Objective.To identify prenatal and perinatal risk factors for clinically severe(stage 3 or 4)retinopathy of prematurity(ROP).Methods.Data were collected prospectively as part of the ongoing Australian and New Zealand Neonatal Network audit of high-risk infants(birth weight of < 1500 g or gestational age GA of < 32 weeks)admitted to a level III neonatal unit in Australia or New Zealand.Prenatal and perinatal factors to 1 minute of age were examined for the subset of infants with GA of< 29 weeks who survived to 36 weeks’ postmenstrual age and were examined for ROP(n=2105).The factors significantly associated with stage 3 or 4 ROP were entered into amultivariate logistic regression model.Results.Two-hundred three infants(9.6%)had stage 3 or more ROP.Prematurity was the dominant risk factor,with infants with GA of< 25 weeks having 20 times greater odds of severe ROP than infants with GA of 28 weeks.Birth weight for GA also had a “ dose-response” effect;the more growthrestricted infants had greater risk,with infants below the 3rd percentile of weight for GA having 4 times greater odds of severe ROP than those between the 25th and 75th percentiles.Male gender was also a significant risk factor(odds ratio:1.73;95% confidence interval:1.25-2.40).Conclusions.These data,for a large,essentially population-based cohort,suggest that factors related to the degree of immaturity,intrauterine growth restriction,and male gender contribute to severe ROP. Objective.To identify prenatal and perinatal risk factors for clinically severe (stage 3 or 4) retinopathy of prematurity (ROP). Methods. Data were collected prospectively as part of the ongoing Australian and New Zealand Neonatal Network audit of high-risk infants (birth weight of <1500 g or gestational age GA of <32 weeks admitted to a level III neonatal unit in Australia or New Zealand. Prenatal and perinatal factors to 1 minute of age were examined for the subset of infants with GA of <29 weeks who survived to 36 weeks’ postmenstrual age and were examined for ROP (n = 2105). The factors significantly associated with stage 3 or 4 ROP were entered into amultivariate logistic regression model. Results. Two hundred-percent three infants (9.6%) had stage 3 or more ROP. Prematurity was the dominant risk factor, with infants with GA of <25 weeks having 20 times greater odds of severe ROP than infants with GA of 28 weeks. Birth weight for GA also had a “dose-response” effect; the more growthrestricted infants had greater risk, with infants below the 3rd percentile of weight for GA having 4 times greater odds of severe ROP than those between the 25th and 75th percentiles. Male gender was also a significant risk factor (odds ratio: 1.73; 95% confidence interval: 1.25-2.40) .Conclusions. These data, for a large, essentially population-based cohort, suggest that factors related to the degree of immaturity, intrauterine growth restriction, and male gender contribute to severe ROP.