Impaired Neurodevelopment in Preemies Screened for Retinopathy: Nature or Nurture?

Having public health insurance was associated with an increased risk of neurodevelopmental impairment among infants screened for retinopathy of prematurity (ROP), a retrospective cohort study suggested.

In a diverse cohort of 706 premature neonates, public heath insurance was associated with an increased risk of moderate to severe neurodevelopmental impairment in cognitive and language domains, and to a lesser extent, in the motor domain, reported Irena Tsui, MD, of the David Geffen School of Medicine at the University of California Los Angeles, and colleagues:

• Cognitive: OR 3.65 (95% CI 2.28-5.86)
• Language: OR 3.96 (95% CI 2.61-6.02)
• Motor: OR 2.60 (95% CI 1.59-4.24)

In unadjusted analyses, infants with ROP who received either laser or anti-vascular endothelial growth factor (VEGF) treatment had lower Bayley Scales of Infant and Toddler Development (BSID) scores in multiple domains at 0 to 12 months, 12 to 24 months, and 24 to 36 months compared with infants without treatment-requiring ROP. However, multivariable analyses found no link between treatment type and worse neurodevelopmental outcomes in any domain, the authors noted in JAMA Ophthalmology.

This study highlights “the complexities of neurodevelopment,” Tsui and colleagues wrote, as well as “the potential role of socioeconomic factors in the neurodevelopment of high-risk infants and supports the early neurodevelopmental safety of anti-VEGF treatment in infants diagnosed with retinopathy of prematurity.”

Timothy G. Murray, MD, of Murray Ocular Oncology and Retina in Miami and past president of the American Society of Retina Specialists, told MedPage Today that “most ophthalmologists think that the use of an anti-VEGF treatment does not alter infants’ neurodevelopment,” adding that concerns about the effects of anti-VEGF treatment on neurological development in premature infants were based on small or underpowered studies.

Current practice patterns reflect a transition to “anti-VEGF treatment, which is much more effective than traditional laser therapy, particularly in micro preemies with advanced, severe ROP,” he said. “The single greatest impact on premature infants’ cognitive development overall is visual function.”

Notably, about 50% of infants born before 28 weeks of gestational age have some degree of neurodevelopmental impairment, Tsui and co-authors said, with outcomes ranging from mild motor and cognitive delay to severe cerebral palsy.

Data on the nature of the association between ROP and neurodevelopmental impairment are conflicting, they added. Some studies have suggested that the increased odds of neurodevelopmental impairment in infants with ROP are due to associated early and late visual impairment, while others have linked neurodevelopmental impairment in this population to interruption of retinal and brain development.

Tsui and co-authors also pointed to their previous research that showed that the “associations between severe neurodevelopmental impairment and ROP were due to shared mediators or confounders such as low birth weight.”

“Our study results suggest that lower birth weight, diagnosis of intraventricular hemorrhage, increased gestational age at time of Bayley assessment, and male sex were independently associated with increased risk of adverse neurodevelopmental outcomes,” they wrote.

“Although certainly public health insurance may come with various barriers to timely access to healthcare, it is important to acknowledge that public health insurance status may reflect social and historical disadvantages other than simply access to care, including financial instability, parental educational opportunities, race and ethnicity, and low familial support,” they noted.

“Obtaining a better understanding of factors correlating neurodevelopmental outcomes in infants screened for ROP, particularly infants found to have severe ROP requiring treatment, can help better inform both clinical decision-making as well as caregiver counseling,” they added.

For this study, Tsui and team used electronic medical records from four California neonatal intensive care units and U.S. Census Bureau income data. The 706 included infants met American Academy of Pediatrics guidelines for ROP screening and had records from at least one BSID neurodevelopment assessment between 0 and 36 months of adjusted age.

Mean gestational age was 28.6 weeks, and 53% were boys. Reflecting the cohort’s diversity, 43.8% were white, 24.8% were Hispanic, 12.3% were Asian, 12% were Black, and 7.1% were unknown or another race. Notably, 29.5% had public health insurance.

As for study limitations, the authors noted that only a subset of infants screened for ROP had Bayley data available, which may have introduced selection bias. In addition, they found that older age at the time of neurodevelopmental assessment was associated with an increased risk of neurodevelopmental impairment in the cognitive and language domains, “which likely reflects the fact that infants considered higher risk for neurodevelopmental impairment are the infants who are followed up to older ages.”

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