）had ambiguous and possibly pathogenic loss of heterozygosity（LOH）.2.The detection rates of CMA abnormality and p CNVs increased in sequence from the mild group,the moderate group,to the severe group（P<0.05）,with statistical differences between the mild group and the severe group（P<0.05）.The detection rates of CMA abnormality and p CNVs were lower in the discrete group than in the non-discrete group,the detection rates of CMA abnormality was lower in the unilateral group than in the bilateral group,but there were no statistical difference in the detection rate of p CNV between the unilateral group and the bilateral group（P<0.05）.3.There were statistically significant differences in the induced labor rate among VM cases with different widening degrees（χ~2=37.966,P<0.05）.The induced labor rate in the severe group was 100.00%（8/8）,higher than 7.02%（4/57）in the mild group and 42.11%（8/19）in the moderate group（χ~2=40.292,7.816,χ~2=37.966,P<0.05）,and the induced labor rate in the moderate group was higher than that in the mild group（χ~2=13.194,P<0.05）.The abnormal rate of neonatal nervous system development was higher in the moderate group than in the mild group,and the neonatal behavioral neurological assessment score was lower than that of the mild group（P<0.05）.The abnormal rate of nervous system development and the total incidence of adverse outcomes in the non-discrete group were higher than those in the discrete group,and the neonatal behavioral neurological assessment score was lower than that of the discrete group（P<0.05）.The abnormal rate of nervous system development in the bilateral group was higher than that in the unilateral group,and the neonatal behavioral neurological assessment score was lower than that of the unilateral group（P<0.05）.4.Correlation analysis showed that the degree of fetal VM was positively correlated with the detection rate of p CNVs,the rate of induced labor and the abnormal rate of nervous system development,but negatively correlated with the neonatal behavioral neurological assessment score（P<0.05）.Multivariate Logistic regression analysis showed that moderate to severe widening of lateral ventricle,bilateral VM,non-discrete VM,and the first time to detect discrete VM at gestational weeks<25 were independent risk factors affecting fetal intrauterine outcome（P<0.05）.ConclusionsDiagnosis with CMA can improve the detection rate of chromosome abnormalities in fetuses with VM,especially the detection rate of p CNVs,and help predict the risk of abnormal pregnancy outcome.In addition,the degree of VM,non-discrete VM,and bilateral VM are associated with intrauterine outcome,pregnancy outcome and prognosis.