Chitty Lyn S, Finning Kirstin, Wade Angela, Soothill Peter, Martin Bill, Oxenford Kerry, Daniels Geoff, Massey Edwin
UCL Institute of Child Health, Great Ormond Street Hospital for Children NHS Foundation Trust and University College London Hospitals NHS Foundation Trust, London WC1N 3BH, UK
International Blood Group Reference Laboratory, NHS Blood and Transplant, Bristol BS34 7QH, UK Kirstin Finning.
BMJ. 2014 Sep 4;349:g5243. doi: 10.1136/bmj.g5243.
To assess the accuracy of fetal RHD genotyping using cell-free fetal DNA in maternal plasma at different gestational ages.
A prospective multicentre cohort study.
Seven maternity units in England.
RhD negative pregnant women who booked for antenatal care before 24 weeks' gestation.
Women who gave consent for fetal RHD genotyping had blood taken at the time of booking for antenatal care and, when possible, at other routine visits such as for Down's syndrome screening between 11 and 21 weeks' gestation, at the anomaly scan at 18-21 weeks, and in the third trimester when blood was taken for the routine antibody check. The results of cord blood analysis, done routinely in RhD negative pregnancies, were also obtained to confirm the fetal RHD genotyping.
The accuracy of fetal RHD genotyping compared with RhD status predicted by cord blood serology.
Up to four analyses per woman were performed in 2288 women, generating 4913 assessable fetal results. Sensitivity for detection of fetal RHD positivity was 96.85% (94.95% to 98.05%), 99.83% (99.06% to 99.97%), 99.67% (98.17% to 99.94%), 99.82% (98.96% to 99.97%), and 100% (99.59% to 100%) at <11, 11-13, 14-17, 18-23, and >23 completed weeks' gestation, respectively. Before 11 weeks' gestation 16/865 (1.85%) babies tested were falsely predicted as RHD negative.
Mass throughput fetal RHD genotyping is sufficiently accurate for the prediction of RhD type if it is performed from 11 weeks' gestation. Testing before this time could result in a small but significant number of babies being incorrectly classified as RHD negative. These mothers would not receive anti-RhD immunoglobulin, and there would be a risk of haemolytic disease of the newborn in subsequent pregnancies.
评估在不同孕周使用孕妇血浆中游离胎儿DNA进行胎儿RHD基因分型的准确性。
一项前瞻性多中心队列研究。
英国的7个产科单位。
在妊娠24周前预约产前检查的RhD阴性孕妇。
同意进行胎儿RHD基因分型的女性在预约产前检查时采血，如有可能，在其他常规就诊时采血，如在妊娠11至21周进行唐氏综合征筛查时、在18至21周进行畸形扫描时以及在妊娠晚期进行常规抗体检查时采血。还获取了RhD阴性妊娠常规进行的脐血分析结果，以确认胎儿RHD基因分型。
与脐血血清学预测的RhD状态相比，胎儿RHD基因分型的准确性。
对2288名女性每人进行了多达4次分析，得出4913个可评估的胎儿结果。在妊娠<11、11 - 13、14 - 17、18 - 23和>23完整孕周时，检测胎儿RHD阳性的敏感性分别为96.85%（94.95%至98.05%）、99.83%（99.06%至99.97%）、99.67%（98.17%至99.94%）、99.82%（98.96%至99.97%）和100%（99.59%至100%）。在妊娠11周前，865例检测婴儿中有16例（1.85%）被错误预测为RHD阴性。
如果在妊娠11周后进行大规模高通量胎儿RHD基因分型，对于预测RhD类型足够准确。在此之前进行检测可能会导致少量但显著数量的婴儿被错误分类为RHD阴性。这些母亲将不会接受抗RhD免疫球蛋白，并且在随后的妊娠中有新生儿溶血病的风险。
