A Clinical Practice Guideline for the Management of Pregnancy Alloimmunized to Red Blood Cell Antigens

Importance Red blood cell alloimmunization is typically associated with the transplacental transfer of incompatible fetal red blood cells into maternal circulation. Subsequent pregnancies can be affected by fetal anemia, hydrops fetalis, and perinatal death. Most cases of Rhesus D (RhD) alloimmunization due to pregnancy can be prevented by the proper administration of Rhesus immune globulin. However, an emerging practice of using low-titer, O, RhD-positive whole blood (LTOWB) in cases of life-threatening hemorrhage has the potential to increase the exposure of the female population to a new source of incompatible red blood cells. Objective To establish recommendations for the management of the red blood cell alloimmunized pregnancy. Evidence Four working groups were assembled that included experts in (1) trauma and transfusion medicine, (2) hematology, (3) maternal-fetal medicine/obstetrics, and (4) neonatology. Patient stakeholders and ethics representatives were included in each working group. The patient/problem, intervention, comparison, outcome (PICO) framework was used to identify key clinical knowledge gaps. Library scientists at Johns Hopkins University performed systematic reviews and meta-analyses on these topics and provided final reports to the working groups. All 4 working groups participated in a Delphi process to refine recommendations and practice points for each PICO question that reflected consideration of the following factors: balance of benefits and harms; certainty of evidence; values and preferences; resource use and costs; ethics; equity; and feasibility. Findings Seven clinical recommendations and 32 practice points were developed by the maternal-fetal medicine/obstetrics working group. Recommendations included the following: use of cell-free fetal DNA to identify the at-risk fetus early in pregnancy, followed by immunomodulation with intravenous immune globulin (IVIG) in select cases; the implementation of middle cerebral artery peak systolic velocity Doppler measurements to detect fetal anemia earlier in pregnancy; the use of IVIG in patients with a documented antigen-positive fetus with a history of either fetal anemia or a fetal loss due to hemolytic disease of the fetus and newborn before 24 weeks’ gestational age in a previous pregnancy; the continuation of intrauterine transfusion therapy until the end of the 35th week of pregnancy; and prolonging gestational age to between 37 weeks 0 days and 38 weeks 6 days before proceeding to delivery. Conclusions and Relevance These recommendations provide an updated approach to the management of red blood cell alloimmunized pregnancies. The lack of high-quality evidence limits the strength of the recommendations but points to the need for a standardized approach to this rare disease.