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.