Introduction: Since anti-D immunoprophylaxis given to D-negative pregnant women is a blood product, blood donations have an impact on the availability of prophylactic doses. The Pan American Health Organization reported, in June 2017, that less than half of blood donors are volunteers in Latin America and the Caribbean. In these countries, guidelines for use of anti-D prophylaxis are still controversial. The aim of this study was to demonstrate the convenience of a simple and cost-effectivene non-invasive prenatal diagnostic assay for anti-D prophylaxis optimization in multiethnic populations. Methods: Cell-free fetal DNA from plasma samples of D-negative pregnant women were analyzed by real-time PCR for simultaneous amplification of sequences of exons 5 and 10 of the RHD gene. Fetal RHD genotype was determined in 111 pregnant women. Neonates' phenotype was determined 72 h after birth. Results: Genotyping predicted fetal phenotype with 100% accuracy. Prenatal diagnosis showed 78% RHD-positive and 22% RHD-negative neonates. Conclusion: We demonstrated that, beyond the large genetic variation of the Rh system and the numerous D variants present in multiethnic groups, non-invasive fetal RHD genotyping using two sequences of the gene can be enough for clinical application in an admixed population. This robust technique of simple implementation allows to determine fetal RHD in maternal blood with high sensitivity, specificity, and accuracy. The introduction of fetal RhD genotyping as part of an antenatal screening program constitutes a reliable manner to optimize anti-D prophylaxis; however, it has not been implemented so far in most American countries.

中文翻译：

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非侵入性胎儿 RHD 基因分型对于优化免疫预防的有用性


简介：由于 D 阴性孕妇接受的抗 D 免疫预防是一种血液制品，因此献血会影响预防剂量的可用性。泛美卫生组织 2017 年 6 月报告称，拉丁美洲和加勒比地区只有不到一半的献血者是志愿者。在这些国家，抗 D 预防的使用指南仍然存在争议。本研究的目的是证明一种简单且经济有效的非侵入性产前诊断测定对于多种族人群中抗 D 预防优化的便利性。方法：通过实时 PCR 分析 D 阴性孕妇血浆样本中的游离胎儿 DNA，同时扩增 RHD 基因外显子 5 和 10 的序列。对 111 名孕妇进行了胎儿 RHD 基因型测定。新生儿的表型在出生后72小时测定。结果：基因分型预测胎儿表型的准确度为 100%。产前诊断显示，78% 的新生儿为 RHD 阳性，22% 的新生儿为 RHD 阴性。结论：我们证明，除了 Rh 系统的巨大遗传变异和多种族群体中存在的众多 D 变异之外，使用该基因的两个序列进行非侵入性胎儿 RHD 基因分型足以在混合人群中进行临床应用。这种简单实施的强大技术允许以高灵敏度、特异性和准确性确定母体血液中的胎儿 RHD。将胎儿 RhD 基因分型作为产前筛查计划的一部分引入，是优化抗 D 预防的可靠方法；但迄今为止，大多数美国国家尚未实施。