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A novel marker for predicting type 1 retinopathy of prematurity: C-reactive protein/albumin ratio

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Abstract

Purpose

We aimed to investigate whether the C-reactive protein (CRP) to albumin ratio (CAR) an inflammatory predictor can be used as a marker for the development of ROP.

Methods

Gestational age, birth weight, gender, neonatal, and maternal risk factors were recorded. The patients were divided into two groups: those who did not develop ROP (ROP −) and those who developed ROP (ROP +). The ROP + group was further separated into two groups: those who required treatment (ROP + T) and those who were not treated (ROP + NT). The following parameters were noted in the first postnatal week and at the end of the first postnatal month: CRP, albumin, CAR, white blood cell (WBC), neutrophil, lymphocyte, neutrophil-to-lymphocyte ratio (NLR), distribution red cell width (RDW), platelet (Plt), and RDW/platelet ratio.

Results

We evaluated 131 premature infants who met the inclusion criteria. There was no difference between the main groups in hemogram parameters and CAR at the postnatal first week. WBC count (p = 0.011), neutrophil count (p = 0.002), and NLR were high (p = 0.004) in the ROP + group at the end of the postnatal 1st month. The CAR level at the end of the first month was higher in the ROP + group (p = 0.027). CAR was similar between the ROP + T and ROP + NT groups (p = 0.112) in the postnatal first week but higher in the treatment-required group at the end of the first month (p < 0.01).

Conclusion

High CAR and high NLR at the end of the postnatal first month can be used to predict the development of severe ROP.

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References

  1. Fielder A, Blencowe H, O’Connor A, Gilbert C (2015) Impact of retinopathy of prematurity on ocular structures and visual functions. Arch Dis Child Fetal Neonatal Ed 100(2):179–184. https://doi.org/10.1136/archdischild-2014-306207

    Article  Google Scholar 

  2. Küçükevcilioğlu M, Mutlu FM, Sarıcı SÜ (2015) Ocular morbidities of premature children with mild or no retinopathy of prematurity. Turk J Pediatr 57(2):129–135

    PubMed  Google Scholar 

  3. Zhu X, Zhao R, Wang Y, Ouyang L et al (2017) Refractive state and optical compositions of preterm children with and without retinopathy of prematurity in the first 6 years of life. Medicine (Baltimore) 96(45):8565. https://doi.org/10.1097/MD.0000000000008565

    Article  Google Scholar 

  4. Kumar P, Sankar MJ, Deorari A, Azad R et al (2011) Risk factors for severe retinopathy of prematurity in preterm low birth weight neonates. Indian J Pediatr 78(7):812–816. https://doi.org/10.1007/s12098-011-0363-7

    Article  PubMed  Google Scholar 

  5. Baş AY, Demirel N, Koc E, Ulubas Isik D et al, TR-ROP Study Group (2018) Incidence, risk factors and severity of retinopathy of prematurity in Turkey (TR-ROP study): a prospective, multicentre study in 69 neonatal intensive care units. Br J Ophthalmol 102(12):1711–1716. https://doi.org/10.1136/bjophthalmol-2017-311789

  6. Chang JW (2019) Risk factor analysis for the development and progression of retinopathy of prematurity. PLoS One 14(7):0219934. https://doi.org/10.1371/journal.pone.0219934

  7. Rao AK, Purkayastha J, Hazarika M, Chaitra R, Adith KM (2013) Analysis of prenatal and postnatal risk factors of retinopathy of prematurity in a tertiary care hospital in South India. Indian J Ophthalmol 61(11):640–644. https://doi.org/10.4103/0301-4738.119347

    Article  PubMed  PubMed Central  Google Scholar 

  8. Rivera JC, Holm M, Austeng D, Morken TS et al (2017) Retinopathy of prematurity: inflammation, choroidal degeneration, and novel promising therapeutic strategies. J Neuroinflammation 14(1):165. https://doi.org/10.1186/s12974-017-0943-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Lee J, Dammann O (2012) Perinatal infection, inflammation, and retinopathy of prematurity. Semin Fetal Neonatal Med 17(1):26–29. https://doi.org/10.1016/j.siny.2011.08.007

