Fetal and neonatal alloimmune thrombocytopenia (FNAIT) risk across racial and ethnic populations: interim data from an international, prospective natural history study

Objective Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare disease that can result in severe bleeding in a fetus or newborn, including intracranial hemorrhage. Maternal-fetal human platelet antigen (HPA)-1a incompatibility is a prerequisite to maternal HPA-1a alloimmunization, which may result in FNAIT. The risk of HPA-1a alloimmunization is approximately 25-times higher in HPA-1a negative (HPA-1b/b) women who are also positive for the HLA-DRB3*01: 01 allele. To date, studies characterizing the frequency of HPA-1a negative women (~2%) who are also positive for HLA-DRB3*01: 01 (~27%) have predominantly been conducted in White European populations. The primary objective of this longitudinal, prospective, non-interventional, natural history study (IPA2002/NCT05345561) is to determine the frequency of higher risk for HPA-1a alloimmunization and subsequent development of FNAIT among a racially and ethnically diverse cohort of pregnant women. Herein we report interim data. Methods Pregnant women aged ≥18 years with no history of FNAIT were enrolled across 28 sites in the United States of America (19), Europe (8), and Canada (1). Blood samples were collected at gestational weeks 10-14 and studied using four sequentially-performed screening tests to identify women at higher risk for HPA-1a alloimmunization: 1. HPA-1b/b genotype (HPA-1a negative); 2. HLA-DRB3*01: 01 allele positive; 3. Anti-HPA-1a-specific antibody test negative (demonstrating no pre-existing HPA-1a alloimmunization); and 4. carrying an HPA-1a positive fetus (cell-free fetal DNA). The proportion of women who were HPA-1a negative and those who were also HLA-DRB3*01: 01 positive were analyzed by region (Europe and North America), race (American Indian or Alaska Native, Asian, Black or African American, Native Hawaiian or Other Pacific Islander, White), and ethnicity (Hispanic/Latino, not Hispanic/Latino). Race and ethnicity were self-reported. Results In total, 14,038 pregnant women provided informed consent, of whom 13,773 (98.1%) had completed all required screening laboratory tests as of December 2024; 30.4% lived in Europe and 69.6% in North America. The screened population was also predominantly White (71.3%), Black or African American (14.9%), or Asian (11.5%); 22.4% were Hispanic/Latino. The frequency of HPA-1a negative pregnant women was 1.7% (233/13,773); 1.9% (78/4,181) in Europe and 1.6% (155/9,592) in North America. The frequency of HLA-DRB3*01: 01 positivity among those women who were HPA-1a negative was 19.7% (46/233); 21.8% (17/78) in Europe and 18.7% (29/155) in North America. HPA-1a negative frequency by race and ethnicity was: White 2.0% (197/9,826); Black or African American 1.0% (21/2,054); Asian 0.7% (11/1,579); American Indian or Alaska Native 2.7% (3/110); and Native Hawaiian/Other Pacific Islander 2.2% (3/132). HPA-1a negative frequency among Hispanic/Latino women was 1.3% (39/3,088) and among non-Hispanic/Latino women it was 1.8% (194/10,685). The frequency by race and ethnicity of HLA-DRB3*01: 01 positive women among those HPA-1a negative was: White 20.3% (40/197); Black or African American 19.1% (4/21); Asian 0% (0/11); American Indian or Alaska Native 0% (0/3); Native Hawaiian/Other Pacific Islander 33.3% (1/3). Among Hispanic/Latino women it was 23.1% (9/39); among non Hispanic/Latino women it was 19.1% (37/194). Conclusion This natural history study is unique in identifying rates of HPA-1a negative FNAIT risk in a racially and ethnically diverse international population of pregnant women. Estimates of HPA-1a negative, and HPA-1a negative/HLA-DRB3*01: 01 positive higher-risk groups in the White population were consistent with previously reported estimates. While differences among groups were observed, the non-White population and the Hispanic/Latino population also included women who were HPA-1a negative and HPA-1a negative/HLA-DRB3*01: 01 positive. These results suggest that screening strategies to assess risk of HPA-1a alloimmunization and FNAIT should include pregnant women of all races and ethnicities.