Neonatal Thromboembolic Disease: Clinical Spectrum and Emerging Evidence for Diagnostic and Therapeutic Strategies Addressing Unmet Needs

Neonatal thromboembolic (TE) disease is an increasingly recognized clinical entity, driven by the physiological uniqueness of developmental hemostasis, improved survival of preterm infants, and the widespread use of invasive supportive technologies. Most neonatal thrombotic events are associated with central venous and arterial catheterization which are considered the most significant modifiable risk factors. The clinical spectrum encompasses catheter-related thrombosis, perinatal stroke and site-specific entities such as renal vein and portal vein thrombosis. Each condition presents distinct challenges such as neurological complications, chronic organ dysfunction and portal hypertension. Diagnosis relies primarily on Doppler ultrasonography, though its sensitivity is limited in deep-vessel scenarios, often requiring advanced modalities like magnetic resonance imaging (MRI) or magnetic resonance angiography (MRA). Therapeutic interventions remain controversial due to a lack of high-quality evidence, with current guidelines largely based on observational data. Ultimately, managing neonatal TE requires a nuanced, individualized approach that balances the risk of thrombus extension against the inherent hemorrhagic vulnerability of the neonate. This review aims to provide a comprehensive and up-to-date overview of neonatal TE, emphasizing major clinical entities and diagnostic strategies. It highlights current evidence gaps and outlines future directions, including the need for standardized management protocols and high-quality prospective research.