Journal Mobile Options
Table of Contents
Vol. 99, No. 2, 2011
Issue release date: February 2011
Section title: Original Paper
Free Access
Neonatology 2011;99:104–111

Blood Gases and Retinopathy of Prematurity: The ELGAN Study

Hauspurg A.K.a · Allred E.N.b–d · Vanderveen D.K.e, f · Chen M.g · Bednarek F.J.h · Cole C.i · Ehrenkranz R.A.a, j · Leviton A.b, c · Dammann O.b, g, k
aYale University School of Medicine, New Haven, Conn., bNeuroepidemiology Unit, Children’s Hospital Boston, cNeurology, Harvard Medical School, dBiostatistics, Harvard School of Public Health, eDepartment of Ophthalmology, Children’s Hospital Boston, fHarvard Medical School, and gDivision of Newborn Medicine, Floating Hospital for Children at Tufts Medical Center, Boston, Mass., hDivision of Neonatology, Department of Pediatrics, UMass Memorial, Worcester, Mass., iDivision of Neonatology, Department of Pediatrics, Boston Medical Center, Boston, Mass., jDepartment of Pediatrics, Yale University School of Medicine, New Haven, Conn., USA; kPerinatal Neuroepidemiology Unit, Hannover Medical School, Hannover, Germany
email Corresponding Author

