| Sex chromosome aneuploidy(SCA)refers to Turner syndrome(45,X),triple X syndrome(47,XXX),Klinefelter syndrome(47,XXY),and Jacob’s syndrome(47,XYY).Traditional prenatal screening methods cannot detect fetal SCA.Prenatal diagnosis has been associated with an increase risk of procedure-related miscarriage,and intrauterine infection.Noninvasive prenatal testing(NIPT)has been highly recommended in clinical practice as a screening method for fortal trisomy 21(T21),trisomy 18(T18),and trisomy 13(T13)with high sensitivity and specificity.However,at present,the application of NIPT in detecting fetal SCA is still being explored and there is a lack of large-scale clinical studies.The aim of this study was to assess the efficiency of NIPT as a prenatal screening method for fetal SCA,and the correlation between fetal SCA frequency and maternal age.Objective To assess the clinical application value of NIPT for fetal SCA testing.To analyze the relationship between maternal age and the frequency of fetal SCA and evaluate whether maternal age is a risk factor for fetal SCA,in order to provide better prenatal consultation for fetal SCA.Methods(1)A total of 45,773 maternal blood samples from singleton pregnancies were collected in the Maternity and Child Health Hospital of Anhui Province between June 1,2015,and June 30,2019.Record maternal age,gestational week,prenatal indications,amniocentesis results and follow-up pregnancy outcome.And exclude pregnant women who do not meet the inclusion criteria.(2)Singleton pregnant women divided into four groups,including 30 years old,30-34 years old,35-39 years old and>39 years old.To analyze whether the incidences of 45,X,47,XXX,47,XXY and47,XYY in different maternal age groups is different.Results(1)The results of NIPT for fetal SCA:Among 45773 singleton pregnancies who underwent NIPT,a total of 314 high-risk SCA cases were screened,including 147 cases 45,X(46.82%),61 cases 47,XXX(19.43%),71 cases 47,XXY(22.61%)and 35 cases 47,XYY(11.15%).143 pregnant women(45.54%)accepted the prenatal diagnosis,58 pregnant women were true-positive,including 45,X(7 cases),47,XXX(15 cases),47,XXY(26 cases),and 47,XYY(10 cases).The remaining 85cases were normal karyotype.The PPV of SCA detected by NIPT was 40.56%(58/143).Overall,the PPVs for 45,X,47,XXX,47,XXY and 47,XYY were 12.5%,51.72%,66.67%and 83.33%,respectively.(2)The positive predictive value of NIPT in the detection of different prenatal indications groups:Among the 45773 singleton pregnant women who underwent NIPT,the number of pregnant women with high or critical risk for serological screening was the largest,19820(43.30%).This was followed by advanced maternal age(age≥35 years),with 16,921 cases(36.97%).The PPV of SCA detected by NIPT was 40.56%(58/143),and the PPV of SCA in pregnant women in the AMA group(≥35 years)was 50.79%(32/63).The PPVs were 30.43%(14/46)in the high or critical risk group,40%(10/25)in the no clinical indications group,25%(1/4)in the missed other screening opportunities group,and 33.33%(1/3)in the increased NT group.(3)The pregnancy outcome and NIPT false positive results:85 pregnant women were false-positive results detected by NIPT,67 were successfully followed up.They all successfully delivered their babies.A total of 171 pregnant women refused prenatal diagnosis,and 126 cases were successfully followed up.Moreover,86 pregnant women refused prenatal diagnosis due to abortion-related anxiety,and 33 pregnant women refused prenatal diagnosis due to B-ultrasound results showing a severe fetal condition.Another 7 pregnant women experienced spontaneous abortion or stillbirth during gestation.A total of 85 false-positive NIPT cases were identified.Importantly,32 cases were suspicious for an abnormal maternal Chr X karyotype,detected by NIPT,including23 cases with an abnormal Chr X gain and 9 cases with an abnormal Chr X loss.Based on genetic counselling,32 cases underwent maternal peripheral blood karyotyping.Moreover,2 cases among 23 cases with an abnormal Chr X gain were diagnosed with47,XXX,while 2 cases among 9 cases with an abnormal Chr X loss were diagnosed with mosaicism 45,X/47,XXX and mosaicism 47,XXX/45,X/46,XY.(4)Seven pregnant women were diagnosed with 45,X,of which 6 terminated the pregnancies(85.71%),and 2 induced labor due to fetal malformations revealed by ultrasound.Of the 15confirmed pregnant women,3 chose to induce labor(20%).26 cases were diagnosed as47,XXY,and 19 pregnant women terminated their pregnancies(73.08%).There were 47XYY pregnant women in 10 cases of confirmed pregnancy,and 1 pregnant woman terminated the pregnancy(10%).(5)The relationship between maternal age and the risk of fetal SCA:the PPV increased with maternal age,and the pregnant women aged>39 years has the highest PPV.The PPV of SCA in AMA women was higher than that in all samples.And the frequency of SCA in AMA group was significantly higher than in the non-AMA group(χ~2=8.229,P=0.004).AMA may be a risk factor for SCA(OR=2.098,95%CI-1.250 to 3.251).The frequencies of 45,X and 47,XYY did not differ among age groups of pregnant women(χ~2=4.328,P>0.05 for 45,X,andχ~2=1.074,P>0.05 for 47,XYY).However,the frequencies of 47,XXX and 47,XXY were different among the different age groups of(χ~2=12.616,P<0.05 for 47,XXX,andχ~2=12.570,P<0.05 for 47,XXY).Conclusions:(1)NIPT performed better in predicting fetal sex chromosome trisomy’s than monosomy X.(2)With the combination of NIPT and maternal peripheral blood karyotype analysis,we found approximately 12.5%of the discordant NIPT SCA results were due to maternal mosaicism.(3)Pregnant women whose fetuses were 45,X or 47,XXY were more eager to terminate pregnancies than those with 47,XXX or47,XYY.The rate of pregnancy termination was closely related to the types of SCA,level of prenatal genetic counselling,history of infertility,economic condition,and related factors.(4)AMA may be a risk factor for SCA.(5)The frequencies of fetal47,XXX and 47,XXY were significantly correlated with maternal age,whereas the frequencies of 45,X and 47,XYY did not show significant correlations. |
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