    Article  PubMed  Google Scholar 

  10. Beaudry-Richard A, Nadeau-Vallée M, Prairie É, Maurice N et al (2018) Antenatal IL-1-dependent inflammation persists postnatally and causes retinal and sub-retinal vasculopathy in progeny. Sci Rep 8(1):11875. https://doi.org/10.1038/s41598-018-30087-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Lynch AM, Berning AA, Thevarajah TS, Wagner BD et al (2018) The role of the maternal and fetal inflammatory response in retinopathy of prematurity. Am J Reprod Immunol 83(1):12986. https://doi.org/10.1111/aji.12986

    Article  Google Scholar 

  12. Sullivan JL (1986) Retinopathy of prematurity and iron: a modification of the oxygen hypothesis. Pediatrics 78(6):1171–1172

    Article  CAS  PubMed  Google Scholar 

  13. Szade A, Grochot-Przeczek A, Florczyk U, Jozkowicz A, Dulak J (2015) Cellular and molecular mechanisms of inflammation-induced angiogenesis. IUBMB Life 67(3):145–159. https://doi.org/10.1002/iub.1358

  14. Yu H, Yuan L, Zou Y, Peng L et al (2014) Serum concentrations of cytokines in infants with retinopathy of prematurity. APMIS 122(9):818–823. https://doi.org/10.1111/apm.12223

    Article  CAS  PubMed  Google Scholar 

  15. Holm M, Morken TS, Fichorova RN, VanderVeen DK, et al. for the ELGAN Study Neonatology and Ophthalmology Committees (2017) Systemic inflammation-associated proteins and retinopathy of prematurity in infants born before the 28th week of gestation. IOVS 58(14);6419–6428. https://doi.org/10.1167/iovs.17-21931

  16. Parrozzani R, Nacci EB , Bini S, Marchione G et al (2021) Severe retinopathy of prematurity is associated with early post-natal low platelet count. Sci Reports 11(1):891. https://doi.org/10.1038/s41598-020-79535-0

  17. Morris I, McCallion N, El-Khuffash A, Molloy EJ (2008) Serum albumin and mortality in very low birth weight infants. Arch Dis Child Fetal Neonatal Ed 93(4):310–312. https://doi.org/10.1136/adc.2007.131375

    Article  Google Scholar 

  18. Lee M, Youn S, Lim BK, Kim JS (2005) Serum albumin concentrations and clinical disorders by gestational ages in Preterm Babies. Korean J Pediatr 48(2):148–153

    CAS  Google Scholar 

  19. Bai M , Wu Y, Ji Z , Wang S et al. (2019) Prognostic value of C-reactive protein/albumin ratio in neurocritically ill patients. Minerva Anestesiol 85(12):1299–1307. https://doi.org/10.23736/S0375-9393.19.13625-5

  20. Ni XF, Wu J, Ji M, Shao YJ et al (2018) Effect of C-reactive protein/albumin ratio on prognosis in advanced non-small-cell lung cancer. Asia Pac J Clin Oncol 14(6):402–409. https://doi.org/10.1111/ajco.13055

    Article  PubMed  Google Scholar 

  21. Güneş H, Yurttutan S , Çobanuşağı M, Doğaner A (2021) CRP/albumin ratio: a promising marker of gram-negative bacteremia in late-onset neonatal sepsis. Turk Arch Pediatr 56(1):32–36. https://doi.org/10.14744/TurkPediatriArs.2020.99076

    Article  Google Scholar 

  22. Sun R, Sun X, Yang H, Liu Q (2016) Retrospective analysis of serum C-reactive protein/albumin ratio for the prognosis of the adult patients with sepsis. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 28(5):413–417

    PubMed  Google Scholar 

  23. International Committee for the Classification of Retinopathy of Prematurity (2005) The International Classification of Retinopathy of Prematurity revisited. Arch Ophthalmol 123(7):991–999. https://doi.org/10.1001/archopht.123.7.991

