Abstract
Objective
To determine whether red blood cell glucose-6-phosphate dehydrogenase (G6PD) activity is associated with retinopathy of prematurity (ROP).
Methods
This case-control study was conducted in a Level-3 neonatal unit. Subjects were inborn boys with birth weight <2000 g. “Cases” were consecutive subjects with ROP of any severity. “Controls” were consecutive unrelated subjects without ROP. Recipients of blood or exchange transfusions were excluded. Sixty cases (out of 98 screened) and 60 controls (out of 93 screened) were enrolled. G6PD activity (quantitative assay) as the candidate risk factor was evaluated.
Results
Sixty cases with 60 controls [mean (SD) gestation 28.80 (2.2) and 30.60 (2.2) wk respectively] were compared. “Cases” had a higher median (1st, 3rd quartile) G6PD activity compared to “controls” [7.39 (4.7, 11.5) vs. 6.28 (4.2, 8.8) U/g Hb, p = 0.084]. G6PD activity was highest among ROP requiring treatment [8.68 (4.7, 12.3)] followed by ROP not requiring treatment [6.91 (4.4, 11.0)], followed by controls (plinear trend = 0.06). Gestation, birth weight, duration of oxygen, breastmilk feeding, and clinical sepsis were other variables associated with ROP on univariable analysis. On multivariable logistic regression, G6PD activity [Adjusted OR 1.14 (1.03, 1.25), p = 0.01] and gestation [Adjusted OR 0.74 (0.56, 0.97), p = 0.03] independently predicted ROP. C-statistic of the model was 0.76 (95% CI 0.67, 0.85).
Conclusions
Higher G6PD activity was independently associated with ROP after adjusting for confounders. Each 1 U/g Hb increase in G6PD increased the odds of ROP by 14%. Severer forms of ROP were associated with higher levels of G6PD activity.
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References
Sullivan JL, Newton RB. Serum antioxidant activity in neonates. Arch Dis Child. 1988;63:748–50.
Francis RO, Jhang JS, Pham HP, Hod EA, Zimring JC, Spitalnik SL. Glucose-6-phosphate dehydrogenase deficiency in transfusion medicine: the unknown risks. Vox Sang. 2013;105:271–82.
van den Broek L, Heylen E, van den Akker M. Glucose-6-phosphate dehydrogenase deficiency: not exclusively in males. Clin Case Rep. 2016;4:1135–7.
Kumar P, Yadav U, Rai V. Prevalence of glucose-6-phosphate dehydrogenase deficiency in India: an updated meta-analysis. Egypt J Med Hum Genet. 2016;17:295–302.
Zeng LH, Wu DZ, Ma QY, Wu LH. Genetic study of retinitis pigmentosa in China. Ophthalmologica. 1987;194:34–9.
Fan X, Monnier VM, Whitson J. Lens glutathione homeostasis: discrepancies and gaps in knowledge standing in the way of novel therapeutic approaches. Exp Eye Res. 2017;156:103–11.
Hecker PA, Lionetti V, Ribeiro RF Jr, et al. Glucose 6-phosphate dehydrogenase deficiency increases redox stress and moderately accelerates the development of heart failure. Circ Heart Fail. 2013;6:118–26.
Lai YK, Lai NM, Lee SW. Glucose-6-phosphate dehydrogenase deficiency and risk of diabetes: a systematic review and meta-analysis. Ann Hematol. 2017;96:839–45.
Cappai G, Songini M, Doria A, Cavallerano JD, Lorenzi M. Increased prevalence of proliferative retinopathy in patients with type 1 diabetes who are deficient in glucose-6-phosphate dehydrogenase. Diabetologia. 2011;54:1539–42.
Cocco P, Todde P, Fornera S, Manca MB, Manca P, Sias AR. Mortality in a cohort of men expressing the glucose-6-phosphate dehydrogenase deficiency. Blood. 1998;91:706–9.
Schutzman DL, Porat R. Glucose-6-phosphate dehydrogenase deficiency: another risk factor for necrotizing enterocolitis? J Pediatr. 2007;151:435–7.
Mbanefo EC, Ahmed AM, Titouna A, et al. Association of glucose-6-phosphate dehydrogenase deficiency and malaria: a systematic review and meta-analysis. Sci Rep. 2017;7:45963.
Pinna A, Carru C, Solinas G, Zinellu A, Carta F. Glucose-6-phosphate dehydrogenase deficiency in retinal vein occlusion. Invest Ophthalmol Vis Sci. 2007;48:2747–52.
Wink DA, Nims RW, Darbyshire JF, et al. Reaction kinetics for nitrosation of cysteine and glutathione in aerobic nitric oxide solutions at neutral pH. insights into the fate and physiological effects of intermediates generated in the NO/O2 reaction. Chem Res Toxicol. 1994;7:519–25.