Prof. Olaf Dammann

Division of Newborn Medicine

Floating Hospital for Children at Tufts Medical Center

800 Washington St., Box 854, Boston, MA 02111 (USA)

Tel. +1 617 636 0240, Fax +1 617 636 3309, E-Mail


  1. Campbell K: Intensive oxygen therapy as a possible cause of retrolental fibroplasia: a clinical approach. Med J Aust 1951;2:48–50.
  2. Patz A, Hoeck LE, De La Cruz E: Studies on the effect of high oxygen administration in retrolental fibroplasia. I. Nursery observations. Am J Ophthalmol 1952;35:1248–1253.
  3. Gibson DL, Sheps SB, Uh SH, Schechter MT, McCormick AQ: Retinopathy of prematurity-induced blindness: birth weight-specific survival and the new epidemic. Pediatrics 1990;86:405–412.
  4. Palmer EA, Flynn JT, Hardy RJ, et al: Incidence and early course of retinopathy of prematurity. The Cryotherapy for Retinopathy of Prematurity Cooperative Group. Ophthalmology 1991;98:1628–1640.
  5. McColm JR, Fleck BW: Retinopathy of prematurity: causation. Semin Neonatol 2001;6:453–460.
  6. Cole CH, Wright KW, Tarnow-Mordi W, Phelps DL, Pulse Oximetry Saturation Trial for Prevention of Retinopathy of Prematurity Planning Study Group: Resolving our uncertainty about oxygen therapy. Pediatrics 2003;112:1415–1419.
  7. Anderson CG, Benitz WE, Madan A: Retinopathy of prematurity and pulse oximetry: a national survey of recent practices. J Perinatol 2004;24:164–168.
  8. Wright KW, Sami D, Thompson L, Ramanathan R, Joseph R, Farzavandi S: A physiologic reduced oxygen protocol decreases the incidence of threshold retinopathy of prematurity. Trans Am Ophthalmol Soc 2006;104:78–84.
    External Resources
  9. Vento M, Moro M, Escrig R, et al: Preterm resuscitation with low oxygen causes less oxidative stress, inflammation, and chronic lung disease. Pediatrics 2009;124:e439–e449.
  10. Kuban K, Adler I, Allred EN, et al: Observer variability assessing US scans of the preterm brain: the ELGAN Study. Pediatr Radiol 2007;37:1201–1208.
  11. Laughon M, Bose C, Allred E, et al: Factors associated with treatment for hypotension in extremely low gestational age newborns during the first postnatal week. Pediatrics 2007;119:273–280.
  12. O’Shea TM, Kuban KC, Allred EN, et al: Neonatal cranial ultrasound lesions and developmental delays at 2 years of age among extremely low gestational age children. Pediatrics 2008;122:e662–e669.
  13. Kuban KC, Allred EN, O’Shea M, et al: An algorithm for identifying and classifying cerebral palsy in young children. J Pediatr 2008;153:466–472.
  14. McElrath TF, Hecht JL, Dammann O, et al: Pregnancy disorders that lead to delivery before the 28th week of gestation: an epidemiologic approach to classification. Am J Epidemiol 2008;168:980–989.
  15. Laughon M, Allred EN, Bose C, et al: Patterns of respiratory disease during the first two postnatal weeks in extremely premature infants. Pediatrics 2009;123:1124–1131.
  16. Olomu IN, Hecht JL, Onderdonk AO, Allred EN, Leviton A, Extremely Low Gestational Age Newborn Study Investigators: Perinatal correlates of Ureaplasma urealyticum in placenta parenchyma of singleton pregnancies that end before 28 weeks of gestation. Pediatrics 2009;123:1329–1336.
  17. Yudkin PL, Aboualfa M, Eyre JA, Redman CW, Wilkinson AR: New birthweight and head circumference centiles for gestational ages 24 to 42 weeks. Early Hum Dev 1987;15:45–52.
  18. Onderdonk AB, Hecht JL, McElrath TF, et al: Colonization of second-trimester placenta parenchyma. Am J Obstet Gynecol 2008;199:52.e1–52.e10.
  19. Hecht J, Allred EN, Kliman H, et al: Histologic characteristics of singleton placentas delivered before the 28th week of gestation. Pathology 2008;40:372–376.
  20. The International Committee for the Classification of the Late Stages of Retinopathy of Prematurity: An international classification of retinopathy of prematurity. II. The classification of retinal detachment. Arch Ophthalmol 1987;105:906–912.
  21. American Academy of Pediatrics. Section on Ophthalmology: Screening examination of premature infants for retinopathy of prematurity. Pediatrics 2001;108:809–811.
  22. Early Treatment for Retinopathy of Prematurity Cooperative Group: Revised indications for the treatment of retinopathy of prematurity: results of the early treatment for retinopathy of prematurity randomized trial. Arch Ophthalmol 2003;121:1684–1694.
  23. Begg MD, Parides MK: Separation of individual-level and cluster-level covariate effects in regression analysis of correlated data. Stat Med 2003;22:2591–2602.
  24. Hellstrom A, Engstrom E, Hard AL, et al: Postnatal serum insulin-like growth factor I deficiency is associated with retinopathy of prematurity and other complications of premature birth. Pediatrics 2003;112:1016–1020.
  25. Young TL, Anthony DC, Pierce E, Foley E, Smith LE: Histopathology and vascular endothelial growth factor in untreated and diode laser-treated retinopathy of prematurity. J AAPOS 1997;1:105–110.
  26. Bharwani SK, Dhanireddy R: Systemic fungal infection is associated with the development of retinopathy of prematurity in very low birth weight infants: a meta-review. J Perinatol 2008;28:61–66.
  27. Dammann O, Brinkhaus MJ, Bartels DB, et al: Immaturity, perinatal inflammation, and retinopathy of prematurity: a multi-hit hypothesis. Early Hum Dev 2009;85:325–329.
  28. Bizzarro MJ, Hussain N, Jonsson B, et al: Genetic susceptibility to retinopathy of prematurity. Pediatrics 2006;118:1858–1863.
  29. Mohamed S, Schaa K, Cooper ME, et al: Genetic contributions to the development of retinopathy of prematurity. Pediatr Res 2009;65:193–197.
  30. Procianoy RS, Garcia-Prats JA, Hittner HM, et al: An association between retinopathy of prematurity and intraventricular hemorrhage in very low birthweight infants. Acta Paediatr Scand 1981;70:473–477.
  31. Lad EM, Nguyen TC, Morton JM, Moshfeghi DM: Retinopathy of prematurity in the United States. Br J Ophthalmol 2008;92:320–325.
  32. Holmes JM, Zhang S, Leske DA, Lanier WL: Carbon dioxide-induced retinopathy in the neonatal rat. Curr Eye Res 1998;17:608–616.
  33. Zhang S, Leske DA, Lanier WL, Berkowitz BA, Holmes JM: Preretinal neovascularization associated with acetazolamide-induced systemic acidosis in the neonatal rat. Invest Ophthalmol Vis Sci 2001;42:1066–1071.
  34. Saito Y, Omoto T, Cho Y, Hatsukawa Y, Fujimura M, Takeuchi T: The progression of retinopathy of prematurity and fluctuation in blood gas tension. Graefes Arch Clin Exp Ophthalmol 1993;231:151–156.
  35. Liao SL, Lai SH, Kuo CY: Effect of carbon dioxide tension in the first three days of life on the development of retinopathy of prematurity. Chang Gung Med J 2000;23:755–760.
  36. Gellen B, McIntosh N, McColm JR, Fleck BW: Is the partial pressure of carbon dioxide in the blood related to the development of retinopathy of prematurity? Br J Ophthalmol 2001;85:1044–1045.
  37. Tin W: Oxygen therapy: 50 years of uncertainty. Pediatrics 2002;110:615–616.
  38. Higgins RD, Bancalari E, Willinger M, Raju TN: Executive summary of the workshop on oxygen in neonatal therapies: controversies and opportunities for research. Pediatrics 2007;119:790–796.
  39. Chen ML, Guo L, Dammann CE, Dammann O: High or low oxygen saturation and severe retinopathy of prematurity: a meta-analysis. Pediatrics 2010;125:e1483–e1492.
  40. Chow LC, Wright KW, Sola A, CSMC Oxygen Administration Study Group: Can changes in clinical practice decrease the incidence of severe retinopathy of prematurity in very low birth weight infants? Pediatrics 2003;111:339–345.
  41. Vanderveen DK, Mansfield TA, Eichenwald EC: Lower oxygen saturation alarm limits decrease the severity of retinopathy of prematurity. J AAPOS 2006;10:445–448.
  42. Sears JE, Pietz J, Sonnie C, Dolcini D, Hoppe G: A change in oxygen supplementation can decrease the incidence of retinopathy of prematurity. Ophthalmology 2009;116:513–518.
  43. Finer N, Leone T: Oxygen saturation monitoring for the preterm infant: the evidence basis for current practice. Pediatr Res 2009;65:375–380.
  44. Miller JD, Carlo WA: Safety and effectiveness of permissive hypercapnia in the preterm infant. Curr Opin Pediatr 2007;19:142–144.
  45. Jankov RP, Tanswell AK: Hypercapnia and the neonate. Acta Paediatr 2008;97:1502–1509.