Prematüre Retinopatisi: Temel Belirleyicilerin Dışındaki Etkenler

Abstract

Amaç: Bu çalışmada, prematüre retinopatisi (ROP) gelişen ve gelişmeyen bebeklerde maternal ve neonatal risk faktörlerini karşılaştırarak, ROP gelişimi ile ilişkili bağımsız belirleyicilerin ortaya konulması amaçlandı.

Materyal ve metod: 1 Ocak 2022-31 Aralık 2024 tarihleri arasında Yenidoğan Yoğun Bakım Ünitemizde izlenen, gebelik haftası ≤34 olan 277 prematüre bebek retrospektif olarak değerlendirildi. Olgular ROP gelişen (n=89) ve gelişmeyen (n=188) olmak üzere iki gruba ayrıldı. Maternal [(preeklampsi, koryoamniyonit (CA)] ve neonatal (gebelik haftası, doğum ağırlığı, Apgar skorları, surfaktan tedavisi ve patent duktus arteriozus [PDA]) parametreler karşılaştırıldı. ROP gelişimi ile ilişkili bağımsız faktörleri belirlemek amacıyla çok değişkenli lojistik regresyon analizi yapıldı.

Bulgular: ROP gelişen grupta ortalama gebelik haftası (28,8±2,3 vs. 31,3±1,4 hafta; p<0,001) ve doğum ağırlığı (1077,1±287,3 g vs. 1492,7±341,7 g; p<0,001) anlamlı derecede daha düşüktü. Doğum boyu, baş çevresi ve 1. ile 5. dakika Apgar skorları da ROP grubunda daha düşüktü (tümü p<0,001). Univaryant analizlerde surfaktan gereksinimi (p=0,004), PDA sıklığı (p=0,041), maternal preeklampsi (p=0,005) ve CA (p=0,032) ROP gelişen olgularda daha yüksek bulundu. Çok değişkenli lojistik regresyon analizinde ise yalnızca düşük gebelik haftası [olasılık oranı (OO)=0,569; %95 güven aralığı (GA): 0,443-0,724; p<0,001)], düşük doğum ağırlığı (OO=0,998; %95 GA: 0,997-1,000; p=0,014) ve maternal preeklampsi (OO=2,770; %95 GA: 1,360-5,842; p=0,005) ROP gelişimi ile bağımsız olarak ilişkili bulundu.

Sonuç: Prematürite derecesi ve düşük doğum ağırlığı ROP gelişiminin temel belirleyicileri olmaya devam etmektedir. Bununla birlikte maternal preeklampsi, gebelik haftası ve doğum ağırlığından bağımsız olarak ROP gelişimi ile ilişkili bulunmuştur. Diğer neonatal faktörler ROP gelişimi ile ilişkili görünmekle birlikte, bu ilişkinin prematüritenin derecesi ile ilişkili olabileceği düşünülmektedir. Bu bulgular, yüksek riskli bebeklerin belirlenmesinde perinatal faktörlerin bütüncül değerlendirilmesinin önemini göstermektedir.

Keywords

• Prematüre retinopatisi
• preeklampsi
• patent duktus arteriozus

Retinopathy of Prematurity: Factors Beyond the Basics

Abstract

Background: This study aimed to compare maternal and neonatal risk factors between infants with and without retinopathy of prematurity (ROP) and to identify independent determinants associated with ROP development.

Materials and Methods: A total of 277 premature infants with a gestational age ≤34 weeks who were followed in our neonatal intensive care unit between January 1, 2022, and December 31, 2024, were retrospectively evaluated. The infants were divided into two groups: those who developed ROP (n=89) and those who did not (n=188). Maternal (preeclampsia, chorioamnionitis) and neonatal (gestational age, birth weight, Apgar scores, surfactant therapy, and patent ductus arteriosus [PDA]) parameters were compared. Multivariate logistic regression analysis was performed to determine independent factors associated with ROP development.