Pinna A, Solinas G, Masia C, Zinellu A, Carru C, Carta A. Glucose-6-phosphate dehydrogenase (G6PD) deficiency in nonarteritic anterior ischemic optic neuropathy in a sardinian population, Italy. Invest Ophthalmol Vis Sci. 2008;49:1328–32.
Batetta B, Bonatesta RR, Sanna F, et al. Cell growth and cholesterol metabolism in human glucose-6-phosphate dehydrogenase deficient lymphomononuclear cells. Cell Prolif. 2002;35:143–54.
Frey RS, Ushio-Fukai M, Malik AB. NADPH oxidase-dependent signaling in endothelial cells: role in physiology and pathophysiology. Antioxid Redox Signal. 2009;11:791–810.
Frongia C, Sorbello O, Demelia L, Capra GF, Laconi E. Glucose-6-phosphate dehydrogenase deficiency is associated with lower fibrosis score in non-progressive HBsAg-positive subjects. J Gastrointestin Liver Dis. 2017;26:319–20.
Mendoza-Milla C, Valero Jimenez A, Rangel C, et al. Dehydroepiandrosterone has strong antifibrotic effects and is decreased in idiopathic pulmonary fibrosis. Eur Respir J. 2013;42:1309–21.
Pes GM, Bassotti G, Dore MP. Colorectal cancer mortality in relation to glucose – 6 – phosphate dehydrogenase deficiency and consanguinity in sardinia: a spatial correlation analysis. Asian Pac J Cancer Prev. 2017;18:2403–7.
Jin L, Zhou Y. Crucial role of the pentose phosphate pathway in malignant tumors. Oncol Lett. 2019;17:4213–21.
Azma RZ, Siti Zubaidah M, Azlin I, et al. Detection of partial G6PD deficiency using OSMMR2000-D kit with hb normalization. Med Health. 2014;9:11–21.
Zhu Z, Hua X, Yu Y, Zhu P, Hong K, Ke Y. Effect of red blood cell transfusion on the development of retinopathy of prematurity: a systematic review and meta-analysis. PLoS ONE. 2020;15:e0234266.
Boo NY, Ainoon BO, Ooi LH, Cheong SK, Haliza BM. Glucose-6-phosphate dehydrogenase enzyme activity of normal term malaysian neonates of different ethnic origins. J Paediatr Child Health. 1994;30:273–4.
Chan EC, Liu GS, Dusting GJ. Redox mechanisms in pathological angiogenesis in the retina: roles for NADPH oxidase. Curr Pharm Des. 2015;21:5988–98.
Santana-Garrido A, Reyes-Goya C, Fernandez-Bobadilla C, et al. NADPH oxidase-induced oxidative stress in the eyes of hypertensive rats. Mol Vis. 2021;27:161–78.
Stanton RC. Glucose-6-phosphate dehydrogenase, NADPH, and cell survival. IUBMB Life. 2012;64:362–9.
Ziberna L, Martelanc M, Franko M, Passamonti S. Bilirubin is an endogenous antioxidant in human vascular endothelial cells. Sci Rep. 2016;6:29240.
Mesner O, Hammerman C, Goldschmidt D, Rudensky B, Bader D, Kaplan M. Glucose-6-phosphate dehydrogenase activity in male premature and term neonates. Arch Dis Child Fetal Neonatal Ed. 2004;89:F555–7.
Ko CH, Wong RP, Ng PC, et al. Oxidative challenge and glucose-6-phosphate dehydrogenase activity of preterm and term neonatal red blood cells. Neonatology. 2009;96:96–101.
Funding
Partially unded by Chandigarh Department of Science and Technology (S&T&RE/RP/147(18–19)/sanc/10/2018/1498-1505 dated 26-10-18. The funding agency did not play any role in the design of the study, analysis, and writing the manuscript
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RP made substantial contributions to the design of the work, acquisition, and analysis of data; drafted the work and revised it critically for important intellectual content; approved the final version to be published and agrees to be accountable for all aspects of the work. SD, PK made substantial contributions to the conception and design of the work, acquisition, analysis and interpretation of data; drafted the work and revised it critically for important intellectual content; approved the final version to be published and agrees to be accountable for all aspects of the work. RD, DK made substantial contributions to the design of the work, acquisition, analysis and interpretation of data; drafted the work and revised it critically for important intellectual content; approved the final version to be published and agrees to be accountable for all aspects of the work. SD will act as guarantor for this manuscript.
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The Institute Ethics Committee approved the study protocol (Approval no: IEC/2018/001859 on 21/11/2018).
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Paulpandian, R., Dutta, S., Das, R. et al. Retinopathy of Prematurity and Glucose-6-Phosphate Dehydrogenase Activity: A Case-Control Study. Indian J Pediatr 90, 1089–1095 (2023). https://doi.org/10.1007/s12098-023-04604-x
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DOI: https://doi.org/10.1007/s12098-023-04604-x