Christopher R. Nitkin, Nicholas A. Bamat, Joanne Lagatta, Sara B. DeMauro, Henry C. Lee, Ravi Mangal Patel, Brian King, Jonathan L. Slaughter, J. Peter Campbell, Troy Richardson, Tamorah Lewis
University of Missouri Kansas City School and Children’s Mercy Hospital. University of Pennsylvania and Children’s Hospital of Philadelphia. Medical College of Wisconsin. Stanford University. Emory University and Children’s Healthcare of Atlanta. University of Pittsburgh. Ohio State University and Nationwide Children’s Hospital. Oregon Health & Science University.
United States
Journal of the American Medical Association Ophthalmology
JAMA Ophthalmol 2022; 140: 1085-1094
DOI: 10.1001/jamaophthalmol.2022.3788
Abstract
Importance: 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.
Objective: 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.
Design, setting, and participants: 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.
Exposures: Anti-VEGF therapy vs laser photocoagulation.
Main outcomes and measures: 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.
Results: 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).
Conclusions and relevance: 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.
Category
Class I. Drug-induced and Toxin-induced Pulmonary Hypertension
Class III. Pulmonary Hypertension Associated with Lung Disease
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication
Article Access
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