Neurodevelopmental Outcomes of Preterm Infants With Retinopathy of Prematurity by Treatment

Abstract

OBJECTIVE: Among extremely preterm infants, we evaluated whether bevacizumab therapy compared with surgery for retinopathy of prematurity (ROP) is associated with adverse outcomes in early childhood. METHODS: This study was a retrospective analysis of prospectively collected data on preterm (22-26 1 6/7 weeks' gestational age) infants admitted to the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers who received bevacizumab or surgery exclusively for ROP. The primary outcome was death or severe neurodevelopmental impairment (NDI) at 18 to 26 months' corrected age (Bayley Scales of Infant and Toddler Development, Third Edition cognitive or motor composite score ,70, Gross Motor Functional Classification Scale level $2, bilateral blindness or hearing impairment). RESULTS: The cohort (N = 405; 214 [53%] boys; median [interquartile range] gestational age: 24.6 [23.9-25.3] weeks) included 181 (45%) infants who received bevacizumab and 224 (55%) who underwent ROP surgery. Infants treated with bevacizumab had a lower median (interquartile range) birth weight (640 [541-709] vs 660 [572.5-750] g; P = .02) and longer durations of conventional ventilation (35 [21-58] vs 33 [18-49] days; P = .04) and supplemental oxygen (112 [94-120] vs 105 [84.5-120] days; P = .01). Death or severe NDI (adjusted odds ratio [aOR] 1.42; 95% confidence interval [CI] 0.94 to 2.14) and severe NDI (aOR 1.14; 95% CI 0.76 to 1.70) did not differ between groups. Odds of death (aOR 2.54 [95% CI 1.42 to 4.55]; P = .002), a cognitive score ,85

Bevacizumab for Retinopathy of Prematurity: 2-Year Neurodevelopmental Follow-up

“…Two studies 10,12 have found worse outcomes in infants treated with IVB. For instance, Morin et al 10 and Natarajan et al 12 found an increase in death or adverse ND outcome in infants treated with bevacizumab by 2 years of corrected age. These studies included infants who were diagnosed and treated at multiple and various medical centers.…”

“…The fact that IVB can seep into the systemic circulation and may potentially affect brain development of the preterm infant is concerning. 7,8 Several retrospective studies [9][10][11][12][13] have assessed the risk of neurodevelopmental impairment (NDI) related to IVB therapy in preterm infants but reported conflicting results. In addition, the population of periviable infants who are at highest risk for posteriorly located ROP disease, and who could be the most vulnerable subjects for the adverse effects of anti-VEGF therapy, was adequately represented in only one study that showed higher death and developmental impairment in the bevacizumab-treated group.…”

Current evidence and outcomes for retinopathy of prematurity prevention: insight into novel maternal and placental contributions

“…These animal findings were substantiated in humans when use of Avastin, a humanized anti-VEGF monoclonal antibody that had proven effective for pathological retinal neovascularization in adults, was first shown to be efficacious in treatment of ROP [35][36][37]. However, there is concern for potential adverse local and systemic effects of intraocular anti-VEGF treatments [38][39][40][41][42][43]. VEGF is now recognized as an important trophic factor for a variety of retinal cell types including retinal neurons, RPE, and glia [44,45].…”

Rétinopathie du prématuré : de la prévention au traitement

“…Or, le VEGF est indispensable au développement cérébral, rénal et pulmonaire. Des inquiétudes se sont faites jour à la suite de la publication d'études épidémiologiques montrant une association entre traitement par anticorps anti-VEGF et anomalies neuro-développementales à long terme [45]. Ces données restent toutefois à confirmer [46].…”