| Objective By following up the pregnancy outcome of Variations of Unknown Significance(VOUS),the practical clinical significance of VOUS is clarified and the clinical database is enriched,so as to provide new evidence for evaluating the pathogenicity of VOUS and provide reference for prenatal genetic counseling.Methods A total of 1508 high-risk pregnant women who underwent chromosomal microarray analysis(CMA)by amniocentesis in the prenatal diagnosis clinic of Inner Mongolia Maternal and Child Health Hospital from June 2017 to December 2021 were collected.Among them,67 fetal samples with CMA results of VOUS were screened,but 3 cases were lost to follow-up,and 64 cases were finally included in this study.The subjects were divided into two groups based on whether parental verification was performed to analyze the origin of VOUS,namely,the parent verification group(12 cases)and the parent unverified group(52 cases).The pregnancy outcome of the subjects and the health status of infants after birth were followed up regularly to analyze the relationship between VOUS of different sources and pregnancy outcome and its influence.At the same time,VOUS,which occurs more frequently,is analyzed statistically,and its intrinsic correlation with pregnancy outcome is analyzed.The prenatal diagnosis indicators were classified to analyze the influence of different prenatal diagnosis indicators on pregnancy outcome.Finally,the relationship between the parent verified group and the parent unverified group and pregnancy outcome was analyzed.Results Among the 1508 pregnant women who received interventional prenatal diagnosis,amniotic fluid CMA was detected,67 cases of VOUS were found,the detection rate was 4.44%(67/1508),3 cases failed follow-up,and finally 64 cases were included in this study.There were13 adverse pregnancy outcomes(20.31%,13/64),of which 9 were induced labor,2 were premature,2 were macrosomia,and the remaining 51(79.69%,51/64)were normal pregnancy outcomes.In the follow-up of the fetus after birth,only one case had developmental delay in the language system,and the rest were normal at follow-up.The detected VOUS was distributed on chromosomes except 12,19 and 21,including 7occurrences in the Xp22.31p22.33 region,5 occurrences in the 15q11.2 region,4 occurrences in the 2q13 region,3 occurrences in the 13q12.12 region,and 1 labor induction in the 2q13 and13q12.12 regions,and the rest of the chromosomal regions were normal pregnancy outcomes.The indications for interventional prenatal diagnosis were divided into five groups: high risk of serological screening,high risk of NIPT,abnormal ultrasound(including abnormal ultrasound soft indexes,abnormal ultrasound structure),advanced age,and other abnormalities(personal history of adverse pregnancy and childbirth,polyhydramnios,parental chromosomal abnormalities,etc.),and compared the adverse pregnancy outcome rates between the groups,and no differences were found in the effect of different types of prenatal diagnosis indications on pregnancy outcomes(P>0.05).According to the parental verification of VOUS,it is divided into three groups: genetic,new,and unknown origin.A total of 12(18.75%,12/64)parents of VOUS fetuses underwent chromosomal examination,and 9(75%,9/12)fetuses inherited VOUS from both parents,of which 4(33.3%,4/12)were inherited from the mother and 5(41.7%,5/12)were inherited from the father.2 cases(16.7%,2/12)of unknown origin;One case(8.3%,1/12)was an emerging variant;The remaining 52 cases(81.25%,52/64)did not undergo parental verification,so the source of VOUS was unknown.The comparison showed no difference in the effect of VOUS from different sources on pregnancy outcomes between the three groups(χ2=0.27,P>0.05).According to the group of parental verification,2 cases(16.67%,2/12)in the 12 parental verification group had adverse pregnancy outcomes,all of which were macrosomia;Among the52 unverified parents,11cases(19.23%,11/52)had adverse pregnancy outcomes,including 9induced labor and 2 preterm births;There was no difference in effect on adverse pregnancy outcomes between the two groups(χ2=0.0025,P>0.05).No difference in the rate of voluntary termination of pregnancy was found between the parent-verified group(0/12)and the parentunverified group(17.31%,9/52)(χ2=1.197,P>0.05).Conclusion The detection rate of VOUS in our hospital is similar to the research results at home and abroad;In this study,it was found that the pregnancy outcome of VOUS fetuses was mostly benign;Fetal pregnancy outcome is not significantly associated with different indications for prenatal diagnosis;Parental verification of VOUS had no significant effect on pregnancy outcome and labor induction rate;It is recommended that parental testing should be carried out in time after VOUS is found in prenatal diagnosis to further evaluate the significance and pathogenicity of VOUS. |
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