Application Of Chromosomal Microarray In The Prenatal Diagnosis Of Fetal Growth Restriction

Background:Fetal growth restriction(FGR)is associated with substantive perinatal morbidity and the prevalence is estimated to be 5-10%.Genetic abnormality is one of the main factors that lead to fetal growth restriction.There are many mental disorders after birth,and there is no effective treatment.Conventional karyotyping is limited by the resolution and it is no longer possible to provide clinicians or geneticists with more diagnostic information.The appearance of chromosomal microarray(CMA)allows us to perform more comprehensive and accurate detection of the genetic changes in the fetus.Therefore,we are going to study the genetic abnormalities of FGR with the combination of chromosomal microarray,quantitative real-time PCR(QF-PCR)and karyotype analysis.Purposes:1.To study the incidence and composition of genetic abnormalities in FGR,and the relationship between clinical features and genetic abnormalities of FGR.2.To explore the application value of CMA in prenatal diagnosis of FGR.3.To explore a rapid,economical and accurate diagnosis of genetic abnormali-ties.Study design:Cases included in this study were singleton pregnancies with gestational ages ranging from 18 to 32 weeks.According to the formp,La of Hadlock,fetal growth re-striction was diagnosed when fetal weight was estimated to be less than the 10th per-centile of the same gestational age.Prenatal diagnosis samples of fetuses were ob-tained by amniocentesis or umbilical cord blood puncture.Excluding intrauterine in-fection with cytomegalovirus(CMV),all cases included in the study were ex-cluded from chromosome aneuploidy by QF-PCR and CMA was performed.Each case was subjected to karyotype analysis.According to the fetal μLtrasound findings,FGR was divided into structural abnormal group,non-structural abnormal group and isolated FGR groups,and the application value of CMA in different groups was dis-cussed.In order to investigate the influence of the diagnosis timing of FGR on the clinical decision and detection of genetic abnormalities,according to the gestational age at the time of diagnosis of FGR,FGR cases were divided into 18-24+6group and 25-32+6 group.Results:A total of 316 cases of fetal growth restriction met the inclusion criteria.Among them,94 pregnant women refused to receive prenatal diagnosis,222 pregnant women signed informed consent to participate in the study,and excluded 3 cases of intrauterine infection of cytomegalovirus(CMV),and 219 cases entered the final study cohort finally.The overall detection rate of genetic abnormalities was 18.3%(40/219).QF-PCR detected 24 cases of chromosome numerical abnormalities,which were completely consistent with the karyotype analysis.The CMA technique detected two cases of uniparental disomy(UPD)and 14 cases of chromosome structural abnormalities.After excluding numerical abnormalities,CMA detected all 4 cases of pathological chromosome abnormalities diagnosed by karyotype analysis.CMA had a 6.2%(12/195)incremental detection rate over karyotype analysis.Eleven cases were pathological chromosome deletions or duplications,two cases were UPDs that did not involve changes in genetic material,two cases were varia-tions of uncertain significance(VOUS)and one case was an aneuploidy with mosaicism.In the structural anomaly group,non-structural anomaly group and iso-lated FGR group,the abnormal detection rate of CMA was 6.7%,11.4%,and 7.9%,respectively,and there was no statistical difference among the groups.In the 18-24+6group and 25-32+6 groups,the abnormal detection rate of CMA was 9.2%and 7.0%respectively,and no statistical difference.Conclusions:FGR was diagnosed before 18-32+6 gestational weeks,regardless of whether the fetus is associated with μLtrasound abnormalities,we recommend invasive prenatal procedure.Compared with karyotype analysis,QF-PCR is the preferred diagnosis technique for FGR with the high risk of aneuploidy;CMA increases the detection rate of genetic abnormality of FGR by 6.2%and is the best choice for prenatal diag-nosis.At the same time,the detection of cytomegalovirus intrauterine infection will help clarify the underlying causes of fetal growth restriction.