van 't Oever Renske M, Verweij E Joanne T, de Haas Masja
Division of Fetal Therapy, Department of Obstetrics, Leiden University Medical Center, Leiden, The Netherlands.
Division of Translational Immunohematology, Department of Sanquin Research and Landsteiner Laboratory, Amsterdam University Medical Center, Amsterdam, The Netherlands.
Blood. 2025 May 15;145(20):2266-2274. doi: 10.1182/blood.2023022893.
Alloimmunization during pregnancy occurs when a mother produces antibodies against fetal antigens, leading to complications like hemolytic disease of the fetus and newborn (HDFN) and fetal and neonatal alloimmune thrombocytopenia (FNAIT). HDFN involves destruction of fetal red blood cells, potentially causing severe anemia, hydrops fetalis, and fetal death. FNAIT affects fetal platelets and possibly endothelial cells, resulting in risk of intracranial hemorrhage and brain damage. Traditional invasive methods for fetal antigen genotyping, like amniocentesis, carried miscarriage risks. The discovery of cell-free fetal DNA (cff-DNA) in maternal plasma enabled safe, noninvasive prenatal testing (NIPT). Initially used for Rhesus antigen D blood group typing, NIPT now covers various blood group antigens. Advances in technology have further enhanced the accuracy of NIPT. Despite challenges such as low cff-DNA fractions and complex genetic variations, NIPT has become essential in managing alloimmunized pregnancies. In NIPT it is important to prevent both false-positive results and false-negative results. Particularly in the coming decades, more possibilities for personalized antenatal treatment for HDFN and FNAIT cases will become apparent and accurate NIPT blood group antigen typing results are crucial for guiding clinical decisions. In this paper we describe this journey and provide practical tools for the clinic.
孕期同种免疫是指母亲产生针对胎儿抗原的抗体，从而导致胎儿和新生儿溶血病（HDFN）以及胎儿和新生儿同种免疫性血小板减少症（FNAIT）等并发症。HDFN涉及胎儿红细胞的破坏，可能导致严重贫血、胎儿水肿和胎儿死亡。FNAIT影响胎儿血小板，也可能影响内皮细胞，导致颅内出血和脑损伤风险。传统的胎儿抗原基因分型侵入性方法，如羊膜穿刺术，存在流产风险。母血中游离胎儿DNA（cff-DNA）的发现使得安全、无创的产前检测（NIPT）成为可能。NIPT最初用于RhD抗原血型分型，现在涵盖多种血型抗原。技术进步进一步提高了NIPT的准确性。尽管存在诸如cff-DNA含量低和基因变异复杂等挑战，但NIPT在管理同种免疫妊娠中已变得至关重要。在NIPT中，防止假阳性结果和假阴性结果都很重要。特别是在未来几十年，针对HDFN和FNAIT病例的个性化产前治疗将有更多可能性，而准确的NIPT血型抗原分型结果对于指导临床决策至关重要。在本文中，我们描述了这一历程并为临床提供实用工具。
