Effect of the type of respiratory support and oxygenation indices on the development of different stages of retinopathy of prematurity
DOI:
https://doi.org/10.31288/Ukr.j.ophthalmol.202643241Keywords:
retinopathy, preterm infants, lung ventilation, saturation, risk factors, laser photocoagulation, vasculogenesis, screening, retinaAbstract
Purpose. To examine the effect size of the type of respiratory support and oxygenation indices on the development of different stages of retinopathy of prematurity (RoP).
Material and methods. We retrospectively reviewed the medical records of 290 preterm infants who were under supervision during 2015-2018. The preterm infants were divided into four groups: group 1 of 117 infants without RoP; group 2 of 86 infants with autoregressive RoP; group 3 of 57 infants that required treatment for RoP; and group 4 of 30 infants with aggressive RoP. All these infants underwent ROP screening in accordance with international standards in due time.
Results. There was a significant difference in gestation age (GA) among the four groups (ANOVA: F= 74.13; p < 0.0001), with a significant pairwise difference between most group pairs, but not between groups 3 and 4 (p = 0.9). Additionally, there was a significant difference in birth body weight (BBW) among the four groups (analysis of variance (ANOVA): F= 54.1; p < 0.0001), but the pairwise difference between groups 3 and 4 was not significant (p = 0.9). For FiO2, Welch's ANOVA was applied when the homogeneity of dispersions was violated (Levene’s test p = 0.03): F = 4.6; p = 0.005; the pairwise differences between groups 1 and 3, 2 and 3, and 3 and 4 were significant (p = 0.0006, p = 0.001, and p = 0.048, respectively). The frequency of mechanical ventilation (MV) use increased from group 1 to group 4 (90/117, 71/86, 55/57, and 30/30, respectively), with a significant difference among groups (Kruskal-Wallis test: H = 17.3; p = 0.006). No significant difference among groups was found for the frequency of use of nasal continuous positive airway pressure (NCPAP) (114/117, 85/86, 57/57, and 30/30, respectively; Kruskal-Wallis test: H = 2.4; p = 0.48). Transcutaneously measured oxygen saturation (SpO2) was similar among groups (Welch ANOVA: F = 0.7; p = 0.5). The effect size as measured by partial η² was the largest for GA (0.437) and BBW (0.36) and less for MV (0.05) and FiO2 (0.046).
Conclusion. GA and BBW had the largest effects (with a partial η² of 0.437 and 0.36, respectively) on the development of different stages of RoP. There was a significant difference among groups in FiO2 or the frequency of MV use (indicating their effects on the development of different stages of RoP), but not in SpO2 or the frequency of NCPAP use.
References
Kim SJ, Port AD, Swan R, Campbell JP, Chan RVP, Chiang MF. Retinopathy of prematurity: a review of risk factors and their clinical significance. Surv Ophthalmol. 2018;63(5):618-637. https://doi.org/10.1016/j.survophthal.2018.04.002
Campbell K. Intensive oxygen therapy as a possible cause of retrolental fibroplasia: a clinical approach. Med J Aust. 1951. https://doi.org/10.5694/j.1326-5377.1951.tb109040.x
Gilbert C, Fielder A, Gordillo L, Quinn G, Semiglia R, Visintin P, et al. Characteristics of infants with severe retinopathy of prematurity in countries with low, moderate, and high levels of development: implications for screening programs. Pediatrics. 2005;115(5):e518-e525. https://doi.org/10.1542/peds.2004-1180
Schaffer DB, Palmer EA, Plotsky DF, Metz HS, Flynn JT, Tung B, et al. Prognostic factors in the natural course of retinopathy of prematurity. Ophthalmology. 1993;100(2):230-237.https://doi.org/10.1016/S0161-6420(93)31665-9
Stenson BJ, Tarnow-Mordi WO, Darlow BA, Simes J, Juszczak E, Askie L, et al. Oxygen saturation and outcomes in preterm infants. N Engl J Med. 2013;368(22):2094-2104.https://doi.org/10.1056/NEJMoa1302298
Carlo WA, Finer NN, Walsh MC, Rich W, Gantz MG, Laptook AR, et al. Target ranges of oxygen saturation in extremely preterm infants. N Engl J Med. 2010;362(21):1959-1969.https://doi.org/10.1056/NEJMoa0911781
Schmidt B, Whyte R, Roberts R. Trade-off between lower or higher oxygen saturations for extremely preterm infants: the First Benefits of Oxygen Saturation Targeting (BOOST) II Trial reports its primary outcome. J Pediatr. 2014;165(1):6-8. https://doi.org/10.1016/j.jpeds.2014.03.004
Katsan SV, Adakhovska AA, Budivska OS. Intraventricular hemorrhages as risk factors for retinopathy of prematurity. J Ophthalmol. 2020;(4):3-7. https://doi.org/10.31288/oftalmolzh2020437
Katsan SV, Adakhovska AA, Budivska OS. The role of maternal factors in the development of retinopathy of prematurity in prematurely born children. Azərbaycan Oftalmologiya Jurnalı. 2019;31(3):58-64. Available from: https://www.oftalmologiya.az/ajo/article/view/221.
