According to the World Health Organization (WHO), preterm birth is defined as birth occurring before 37 completed weeks of gestation (GA).⁽¹⁾ In Brazil, approximately 3 million preterm births were recorded between 2011 and 2021, corresponding to an average prevalence of 11%, placing the country among those with the highest number of preterm births worldwide.^(1,2)

Prematurity is the leading cause of death in children under five years of age and a major contributor to neonatal mortality.⁽³⁾ It is also associated with several adverse health outcomes.^(4,5) Among the complications affecting very low birth weight (VLBW) preterm neonates (PTN), retinopathy of prematurity (ROP) is one of the main causes of childhood visual impairment and the leading cause of blindness in preterm infants.⁽⁶⁾

Retinopathy of prematurity is a multifactorial disease, and well-established risk factors include low GA (below 30 to 32 weeks) and VLBW (below 1,000 to 1,500 g).⁽⁷⁾ Other factors, such as oxygen exposure and prolonged mechanical ventilation, have also been associated with an increased risk of the disease.⁽⁸⁾

Despite the recognition of these risk factors, understanding the epidemiology and management of ROP in public university hospitals remains essential. These institutions may face challenges related to limited resources, access to specialized care, and the implementation of standardized protocols, which can affect early diagnosis and treatment.

Given the increased risks of morbidity and mortality among PTN,^(9,10) as well as the associated healthcare costs,^(11,12) prematurity represents an important public health concern. Preventive strategies for ROP require a multidisciplinary approach that begins before birth and continues throughout childhood.⁽¹³⁾ In addition, advances in neonatal care have improved PTN survival rates, increasing the number of infants at risk for ROP and reinforcing the importance of early detection and timely treatment.

Thus, the present study aimed to evaluate the incidence, epidemiological profile, risk factors, and severity of ROP in PTNB and VLBW infants at a university hospital.

Between January 1st, 2014, and December 31st, 2022, 853 VLBW preterm newborns were included in the study, of whom 171 were diagnosed with ROP (Figure 1).

Table 1 presents the characterization data of the groups according to maternal information. The group of newborns diagnosed with ROP had a lower proportion of mothers with systemic arterial hypertension, as well as a higher proportion of vaginal deliveries, chorioamnionitis, and magnesium sulfate use.

The characterization of the newborns is presented in table 2. Newborns diagnosed with ROP had a lower gestational age, lower birth weight, and lower Apgar scores (both at 1 and 5 minutes). These individuals also had a greater need for resuscitation, positive pressure ventilation, intubation with an endotracheal tube, occurrence of respiratory distress syndrome, longer oxygen therapy duration, longer invasive ventilation duration, need for non-invasive ventilation, postnatal corticosteroid use for bronchopulmonary dysplasia, oxygen use (both at 28 days and at 36 weeks of corrected age), higher proportions of severe grades of periventricular-intraventricular hemorrhage, patent ductus arteriosus, necrotizing enterocolitis, and blood transfusions compared to newborns without an ROP diagnosis.

The average incidence of ROP during the study period was 20%, with the lowest value recorded in 2015 (14.4%). In subsequent years, an increase in ROP incidence was observed, reaching its highest value in 2022 (28.2%) (Figure 2). No significant difference was found between the years studied (p = 0.345).

Among preterm newborns diagnosed with ROP, most cases presented mild retinal impairment (49.1%, stage I), followed by stage II (28.6%) and stage III (22.6%). Of the total 171 diagnoses, four newborns (2.34%) received treatment with anti-vascular endothelial growth factor (VEGF), and 25 (14.6%) underwent retinal surgery (data not presented in tables).

The Poisson regression analysis of sociodemographic characteristics, lifestyle habits, health conditions, pregnancy, and delivery factors associated with ROP is shown in table 3. The possible risk factors for ROP occurrence were systemic arterial hypertension, lower Apgar scores, endotracheal intubation in the delivery room, respiratory distress syndrome, longer oxygen therapy duration, longer mechanical ventilation duration, need for non-invasive ventilation (CPAP), postnatal corticosteroid use for bronchopulmonary dysplasia, higher grades of periventricular-intraventricular hemorrhage, patent ductus arteriosus, necrotizing enterocolitis, and blood transfusion when analyses were performed without adjustments for confounding factors (Model 1). After adjusting for gestational age, birth weight, and mechanical ventilation as covariates in the regression model (Model 2), the risk factors for ROP were longer oxygen therapy duration, longer mechanical ventilation duration, postnatal corticosteroid use for bronchopulmonary dysplasia, patent ductus arteriosus, and blood transfusion. On the other hand, the use of vasoactive drugs was found to be a protective factor against ROP occurrence.

