Direct Measurement of RhD Sensitization Following Bleeding in Pregnancy Less than 12 Weeks Gestation

Rh Immunoglobulin (RhIg) is a human blood product with finite supply. There is currently a shortage in the United States, and international shortages are common. There is proven benefit for giving RhIg at delivery and in the 3rd trimester. However, there is mounting evidence from population studies and indirect clinical research showing that there is limited benefit to giving RhIg for bleeding in pregnancy at <12 weeks gestation. Professional medical societies are divided in their clinical guidance. The World Health Organization (WHO), Society of Family Planning (SFP), and American College of Obstetricians and Gynecologists (ACOG), among others, do not recommend giving RhIg at <12 weeks gestation. The Society for Maternal Fetal Medicine in the United States still recommends RhIg at all gestational ages, and some international recommendations fall in between. Many organizations allow for shared decision-making with patients outside of routine recommendations; however, to date we do not have published data on patient preferences about RhIg. There is not currently a unified standard of care and patients are caught in the middle. The long-term goal of this research is to identify the earliest gestational age at which RhIg administration is necessary and redistribute this finite human blood product for evidence-based indications. The specific objectives of this proposal are to directly measure the rate of sensitization in pregnant patients with bleeding at <12 weeks gestation and ascertain patient risk tolerance pertaining to RhIg. The central hypothesis is that <1.5% of patients will become sensitized following bleeding at <12 weeks gestation. The rationale for the proposed research is that directly measuring sensitization will align professional medical organization recommendations, conserve this human blood product for evidence-based indications, and potentially save the U.S. healthcare system $313 million annually. This study will fill that gap from two perspectives: direct scientific evidence determining the RhD-sensitization rate after bleeding in RhD-negative patients foregoing RhIg, and patient perspectives on risk using discrete choice experiments. The proposed work is innovative because it has the power to shift the paradigm for RhD status determination and RhIg administration in early pregnancy and inform alignment of professional medical organization recommendations around evidence-based, patient-informed care. At the completion of this project, results from Aim 1 will inform the science and recommendations for clinical care, and Aim 2 will provide the patient perspective to allocate this finite resource where it is most valued, and support evidence-based, high-value healthcare. Project Number: 1R01HD116890-01A1 | Fiscal Year: 2025 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: Sarah Horvath | Institution: PENNSYLVANIA STATE UNIV HERSHEY MED CTR, HERSHEY, PA | Award Amount: $666,573 | Activity Code: R01 | Study Section: Special Emphasis Panel[ZRG1 HSS-G (90)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R01HD11689001A1