The Impact of Oral Sildenafil on Retinopathy of Prematurity in Very Preterm Newborns With Early-Onset Pulmonary Hypertension: A Retrospective Cohort Study Publisher



Nouhi N ; Sagheb S ; Sadeghi K ; Azadnajafabad S ; Mosayebi Z ; Lamsehchi A
Source: Shiraz E Medical Journal Published:2026

Abstract

Background: Sildenafil, a phosphodiesterase type 5 inhibitor, is increasingly used in neonatal intensive care units (NICUs) to treat pulmonary arterial hypertension in preterm infants. Objectives: This study aimed to evaluate whether oral sildenafil therapy in very preterm infants with early-onset pulmonary hypertension is associated with the development of retinopathy of prematurity (ROP). Methods: We conducted a retrospective cohort study of preterm neonates with a gestational age ≤ 31 weeks and early-onset pulmonary hypertension who were admitted to 2 tertiary NICUs in Tehran between 2017 and 2022. Infants who received oral sildenafil comprised the exposed group, and those managed without sildenafil comprised the unexposed group. Retinopathy of prematurity screening was performed according to national guidelines. Univariable and multivariable Poisson regression models were used to estimate crude and adjusted risk ratios for ROP. Results: Of 303 screened neonates, 74 met the inclusion criteria, including 38 sildenafil-exposed infants and 36 unexposed infants. The mean (SD) gestational age was 28.5 ± 1.5 weeks. The overall incidence of retinopathy of prematurity did not differ significantly between the sildenafil-exposed and unexposed groups (68.6% vs 72.2%; P = 0.700). Treatment-requiring retinopathy of prematurity occurred in 26.5% of infants in the sildenafil-exposed group and 27.8% of infants in the unexposed group, with no significant difference between groups (P > 0.99). The distribution of ROP stages did not differ significantly between the sildenafil-exposed and unexposed groups (P-value = 0.8). Univariable analysis showed no association between sildenafil exposure and retinopathy of prematurity (crude risk ratio, 0.95; 95% CI, 0.70 - 1.29; P = 0.740), and this association remained nonsignificant after adjustment for relevant clinical covariates (adjusted risk ratio, 1.04; 95% CI, 0.70 - 1.55; P = 0.840). Conclusions: Early oral sildenafil therapy was not associated with an increased risk of ROP in very preterm infants. Larger prospective studies are warranted to confirm its ocular safety. Copyright © 2026, Nouhi et al.