Predictors for the Development of Referral-Warranted Retinopathy of Prematurity in the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) Study

IMPORTANCE Detection of treatment-requiring retinopathy of prematurity (ROP) involves serial eye examinations. An ROP prediction model using predictive factors could identify high-risk infants and reduce required eye examinations. OBJECTIVE To determine predictive factors for the development of referral-warranted (RW) ROP. DESIGN, SETTING, AND PARTICIPANTS This multicenter observational cohort study included secondary analysis of data from the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity Study. Infants included in the study had a birth weight (BW) of less than 1251 g. EXPOSURES Serial ROP examinations of premature infants who had 2 or more ROP examinations. MAIN OUTCOMES AND MEASURES Incidence of RW-ROP (defined as the presence of plus disease, zone I ROP, or ROP stage 3 or greater in either eye) and associations with predictive factors. RESULTS Among 979 infants without RW-ROP at first study-related eye examination (median postmenstrual age, 33 weeks; range, 29-40 weeks) who underwent at least 2 eye examinations, 149 (15.2%) developed RW-ROP. In a multivariate model, significant predictors for RW-ROP were male sex (odds ratio [OR], 1.80; 95% CI, 1.13-2.86 vs female), nonblack race (OR, 2.76; 95% CI, 1.50-5.08 for white vs black race and OR, 4.81; 95% CI, 2.19-10.6 for other vs black race), low BW(OR, 5.16; 95% CI, 1.12-7.20 for <= 500 g vs >1100 g), younger gestational age (OR, 9.79; 95% CI, 3.49-27.5 for <= 24 weeks vs >= 28 weeks), number of quadrants with preplus disease (OR, 7.12; 95% CI, 2.53-20.1 for 1-2 quadrants and OR, 18.4; 95% CI, 4.28-79.4 for 3-4 quadrants vs no preplus disease), stage 2 ROP (OR, 4.13; 95% CI, 2.13-8.00 vs no ROP), the presence of retinal hemorrhage (OR, 4.36; 95% CI, 1.57-12.1 vs absence), the need for respiratory support (OR, 4.99; 95% CI, 1.89-13.2 for the need for controlled mechanical ventilator; OR, 11.0; 95% CI, 2.26-53.8 for the need for high-frequency oscillatory ventilation vs no respiratory support), and slow weight gain (OR, 2.44; 95% CI, 1.22-4.89 for weight gain <= 12 g/d vs > 18 g/d). These characteristics predicted the development of RW-ROP significantly better than BW and gestational age (area under receiver operating characteristic curve, 0.88 vs 0.78; P < .001). CONCLUSIONS AND RELEVANCE When controlling for very low BW and prematurity, the presence of preplus disease, stage 2 ROP, retinal hemorrhage, and the need for ventilation at time of first study-related eye examination were strong independent predictors for RW-ROP. These predictors may help identify infants in need of timely eye examinations.