Retinopathy of Prematurity Is a Biomarker for Pathological Processes in the Immature Brain

Introduction: Retinopathy of prematurity (ROP) is considered a neurovascular disease. We investigated whether ROP, mild or severe, is associated with neurodevelopmental impairment (NDI) in extremely preterm children. Methods: We conducted a multicenter retrospective cohort study in southern Taiwan. A total of 394 children <28 weeks of gestation who survived to discharge from 2011 to 2018 received neurodevelopmental assessment at corrected age of 24 months. Severe ROP was defined as ROP of stages 2 plus or worse, or recipients of retinal therapy, and mild ROP as stage 1 or 2 in at least one eye. NDI was defined as cognitive or motor impairment using the Bayley Scales of Infant and Toddler Development, moderate to severe cerebral palsy, or profound hearing loss. Results: Among the 374 children validated for analysis, 157 children (42%) had non-ROP, 145 (39%) mild ROP, and 72 (19%) severe ROP. As ROP severity increased progressively from non-ROP, to mild ROP, and to severe ROP, the rates of NDI increased from 25%, to 46%, and to 61%. The multivariable logistic regression showed that the model included three levels of ROP, and neonatal morbidities achieved better overall performance for NDI than the model that included neonatal morbidities alone. Compared with non-ROP, mild ROP and severe ROP had adjusted odds ratios of 1.90 (95% CI: 1.10-3.28) and 2.75 (95% CI: 1.33-5.67) for NDI, respectively. Conclusion: Mild ROP and severe ROP are independent neonatal morbidities associated with NDI. Neurodevelopmental follow-up of extremely preterm children with any stage of ROP is needed.