Fedotova SG, Adakhovska AA, Zaichko OS, Katsan SV. Risk factors for the development of retinopathy of prematurity in prematurely born children. Ophthalmological Journal of Kazakhstan. 2017;(1):69-76. Available from: https://eyeinst.kz/upload/files/79749_783038_17.pdf.
Chan-Ling T, Gock B, Stone J. The effect of oxygen on vasoformative cell division: evidence that "physiological hypoxia" is the stimulus for normal retinal vasculogenesis. Invest Ophthalmol Vis Sci. 1995;36(7):1201-1214. PMID:7775098.
Ferrara N, Houck K, Jakeman L, Leung DW. Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocr Rev. 1992;13(1):18-32. https://doi.org/10.1210/edrv-13-1-18
Smith LEH. IGF-1 and retinopathy of prematurity in the preterm infant. Biol Neonate. 2005;88(3):237-244. https://doi.org/10.1159/000087587
Pierce EA, Avery RL, Foley ED, Aiello LP, Smith LEH. Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization. Proc Natl Acad Sci U S A. 1995;92(3):905-909. https://doi.org/10.1073/pnas.92.3.905
Pierce EA, Foley ED, Smith LEH. Regulation of vascular endothelial growth factor by oxygen in a model of retinopathy of prematurity. Arch Ophthalmol. 1996;114(10):1219-1228. https://doi.org/10.1001/archopht.1996.01100140419009
Sweet DG, Carnielli V, Greisen G, Hallman M, Ozek E, te Pas A, et al. European consensus guidelines on the management of respiratory distress syndrome. Neonatology. 2019;115(4):432-450. https://doi.org/10.1159/000499361
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(2):339-345. https://doi.org/10.1542/peds.111.2.339
Rysavy MA, Li L, Bell EF, Das A, Hintz SR, Stoll BJ, et al. Oxygen saturations and retinopathy of prematurity in extreme preterms. Arch Dis Child Fetal Neonatal Ed. 2020;105(2):138-144.https://doi.org/10.1136/archdischild-2018-316464
Askie LM, Brocklehurst P, Darlow BA, Finer N, Schmidt B, Tarnow-Mordi W. NeOProM: Neonatal Oxygenation Prospective Meta-analysis Collaboration study protocol. BMC Pediatr. 2011;11:6.https://doi.org/10.1186/1471-2431-11-6
Darlow BA, Husain S. Primary prevention of ROP and the oxygen saturation targeting trials. Semin Perinatol. 2019;43(6):333-340. https://doi.org/10.1053/j.semperi.2019.05.004
STOP-ROP Multicenter Study Group. Supplemental Therapeutic Oxygen for Prethreshold Retinopathy of Prematurity (STOP-ROP), a randomized, controlled trial. I: primary outcomes. Pediatrics. 2000;105(2):295-310. https://doi.org/10.1542/peds.105.2.295
Yang R, Fang Z, Liu KZ, et al. Comparison of two fractions of inspired oxygen thresholds (0.25 vs 0.30) for surfactant administration in very preterm infants with respiratory distress syndrome under nasal intermittent positive pressure ventilation: study protocol for a multicentre randomised controlled superiority trial. BMJ Paediatr Open. 2025;9:e003998.https://doi.org/10.1136/bmjpo-2025-003998
Trubuhovich RV. 19th century pioneers of intensive therapy in North America. Part 1: George Edward Fell. Crit Care Resusc. 2007;9(4):377-393. https://doi.org/10.1016/S1441-2772(23)01671-X
Lin WC, Jordan BK, Scottoline B, et al. Oxygenation fluctuations associated with severe retinopathy of prematurity: insights from a multimodal deep learning approach. Ophthalmol Sci. 2023;4(2):100417. https://doi.org/10.1016/j.xops.2023.100417
Committee on Fetus and Newborn, American Academy of Pediatrics. Respiratory support in preterm infants at birth. Pediatrics. 2014;133(1):171-174. https://doi.org/10.1542/peds.2013-3442
Chen J, Lin Y, Du L, et al. The comparison of HHHFNC and NCPAP in extremely low-birth-weight preterm infants after extubation: a single-center randomized controlled trial. Front Pediatr. 2020;8:250. https://doi.org/10.3389/fped.2020.00250
Luo K, Huang Y, Xiong T. High-flow nasal cannula versus continuous positive airway pressure in primary respiratory support for preterm infants: a systematic review and meta-analysis. Front Pediatr. 2022;10:980024. https://doi.org/10.3389/fped.2022.980024
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