BACKGROUND: Fetal/neonatal alloimmune thrombocytopenia (FNAIT) results from maternal alloimmunization against fetal human platelet antigens (HPA). It is a rare and potentially devastating condition that can cause intracranial hemorrhage in the fetus/neonate and subsequent death or lifelong disability. Prenatal screening does not usually include FNAIT; no therapy is available to prevent alloimmunization. Mother–fetus mismatch on antigen HPA-1a accounts for 75%-80% of FNAIT cases; alloimmunizat ion is ~25-fold more frequent in women also positive for the allele HLA-DRB3*01:01. RLYB212 is in development to prevent HPA-1a–related FNAIT and its consequences. Clinical development of RLYB212 requires real-world evidence on the size of the atrisk population and frequency of pregnancy/neonatal outcomes from FNAIT under standard care. This literature review was conducted to fill this knowledge gap.
OBJECTIVE: To quantify the frequency of HPA-1a–negative, HLA-DRB3*01:01–positive pregnant women, those who were newly alloimmunized (in the current pregnancy or parturition) and carrying an HPA-1a positive fetus, and associated pregnancy/neonatal outcomes.
METHODS: PubMed and Embase were searched for articles published in 2008-2021; earlier studies were identified from existing reviews. Two reviewers independently applied prespecified criteria to determine inclusion. Article quality was assessed.
Results of meta-analysis using random-effects models are presented (PROSPERO registration: CRD42022309672).
RESULTS: Searches identified 501 unique records; 12 observational cohort studies from Europe, Canada, and Egypt published from 1985 through 2018 were selected. Article quality was generally adequate. Of 198,062 screened pregnant women, 2.2% (95% confidence interval, 2.0%-2.5%) were HPA-1a negative; 32.3% (28.6%-36.1%) of HPA-1a–negative women were HLA-DRB3*01:01 positive (at higher risk for alloimmunization). Articles did not report on newly alloimmunized women who carried HPA-1a positive fetuses. Approximately 10% of HPA-1a–negative women were alloimmunized to HPA-1a. The prevalence of intracranial hemorrhage was 2.2% (0.7%-4.4%) among newborns of HPA-1a–negative women with unknown HLA-DRB3 status and an HPA-1a–positive/genotype unknown partner/fetus.
CONCLUSIONS: Published research did not report on new alloimmunization, which is needed to inform RLYB212 clinical development, but confirmed frequency of FNAIT risk factors and outcomes. A natural history study to fill this knowledge gap, along with the planned trial to assess RLYB212’s efficacy, is needed to characterize the potential value of RLYB212 in standard care.
