Maternal Preeclampsia Protects Preterm Infants against Severe Retinopathy of Prematurity Joa ˜ o Borges Fortes Filho, MD, PhD, Marlene C. Costa, RN, Gabriela U. Eckert, MD, Paula G. B. Santos, MD, Rita C. Silveira, MD, PhD, and Renato S. Procianoy, MD, PhD Objective To study the influence of maternal preeclampsia on the occurrence of retinopathy of prematurity. Study design A prospective cohort study of 324 preterm neonates with birth weight #1500 g and gestational age #32 weeks. Multiple maternal and perinatal factors were analyzed for association and confounding by multiple logistic regression analysis. Results Mean birth weight was 1128  240 g, and mean gestational age 29.7  1.9 weeks. Twenty-four newborns (7.4%) had severe retinopathy of prematurity; 97 had any stage of retinopathy, and 227 had no retinopathy of pre- maturity. Preeclampsia and complete antenatal steroid treatment course reduced the risk for any stage of retinop- athy of prematurity by 60% and 54%, respectively. Preeclampsia reduced the risk for severe retinopathy of prematurity by 80%. Conclusions Preeclampsia lowered the risk for occurrence of any stage and severe retinopathy of prematurity in very low birth weight infants. (J Pediatr 2011;158:372-6). M aternal preeclampsia is a frequent cause of prematurity. Retinopathy of prematurity (ROP) remains one of the leading causes of preventable childhood blindness. ROP occurs frequently in middle-income countries where improvements in the perinatal care have increased survival rates of very low birth weight (VLBW) infants. ROP pathogenesis has evolved over 50 years. Initially the uncontrolled use of oxygen therapy was mainly responsible for ROP. More recently, risk factors for ROP are low birth weight and short gestational age. 1 ROP rates differ perhaps related to geographic areas, genetics differences, or environmental susceptibility. 2-7 Many studies have evaluated postnatal factors that contribute to ROP. On the other hand, antenatal or maternal risk factors have been minimally studied. 8,9 Gotsch et al 10 reported an antiangiogenic state in patients with preeclampsia resulting from changes in the concentrations of circulating angiogenic factors. Because ROP is a vasoproliferative disease, an antiangiogenic state in mothers with preeclampsia might protect the infant for ROP. An association between preeclampsia and ROP has not been reported. We evaluated maternal and perinatal factors for their association with the development of any stage and severe ROP, and if these factors were inde- pendent of the birth weight and gestational age. Methods A prospective cohort study included all preterm infants screened for ROP with birth weight #1500 g and gestational age #32 weeks at birth. The mothers were admitted to Hospital de Clı´nicas de Porto Alegre between October 2002 and July 2009. The study included all preterm infants screened for ROP who survived until the initial ophthalmologic examination per- formed between the 4th and 6th week after birth. The infants were examined at 45 weeks postmenstrual age (postmenstrual age = gestational age at birth + weeks of life) or until effective stabilization of retinopathy was achieved after treatment. The data were prospectively collected, and there were no exclusion criteria. All patients had eye examinations, consisting of binoc- ular indirect ophthalmoscopy after pupil dilation in both eyes with 0.5% tropicamide and 2.5% phenylephrine eye drops, with a 28-diopter lens (Nikon, Melville, New York), and a newborn infant eyelid speculum (Alfonso Eye Speculum; Storz, Bausch & Lomb Inc, San Dimas, California). Scleral indentation was performed when necessary. Screening sessions were performed and scheduled according to the Brazilian guidelines to detect and treat ROP. Subsequent examinations were determined by the find- ings in the first examination. 11,12 Clinical outcomes included the onset of any stage of ROP and development of ROP requiring treatment. ROP was classified according to the 1984/1987 International Classification of ROP in stages 1 to 5. 13,14 Threshold ROP was defined as 5 contiguous or 8 cumulative clock hours of stage 3 ROP with plus disease in zone I or II, From the Departments of Pediatrics and Ophthalmology Newborn Section, Universidade Federal do Rio Grande do Sul and Hospital de Clinicas de Porto Alegre, Porto Alegre, RS, Brazil The authors declare no conflicts of interest. 0022-3476/$ - see front matter. Copyright ª 2011 Mosby Inc. All rights reserved. 10.1016/j.jpeds.2010.08.051 IVH Intraventricular hemorrhage ROP Retinopathy of prematurity SGA Small for gestational age VEGF Vascular endothelial growth factor VLBW Very low birth weight 372