Cerebral injury and retinopathy as risk factors for blindness in extremely preterm infants.

Objective: This study investigates whether and to what extent cerebral injury is associated with bilateral blindness in extremely preterm infants, which has been attributed mainly to retinopathy of prematurity (ROP).
Design: Multicentre analysis of children born from 1994 to 2021 at gestational age 22 0/7 to 28 6/7 weeks with follow-up at 18-26 months. Logistic regression examined the adjusted association of bilateral blindness with severe ROP and/or cerebral injury among extremely preterm infants.
Exposures: Severe ROP and cerebral injury, the latter defined as any of the following on cranial imaging: ventriculomegaly; blood/increased echogenicity in the parenchyma; cystic periventricular leukomalacia.
Main Outcome Measures: Bilateral blindness, defined as a follow-up examination meeting criteria of 'blind-some functional vision' or 'blind-no useful vision' in both eyes.
Results: The 19 863 children included had a mean gestational age of 25.6±1.7 weeks, mean birth weight of 782±158 g and 213 (1%) had bilateral blindness. Multiplicative interaction between ROP and cerebral injury was statistically significant. For infants with only severe ROP (n=3130), odds of blindness were 8.14 times higher (95% CI 4.52 to 14.65), and for those with only cerebral injury (n=2836), odds were 8.38 times higher (95% CI 5.28 to 13.28), compared with the reference group without either condition. Risks were not synergistic for infants with both severe ROP and cerebral injury (n=1438, adjusted OR=28.7, 95% CI 16.0 to 51.7, p<0.0001).
Conclusions: In a group of extremely preterm infants, severe ROP and cerebral injury were equally important risk factors for blindness. Besides ROP, clinicians should consider cerebral injury as a cause of blindness in children born extremely preterm.
Trial Registration Number: NCT00063063.
Competing Interests: Competing interests: NA is an advisor to ResBiotic and Alveolus Bio and serves on the Data and Safety Monitoring Board for Shire/Oak Hill Bio. CMC has a consulting agreement with ReAlta Life Sciences (for a new drug in clinical trials for hypoxic ischaemic encephalopathy), and IP in a company, CryoCell (for a cell therapy for HIE). AD has a grant from the Neonatal Research Network (NRN). CPT is supported by grants from the National Institutes of Health (K23HL157618). CPT is supported by a grant from Owlet Baby Care for an investigator-initiated study (ClinicalTrials.gov identifier: NCT05774470) and also has a patent application pending for a bradycardia predictor and interrupter. VVS is supported by a grant from the American Heart Association (23CDA1048106).
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