RhD免疫性溶血产前诊断与治疗的研究

Diagnosis and therapy of Rh(D) hemolytic diseases caused by maternal-fetal blood group incompatibility.

目的探讨应用荧光定量PCR方法对Rh阴性孕妇血浆中游离胎儿DNA;;进行无创性产前诊断胎儿RhD血型及应用血浆置换疗法配合药物治疗孕妇及胎儿Rh(D)血型不合的免疫性溶血病的疗效,预防孕妇早孕自然流产或不足月死胎。方法产前采用荧光定量PCR技术产前检测胎儿RhD血型,分娩后用血清学方法证实。对照组14例用药物治疗孕妇及胎儿Rh(D)血型不合者,实验组15例用血浆置换配合药物治疗对孕妇及胎儿Rh(D)血型不合者进行治疗,观察IgG抗-D抗体效价以及新生儿直接抗人球蛋白试验、游离IgG抗-D抗体、放散试验,胆红素。结果产前荧光定量PCR与产后血清学法Rh(D)血型结果一致。对照组14例孕妇孕期血浆抗体滴度为1∶32～1∶256;实验组15例孕妇PE 2～5次/例,血浆置换前后血浆抗体滴度分别为1∶(96±43.6)、1∶(18±14.7),二者比较有显著统计学差异(t=6.77,P<0.01)。对照组10例发生新生儿溶血病,实验组4例发生新生儿溶血病。对照组10例直接抗人球蛋白试验、游离IgG抗-D抗体、放散试验均阳性,血清胆红素:(84.2～205)μmol/L,平均(154.6±46)μmol/L;实验组4例直接抗人球蛋白试验、游离IgG抗-D抗体、放散试验阳性,血清胆红素:38.3μmol/L～141.2μmol/L,平均(76.5±36)μmol/L。结论应用荧光定量PCR方法进行无创性胎儿RhD血型检测可用于新生儿溶血病的预防和诊断;血浆置换配合药物治疗孕妇及胎儿RhD血型不合的免疫性溶血病的疗效优于单纯药物治疗,值得临床推广应用。

Objective： To explore using fluorescence quantitative PCR（FQ-PCR） for noninvasive prenatal diagnosis of fetal RhD blood type with free fetal DNA in RhD-negative maternal plasma and the effective of treating maternal-fetal Rh（D） incompatibility hemolysis disease with plasma exchange with comprehensive medications,prevent the spontaneous abortion and fatal death.Methods： The prenatal diagnosis of RHD genetyping was confirmed by FQ-PCR.The results of fetal RHD were confirmed with cord blood.We enrolled 29 women with maternal-fetal Rh（D） incompatibility hemolysis disease and divided them into two groups： Group A（n = 15） underwent plasma exchange combined with comprehensive medications;Group B（n = 14） was treated with comprehensive medicine alone.The titer of special anti-D IgG and Rh hemolytic disease of the newborn were detected in each group.Results： All cases were confirmed as accurate through serological measure of fetal umbilie blood after delivery.In group A,the titer of special anti-D IgG was 1∶（96±43.6） before plasma exchange,but it decreased to 1∶（18±14.7） after plasma exchange.There were significant difference between the titer of special anti-D IgG of pre-and post-treatment.It was from 1∶ 32 to 1∶ 256 during pregnancy in group B.There were 10 patients with maternal-fetal Rh（D） incompatibility hemolysis disease in group B,but it decreased to 4 patients in group A.The 10 cases of IgG anti-D,straight Coombs′test,liberation antibody were detected out in group B,but it decreased to 4 cases in group A.The serum bilirubin was（76.5±36）μmol/ L in group A and it was（154.6±46）μmol/ L in group B.Conclusion： FQ-PCR analysis for noninvasive prenatal of fetal RhD genotyping could be useful in prevention and diagnosis of hemolytic disease of newborn.The plasma exchange combined with comprehensive medications is safety,effective and recommendable in treating maternal-fetal Rh（D） incompatibility hemolysis disease.