The Effect of High-Dose Erythropoietin Perinatally on Retinal Function in School-Aged Children Born Extremely or Very Preterm

Purpose: To investigate the long-term effects of high-dose recombinant human erythropoietin (rhEPO) administered during the perinatal period on retinal and visual function in children born extremely or very preterm.

Design: Randomized, double-blind clinical trial follow-up plus cohort study.

Methods: Setting: Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland.

Study population: Extremely or very preterm-born children aged 7 to 15 years, previously randomized to receive either high-dose rhEPO or placebo in the perinatal period.

Inclusion criteria: participation in an ongoing neuropediatric study (EpoKids), written informed consent.

Exclusion criteria: previous ocular trauma or surgery; retinal or developmental disease unrelated to prematurity. Healthy control (HC) children of comparable age were recruited.

Inclusion criteria: term birth, informed consent.

Exclusion criteria: any ocular/visual abnormality, high refractive error. Intervention status (rhEPO/placebo) was unknown to examiners and subjects at examination, with examiners unblinded only after completion of all analyses.

Observation procedures: The electroretinogram (ERG) was performed with the RETeval device (LKC Technologies, Inc). Ophthalmological and orthoptic examinations excluded comorbidity in the prematurely born cohort and ocular diseases in the HC group.

Main outcome measures: Scotopic and photopic ERG response amplitudes and peak times (6 amplitudes; 6 peak times). Secondary outcomes were habitual visual acuity and color discrimination performance (for descriptive summary only).

Results: No differences in ERG parameters between EPO (n = 52; 104 eyes) and placebo (n = 35; 70 eyes) subgroups were observed (all corrected P > .05). Two cone system-mediated peak times were slightly slower in the placebo than HC (n = 52; 104 eyes) subgroup (coefficient/95% confidence interval = 0.53/0.21-0.85 and 0.36/0.13-0.60; P = .012 and .022); a predominantly rod system-mediated peak time was slightly faster in the EPO than the HC subgroup (coefficient/95% confidence interval = -4.33/-6.88 to -1.78; P = .011). Secondary outcomes were comparable across subgroups.

Conclusions: Administration of high-dose rhEPO to infants born extremely or very preterm during the perinatal period has no measurable effects on retinal function in childhood compared to placebo. Premature birth may cause small, likely clinically insignificant effects on retinal function in childhood, which may be partially mitigated by administration of rhEPO during the perinatal period.