Am J Perinatol 2016; 33(04): 393-400
DOI: 10.1055/s-0035-1565999
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Insulin, Hyperglycemia, and Severe Retinopathy of Prematurity in Extremely Low-Birth-Weight Infants

Jan Hau Lee
1   Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina
2   Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
3   Children's Intensive Care Unit, KK Women's and Children's Hospital, Singapore
,
Christoph P. Hornik
1   Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina
2   Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
,
Daniela Testoni
2   Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
4   Division of Neonatal Medicine, Ecola Paulista de Medicine, Universidade Federal de São Paulo, São Paulo, Brazil
,
Matthew M. Laughon
5   Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina
,
C. Michael Cotten
1   Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina
,
Ramiro S. Maldonado
1   Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina
,
Marc R. Belcastro
6   Pediatrix Medical Group, MEDNAX, Inc., Jacksonville, Florida
,
Reese H. Clark
6   Pediatrix Medical Group, MEDNAX, Inc., Jacksonville, Florida
,
P. Brian Smith
1   Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina
2   Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
› Author Affiliations
Further Information

Publication History

22 April 2015

27 August 2015

Publication Date:
20 October 2015 (online)

Abstract

Objective This study aims to determine the association between hyperglycemia, insulin therapy, and severe retinopathy of prematurity (ROP) in extremely low-birth-weight (ELBW) infants.

Study Design In this retrospective database study, we included all ELBW infants who were ≤ 32 weeks gestational age (GA). We excluded infants without any ophthalmology evaluation and infants who died before 28 days of life. A multivariable model was constructed to determine the association between hyperglycemia, insulin use, and severe ROP. We defined hyperglycemia as blood glucose (BG) > 180 mg/dL. Covariates were GA, small for GA status, discharge year, sex, Apgar score at 5 minutes, mechanical ventilation, oxygen use, bacteremia, and postnatal steroid exposure. We defined severe ROP as ROP requiring bevacizumab, cryotherapy, laser therapy, or vitrectomy. Sensitivity analysis using BG > 150 mg/dL and > 200 mg/dL was performed.

Results A total of 24,548 infants were included; 2,547 (10%) had severe ROP. Hyperglycemia alone was not associated with severe ROP (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.66–1.17). Hyperglycemia and insulin use were not associated with severe ROP (OR, 1.43; 95% CI, 0.91–2.23). BG > 150 mg/dL and insulin use were associated with severe ROP (OR, 1.34; 95% CI, 1.02–1.76).

Conclusions Hyperglycemia alone was not associated with severe ROP in ELBW infants. However, we did observe a possible trend between the use of insulin and severe ROP.

 
  • References

  • 1 Rahi JS, Cable N ; British Childhood Visual Impairment Study Group. Severe visual impairment and blindness in children in the UK. Lancet 2003; 362 (9393) 1359-1365
  • 2 van Sorge AJ, Termote JU, de Vries MJ, Boonstra FN, Stellingwerf C, Schalij-Delfos NE. The incidence of visual impairment due to retinopathy of prematurity (ROP) and concomitant disabilities in the Netherlands: a 30 year overview. Br J Ophthalmol 2011; 95 (7) 937-941
  • 3 Hartnett ME, Penn JS. Mechanisms and management of retinopathy of prematurity. N Engl J Med 2012; 367 (26) 2515-2526
  • 4 Farooqi A, Hägglöf B, Sedin G, Serenius F. Impact at age 11 years of major neonatal morbidities in children born extremely preterm. Pediatrics 2011; 127 (5) e1247-e1257
  • 5 Hays SP, Smith EO, Sunehag AL. Hyperglycemia is a risk factor for early death and morbidity in extremely low birth-weight infants. Pediatrics 2006; 118 (5) 1811-1818
  • 6 van der Lugt NM, Smits-Wintjens VE, van Zwieten PH, Walther FJ. Short and long term outcome of neonatal hyperglycemia in very preterm infants: a retrospective follow-up study. BMC Pediatr 2010; 10: 52
  • 7 Beardsall K, Vanhaesebrouck S, Ogilvy-Stuart AL , et al. Prevalence and determinants of hyperglycemia in very low birth weight infants: cohort analyses of the NIRTURE study. J Pediatr 2010; 157 (5) 715-9.e1 , 3
  • 8 Garg R, Agthe AG, Donohue PK, Lehmann CU. Hyperglycemia and retinopathy of prematurity in very low birth weight infants. J Perinatol 2003; 23 (3) 186-194
  • 9 Ertl T, Gyarmati J, Gaál V, Szabó I. Relationship between hyperglycemia and retinopathy of prematurity in very low birth weight infants. Biol Neonate 2006; 89 (1) 56-59
  • 10 Blanco CL, Baillargeon JG, Morrison RL, Gong AK. Hyperglycemia in extremely low birth weight infants in a predominantly Hispanic population and related morbidities. J Perinatol 2006; 26 (12) 737-741
  • 11 Mohamed S, Murray JC, Dagle JM, Colaizy T. Hyperglycemia as a risk factor for the development of retinopathy of prematurity. BMC Pediatr 2013; 13: 78
  • 12 Beardsall K, Vanhaesebrouck S, Ogilvy-Stuart AL , et al. Early insulin therapy in very-low-birth-weight infants. N Engl J Med 2008; 359 (18) 1873-1884
  • 13 Bottino M, Cowett RM, Sinclair JC. Interventions for treatment of neonatal hyperglycemia in very low birth weight infants. Cochrane Database Syst Rev 2011; (10) CD007453
  • 14 Sinclair JC, Bottino M, Cowett RM. Interventions for prevention of neonatal hyperglycemia in very low birth weight infants. Cochrane Database Syst Rev 2011; (10) CD007615
  • 15 Kaempf JW, Kaempf AJ, Wu Y, Stawarz M, Niemeyer J, Grunkemeier G. Hyperglycemia, insulin and slower growth velocity may increase the risk of retinopathy of prematurity. J Perinatol 2011; 31 (4) 251-257
  • 16 Heald A, Abdel-Latif ME, Kent AL. Insulin infusion for hyperglycaemia in very preterm infants appears safe with no effect on morbidity, mortality and long-term neurodevelopmental outcome. J Matern Fetal Neonatal Med 2012; 25 (11) 2415-2418
  • 17 Beardsall K, Ogilvy-Stuart AL, Frystyk J , et al. Early elective insulin therapy can reduce hyperglycemia and increase insulin-like growth factor-I levels in very low birth weight infants. J Pediatr 2007; 151 (6) 611-617 , 617.e1
  • 18 Hellström A, Perruzzi C, Ju M , et al. Low IGF-I suppresses VEGF-survival signaling in retinal endothelial cells: direct correlation with clinical retinopathy of prematurity. Proc Natl Acad Sci U S A 2001; 98 (10) 5804-5808
  • 19 Juul A, Dalgaard P, Blum WF , et al. Serum levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in healthy infants, children, and adolescents: the relation to IGF-I, IGF-II, IGFBP-1, IGFBP-2, age, sex, body mass index, and pubertal maturation. J Clin Endocrinol Metab 1995; 80 (8) 2534-2542
  • 20 International Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity revisited. Arch Ophthalmol 2005; 123 (7) 991-999
  • 21 Zin A, Gole GA. Retinopathy of prematurity-incidence today. Clin Perinatol 2013; 40 (2) 185-200
  • 22 Horbar JD, Carpenter JH, Badger GJ , et al. Mortality and neonatal morbidity among infants 501 to 1500 grams from 2000 to 2009. Pediatrics 2012; 129 (6) 1019-1026