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. 2022 Nov 1;140(11):1085-1094.
doi: 10.1001/jamaophthalmol.2022.3788.

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

Christopher R Nitkin  1 , Nicolas A Bamat  2 , Joanne Lagatta  3 , Sara B DeMauro  2 , Henry C Lee  4 , Ravi Mangal Patel  5 , Brian King  6 , Jonathan L Slaughter  7 , J Peter Campbell  8 , Troy Richardson  9 , Tamorah Lewis  1
Affiliations

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

Christopher R Nitkin et al. JAMA Ophthalmol. .

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Nitkin reported grants from United Therapeutics (industry-funded research study of bronchopulmonary dysplasia) and grants from Allergan (industry-funded research study of dalbavancin), outside the submitted work. Dr Bamat reported grants from the National Institute of Child Health and Human Development during the conduct of the study and grants from the National Institute of Child Health and Human Development, outside the submitted work. Dr Demauro reported grants from the National Institutes of Health, the Agency for Healthcare Research and Quality, and Thrasher Research Fund, outside the submitted work. Dr Patel reported grants from the National Institutes of Health, outside the submitted work. Dr Campbell reported grants from Genentech, personal fees from Boston AI, owner equity from Siloam Vision, and grants from National Institute of Health and Research to Prevent Blindness, outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Cohort Selection Flow Diagram
GA indicates gestational age; NICU, neonatal intensive care unit; ROP, retinopathy of prematurity; VEGF, vascular endothelial growth factor.
Figure 2.
Figure 2.. Primary Results: Use of Pulmonary Vasodilators Following Retinopathy of Prematurity (ROP) Treatments
Adjusted analyses include year of treatment and site. PH indicates pulmonary hypertension; VEGF, vascular endothelial growth factor.
Figure 3.
Figure 3.. Trends of Retinopathy of Prematurity Therapy Modality Over Time
Number of infants treated with each modality over study period. P < .001 for trend. VEGF indicates vascular endothelial growth factor.
See this image and copyright information in PMC

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