Received: 21 January 2019; Published on-line: 27 June 2019

Serum VEGF levels in infants at risk for developing retinopathy of prematurity

S.V. Katsan, Cand Sc (Med); S.G. Fedotova, Ophthalmologist

Filatov Institute of Eye Diseases and Tissue Therapy; Odesa (Ukraine)

E-mail:  adakhovskayaa@gmail.com

Background: Because excessive growth of abnormal retinal vessels in the developing eye of the premature infant underlies retinopathy of prematurity (ROP), it may be hypothesized that a change in vascular endothelial growth factor (VEGF) level in the infant’s vascular bed predicts the course of the disease.

Purpose: To determine serum VEGF levels and to assess changes in these levels over time in infants at risk for developing ROP.

Materials and Methods: Twenty three infants born preterm underwent examinations for ROP. Two examinations were performed 14±3 days apart. A 1-ml blood sample was collected to obtain a 0.5-ml serum sample from each infant. Serum was frozen at -20° С until analysis. Serum VEGF levels were assessed by enzyme-linked immunosorbent assay (ELISA) method using Human VEGF-A ELISA Kit (Ray Biotech Inc., Norcross, GA) following the manufacturer’s instructions. Newborns were divided into two groups: those who exhibited ROP progression or absence of improvement (Group 1), and those who exhibited regression of ROP (Group 2). A Student’s t-test or Wilcoxon rank-sum test was used for two-group comparison.

Results: There were no significant differences between groups with regard to birth weight or gestational age (p<0.17; p<0.06). In addition, there was no significant difference with regard to serum VEGF level between groups at the first and second screening examinations (p<0.56). The difference in serum VEGF levels between two screening examinations for Group 1 was not significant (Friedman test, p = 0.27), whereas a decrease in serum VEGF levels between these examinations for Group 2 was significant (Friedman test, p = 0.046).

Conclusion: There was no significant difference with regard to serum VEGF level between groups at the first and second screening examinations. The increase in serum VEGF level between two examinations for infants who exhibited ROP progression or absence of improvement was not statistically significant. Infants with disease regression demonstrated a significant decrease in serum VEGF level at the second examination compared to the first examination.

Keywords: retinopathy of prematurity, VEGF


1.Saidasheva EI, Somov EE, Fomina NV. [Selected lectures on neonatal ophthalmology]. St. Petersburg: Nestor Istoriya; 2006. Russian.

2.Fierson WM, American academy of pediatrics Section on Ophthalmology, American academy of ophthalmology, American association for pediatric ophthalmology and strabismus, American association of certified orthoptists. Screening Examination of Premature Infants for Retinopathy of Prematurity. Pediatrics. 2018 Dec;142(6). pii: e20183061. 

Crossref   PubMed

3.Jefferies AL, Canadian Paediatric Society, Fetus and Newborn Committee. Retinopathy of prematurity: Recommendations for screening. Paediatr Child Health. 2010 Dec; 15(10): 667–70.

Crossref   PubMed

4.Tasman W. Retinopathy of prematurity: Do we still have a problem?: The Charles L. Schepens lecture. Arch Ophthalmol. 2011 Aug;129(8):1083-6. 

Crossref    PubMed 

5.Verma A, Nema N, Patel S, Ishrat S, Sidharth M.  Retinopathy of Prematurity: Incidence and Risk Factors Research Article. Int J Ophthalmol Eye Sci. 2016;4:198–201.

6.Royal College of Paediatrics and Child Health. Guideline for the Screening and Treatment of Retinopathy of Prematurity. 2010.

7.Taqui AM, Syed R, Chaudhry TA, Ahmad K, Salat MS. Retinopathy of prematurity: frequency and risk factors in a tertiary care hospital in Karachi, Pakistan.  J Pak Med Assoc. 2008;58:186–90.

8.Abdel HA, Mohamed GB, Othman MF. Retinopathy of Prematurity: A Study of Incidence and Risk Factors in NICU of Al-Minya University Hospital in Egypt.  J Clin Neonatol. 2012 Apr;1(2):76-81. doi: 10.4103/2249-4847.96755.

Crossref   PubMed

9.Visser Kift E, Freeman N, Cook C, Myer L. Retinopathy of prematurity screening criteria and workload implications at Tygerberg Children's Hospital, South Africa: A cross-sectional study. S Afr Med J. 2016 May 12;106(6). 

Crossref   PubMed

10.Hellgren G, Löfqvist C, Hård AL, et al. Serum concentrations of vascular endothelial growth factor in relation to retinopathy of prematurity. Pediat Res. 2016 Jan;79(1-1):70-5. 

