Skip to main content
NCBI home page
Medical Journal, Armed Forces India logoLink to Medical Journal, Armed Forces India
letter
. 2020 Aug 7;76(4):480–481. doi: 10.1016/j.mjafi.2020.06.006

Neonatal hyperglycemia and retinopathy of prematurity

Vishal Vishnu Tewari 1, Subhash Chandra Shaw 2,∗, G Shridhar 2
PMCID: PMC7606103  PMID: 33162664

Dear Editor,

We read with great interest the article “Hyperglycaemia as a risk factor for the development of retinopathy of prematurity: A cohort study” by Vannadil et al., published in Medical Journal Armed Forces India 2020. 76; 95–102.1 The study concludes that the high average blood glucose level in neonates during the first week of life is an indicator for developing retinopathy of prematurity (ROP) at a later date. Having gone through the article, we would like to add the following:

There are standard guidelines available from both National Neonatology Forum and the Government of India for screening and management of ROP.2,3 It will be of interest to note the study period and the site(s) of the study. Thirty-one percent of “at-risk” neonates developing ROP seem to be an inappropriately high figure. We would be interested to know the breakup of different stages of ROP and how many infants developed severe ROP needing intervention. The association of severe ROP with hyperglycemia, if any, will be of more relevance. We would also like to know about the ROP rates at different gestational ages and birth weights as the risk of ROP varies at different gestation ages and birth weights of neonates.

In this study, an arbitrary cutoff of the mean glucose value of 107.5 mg/dL was used to divide the study sample into the high blood sugar and low blood sugar group. On the contrary, although the definition varies in the literature, a blood glucose level higher than 125 mg/dL or a plasma or serum glucose concentration higher than 150 mg/dL has been used as the cutoff for hyperglycemia.4 The relative risk (RR) and confidence interval (CI) of the glycemic index show the same values for both Gmin and Gmax (RR = 1.311 and CI = 0.7326–2.346), which needs clarification.

The biologic plausibility of hyperglycemia predisposing to ROP has been the basis for observational studies. However, hyperglycemia is seen in preterm neonates during the early period of admission as the preterm neonate adapts to extrauterine survival.5,6 During this period, the disease process of ROP is in the vasoattenuative phase. The vasoproliferative state appears later when neonates are stably growing and maintaining normal blood glucose levels.7 Therefore, hyperglycemia as a risk factor for ROP, if at all, would lie in the latter period of hospitalization. May be due to this reason, the association between hyperglycemia and ROP is not convincingly shown in many recent meta-analyses.8,9 The mere presence of association in observational studies should not be accepted as causality. Moreover, hyperglycemia in the neonatal period is dependent on severity of sickness in a neonate, which in turn may be responsible for the occurrence and severity of ROP, and at this point, implicating hyperglycemia as an independent risk factor may not be appropriate.10

