Neurovascular Biomarkers for Retionpathy of Prematurity - Methodological and Clinical Aspects

Abstract

Background: Preterm infants face significantly increased risks of diseases, including retinopathy of prematurity (ROP), a potentially blinding neurovascular eye disease. ROP is caused by abnormal retinal neuro-vascularisation in the relatively oxygen-rich environment outside the womb and is exacerbated by suboptimal nutrition and environmental exposures. Although blood-based biomarkers show promise in predicting and monitoring ROP development, none is currently used in the clinic. Aim: This thesis investigated neurovascular biomarkers in the context of ROP, focusing on the clinical, methodological, and sample availability aspects necessary to advance biomarker research in preterm infants. Methods: • Paper I: A systematic review and meta-analysis of data on blood vascular endothelial growth factor-A (VEGF-A) levels as a vascular biomarker for predicting ROP and the systemic response to ROP treatment. • Papers II–III: Two cohort studies explored the association between serum brain injury biomarkers, particularly neurofilament light chain (NfL), and ROP development in preterm infants. • Paper IV: Feasibility study of a neonatal biobank using left-over clinical blood samples for biomarker research in extremely preterm infants. Main findings: Circulating VEGF-A showed post-treatment changes but lacked predictive value for ROP development. Serum NfL levels during the first postnatal weeks showed the potential to predict ROP in infants born at a gestational age ≥25 weeks but were unrelated to ROP in infants born at <25 weeks gestational age. Left-over clinical blood samples were a feasible resource for ethical biomarker studies. Conclusion: This thesis highlights the potential of biomarkers in neonatal research for disease prediction and treatment monitoring but notes limitations in traditional research methods. It identifies a link between a marker of neuronal damage and ROP development and demonstrates an ethical approach to collecting blood samples for research in a fragile population. These results may help to advance the use of biomarkers in neonatal medicine.