Crossref    PubMed

11.Galazios  G, Papazoglou  D, Giagloglou  K, Vassaras  G, Koutlaki  N, Maltezos E. Umbilical cord serum vascular endothelial growth factor (VEGF) levels in normal pregnancies and in pregnancies complicated by preterm delivery or pre-eclampsia. Int J Gynaecol Obstet. 2004 Apr;85(1):6-11.

Crossref    PubMed  

12.Malamitsi-Puchner A, Tziotis J, Tsonou A, Protonotariou E, Sarandakou A, Creatsas G. Changes in serum levels of vascular endothelial growth factor in males and females throughout life. J Soc Gynecol Investig. 2000 Sep-Oct;7(5):309-12.

Crossref    PubMed   

13.Teksam O, Tekinalp G,  Yurdakok M, Yigit S, Korkmaz A. Dicle G. Vascular Endothelial Growth Factor Levels in Newborns with Meconium Stained Amniotic Fluid. Indian J Pediatr. 2008 Oct;75(10):1015-7. doi: 10.1007/s12098-008-0174-7.

Crossref    PubMed   

14.Tsao PN, Wei SC, Chou РС, et al. Vascular Endothelial Growth Factor in Preterm Infants With Respiratory Distress Syndrome.  Pediatr Pulmonol. 2005 May;39(5):461-5.

Crossref    PubMed   

15.Kenan S, Kimberly AD, Antonio Capone Jr, Michael T, Trese MT. Vitreous Levels of Stromal Cell–Derived Factor 1 and Vascular Endothelial Growth Factor in Patients with Retinopathy of Prematurity. Ophthalmology. 2008 Jun;115(6):1065-1070.e1.

Crossref    PubMed   

16.Kandasamy Y, Hartley L, Rudd D. Vascular Endothelial Growth Factor-A Levels inTerm Neonates. J Child Sci. 2017; 7: e151-e154.


17.Gariano RF, Thomas WG. Retinal angiogenesis in development and disease. Nature. 2005 Dec 15;438(7070):960-6.

Crossref   PubMed  

18.Hartnett ME. Pathophysiology and mechanisms of severe retinopathy of prematurity. Ophthalmology. – 2015 Jan;122(1):200-10. 

Crossref    PubMed

19.Hartnett ME, Penn JS. Mechanisms and management of retinopathy of prematurity. N Engl J Med. 2012 Dec 27;367(26):2515-26. 

Crossref     PubMed

20.Hughes S, Yang H, Chan-Ling T. Vascularization of the human fetal retina: roles of vasculogenesis and angiogenesis. Invest Ophthalmol Vis Sci. 2000 Apr;41(5):1217-28.

21.Lashkari K, Hirose T, Yazdany J, Wallace JM, Kazlauskas A, Rahimi N. Vascular Endothelial Growth Factor and Hepatocyte Growth Factor Levels Are Differentially Elevated in Patients with Advanced Retinopathy of Prematurity. Am J Pathol. 2000 Apr;156(4):1337-44.


22.Penna JS, Madanb A, Caldwellc RB, Bartolic M, Caldwellc RW, Hartnettd ME. Vascular Endothelial Growth Factor in Eye Disease. Prog Retin Eye Res. 2008 Jul;27(4):331-71.

Crossref   PubMed   

23.Reddy B, Doddamani R, Koujalagi MB, Guruprasad G, Ashwini RC, Aradya GH, Raghoji C. Retinopathy of prematurity in a tertiary care hospital: incidence and risk factors. Int J Pediat Res. 2016; 3(5):364-70. doi:10.17511.ijpr.2016.5.16

24.Smith LE. Through the eyes of a child: understanding retinopathy through ROP the Friedenwald lecture. Invest Ophthalmol Vis Sci. 2008;49(12):5177–82.

Crossref   PubMed

25.Smith LE, Wesolowski E, McLellan A. Oxygen-induced retinopathy in the mouse. Invest Ophthalmol Vis Sci. 1994;35:101–11.

26.Woo SJ, Park KH, Lee SY. The relationship between cord blood cytokine levels and perinatal factors and retinopathy of prematurity: a gestational age-matched case-control study. Invest Ophthalmol Vis Sci. 2013 May 15;54(5):3434-9. 

Crossref    PubMed

27.Yenice O, Çerman E, Ashour A, Ridvan F, Goncagul H, Sirikci O, Akman I, Kazokoglu H. Serum Erythropoietin, Insulin-like Growth Factor 1, and Vascular Endothelial Growth Factor in Etiopathogenesis of Retinopathy of Prematurity.

The authors certify that they have no conflicts of interest in the subject matter or materials discussed in this manuscript.