    Article  Google Scholar 

  24. Early Treatment For Retinopathy Of Prematurity Cooperative Group (2003) Revised indications for the treatment of retinopathy of prematurity: results of the early treatment for retinopathy of prematurity randomized trial. Arch Ophthalmol 121(12):1684–1694. https://doi.org/10.1001/archopht.121.12.1684

    Article  Google Scholar 

  25. Ingvaldsen SH, Morken TS, Austeng D, Dammann O (2022) Visuopathy of prematurity: is retinopathy just the tip of the iceberg? Pediatr Res 91(5):1043–1048. https://doi.org/10.1038/s41390-021-01625-0

    Article  PubMed  Google Scholar 

  26. Dammann O (2010) Inflammation and retinopathy of prematurity. Acta Paediatr 99(7):975–977. https://doi.org/10.1111/j.1651-2227.2010.01836.x

    Article  PubMed  PubMed Central  Google Scholar 

  27. Woo SJ, Park KH, Lee SY, Ahn SJ, et al. (2013) 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 15;54(5):3434–3439. https://doi.org/10.1167/iovs.13-11837

  28. Gessler P, Dahinden C (2013) Increased respiratory burst and increased expression of complement receptor-3 (CD11b/CD18) and of IL-8 receptor-A in neutrophil granulocytes from newborns after vaginal delivery. Biol Neonate 83(2):107–112. https://doi.org/10.1159/000067962

    Article  CAS  Google Scholar 

  29. Dammann O, Brinkhaus MJ, Bartels DB, Dördelmann M et al (2009) Immaturity, perinatal inflammation, and retinopathy of prematurity: a multi-hit hypothesis. Early Human Dev 85(5):325–329. https://doi.org/10.1016/j.earlhumdev.2008.12.010

    Article  Google Scholar 

  30. Klinger G, Levy I, Sirota L, Boyko V et al, Israel Neonatal Network (2010) Outcome of early-onset sepsis in a national cohort of very low birth weight infants. Pediatrics 125(4):736–740. https://doi.org/10.1542/peds.2009-2017

  31. Chiesa C , Natale F, Pascone R, Osborn JF et al (2011) C reactive protein and procalcitonin: reference intervals for preterm and term newborns during the early neonatal period. Clin Chim Acta 412(11–12):1053–1059. https://doi.org/10.1016/j.cca.2011.02.020

    Article  CAS  PubMed  Google Scholar 

  32. Ishibashi M, Takemura Y, Ishida H, Watanabe K et al (2002) C-reactive protein kinetics in newborns: application of a high-sensitivity analytic method in its determination. Clin Chem 48(7):1103–1106

    Article  CAS  PubMed  Google Scholar 

  33. Torer B, Hanta D, Yapakci E, Gokmen Z et al (2016) Association of serum albumin level and mortality in premature infants. J Clin Lab Anal 30(6):867–872. https://doi.org/10.1002/jcla.21949

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Akdogan M, Ustundag Y, Cevik SG, Dogan P et al (2016) Correlation between systemic immune-inflammation index and routine hemogram-related inflammatory markers in the prognosis of retinopathy of prematurity. Indian J Ophthalmol 30(6):867–872. https://doi.org/10.4103/ijo.IJO_2745_20

    Article  Google Scholar 

  35. Kurtul BE, Kabatas EU, Zenciroglu A, Altiaylik Ozer P et al (2015) Serum neutrophil-to-lymphocyte ratio in retinopathy of prematurity. J AAPOS 19(4):327–331. https://doi.org/10.1016/j.jaapos.2015.04.008

    Article  PubMed  Google Scholar 

  36. Celik K, Ekinci D, Asena M, Okur Matur N (2021) Can hematological parameters be an indicator risk factor in the development of retinopathy of prematurity?? Klin Padiatr 233(05):216–220. https://doi.org/10.1055/a-1289-0105

