Improving prediction of fetal/neonatal intracranial hemorrhage in HPA‐1a alloimmunized pregnancies to guide antenatal management: An observational cohort study

Introduction Maternal alloimmunization against human platelet antigen‐1a (HPA‐1a) may lead to severe intracranial hemorrhage (ICH) in the fetus or newborn as a life‐threatening complication of fetal neonatal alloimmune thrombocytopenia (FNAIT). Most women who are HPA‐1a‐alloimmunized do not have a fetus/neonate with ICH. In the absence of predictive tools to identify pregnancies with high risk of ICH outcome, most countries offer weekly antenatal IVIg to all recognized HPA‐1a‐alloimmunized pregnancies. Norwegian FNAIT guidelines are restrictive regarding antenatal IVIg administration and have a long‐standing tradition of longitudinal anti‐HPA‐1a antibody measurements when at‐risk pregnancies are identified, facilitating exploration of the natural history of alloimmunized pregnancies. We aimed to explore associations between maternal anti‐HPA‐1a antibody levels and risk of fetal/neonatal ICH in non‐IVIg treated HPA‐1a alloimmunized pregnancies and assess if an antibody level threshold can be useful for identifying pregnancies with increased ICH risk. Material and Methods We compared anti‐HPA‐1a levels both from clinically referred and prospectively identified, non‐IVIg treated, HPA‐1a‐immunized pregnancies stratified by previous neonatal FNAIT outcome (ICH or FNAIT without ICH) in Norway 1997–2023. Results Anti‐HPA‐1a levels in pregnancies with ICH outcome were higher (median 29.6 IU/mL, range 0.1–222.1, n = 15) compared to no ICH FNAIT pregnancies (median 10.4 IU/mL, range 0.0–83.1, n = 55; p = 0.046, Mann–Whitney U test). A suggestive anti‐HPA‐1a threshold of 70 IU/mL was chosen based on receiver operating characteristic (ROC) analysis, with high specificity values (96.4%). Conclusion Antenatal anti‐HPA‐1a levels may be useful when assessing the risk of ICH outcome and may enable a more targeted antenatal IVIg treatment both in a nonscreening and screening situation.