References

  • 1.Vannadil H., Moulick P.S., Khan M.A., Shankar S., Kaushik J., Sati A. Hyperglycaemia as a risk factor for the development of retinopathy of prematurity: a cohort study. MJAFI (Med J Armed Forces India) 2020;76:95–102. doi: 10.1016/j.mjafi.2019.04.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Pejaver R.K., Bilagi A.P., Vinekar A. NNF India, Guidelines; 2010. National Neonatology Foundation's Evidence Based Clinical Practice Guidelines 2010; pp. 253–262. (Retinopathy of Prematurity). [Google Scholar]
  • 3.Guidelines for universal eye screening in newborns including retinopathy of prematurity. Rashtriya Bal Swasthya Karyakram, Ministry of Health & Family Welfare. Government of India; June 2017. https://nhm.gov.in/images/pdf/programmes/RBSK/Resource_Documents/Revised_ROP_Guidelines-Web_Optimized.pdf [Google Scholar]
  • 4.Rozance P.J., Hay W.W. Neonatal hyperglycemia. NeoReviews. 2010;11:e632–e639. doi: 10.1542/neo.11-11-e632. [DOI] [Google Scholar]
  • 5.Dweck H.S., Cassady G. Glucose intolerance in infants of very low birth weight. I. Incidence of hyperglycemia in infants of birth weights 1,100 grams or less. Pediatrics. 1974;53:189–195. [PubMed] [Google Scholar]
  • 6.Beardsall K., Vanhaesebrouck S., Ogilvy-Stuart A.L. Prevalence and determinants of hyperglycemia in very low birth weight infants: cohort analyses of the NIRTURE study. J Pediatr. 2010;157:715–719. doi: 10.1016/j.jpeds.2010.04.032. e711-713. [DOI] [PubMed] [Google Scholar]
  • 7.Cayabyeb R., Ramanathan R. Retinopathy of prematurity: therapeutic strategies based on pathophysiology. Neonatology. 2016;109:369–376. doi: 10.1159/000444901. Epub 2016 Jun 3. [DOI] [PubMed] [Google Scholar]
  • 8.Au S.C., Tang S.M., Rong S.S., Chen L.J., Yam J.C. Association between hyperglycemia and retinopathy of prematurity: a systemic review and meta-analysis. Sci Rep. 2015;5:9091. doi: 10.1038/srep09091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Lee J.H., Hornik C.P., Testoni D. Insulin, hyperglycemia, and severe retinopathy of prematurity in extremely low-birth-weight infants. Am J Perinatol. 2016;33:393–400. doi: 10.1055/s-0035-1565999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Garg R., Agthe A.G., Donohue P.K., Lehmann C.U. Hyperglycemia and retinopathy of prematurity in very low birth weight infants. J Perinatol. 2003;23:186–194. doi: 10.1038/sj.jp.7210879. [DOI] [PubMed] [Google Scholar]

References

Reply to ‘Neonatal hyperglycemia and retinopathy of prematurity’.

Dear Editor,

We thank the readers for taking keen interest in the article. The clarifications are as under: In the given study period, of 103 neonates, 32 were found to have retinopathy of prematurity (ROP) at different stages. 71 neonates did not have ROP at screening. This figure is in agreement with the incidence found in previous studies on Indian population where the incidence ranged from 25.4% to 47.27% among the ‘at-risk’ infants.1, 2, 3, 4 The incidence varies with practice and admission patterns of different Neonatal Intensive Care Units.

The letter also submitted that the level of hyperglycemia is arbitrary. The definition of hyperglycaemia in neonates varies highly depending on the point of care.5, 6, 7 It seems that due to this disparity, various studies looking into the association of hyperglycaemia and ROP has generated their cut off levels of euglycemia from their own inherent sample.8, 9, 10, 11, 12, 13, 14 This disparity extends further into the way these values are reported in the respective study as reflected in the review article by Sunny Au et al.9 In our study, the level of blood glucose defined as hyperglycaemia is generated from the cohort of neonates being studied. This process was followed by test of statistical significance in the difference of means in these groups, which showed that these two groups were indeed statistically different in terms of their blood sugar values.

Retinopathy of prematurity (ROP) being a disease of prematurity, its incidence co-exists with other problems of prematurity like VLBW, apnoea, metabolic disturbances etc. These factors confound the exclusivity of hyperglycaemia as a risk factor of ROP. In order to conclude that hyperglycaemia is an independent indicator of ROP in evolution further studies with larger sample size and adjusted risk ratios are needed. We agree with the comment by the reader that “Moreover, hyperglycaemia in neonatal period is dependent on severity of sickness in a neonate which in turn may be responsible for the occurrence and severity of ROP and at this point implicating hyperglycaemia as an independent risk factor may not be appropriate” which is in line with the conclusion drawn from our study.

