ORIGINAL ARTICLE Contribution of early glycemic status in the development of severe retinopathy of prematurity in a cohort of ELBW infants R Chavez-Valdez 1,2 , J McGowan 2,3 , E Cannon 1 and CU Lehmann 2 1 Division of Neonatology, Department of Pediatrics, Texas Tech University Health Sciences Center, Odessa, TX, USA; 2 Division of Neonatology, Department of Pediatrics, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, MD, USA and 3 Division of Neonatology, Department of Pediatrics, Drexel University College of Medicine, Philadelphia, PA, USA Objective: The objective of this study is to investigate the relationship between glycemic status and severe retinopathy of prematurity (ROP). Study Design: This is a retrospective cohort study of 114 infants <1000 g admitted to a level IV neonatal intensive care unit within 48 h of life. A cumulative, time-weighted glucose level (TWGL) derived from plotting glucose values over time was included in logistic regression analysis to identify predictors for severe ROP. Result: Infants had 26.6 ± 2 weeks gestational age and had a birth weight of 782±136 g. TWGL during first 10 and 30 days of life were greater in the severe ROP group (P <0.01). Unlike single events of glucose levels X150 mg dl À1 , 10 days TWGL X100 mg dl À1 (odds ratio (OR) 5.2, P <0.02) and 30 days TWGL X118 mg dl À1 (OR 5.7, P<0.02) were predictors for severe ROP (univariate). Multivariate regression confirmed 30 days TWGL X118 mg dl À1 (OR 9.4 to 10) and gram-positive sepsis (OR 4.1 to 5) as predictors for severe ROP (P <0.05). Conclusion: High overall glycemic status is associated with the development of severe ROP. Journal of Perinatology (2011) 31, 749–756; doi:10.1038/jp.2011.19; published online 17 March 2011 Keywords: hyperglycemia; hypoglycemia; severity of illness; sepsis Introduction Extremely low birth weight (ELBW) infants (<1000 g) are at high risk to develop glucose instability during their early neonatal intensive care unit (NICU) course, 1,2 although the risk decreases with increasing gestational age (GA). 1 Identification of the consequences of early glucose intolerance is complicated by the lack of definitions for hypo- and hyperglycemia in ELBW infants. 3 Renal glucose excretion and neurological signs have been used as indicators of significant hyperglycemia and hypoglycemia, respectively; however, these findings are often misleading because of other physiological abnormalities. 4,5 Retinopathy of prematurity (ROP) is a vasoproliferative disorder linked to early exposure to relatively high retinal oxygen levels, 6,7 with an incidence of >50% in ELBW infants. 8 Recently, high glucose levels have been associated with an increased ROP incidence in ELBW infants. 1,9,10 However, there is no evidence demonstrating a direct cause–effect relationship. The lack of an accepted severity of illness score for newborns after the first 24 h of life 11 complicates interpretation of the data, as glucose instability can be an expression of severity of illness, 12,13 which may be the risk factor for ROP. Several studies have described similarities between oxygen- induced retinopathy (ROP) and glucose-induced diabetic retinopathy. 14,15 Given these data, we hypothesized that, rather than being caused by a single random event of glucose instability, the development of ROP in ELBW is caused by a dysregulation of glycemic status with persistently higher glucose levels in those infants with severe ROP. Therefore, we carried out a retrospective analysis of data from a cohort of ELBW infants to determine the relationship between glycemic status and development of severe ROP. Methods This study complied with the Guidelines for Human Experimentation from the US Department of Health and Human Services and was approved by The Johns Hopkins Hospital Institutional Review Board. As data were de-identified, no parental informed consent was required. All infants <1000 g born in or transferred to the Johns Hopkins Hospital NICU between March 1 2004 and February 28 2007 were included. Any infant X48 h old at time of transfer as well as infants who did not survive beyond 10 days of life and those for whom glucose levels or ROP status were not available were excluded, as were babies with major genetic disorders or malformations, intrauterine growth restriction or suspected viral infection. Received 4 November 2010; revised 7 January 2011; accepted 4 February 2011; published online 17 March 2011 Correspondence: Dr R Chavez-Valdez, Division of Neonatology, Department of Pediatrics, Texas Tech University Health Sciences Center, 701 West 5th Street. Suite 3142, Odessa, TX 79763, USA. E-mail: r.chavez-valdez@ttuhsc.edu or chavezva@gmail.com Journal of Perinatology (2011) 31, 749–756 r 2011 Nature America, Inc. All rights reserved. 0743-8346/11 www.nature.com/jp