Placenta-associated biomarkers and pregnancy outcome in HPA-1a alloimmunization: A prospective cohort study.

Introduction: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) results from parental incompatibility in human platelet antigens (HPA) and subsequent maternal sensitization. The HPA-1a epitope is also expressed on placental tissue. Chronic placental inflammation and lower birth weight is observed more often in HPA-1a alloimmunized pregnancies, suggesting a placental component in the pathophysiology of FNAIT. Today, prediction of FNAIT severity is limited. The aim of the study was to investigate whether dysregulated maternal angiogenic proteins are associated with neonatal outcome in HPA-1a alloimmunized pregnancies.
Material and Methods: Eighty-seven HPA-1a negative pregnant women were identified from a large prospective screening study in Poland (PREVFNAIT) including 43 HPA-1a immunized and 44 non-immunized controls. Placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) were measured in maternal plasma from 2nd and 3rd trimester by enzyme-linked immunosorbent assay and levels/ratios were compared between study groups, using uni- and multivariable analyses. Main outcome measures were either classic FNAIT-related (severe thrombocytopenia, petechia, intracranial hemorrhage), placenta-related (small for gestational age) or a composite variable combining them all.
Results: There were no significant differences in plasma concentrations of sFlt-1, PlGF, sEng nor sFlt-1/PlGF ratio when comparing immunized and non-immunized pregnancies. Among HPA-1a alloimmunized pregnancies, increasing levels of the sFlt-1 protein in 3rd trimester were significantly associated with lower neonatal platelet count (multivariable linear regression, p = 0.024). Increased sFlt-1 and sFlt-1/PlGF ratio in 3rd trimester were significantly associated with higher odds of a composite adverse neonatal outcome in alloimmunized pregnancies (multivariable logistic regression, p = 0.029 and p = 0.019, respectively).
Conclusion: An anti-angiogenic profile in HPA-1a alloimmunized mothers is associated with a composite adverse neonatal outcome. This suggests that sFlt-1 and the sFlt-1/PlGF ratio may assist in predelivery risk stratification and clinical management decisions for FNAIT.
Competing Interests: Declaration of competing interest AH is one of the founders and owners of Prophylix Pharma AS, which has been developing a prophylaxis for the prevention of FNAIT. All rights of the company were sold to RallyBio in 2019. ACT has in some previous research studies been provided with in-kind reagents from Roche Diagnostics (Rotkreuz, Switzerland) for sFlt-1 and PlGF biomarker analysis. HT received consulting fees as a research consultant and as member of steering committee for Janssen Research & Development, LLC, Spring House, PA, USA and previous payment from Prophylix AS related to patent on a monoclonal anti-HPA-1a antibody. HT is local study site principal investigator in an ongoing multicenter natural history study on FNAIT sponsored by Rallybio. The other authors report no conflict of interest.
(Copyright © 2024. Published by Elsevier Ltd.)