Bevacizumab and neurodevelopmental outcomes of preterm infants with retinopathy of prematurity: should we still worry?

AIM

Bevacizumab may affect preterm infants' ongoing organogenesis with its antiangiogenic effects. We aimed to compare neurodevelopmental outcomes (NDO) of preterm infants treated for retinopathy of prematurity (ROP) with laser photocoagulation (LP), intravitreal bevacizumab (IVB) or both treatments, and to find out the effects of IVB on NDO.

METHODS

Medical records of preterm infants with ROP treatment and evaluation for NDO were retrospectively collected between 1 January 2017 and 31 June 2019. Primary outcome was Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III) scores including cognitive, language, and motor scores. Secondary outcomes were neurodevelopmental impairments (NDIs) classified as the presence of any of cerebral palsy (CP), sensorineural/mixed hearing loss, visual impairment, and developmental delay with any Bayley-III score <85. Severe NDI (sNDI) was defined as presence of any of CP with a Gross Motor Function Classification Scale of 3, 4, or 5, requirement for hearing aids or cochlear implants, bilateral visual impairment or severe developmental delay with any Bayley-III score <70.

RESULTS

LP, IVB, and IVB + LP groups included 32, 12, and 10 patients, respectively. Patent ductus arteriosus treatment rates were as 68.7, 75, and 90% in groups, respectively (<.05 between LP and IVB + LP groups). Grades 3 and 4 intraventricular hemorrhage (IVH) was lower in LP group than IVB group (9.4% vs. 33.4%, <.05) while IVB + LP group had no grades 3 and 4 IVH. Other neonatal characteristics were similar ( > .05). CP was in 50%, 28%, and 0% of LP, IVB, and IVB + LP groups (<.05). There was no difference in median Bayley-III cognitive, language, and motor scores between groups ( > .05). Moderate and severe developmental delays were similar between groups ( > .05) whereas IVB group had more moderate cognitive delay; and more severe cognitive, language, and motor delay. NDI rate was not different (59.3%, 50%, and 40% in groups,  > .05). sNDI was highest in IVB group but not statistically significant (31.2, 41.7, and 10% in groups,  > .05). Multiple logistic regression analysis showed that ROP treatment type and grades 3 and 4 IVH did not have any significant effect on NDO ( > .05). Odds of NDI was not effected by ROP treatment type ( > .05).

CONCLUSIONS

Patients treated with bevacizumab should be carefully monitored for neurodevelopmental problems, although the frequency of grades 3 and 4 IVH in the bevacizumab group is thought to contribute to higher rates of sNDI and Bayley-III score <70.