References

  • 1.Goyal A., Giridhar A., Gopalakrishnan M. Real-world scenario of retinopathy of prematurity in Kerala. Kerala J Ophthalmol. 2017;29(1):30. doi: 10.4103/kjo.kjo_45_17. [DOI] [Google Scholar]
  • 2.Dwivedi A., Dwivedi D., Lakhtakia S., Chalisgaonkar C., Jain S. Prevalence, risk factors and pattern of severe retinopathy of prematurity in eastern Madhya Pradesh. Indian J Ophthalmol. 2019;67(6):819. doi: 10.4103/ijo.IJO_1789_18. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Charan R., Dogra M.R., Gupta A., Narang A. The incidence of retinopathy of prematurity in a neonatal care unit. Indian J Ophthalmol. 1995;43(3):123–126. [PubMed] [Google Scholar]
  • 4.Ahuja A., Reddy Y.C.V., Adenuga O.O., Kewlani D., Ravindran M., Ramakrishnan R. Risk factors for retinopathy of prematurity in a district in South India: A prospective cohort study. Oman J Ophthalmol. 2018;11(1):33–37. doi: 10.4103/ojo.OJO_97_2016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Prince R., Hospital A. RPA Newborn Care Protocol Book Neonatal Hyperglycemia Definition : Risk factors. RPA Newborn care Protoc B. 2009;1(1):8–10. [Google Scholar]
  • 6.Cowett R.M., Farrag H.M. Selected principles of perinatal–neonatal glucose metabolism. Semin Neonatol. 2004;9(1):37–47. doi: 10.1016/S1084-2756(03)00113-1. [DOI] [PubMed] [Google Scholar]
  • 7.Hey E. Hyperglycaemia and the very preterm baby. Semin Fetal Neonatal Med. 2005;10(4):377–387. doi: 10.1016/j.siny.2005.04.008. [DOI] [PubMed] [Google Scholar]
  • 8.Garg R., Agthe A.G., Donohue P.K., Lehmann C.U. Hyperglycemia and retinopathy of prematurity in very low birth weight infants. J Perinatol. 2003;23(3):186–194. doi: 10.1038/sj.jp.7210879. [DOI] [PubMed] [Google Scholar]
  • 9.Au S.C.L., Tang S.-M., Rong S.-S., Chen L.-J., Yam J.C.S. Association between hyperglycemia and retinopathy of prematurity: a systemic review and meta-analysis. Sci Rep. 2015;5(1):1–6. doi: 10.1038/srep09091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Mohsen L., Abou-Alam M., El-Dib M., Labib M., Elsada M., Aly H. A prospective study on hyperglycemia and retinopathy of prematurity. J Perinatol. 2014;34(November 2013):1–5. doi: 10.1038/jp.2014.49. [DOI] [PubMed] [Google Scholar]
  • 11.Blanco C.L., Baillargeon J.G., Morrison R.L., Gong A.K. Hyperglycemia in extremely low birth weight infants in a predominantly Hispanic population and related morbidities. J Perinatol. 2006;26(12):737–741. doi: 10.1038/sj.jp.7211594. [DOI] [PubMed] [Google Scholar]
  • 12.Heimann K., Peschgens T., Kwiecien R., Stanzel S., Hoernchen H., Merz U. Are recurrent hyperglycemic episodes and median blood glucose level a prognostic factor for increased morbidity and mortality in premature infants ≤1500 g? J Perinat Med. 2007;35(3):245–248. doi: 10.1515/JPM.2007.057. [DOI] [PubMed] [Google Scholar]
  • 13.Ertl T., Gyarmati J., Gaál V., Szabó I. Relationship between Hyperglycemia and Retinopathy of Prematurity in Very Low Birth Weight Infants. Neonatology. 2006;89(1):56–59. doi: 10.1159/000088199. [DOI] [PubMed] [Google Scholar]
  • 14.Chavez-Valdez R., McGowan J., Cannon E., Lehmann C.U. Contribution of early glycemic status in the development of severe retinopathy of prematurity in a cohort of ELBW infants. J Perinatol. 2011;31(12):749–756. doi: 10.1038/jp.2011.19. [DOI] [PubMed] [Google Scholar]

Articles from Medical Journal, Armed Forces India are provided here courtesy of Elsevier

RESOURCES