妊娠早期利用母血血浆胎儿游离DNA诊断胎儿染色体异常的价值
임신조기이용모혈혈장태인유리DNA진단태인염색체이상적개치
Diagnosis of fetal chromosomal aneuploidy by free fetal DNA in maternal plasma in the first trimester
  • 万方数据
    中华围产医学杂志 중화위산의학잡지
    CHINESE JOURNAL OF PERINATAL MEDICINE
    2014年 1期 14-18 ,共5页

    常颖%陈叙%崔洪艳%任晨春

    상영%진서%최홍염%임신춘

    非整倍性%产前诊断%DNA%妊娠初期 非整倍性%產前診斷%DNA%妊娠初期
    비정배성%산전진단%DNA%임신초기
    Aneuploidy%Prenatal diagnosis%DNA%Pregnancy trimester,first
    目的 评估妊娠11～13+6周利用母血血浆中的胎儿游离DNA诊断胎儿染色体非整倍体畸形的临床价值. 方法 选取2010年1月1日至2010年12月31日于天津市中心妇产科医院进行产前检查的妊娠11～13+6周孕妇共2 650例,超声检测胎儿颈部透明层厚度.同时取孕妇外周血5 ml,以时间分辨仪检测血清游离人绒毛膜促性腺激素β亚基单位和妊娠相关血浆蛋白A的浓度.所得数据输入数据库,根据孕妇的年龄、体重、种族、吸烟史、妊娠方式、孕周数等转化成该指标的中位数倍数(multiple of median,MoM),计算风险值.风险截断值为1∶270.对高风险孕妇行介入性产前诊断(绒毛活检)和非介入性产前诊断.采用f检验、秩和检验、Mann-Whitney U检验、x2检验或Fisher精确概率法进行组间比较. 结果 (1)2 650例孕妇中,高风险孕妇74例.35例进行绒毛活检,37例于妊娠20周行羊水穿刺.35例行绒毛活检的孕妇中选取1 8例同时行游离胎儿DNA(cell-free fetal DNA,cffDNA)检测.2例Rh阴性孕妇直接行非介入性产前诊断(即cffDNA检测),未行绒毛活检或羊水穿刺.这20例孕妇中,6例胎儿染色体核型异常,其中5例为非整倍体核型异常,包括21-三体2例,18-三体及45,XO各1例,另1例为染色体平衡易位[t(1;2)(p11.1; p11.2)].将这2例21-三体及14例染色体核型正常孕妇的血浆进一步行胎盘特定基因4(placenta-specific 4,PLAC4)RNA-单核苷酸多态性(single nucleotide polymorphism,SNP)检测.(2)通过对母血血浆cffDNA进行检测,准确诊断出2例21-三体、1例18-三体及2例45,XO.2例Rh阴性血型孕妇的胎儿染色体核型正常.(3)2例妊娠有21-三体胎儿的孕妇母血血浆PLAC4 RNA-SNP等位基因鸟苷酸-腺苷酸等位基因比率为1.00(0.98,1.02),14例核型正常孕妇的PLAC4 RNA-SNP等位基因鸟苷酸-腺苷酸等位基因比率为1.05(1.02,1.13).2组差异无统计学意义(Z=3.5,P=0.066). 结论 利用母血血浆中胎儿游离DNA产前诊断胎儿染色体非整倍体畸形具有无创的特点,且非介入性产前诊断具有较好的阴性预测价值,可以作为特殊人群,如Rh阴性血型孕妇的一种产前筛查和诊断手段.
    목적 평고임신11～13+6주이용모혈혈장중적태인유리DNA진단태인염색체비정배체기형적림상개치. 방법 선취2010년1월1일지2010년12월31일우천진시중심부산과의원진행산전검사적임신11～13+6주잉부공2 650례,초성검측태인경부투명층후도.동시취잉부외주혈5 ml,이시간분변의검측혈청유리인융모막촉성선격소β아기단위화임신상관혈장단백A적농도.소득수거수입수거고,근거잉부적년령、체중、충족、흡연사、임신방식、잉주수등전화성해지표적중위수배수(multiple of median,MoM),계산풍험치.풍험절단치위1∶270.대고풍험잉부행개입성산전진단(융모활검)화비개입성산전진단.채용f검험、질화검험、Mann-Whitney U검험、x2검험혹Fisher정학개솔법진행조간비교. 결과 (1)2 650례잉부중,고풍험잉부74례.35례진행융모활검,37례우임신20주행양수천자.35례행융모활검적잉부중선취1 8례동시행유리태인DNA(cell-free fetal DNA,cffDNA)검측.2례Rh음성잉부직접행비개입성산전진단(즉cffDNA검측),미행융모활검혹양수천자.저20례잉부중,6례태인염색체핵형이상,기중5례위비정배체핵형이상,포괄21-삼체2례,18-삼체급45,XO각1례,령1례위염색체평형역위[t(1;2)(p11.1; p11.2)].장저2례21-삼체급14례염색체핵형정상잉부적혈장진일보행태반특정기인4(placenta-specific 4,PLAC4)RNA-단핵감산다태성(single nucleotide polymorphism,SNP)검측.(2)통과대모혈혈장cffDNA진행검측,준학진단출2례21-삼체、1례18-삼체급2례45,XO.2례Rh음성혈형잉부적태인염색체핵형정상.(3)2례임신유21-삼체태인적잉부모혈혈장PLAC4 RNA-SNP등위기인조감산-선감산등위기인비솔위1.00(0.98,1.02),14례핵형정상잉부적PLAC4 RNA-SNP등위기인조감산-선감산등위기인비솔위1.05(1.02,1.13).2조차이무통계학의의(Z=3.5,P=0.066). 결론 이용모혈혈장중태인유리DNA산전진단태인염색체비정배체기형구유무창적특점,차비개입성산전진단구유교호적음성예측개치,가이작위특수인군,여Rh음성혈형잉부적일충산전사사화진단수단.