    Article  PubMed  Google Scholar 

  37. Juul SE, Haynes JW, McPherson RJ (2004) Evaluation of neutropenia and neutrophilia in hospitalized preterm infants. J Perinatol 24(3):150–157. https://doi.org/10.1038/sj.jp.7211057

    Article  PubMed  Google Scholar 

  38. Walker JC, Smolders MAJC, Gemen EFA, Antonius TAJ et al (2011) Development of lymphocyte subpopulations in preterm infants. Scand J Immunol 73(1):53–58. https://doi.org/10.1111/j.1365-3083.2010.02473.x

    Article  CAS  PubMed  Google Scholar 

  39. Said AS, Spinella PC, Hartman ME, Steffen KM et al (2017) RBC distribution width: biomarker for red cell dysfunction and critical illness outcome? Pediatr Crit Care Med 18(2):134–142. https://doi.org/10.1097/PCC.0000000000001017

    Article  PubMed  PubMed Central  Google Scholar 

  40. Comez A, Yurttutan S, Seringec Akkececi N, Bozkaya A et al (2021) Red cell distribution width and its association with retinopathy of prematurity. Int Ophthalmol 41(2):699–706. https://doi.org/10.1007/s10792-020-01627-7

    Article  PubMed  Google Scholar 

  41. Italiano JE, Richardson JL, Patel-Hett S, Battinelli E et al (2008) Angiogenesis is regulated by a novel mechanism: pro- and antiangiogenic proteins are organized into separate platelet alpha granules and differentially released. Blood 111(3):1227–1233. https://doi.org/10.1182/blood-2007-09-113837

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Sancak S, Toptan HH, Gokmen Yıldırım T, Karatekın G et al (2019) Thrombocytopenıa as a rısk factor for retınopathy of prematurıty. Retina 39(4):706–711. https://doi.org/10.1097/IAE.0000000000002028

    Article  CAS  PubMed  Google Scholar 

  43. Karabulut B, Arcagok BC (2020) New diagnostic possibilities for early onset neonatal sepsis: red cell distribution width to platelet ratio. Fetal Pediatr Pathol 39(4):297–306. https://doi.org/10.1080/15513815.2019.1661051

    Article  PubMed  Google Scholar 

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Funding

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Authors and Affiliations

  1. Diyarbakir Gazi Yasargil Training and Research Hospital, University of Health Sciences, Department of Ophthalmology, Elazig Yolu, 10. Km, Uckuyular, 21070, Kayapinar/Diyarbakir, Turkey

    Dilbade Yildiz Ekinci

  2. Trabzon Kanuni Training and Research Hospital, Division of Neonatology, Trabzon, Turkey

    Handan Bezirganoglu

  3. Diyarbakir Gazi Yasargil Training and Research Hospital, University of Health Sciences, Department of Pediatrics, Division of Neonatology, Diyarbakir, Turkey

    Nilufer Okur

  4. Diyarbakır Gazi Yasargil Training and Research Hospital, University of Health Sciences, Department of Pediatrics, Diyarbakir, Turkey

    Muhammed Tas

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  1. Dilbade Yildiz Ekinci
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  2. Handan Bezirganoglu
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  3. Nilufer Okur
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  4. Muhammed Tas
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Contributions

DYE, HB, NO, and MT collected the data. Statistical analysis was performed by NO. DYE and HB wrote the main manuscript text. NO prepared the tables. All authors reviewed the manuscript.

Corresponding author

Correspondence to Dilbade Yildiz Ekinci.

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All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this manuscript.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the (Diyarbakir Gazi Yasargil Training and Research Hospital Ethics Committee, 873/09.03.2021) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Ekinci, D.Y., Bezirganoglu, H., Okur, N. et al. A novel marker for predicting type 1 retinopathy of prematurity: C-reactive protein/albumin ratio. Int Ophthalmol 43, 3345–3353 (2023). https://doi.org/10.1007/s10792-023-02740-z

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  • DOI: https://doi.org/10.1007/s10792-023-02740-z

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