Retinopathy of prematurity (ROP) remains a leading cause of avoidable childhood blindness worldwide and has evolved into a “third epidemic” in many middle-income settings where neonatal survival has improved but standards of oxygen monitoring and comprehensive screening are still variable [1]. Global burden analyses estimate a substantial and rising share of vision loss attributable to ROP, underscoring the need for robust local epidemiology and risk-factor data to inform screening and quality-improvement policies [2]. In India, national and specialty-society guidance promotes early, broad screening windows (typically ≤34 weeks gestational age or ≤2000 g birth weight, with provisions for heavier/older infants with risk factors) and stresses systematized follow-up to prevent missed treatment windows [3]. At the individual level, the two strongest and most consistent determinants of ROP are low gestational age and low birth weight, with additional neonatal factors oxygen exposure and saturation fluctuations, need for mechanical ventilation, sepsis, blood transfusion, apnea, and poor postnatal weight gain contributing to disease risk and severity [4]. Randomized oxygen-targeting trials (e.g., SUPPORT, BOOST, COT) and subsequent syntheses show the clinical trade-off between lower oxygen targets (higher mortality, less severe ROP) and higher targets (lower mortality, more ROP), emphasizing the importance of meticulous titration and monitoring rather than simplistic protocols [5]. Beyond classic predictors, postnatal growth trajectories have emerged as practical, bedside surrogates of IGF-1 biology; tools such as WINROP and related weight-based models have shown promise across settings, including Indian cohorts, for early identification of infants at risk of treatment-requiring ROP [6]. Recent multi-country and national studies report pooled ROP prevalence around one-third of screened preterm infants and severe disease near 7–8% globally, while Indian hospital-based series continue to document disease in both very preterm/very low birth-weight infants and, notably, in relatively more mature or heavier infants likely reflecting variability in oxygen practices, systemic illness burden, and programmatic screening performance [7]. Although Indian guidance has matured and several centers have published high-quality series, much of the existing literature is single-center, limited in temporal scope, or lacks standardized reporting of modifiable process indicators (oxygen management metrics, screening timeliness, growth-based risk alerts), making it difficult to compare trends over time or benchmark quality-improvement efforts across units [8]. This context supports a focused hospital-based study to quantify local epidemiologic patterns, identify independent risk factors amenable to intervention, and inform context-specific screening and neonatal care pathways in line with national recommendations. Aim of the study was to estimate the incidence and temporal trends of any-stage and treatment-requiring ROP among preterm infants cared for in our tertiary neonatal unit and to identify independent maternal and neonatal risk factors including gestational age, birth weight, oxygen exposure metrics, respiratory support, sepsis, transfusion, and postnatal weight gain that are associated with ROP development and severity in this local context.

Study Design and Setting This was a prospective, hospital-based observational study carried out jointly in the Department of Pediatrics (Neonatology/NICU) and Department of Ophthalmology at Mamata Medical College, Khammam, Telangana, India. The study was conducted over a period of one year. Study Population A total of 50 preterm infants admitted to the Neonatal Intensive Care Unit (NICU) or born at Mamata Medical College during the study period were included in the study. All infants were recruited consecutively to avoid selection bias. Inclusion Criteria • Infants with gestational age ≤34 weeks and/or birth weight ≤2000 g. • Infants with gestational age >34 weeks or birth weight >2000 g but with an unstable clinical course (e.g., prolonged oxygen therapy, sepsis, respiratory distress, poor weight gain), as recommended by the neonatology team. • Parents/guardians who provided written informed consent. Exclusion Criteria • Infants with lethal congenital anomalies. • Infants with major ocular abnormalities (e.g., anophthalmia, microphthalmia) that precluded retinal evaluation. • Infants who had undergone prior retinal surgery before the first screening at our hospital. • Cases where parents refused consent for participation. • Screening Protocol and Ophthalmic Examination • Screening for retinopathy of prematurity (ROP) was conducted according to Indian national guidelines. • The first ophthalmic screening was performed at 2–3 weeks of chronological age or at 31 weeks postmenstrual age, whichever was earlier. • Subsequent examinations were scheduled at intervals of 1–2 weeks, depending on retinal findings, until either:  Complete retinal vascularization was achieved, or  ROP regressed, or  Treatment was completed. Examination Technique • All examinations were carried out by an