Application Value Of ADAM12 Combined With Serological Triad In Screening Of Chromosome Aneuploidy In The Second Trimester Of Pregnancy

Objective: In this study,we selected 15,992 pregnant women who undergoing prenatal screening in our hospital from January 2014 to June 2019,including 58 diagnosed with fetal chromosome aneuploidy,and the combined detection techniques of serological triad,chromosome karyotype analysis,fluorescence in situ hybridization and a disintegrin and metalloprotease 12(ADAM 12)were used to optimize the serological screening mode,to improve the detection ratio of serological prenatal screening and reduce the false negative ratio.Our study will provide experimental basis for the clinical popularization and application of combined screening for chromosomal aneuploidy in the second trimester of pregnancy.Methods:(1)Concentrations of alpha-fetoprotein(AFP),free human chorionic gonadotropin beta subunit(free β-h CG)and unconjugated estriol(u E3)in pregnant women at 14+0 ~ 20+6 weeks of gestation were measured by time-resolved immunofluorescence analysis(TRFIA),and risk assessment was performed by Lifecycle 4.0 software.According to screening risk and patient’s voluntary principle,amniotic fluid cell karyotype analysis and/or amniotic fluid interphase cell fluorescence in situ hybridization were performed for prenatal diagnosis.To evaluate the detection efficiency of serological triple in screening for chromosomal aneuploidy through pregnancy outcome;to confirm the clinical application value of the two prenatal diagnosis methods in prenatal screening of high-risk population by comparing the results of chromosomal karyotype analysis and fluorescence in situ hybridization.(2)58 pregnant women with 15+0~ 20+6w gestational weeks from January 2014 to June 2019 who were diagnosed as chromosomal aneuploidy fetuses in Linyi People’s Hospital were collected as the experimental group,including 28 pregnant women with 21-trisomy syndrome(DS)fetus(9 false negative),7 pregnant women with 18-trisomy syndrome(ES)(2 false negative),7 pregnant women with 13-trisomy syndrome(PS)(2 false negative),16 cases of sex chromosomal syndrome(SS)(5 false negative);174 cases of pregnant women with normal pregnancy outcome(24 cases of 21-trisomy false positive,10 cases of 18-trisomy false positive)were randomly selected as the control group.The content of ADAM12 in the serum of pregnant women in the experimental group and the control group was detected by ELISA double antibody sandwich method.The correlation between ADAM12 and AFP,free β-h CG,u E3 in the control group was analyzed.The level of ADAM12 between the experimental group and the control group was compared to explore the clinical application value of ADAM12 in chromosomal aneuploidy screening.Results: From January 2014 to June 2019,15992 pregnant women met the inclusion criteria of the study,58 fetuses with chromosomal aneuploidy;the detection rate of chromosomal abnormal karyotypes was 68.97%,the false-positive rate was 5.06%,and the positive predictive value was 5.38% in the mid pregnancy serological triple screening;170 high-risk pregnant women were detected by both amniotic fluid culture karyotype analysis and FISH technology.Except for one case of intra-arm inversion,14 cases of abnormal karyotype FISH were detected,and the results were consistent with the results of chromosome karyotype analysis.The coincidence rate of FISH technology and chromosome karyotype analysis reached 99.41%;from 15 to 20 weeks gestation,there was a positive correlation between serum ADAM 12 level and gestational age in the control group,which was negatively correlated with the age and weight of pregnant women;there was a significant difference in ADAM12 between the DS group and the control group(P<0.05);there was a significant difference in ADAM12 between the control group and the SS group(P<0.05);ADAM12 was used for second-trimester prenatal screening alone,and 12 cases of 28 fetuses with DS were detected,including 4 false negatives.The detection rate of DS for ADAM12 combined with serological triad screening increased from 67.86% to 82.14%;ADAM12 was used for second-trimester prenatal screening alone,and 7 cases of 16 fetuses with SS were detected,including 2 false negatives.The SS detection rate of ADAM12 combined with serological triad screening increased from 68.75% to 81.25%;there was no significant difference in ADAM12 between ES group,PS group and control group(P>0.05).Conclusion:1.Serological triad screening in the second trimester has important value in chromosome aneuploidy screening;and also has a certain warning role in the diagnosis of other birth defects.2.Serum ADAM12 of second trimester pregnant women can be used for the screening of Down’s Syndrome and sex chromosome abnormalities.It is expected to be used in the screening of 18-trisomy and 13-trisomy syndrome,and needs to be further validated by expanding the sample size.3.ADAM12 combined with serological triad can significantly improve the detection rate of chromosome aneuploidy,improve the diagnostic accuracy,and reduce false negative and false positive rates,and is a reliable and effective serological screening indicator.