Department of Immunology and Transfusion Medicine, Oslo University Hospital, Oslo, Norway.
Department of Immunology and Transfusion Medicine, Akershus University Hospital, Lørenskog, Norway.
Acta Obstet Gynecol Scand. 2022 Apr;101(4):431-440. doi: 10.1111/aogs.14328. Epub 2022 Feb 27.
In September 2016, a nationwide targeted routine antenatal anti-D prophylaxis program was implemented in Norway. The prophylaxis (anti-D immunoglobulin) aims to cover the whole third trimester and is administered in gestational week 28 to RhD-negative women who carry RhD-positive fetuses. However, in many women, antibody screening at delivery does not detect anti-D immunoglobulin. The goal of this study was to investigate the presumable role of dose and timing of antenatal anti-D immunoglobulin administration in non-detectable prophylaxis at the time of delivery.
In this retrospective observational study, RhD-negative pregnant women who gave birth at Oslo University Hospital and Akershus University Hospital between January 2017 and December 2019 were analyzed. Women who received antenatal anti-D immunoglobulin (1500 IU at Oslo University Hospital and 1250 IU at Akershus University Hospital) when fetal RHD genotyping at gestational week 24 predicted an RhD-positive fetus were included if an antibody screen at delivery was available. Data from the blood bank, maternity information systems, and electronic patient records were used.
Analysis of the 984 RhD-negative women at the two hospitals revealed that 45.4% had non-detectable anti-D at delivery. A significant difference between the two hospitals was observed: 40.5% at Oslo University Hospital (n = 509) and 50.7% at Akershus University Hospital (n = 475) (p = 0.001). The proportion with non-detectable anti-D increased to 56.0 and 75.3%, respectively (p = 0.008) in the group of women who gave birth 12 weeks after routine antenatal anti-D prophylaxis. Significantly fewer women had detectable anti-D at delivery when the lower anti-D immunoglobulin dose (1250 IU) was administered antenatally. Multiple logistic regression indicated that the time interval between routine antenatal anti-D prophylaxis and delivery, in addition to anti-D dose, were significantly associated with detectable anti-D at delivery (p < 0.001).
We do not know which RhD-negative pregnant women, despite antenatal anti-D prophylaxis, are at risk of RhD alloimmunization, when antibody screening is negative at delivery. Administration of antenatal prophylaxis should probably be moved closer to delivery, since the risk of fetomaternal hemorrhage is higher during the last weeks of the third trimester.
2016 年 9 月，挪威在全国范围内实施了一项针对常规产前抗-D 预防的靶向计划。该预防措施（抗-D 免疫球蛋白）旨在覆盖整个第三个孕期，并在孕 28 周时为携带 RhD 阳性胎儿的 RhD 阴性妇女进行注射。然而，在许多妇女中，分娩时的抗体筛查并未检测到抗-D 免疫球蛋白。本研究的目的是探讨产前抗-D 免疫球蛋白的剂量和时间对分娩时无法检测到预防措施的可能作用。
在这项回顾性观察研究中，分析了 2017 年 1 月至 2019 年 12 月在奥斯陆大学医院和阿克什胡斯大学医院分娩的 RhD 阴性孕妇。如果分娩时的抗体筛查可用，且当胎儿在孕 24 周时进行 RHD 基因分型预测为 RhD 阳性胎儿时，接受过产前抗-D 免疫球蛋白（在奥斯陆大学医院为 1500IU，在阿克什胡斯大学医院为 1250IU）治疗的 RhD 阴性孕妇被纳入分析。本研究使用了血库、产妇信息系统和电子病历中的数据。
对两家医院的 984 名 RhD 阴性孕妇进行分析后发现，45.4%的孕妇在分娩时无法检测到抗-D。两所医院之间存在显著差异：奥斯陆大学医院为 40.5%（n=509），阿克什胡斯大学医院为 50.7%（n=475）（p=0.001）。在常规产前抗-D 预防后 12 周分娩的孕妇中，无法检测到抗-D 的比例分别上升至 56.0%和 75.3%（p=0.008）。在接受较低剂量（1250IU）产前抗-D 免疫球蛋白治疗的孕妇中，分娩时可检测到的抗-D 明显减少。多变量逻辑回归表明，除了抗-D 剂量外，常规产前抗-D 预防与分娩之间的时间间隔与分娩时可检测到的抗-D 显著相关（p<0.001）。
尽管进行了产前抗-D 预防，但我们仍不清楚哪些 RhD 阴性孕妇存在 RhD 同种免疫的风险，当分娩时的抗体筛查为阴性时。由于在第三个孕期的最后几周胎儿-母亲出血的风险更高，产前预防措施的给药时间可能需要更接近分娩。