Results: The mean gestational age (28.8±2.3 vs. 31.3±1.4 weeks; p<0.001) and birth weight (1077.1±287.3 g vs. 1492.7±341.7 g; p<0.001) were significantly lower in the ROP group. Birth length, head circumference, and 1- and 5-minute Apgar scores were also significantly lower in infants with ROP (all p<0.001). In univariate analyses, the need for surfactant therapy (p=0.004), the frequency of PDA (p=0.041), maternal preeclampsia (p=0.005), and chorioamnionitis (p=0.032) were higher in the ROP group. In multivariate logistic regression analysis, only lower gestational age [odds ratio (OR)=0.569; 95% confidence interval (CI): 0.443-0.724; p<0.001)], lower birth weight (OR=0.998; 95% CI: 0.997-1.000; p=0.014), and maternal preeclampsia (OR=2.770; 95% CI: 1.360-5.842; p=0.005) remained independently associated with ROP development.

Conclusions: The degree of prematurity and low birth weight remain the primary determinants of ROP development. Additionally, maternal preeclampsia was found to be independently associated with ROP development beyond gestational age and birth weight. Other neonatal factors appeared to be associated with ROP; however, these associations may largely reflect the degree of prematurity. These findings highlight the importance of a comprehensive perinatal assessment for identifying high-risk infants.

Keywords

• Retinopathy of prematurity
• preeclampsia
• patent ductus arteriosus

References

1. 1. Hakeem A, Mohamed G, Othman M. Retinopathy of prematurity: a study of prevalence and risk factors. Middle East Afr J Ophthalmol. 2012;19(3):289.
2. 2. Domanico R, Davis DK, Coleman F, Davis BO. Documenting the NICU design dilemma: comparative patient progress in open-ward and single family room units. J Perinatol. 2011;31(4):281-8.
3. 3. Alajbegovic-Halimic J, Zvizdic D, Alimanovic-Halilovic E, Dodik I, Duvnjak S, Alajbegovic-Halimic A. Risk factors for retinopathy of prematurity in premature born children. Med Arch. 2015;69(6):409-13.
4. 4. Darlow BA, Hutchinson JL, Henderson-Smart DJ, Donoghue DA, Simpson JM, Evans NJ. Prenatal risk factors for severe retinopathy of prematurity among very preterm infants. Pediatrics. 2005;115(4):990-6.
5. 5. Saugstad OD. Oxygen and retinopathy of prematurity. J Perinatol. 2006;26(Suppl 1):S46-50.
6. 6. Villamor-Martinez E, Cavallaro G, Raffaeli G, Rahim OMM, Gulden S, Ghazi AMT, et al. Chorioamnionitis as a risk factor for retinopathy of prematurity: an updated systematic review and meta-analysis. PLoS One. 2018;13(10):e0205838. doi:10.1371/journal.pone.0205838.
7. 7. Karna P, Muttineni J, Angell L, Karmaus W. Retinopathy of prematurity and risk factors: a prospective cohort study. BMC Pediatr. 2005;5:18.
8. 8. Yucel OE, Eraydin B, Niyaz L, Terzi O. Incidence and risk factors for retinopathy of prematurity in premature, extremely low birth weight and extremely low gestational age infants. BMC Ophthalmol. 2022;22(1):423.

