Effect of high throughput RHD typing of fetal DNA in maternal plasma on use of anti-RhD immunoglobulin in RhD negative pregnant women:: prospective feasibility study
Effect of high throughput RHD typing of fetal DNA in maternal plasma on use of anti-RhD immunoglobulin in RhD negative pregnant women:: prospective feasibility study
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DOI：
10.1136/bmj.39518.463206.25
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发表时间：
2008-04-01
影响因子：
--
通讯作者：
Daniels, Geoff
中科院分区：
文献类型：
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作者：
Finning, Kirstin;Martin, Pete;Daniels, Geoff
目的 评估应用高通量方法和自动化机器人技术，根据 RhD 阴性孕妇血浆中胎儿 DNA 预测胎儿 RhD 表型的可行性，以避免不必要的抗 RhD 免疫球蛋白治疗。设计 对母体血浆中胎儿 DNA 确定的胎儿 RHD 基因型与脐带血血清学确定的胎儿 RhD 表型进行前瞻性比较。在英格兰中部和北部设立产前诊所和产前检测实验室，并建立国际血液中心组参考实验室。参与者 已知妊娠期的孕妇，经产前检测实验室鉴定为 RhD 阴性。在第 28 周产前检查时或之前采集了 1997 名妇女的样本。 主要结果指标 母体血浆中胎儿 RhD 的检出率、错误率、假阳性率以及阳性结果受影响的几率。 结果 从 1869 份脐带血样本中获得了血清学测定的 RhD 表型。 95.7% (n=1788) 的胎儿 RhD 表型通过基因分型测试预测正确。 3.4% (n=64) 的结果要么无法获得，要么不确定。 0.8%（14 个样本）出现假阳性结果，可能是由于胎儿 RHD 基因未表达或表达较弱。仅三个样本 (0.2%) 获得假阴性结果。如果将这些结果用作治疗指南，则只有 2% 的妇女会不必要地接受抗 RhD，相比之下，如果没有进行基因分型，这一比例为 38%。 结论 对所有 RhD 阴性妇女的胎儿进行高通量 RHD 基因分型是可行的，并且将大大减少对胎儿为 RhD 阴性的孕妇不必要的抗 RhD 免疫球蛋白注射。
Objectives To assess the feasibility of applying a high throughput method, with an automated robotic technique, for predicting fetal RhD phenotype from fetal DNA in the plasma of RhD negative pregnant women to avoid unnecessary treatment with anti-RhD immunoglobulin.Design Prospective comparison of fetal RHD genotype determined from fetal DNA in maternal plasma with the serologically determined fetal RhD phenotype from cord blood.Setting Antenatal clinics and antenatal testing laboratories in the Midlands and north of England and an international blood group reference laboratory.Participants Pregnant women of known gestation identified as RhD negative by an antenatal testing laboratory. Samples from 1997 women were taken at or before the 28 week antenatal visit.Main outcome measures Detection rate of fetal RhD from maternal plasma, error rate, false positive rate, and the odds of being affected given a positive result.Results Serologically determined RhD phenotypes were obtained from 1869 cord blood samples. In 95.7% (n=1788) the correct fetal RhD phenotype was predicted by the genotyping tests. In 3.4% (n=64) results were either unobtainable or inconclusive. A false positive result was obtained in 0.8% (14 samples), probably because of unexpressed or weakly expressed fetal RHD genes. In only three samples (0.2%) were false negative results obtained. If these results had been applied as a guide to treatment, only 2% of the women would have received anti-RhD unnecessarily, compared with 38% without he genotyping.Conclusions High throughput RHD genotyping of fetuses in all RhD negative women is feasible and would substantially reduce unnecessary administration of anti-RhD immunoglobulin to RhD negative pregnant women with an RhD negative fetus.