Authors’ Response: Risk factor-based models to predict severe retinopathy of prematurity in preterm Thai infants

Dear Editor, We thank the author of the Letter to Editor titled ‘Comment on: Risk factor-based models to predict severe retinopathy of prematurity in preterm Thai infants.’[1] for the thoughtful and constructive comments on our article titled “Risk factor-based models to predict severe retinopathy of prematurity in preterm Thai infants.”[2] We appreciate the opportunity to discuss our findings further. First, concerning the lengthy study period possibly affecting the incidence and severity of retinopathy of prematurity (ROP), and the suggestion to conduct time segmentation analysis and interaction term analysis, we agree that neonatal care and medical devices used in our unit have evolved over the past 10 years. However, our prevalence of ROP and severe ROP over an 11-year study period, using Chi-squared test for trend,[3] was not statistically significant (P = 0.71 and 0.53, respectively). Although neonatal care has evolved, the risk factors used in our predictive model are objective and have remained consistently relevant. This consistency supports the generalizability of our findings across the lengthy study period. Second, regarding the analysis of other possible confounders, we found that gender and multiple pregnancies, using univariate analysis, were not significantly associated with ROP and severe ROP.[2] Racial variation in socioeconomic status may be related to low birth weight, small for gestational age, and preterm birth.[4] Unfortunately, we did not have data on the socioeconomic status of the families. Most studies identify several factors related to oxygen administration as risk factors of ROP, such as the duration of oxygen therapy, prolonged mechanical ventilation, high fraction of inspired oxygen (FiO2), and hyperoxemia, which are measured using either oxygen saturation (SpO2) on pulse oximeter, partial pressure of oxygen (PaO2) on arterial blood gases, or fluctuation in SpO2.[5] We found it very difficult to obtain accurate data on SpO2, PaO2, and FiO2 throughout the month-long neonatal intensive care unit admissions of these tiny infants. Therefore, we decided to use the duration of oxygen supplementation, regardless of the delivery mode, as a risk factor for ROP. Lastly, we would like to address the author’s observation regarding the inclusion criteria of preterm infants considered clinically unstable by neonatologists. Our ROP screening criteria, similar to the American Academy of Pediatrics (AAP)’s criteria,[6] include preterm infants with an unstable clinical course as judged by neonatologists. This criterion does not have a strict definition and is subject to the attending neonatologist’s discretion. Typically, these infants are preterm infants with a gestational age of more than 33 weeks, have been on a ventilator for at least several days, and often require inotropic support. ROP is a significant cause of visual impairment, including blindness, and may be associated with adverse neurodevelopmental outcomes.[7] Timely screening for ROP is crucial to facilitate early intervention. However, gestational age- and birth weight-based screening criteria can cause unnecessary stress and pain in many infants. We proposed our risk factor-based screening criteria in the hope of minimizing the number of unnecessary eye examinations while ensuring no infants with ROP are missed. Acknowledging the retrospective nature of our data acquisition, we are currently conducting a prospective study in our unit. We believe that addressing these points has further strengthened the understanding of the results of our article titled “Risk factor-based models to predict severe retinopathy of prematurity in preterm Thai infants.”[2] We thank you once again for the valuable comments. Financial support and sponsorship: Nil. Conflicts of interest: There are no conflicts of interest.