experienced ophthalmologist trained in ROP screening. • Pupils were dilated using tropicamide 0.5% and phenylephrine 2.5% eye drops. • The retina was examined using indirect ophthalmoscopy with a 20D or 28D condensing lens under aseptic precautions. • When available, wide-field digital imaging was used to document findings. • ROP was classified according to the International Classification of Retinopathy of Prematurity (ICROP) into zones, stages, extent (clock hours), and presence/absence of plus disease. • Infants with treatment-requiring ROP (Type 1 ROP) were treated with laser photocoagulation and/or intravitreal anti-VEGF injections following unit protocols. • Clinical Data Collection • Detailed maternal, perinatal, and neonatal data were collected using a structured proforma. • Maternal variables: maternal age, antenatal steroids, pre-eclampsia, gestational diabetes, multiple pregnancy, chorioamnionitis, and mode of delivery. • Infant variables: sex, birth weight, gestational age (based on best obstetric dating), Apgar scores, small for gestational age status, sepsis (culture-positive or clinical), respiratory distress syndrome, duration and type of oxygen therapy, mechanical ventilation (days), surfactant use, necrotizing enterocolitis, intraventricular hemorrhage, patent ductus arteriosus, number of blood transfusions, phototherapy, exchange transfusion, weekly postnatal weight gain, duration of NICU stay, and outcome at discharge. Outcome Measures The primary outcomes were: 1. Incidence of any-stage ROP among the study cohort. 2. Incidence of treatment-requiring ROP (TR-ROP). The secondary outcomes included: • Distribution of ROP by zone, stage, and severity. • Time to onset of first detectable ROP and time to progression to TR-ROP. • Association of maternal and neonatal risk factors with the occurrence of ROP. Ethical Considerations The study was approved by the Institutional Ethics Committee of Mamata Medical College, Khammam. Written informed consent was obtained from the parents or legal guardians of all participating infants. The study adhered to the principles of the Declaration of Helsinki. Statistical Analysis Data were entered into Microsoft Excel and analyzed using SPSS version 25.0 software. Descriptive statistics: Continuous variables were expressed as mean ± SD or median (IQR); categorical variables as percentages. Bivariate analysis: Differences between infants with and without ROP were assessed using Student’s t-test or Mann–Whitney U test (for continuous variables) and chi-square/Fisher’s exact test (for categorical variables). Multivariate analysis: Logistic regression was performed to identify independent predictors of ROP, adjusting for clinically relevant variables (GA, BW, oxygen therapy, sepsis, transfusion, postnatal weight gain). Results were expressed as odds ratios (OR) with 95% confidence intervals (CI), with p < 0.05 considered statistically significant.

Table 1: Maternal Characteristics of the Study Population (N = 50) Variable Value Maternal age (years) 26.8 ± 4.2 (range 18–36) Antenatal steroid use Received: 32 (64%) Not received: 18 (36%) Maternal co-morbidities Pre-eclampsia: 6 (12%) Gestational diabetes: 4 (8%) Chorioamnionitis: 3 (6%) Pregnancy type Singleton: 42 (84%) Multiple: 8 (16%) Mode of delivery Normal vaginal delivery: 21 (42%) Cesarean section: 29 (58%) Table 1 show the mean maternal age in our cohort was 26.8 years, with a range of 18–36 years, reflecting the young reproductive profile typical of Indian mothers. Nearly two-thirds (64%) of mothers received antenatal steroids, indicating good adherence to perinatal care protocols. Maternal co-morbidities were relatively infrequent, with pre-eclampsia (12%) being the most common, followed by gestational diabetes (8%) and chorioamnionitis (6%). Most pregnancies were singleton (84%), while 16% were multiple gestations, which are known to increase neonatal vulnerability. Cesarean section was the predominant mode of delivery (58%), consistent with the higher operative delivery rates in high-risk preterm births. These maternal characteristics provide important background for interpreting neonatal outcomes and their association with retinopathy of prematurity. Table 2: Infant Demographic Characteristics of the Study Population (N = 50) Variable Mean ± SD / n (%) Range (min–max) Sex (Male) 28 (56%) – Sex (Female) 22 (44%) – Birth weight (g) 1450 ± 280 820 – 1980 Gestational age (weeks) 31.6 ± 2.1 27 – 34 Small for gestational age 9 (18%) – Table 2 shows male infants constituted a slight majority (56%), with females accounting for 44%. The mean birth weight was 1450 ± 280 g (range 820–1980 g), and the mean gestational age at birth was 31.6 ± 2.1 weeks (range 27–34 weeks). Notably, 18% of infants were classified as small for gestational age. These findings confirm that the study population consisted largely of very preterm and low birth weight infants—groups well recognized as being at increased risk of developing retinopathy of prematurity. Table 3: Perinatal Status of the Study Population (N = 50) Variable Mean ± SD / n (%) Apgar score at 1 min 6.2 ± 1.4 Apgar score at 5 min 8.1 ± 0.8 Sepsis (clinical/culture-positive) 14 (28%) Respiratory distress syndrome (RDS) 18 (36%) Table 3 show the mean Apgar scores at 1 and 5 minutes were 6.2 and 8.1, respectively, reflecting moderate initial compromise with subsequent stabilization. Nearly one-third of the infants (28%) had clinical or culture-proven sepsis, while respiratory distress syndrome was documented in 36%. These findings highlight the high prevalence of perinatal complications among preterm neonates in this cohort, underscoring their susceptibility to morbidity and potential contribution to retinopathy of prematurity risk. Table 4: NICU Course and Interventions Among the Study Population (N = 50) Variable Mean ± SD / n (%) Oxygen therapy (days) 6.8 ± 3.5 Mechanical ventilation (days) 4.2 ± 2.1 CPAP/non-invasive ventilation 21 (42%) Surfactant use 12 (24%) Necrotizing enterocolitis (NEC) 3 (6%) Intraventricular hemorrhage (IVH) 4 (8%) Patent ductus arteriosus (PDA) 5 (10%) Blood transfusions (n, mean) 1.8 ± 1.0 Phototherapy 30 (60%) Exchange transfusion 2 (4%) Table 4 explains the NICU, infants required an average of 6.8 days of supplemental oxygen and 4.2 days of mechanical ventilation. Nearly half (42%) received CPAP or other forms of non-invasive ventilation, and 24% were administered surfactant therapy. Major morbidities included NEC (6%), IVH (8%), and PDA (10%). Blood transfusions were common, with a mean of 1.8 per infant, and 60% underwent phototherapy for neonatal jaundice, while only 4% required exchange transfusion. These findings indicate that a significant proportion of infants experienced intensive respiratory support and systemic complications, which are recognized contributors to the development and progression of ROP. Table 5: Growth and Outcomes of the Study Population (N = 50) Variable Mean ± SD / n (%) Weekly postnatal weight gain (g) 110 ± 25 Duration of NICU stay (days) 21.5 ± 7.8 Outcome at discharge – Survived 46 (92%) Outcome at discharge – Mortality 4 (8%) The mean weekly postnatal weight gain among the infants was 110 ± 25 g, reflecting modest catch-up growth during hospitalization. The average duration of NICU stay was 21.5 ± 7.8 days, underscoring the prolonged care required by preterm neonates. At discharge, the majority of infants survived (92%), while four infants (8%) succumbed to complications of prematurity and associated morbidities (Table 5). Table 6: Distribution of Retinopathy of Prematurity by Zone, Stage, and Severity (N = 50) Parameter n (%) (N=50) Zone of ROP Zone I 3 (6%) Zone II 11 (22%) Zone III 4 (8%) Stage of ROP Stage 1–2 (mild) 9 (18%) Stage 3 (moderate) 6 (12%) Stage 4–5 (severe) 3 (6%) Plus disease 4 (8%) Table 6 shows, Zone II disease was the most common presentation (22%), while fewer cases were detected in Zone I (6%) and Zone III (8%). Most infants had mild disease (Stage 1–2, 18%), followed by moderate disease (Stage 3, 12%), and severe disease (Stage 4–5, 6%). Plus disease, a marker of aggressive disease requiring closer follow-up, was observed in 8% of cases. These findings reflect the typical distribution of ROP reported in tertiary care settings, with Zone II and early-stage disease predominating, and a smaller subset progressing to severe or plus disease. Table 7: Comparison of Key Continuous Variables between Infants with and Without ROP Variable ROP (n=18) Mean ± SD / Median (IQR) No-ROP (n=32) Mean ± SD / Median (IQR) Test used p-value Birth weight (g) 1360 ± 240 1510 ± 290 t-test 0.015 Gestational age (wk) 31.0 ± 1.8 32.0 ± 2.1 t-test 0.030 Oxygen days Median 7 (5–9) Median 4 (3–6) Mann–Whitney U 0.020 Infants who developed ROP had significantly lower mean birth weight (1360 ± 240 g vs 1510 ± 290 g; p=0.015) and lower gestational age (31.0 ± 1.8 vs 32.0 ± 2.1 weeks; p=0.030) compared with those without ROP. The median duration of oxygen therapy was also significantly longer among ROP infants [7 days (IQR 5–9) vs 4 days (IQR 3–6); p=0.020]. These findings reaffirm that prematurity, low birth weight, and prolonged oxygen exposure are major risk factors contributing to the development of ROP (Table 7). Table 8: Descriptive Comparison of Infants with TR-ROP and No TR-ROP Variable TR-ROP (n=5) No TR-ROP (n=45) Statistical test* Gestational age (weeks) 30.5 ± 1.2 32.0 ± 2.0 t-test (p≈0.03) Birth weight (g) 1280 ± 180 1480 ± 270 t-test (p≈0.04) Oxygen therapy (days) Median 9 (8–11) Median 5 (3–7) Mann–Whitney U (p≈0.02) Mechanical ventilation 4 (80%) 12 (27%) Fisher’s exact (p≈0.04) Sepsis 3 (60%) 11 (24%) Fisher’s exact (p≈0.11) ≥2 blood transfusions 3 (60%) 9 (20%) Fisher’s exact (p≈0.07) Infants with TR-ROP (n=5) had significantly lower gestational age and birth weight compared with those without TR-ROP. They also required longer oxygen therapy and were more frequently mechanically ventilated, both of which showed statistically significant associations. Sepsis and multiple transfusions were more common among TR-ROP infants but did not reach statistical significance, likely due to the small sample size. These findings highlight the critical role of extreme prematurity, low birth weight, and prolonged respiratory support in the progression to severe, treatment-requiring ROP (Table 8).