9. 9. Benitz WE, Committee on Fetus and Newborn, American Academy of Pediatrics. Patent ductus arteriosus in preterm infants. Pediatrics. 2016;137(1):e20153730.
10. 10. Chiang MF, Quinn GE, Fielder AR, Ostmo SR, Chan RV, Berrocal A, et al. International classification of retinopathy of prematurity, third edition. Ophthalmology. 2021;128(10):e51-68.
11. 11. Siswanto JE, Ronoatmodjo S, Adisasmita A, Soemantri A, Sitorus RS, Sauer PJJ. Risk factors for the development and progression of retinopathy of prematurity in preterm infants in Indonesia. J Neonatal Perinatal Med. 2020;13(2):253-60.
12. 12. Yu CW, Popovic MM, Dhoot AS, Arjmand P, Muni RH, Tehrani NN, et al. Demographic risk factors of retinopathy of prematurity: a systematic review of population-based studies. Neonatology. 2022;119(2):151-63.
13. 13. Holmström G, Tornqvist K, Al-Hawasi A, Nilsson Å, Wallin A, Hellström A. Increased frequency of retinopathy of prematurity over the last decade and significant regional differences. Acta Ophthalmol. 2018;96(2):142-8.
14. 14. Kim SJ, Port AD, Swan R, Campbell JP, Chan RV, Chiang MF. Retinopathy of prematurity: a review of risk factors and their clinical significance. Surv Ophthalmol. 2018;63(5):618-37.
15. 15. Villar J, Say L, Gulmezoglu AM, Critchly H, MacLean A, Poston L, et al. Eclampsia and preeclampsia: a 2000-year-old health problem. In: Critchly H, MacLean A, Poston L, Walker J, editors. Preeclampsia. London: RCOG Press; 2003. p. 189-207.
16. 16. Özkan H, Cetinkaya M, Koksal N, Özmen A, Yildiz M. Maternal preeclampsia is associated with an increased risk of retinopathy of prematurity. J Perinat Med. 2011;39(5):523-7.
17. 17. Roberts JM, Hubel CA. The two-stage model of preeclampsia: variations on the theme. Placenta. 2009;30(Suppl A):S32-7.
18. 18. Athikarisamy SE, Lam GC, Cooper MN, Strunk T. Retinopathy of prematurity and placental histopathology findings: a retrospective cohort study. Front Pediatr. 2023;11:1099614.
19. 19. Araz-Ersan B, Kir N, Akarcay K, et al. Epidemiological analysis of retinopathy of prematurity in a referral center in Turkey. Br J Ophthalmol. 2013;97(1):15-7.
20. 20. Yu XD, Branch DW, Karumanchi SA, Zhang J. Preeclampsia and retinopathy of prematurity in preterm births. Pediatrics. 2012;130(1):e101-7.
21. 21. Chan PYL, Tang SM, Au SCL, et al. Association of pregnancy hypertensive disorders with retinopathy of prematurity: a systematic review and meta-analysis. Sci Rep. 2016;6:30732.
22. 22. Zhu T, Zhang L, Zhao F, Qu Y, Mu D. Association of maternal hypertensive disorders with retinopathy of prematurity: a systematic review and meta-analysis. PLoS One. 2017;12(4):e0175374.
23. 23. Shulman JP, Weng C, Wilkes J, Greene T, Hartnett ME. Association of maternal preeclampsia with infant risk of premature birth and retinopathy of prematurity. JAMA Ophthalmol. 2017;135(9):947-53.
24. 24. Slidsborg C, Jensen A, Forman JL, Rasmussen S, Bangsgaard R, Fledelius HC, et al. Neonatal risk factors for treatment-demanding retinopathy of prematurity: a Danish national study. Ophthalmology. 2016;123(4):796-803.
25. 25. Thivya S, et al. Association of timing of surfactant administration with incidence and severity of retinopathy of prematurity: a prospective observational study. Int J Pharm Qual Assur. 2025;16(4):91-5.
26. 26. Seymen Z. Neonatal risk factors and incidence of retinopathy of prematurity. Turkiye Klinikleri J Pediatr. 2020;29(1).
27. 27. Rankin SJ, Tubman TR, Halliday HL, Johnston SS. Retinopathy of prematurity in surfactant treated infants. Br J Ophthalmol. 1992;76(4):202-4.
28. 28. Askie LM, Darlow BA, Finer N, Schmidt B, Stenson B, Tarnow-Mordi W, et al.; NeOProM Collaboration. Association between oxygen saturation targeting and death or disability in extremely preterm infants. JAMA. 2018;319(21):2190-201.
29. 29. Ford A, Beauchene M, Stanford AH, Klein JM, Dagle JM, Rios DR, et al. Exposure to persistent hemodynamically significant patent ductus arteriosus is associated with retinopathy of prematurity. J AAPOS. 2024;28(3):159.e1-159.e6.
30. 30. Gunes S, Sahin S, Durmaz Engin C, Ergin F, Aldemir Sonmez A, Bozkurt Ö, et al. Association between patent ductus arteriosus and the development of treatment-requiring retinopathy of prematurity in preterm infants. Children (Basel). 2025;12(6):713.
31. 31. Clyman RI, Hills NK. Patent ductus arteriosus and pulmonary morbidity: can early targeted pharmacologic PDA treatment decrease the risk of bronchopulmonary dysplasia? Semin Perinatol. 2023;47(2):151718.