The main findings of this study indicate that prolonged oxygen therapy, longer duration of mechanical ventilation, postnatal corticosteroid use for bronchopulmonary dysplasia, patent ductus arteriosus, and blood transfusion were risk factors for the development of ROP, even after adjustment for confounding variables. In contrast, the use of vasoactive drugs was identified as a protective factor. In addition, an increase in ROP incidence was observed in 2022 compared with previous years.

The average incidence of ROP between 2014 and 2022 was 20%. Although a higher number of cases were observed in the last year evaluated, this difference was not statistically significant and may be related to an increase in the number of preterm births during this period. In the literature, the global incidence of ROP varies considerably according to the region studied. Huang et al.⁽¹⁵⁾ evaluated extremely preterm newborns at a university hospital in Hong Kong between January 2015 and August 2018 and reported an incidence of ROP of 21% among infants with gestational age below 32 weeks. In Brazil, a study conducted at the Santa Casa de Misericórdia de Belo Horizonte (MG) included 236 newborns, of whom 208 (88.1%) underwent ophthalmologic examination during hospitalization, identifying ROP in 62 cases (29.8%).⁽¹⁶⁾ Another Brazilian study reported an incidence of 33.9%.⁽¹⁷⁾ These variations in incidence rates across studies are possibly due to differences in screening protocols, population characteristics, and healthcare conditions.

The main risk factors for the development of ROP described in the literature include low birth weight, lower gestational age, blood transfusions, prolonged oxygen therapy,⁽¹⁸⁾ longer NICU stays, infections,^(19,20) and intracranial hemorrhage.⁽¹⁹⁾ The findings of the present study are consistent with previous research and reinforce the importance of carefully evaluating the clinical characteristics of preterm newborns in order to identify those at higher risk for the disease. Early identification of these risk factors may help optimize screening strategies and contribute to timely interventions, potentially reducing the risk of severe complications and preventable blindness.

An interesting finding of this study was the identification of vasoactive drug use as a protective factor for ROP. These medications are essential for restoring tissue perfusion and oxygen delivery in critically ill patients, who would typically be expected to present a higher risk of ROP.⁽²¹⁾ One possible explanation is that adequate hemodynamic management may contribute to this protective effect. However, the literature presents inconsistent findings. Mayer et al.⁽²²⁾ identified vasoactive drug use as a risk factor, while Huang et al.⁽¹⁵⁾ found no significant association with ROP development. Therefore, further studies are needed to better understand the relationship between vasoactive drug use and ROP occurrence.

Currently, the only well-established protective factor described in the literature is the use of breast milk in the nutrition of preterm newborns, which was not evaluated in the present study.⁽²³⁾

Regarding disease severity, most preterm newborns in this study presented mild retinal impairment, with stage I ROP observed in 49.1% of cases. This finding is consistent with previous reports indicating a higher frequency of mild cases. Cestari et al.,⁽²⁴⁾ for example, observed that stage 1 ROP was the most common presentation (11.9%), followed by stages 2, 3, 4, and 5 (5.8%, 4.1%, 0.4%, and 0.4%, respectively). Although severe cases were less frequent, they remain clinically relevant due to their potential impact on quality of life.

This study has some limitations. Its single-center, retrospective design, based on database records, limits the ability to establish causal relationships. Nevertheless, the study also has important strengths, including the long study period and the large number of variables analyzed.

The incidence of retinopathy of prematurity during the study period was 20%, with a predominance of mild cases. The main risk factors identified were prolonged oxygen therapy, longer duration of mechanical ventilation, postnatal corticosteroid use for bronchopulmonary dysplasia, patent ductus arteriosus, and blood transfusion. Retinopathy of prematurity remains a leading cause of childhood blindness among preterm infants. Early detection through screening is essential to prevent severe outcomes. Appropriate management of oxygen therapy and ventilation, combined with timely screening and treatment, can reduce the risk of vision loss. Therefore, comprehensive strategies focusing on prevention, screening, and early treatment are fundamental to minimize the impact of retinopathy of prematurity.