Pulmonary Hypertension in Preterm Infants Treated With Laser vs Anti–Vascular Endothelial Growth Factor Therapy for Retinopathy of Prematurity

Abstract

Anti-vascular endothelial growth factor (VEGF) therapy for retinopathy of prematurity (ROP) has potential ocular and systemic advantages compared with laser, but we believe the systemic risks of anti-VEGF therapy in preterm infants are poorly quantified. To determine whether there was an association with increased risk of pulmonary hypertension (PH) in preterm infants with ROP following treatment with anti-VEGF therapy as compared with laser treatment. This multicenter retrospective cohort study took place at neonatal intensive care units of 48 children's hospitals in the US in the Pediatric Health Information System database from 2010 to 2020. Participants included preterm infants with gestational age at birth 22 0/7 to 31 6/7 weeks who had ROP treated with anti-VEGF therapy or laser photocoagulation. Anti-VEGF therapy vs laser photocoagulation. New receipt of pulmonary vasodilators at least 7 days after ROP therapy was compared between exposure groups, matched using propensity scores generated from preexposure variables, and adjusted for birth year and hospital. The odds of receiving an echocardiogram after 30 days of age was also included to adjust for secular trends and interhospital variation in PH screening. Among 1577 patients (55.9% male) meeting inclusion criteria, 689 received laser photocoagulation and 888 received anti-VEGF treatment (95% bevacizumab, 5% ranibizumab). Patients were first treated for ROP at median 36.4 weeks' postmenstrual age (IQR, 34.6-38.7). A total of 982 patients (491 in each group) were propensity score matched. Good covariate balance was achieved, as indicated by a model variance ratio of 1.15. More infants who received anti-VEGF therapy were treated for PH, but when adjusted for hospital and year, this was no longer statistically significant (6.7%; 95% CI, 2.6-6.9 vs 4.3% 95% CI, 4.4-10.2; adjusted odds ratio, 1.62; 95% CI, 0.90-2.89; P = .10). Anti-VEGF therapy was not associated with greater use of pulmonary vasodilators after adjustment for hospital and year. Our findings suggest exposure to anti-VEGF may be associated with PH, although we cannot exclude the possibility of residual confounding based on systemic comorbidities or hospital variation in practice. Future studies investigating this possible adverse effect seem warranted.