Neonatal antiphospholipid syndrome-associated thrombosis: Diagnostic pitfalls and therapeutic frontiers

Neonatal antiphospholipid syndrome (APS) is an exceptionally rare but clinically significant thrombotic disorder associated with antiphospholipid antibodies (aPL) in the neonatal period. Two principal pathogenic mechanisms have been proposed: passive transplacental transfer of maternal antiphospholipid antibodies and de novo neonatal production of aPL. Although approximately 30% of neonates born to aPL-positive mothers exhibit detectable antibodies at birth, thrombotic complications remain exceedingly uncommon. A "second-hit" model involving additional prothrombotic triggers such as infection, perinatal stress, inherited thrombophilia, or vascular catheters likely contributes to thrombogenesis. Available evidence from case reports and small series indicates that arterial thrombosis predominates, particularly neonatal arterial ischemic stroke, while venous thrombosis is less frequent. Diagnosis remains challenging because no validated neonatal-specific classification criteria exist, and interpretation of laboratory findings is confounded by transient maternal antibody transfer. Current diagnostic approaches rely on clinical suspicion, thrombosis confirmation, maternal antibody testing, serial neonatal aPL measurements, and exclusion of other prothrombotic conditions. Management strategies are extrapolated from pediatric and adult APS guidelines, with low-molecular-weight heparin representing the mainstay of anticoagulant therapy in affected neonates. Neonatal APS remains a diagnostic challenge due to its rarity and atypical presentations. Establishing age-specific criteria and long-term neurodevelopmental follow-up is critical for improving clinical outcomes and understanding the prognosis of this early-onset autoimmune condition. This narrative review aims to summarize current evidence regarding the pathophysiology, clinical manifestations, diagnostic challenges, and management of APS-associated thrombosis regarding the distinct neonatal population.