    Objective To assess the clinical value of fetal chromosomal aneuploidy diagnosed by free fetal DNA in maternal plasma in 11-13+6 gestational weeks.Methods A total of 2 650 pregnant women who had prenatal care in Tianjin Center Hospital of Obstetrics and Gynecology from January 1,2010 to December 31,2010 were included.Each of them had an ultrasound scan to measure fetal nuchal translucency thickness.Maternal serum free β-human chorionic gonadotropin and pregnancy-associated plasma protein A test was performed as part of screening for chromosomal abnormalities.Results of ultrasound and maternal plasma biochemical analysis were entered into the database,and converted into multiple of median (MoM) by factors such as maternal age,weight,ethnicity,smoking history and mode of conception.The cutoff value was 1 ∶ 270.Meanwhile,20 cases had cell free fetal DNA (cffDNA) test and the ratio of the single nucleotide polymorphism on two alleles of plancenta-specific 4 (PLAC4) were measured in 16 cases.T-test,rank sum test,MannWhitney U test and Chi-square test were used as statistical methods.Results (1) A total of 74 cases were judged as high-risk,among which 35 cases underwent transabdominal chorionic villus sampling (18 cases had cffDNA test),37 cases underwent amniocentesis at the week of 20,and two cases of Rh negative did not receive the invasive examination.Totally 20 cases,including two Rh negative cases,had the cell-free fetal DNA test.(2) By cffDNA test of maternal plasma,two cases of 21 trisomy,one case of 18 trisomy,two cases of 45,XO and one case of balanced translocation were diagnosed.(3) In the two cases of 21 trisomy,maternal plasma G/A ratio ofPL4C4 RNA-single nucleotide polymorphism alleles was 1.00 (0.98,1.02) ; in 14 pregnancies with normal chromosome,the ratio was 1.055 (1.02,1.13,Z=3.5).There was no significant difference (P=0.066).Conclusion Diagnosing of fetal chromosomal aneuploidy by cffDNA in maternal plasma is feasible and noninvasive with high negative predictive value,and can be used in Rh-negative pregnant women for prenatal screening and diagnosis.
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