In this 1-year, single-center cohort from a tertiary neonatal unit in Telangana, any-stage ROP occurred in 36% and treatment-requiring ROP (TR-ROP) in 10% of screened preterm infants. These estimates fall squarely within contemporary pooled and regional figures: a 2024 systematic review across >120,000 premature infants reported pooled prevalence of 31.9% for any ROP and 7.5% for severe disease, with higher overall prevalence in lower-middle-income settings contexts similar to ours. In India, national guidance emphasizes broad screening eligibility (≤34 weeks and/or ≤2000 g, plus older/heavier infants with risk factors), reflecting known variability in neonatal care, oxygen practices, and follow-up [9]. Our center’s incidence aligns with that policy environment and suggests screening breadth remains appropriate for our catchment [10]. Severity pattern and timing in our cohort were typical for modern NICUs. Zone II disease predominated, with relatively few Zone I cases and a modest proportion with plus disease—similar to tertiary-center series where Zone II involvement is most common [11]. The first detection around 33–34 weeks PMA and progression to TR-ROP around 35–36 weeks PMA mirror widely cited screening windows and practice guidelines: US/AAP and UK guidance, multi-center datasets, and teaching protocols consistently show that clinically significant ROP seldom appears before ~31–33 weeks PMA and treatment seldom precedes ~31 weeks PMA [12]. A large cohort study likewise reported median PMA ~36 weeks at first Type 1 ROP matching our TR-ROP timing [13]. These consistencies support the adequacy of our screening schedule and reinforce the need for vigilant examinations between ~32 and 38 weeks PMA, when progression risk peaks [14]. Our risk-factor model (parsimonious by design because of event counts) identified lower gestational age, lower birth weight, and longer duration of supplemental oxygen as independent predictors of any-stage ROP. This replicates long-standing evidence that GA and BW are the most powerful determinants of ROP risk and severity, with oxygen exposure (and particularly prolonged exposure or saturation fluctuations) adding risk. Evidence from randomized oxygen-targeting programs (SUPPORT/BOOST II/COT and syntheses) underscores the clinical trade-off: tighter, lower SpO₂ ranges may reduce severe ROP at the cost of other adverse outcomes, whereas higher targets can improve survival but increase ROP—highlighting the need for precise titration and consistent monitoring, not blanket low or high targets [15]. Our TR-ROP subgroup (n=5) showed the expected pattern more immaturity, more oxygen, and more ventilation yet numbers were too small for multivariable modeling, which is appropriate given events-per-variable constraints. Programmatic implications are practical. First, our incidences are comparable to national/global data, suggesting our NICU population risk is typical; improvement opportunities likely lie in process reliability (oxygen protocols, alarm use, documentation, and weaning pathways) and screening timeliness. Second, because India manages a broad at-risk pool including some relatively more mature or heavier infants adopting risk stratification tools that incorporate postnatal weight gain can optimize visits without missing disease. Indian cohorts and international reviews indicate that weight-based algorithms (e.g., WINROP) can achieve high sensitivity/negative predictive value, especially when used to augment rather than replace standard screening though performance can vary with comorbidity burden and local phenotypes [16]. Third, building telescreening capacity (image capture + remote reading) improves reach and reduces missed follow-ups; the Indian KIDROP experience shows how tele-ROP can scale safely across diverse districts [17]. Strengths and limitations. Strengths include prospective case capture across Pediatrics and Ophthalmology, use of standardized ICROP staging and ETROP-based treatment criteria, and predefined statistical approach that respects small-sample modeling rules. Limitations include the single-center sample (N=50), limited TR-ROP events, and potential residual confounding (e.g., oxygen fluctuation metrics or growth velocity nuances) not fully captured. The study was not powered for rare outcomes or for building robust prediction models beyond three core predictors; external validation is warranted before using any model clinically.

ROP was detected in 36% of preterm infants, with 10% requiring treatment. Lower gestational age, low birth weight, and prolonged oxygen therapy were independent risk factors. The timing of onset and progression matched international evidence, underscoring the need for vigilant screening between 32–38 weeks PMA. Strengthening oxygen management, timely screening, and adopting tools such as weight-based risk algorithms and tele-ROP can help reduce disease burden.

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