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 fetuses/neonates and subsequent death or lifelong disability. FNAIT can occur in the antenatal period of a first pregnancy, where anti-HPA-1a alloantibodies have been observed as early as gestational week 17. HPA-1a alloimmunization and FNAIT are not included in standard prenatal screening. RLYB212 is being developed as the first potential drug to prevent alloimmunization against fetal HPA 1a and, therefore, prevent HPA-1a–related FNAIT.
OBJECTIVES: The main objective of the systematic literature review was to quantify the proportion of women at higher risk of HPA-1a alloimmunization and FNAIT (HPA-1a–negative, HLA-DRB3*0101–positive pregnant women) and those who became newly alloimmunized during an index pregnancy and postpartum period. We highlight the challenges of achieving this goal.
METHODS: PubMed and Embase were searched for articles published from 2008 through 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 Canada, Egypt, England, France, Germany, Ireland, Norway, Poland, and Scotland, published from 1985 through 2018, were included. Of 198,062 screened pregnant women, 2.2% (95% CI, 2.0%-2.5%) were HPA-1a negative; 32.3% (95% CI, 28.6%-36.1%) of HPA-1a–negative women were HLA-DRB3*01:01 positive (at higher risk of alloimmunization). None of the articles reported on newly alloimmunized women who carried HPA-1a−positive fetuses. The main challenges we encountered were: (1) published studies mostly sought to identify the number of individuals that would need treatment for FNAIT, rather than the number at risk for FNAIT; (2) there was high variability across studies in the di agnostic testing for risk of FNAIT (3) it was sometimes unclear whether the rarest outcomes were not assessed or simply not found.
CONCLUSIONS: Published studies did not answer the main objective of the systematic literature review. Studies on the natural history of HPA-1a alloimmunization and FNAIT are needed to fill this knowledge gap. Heterogeneity in study methodology, populations, and diagnostic testing of individuals at risk or who developed FNAIT further complicates the understanding of the natural history and consequences of FNAIT.
