The risk factors and progression of retinopathy of prematurity in extremely low birth weight infants

The number of premature babies, including those with extremely low birth weight (ELBW), is steadily growing every year. In surviving ELBW infants, retinopathy of prematurity (ROP) more often develops, which has a more severe course, depending not only on the degree of immaturity and somatic burden of premature babies but also on the quality of nursing.

The aim of this work is to determine the risk factors for ROP progression in profoundly premature ELBW infants to optimize the tactics of their treatment.

Materials and methods. We studied the case histories of 155 surviving premature ELBW infants with ROP of various stages treated in perinatal centres of the Belgorod region in 2014–2019.

Results. In premature ELBW infants, ROP of varying severity was found to be diagnosed in 90% of cases. The anamnesis of the mothers of the examined patients with moderate and severe ROP was dominated by unfavorable preceding pregnancies (miscarriages, silent miscarriage and ectopic pregnancies, medical abortions).The need for preterm infants in mechanical ventilation was established to depend on the severity of ROP and the duration of mechanical ventilation (p < 0.05). Frequent, not always justified red blood transfusions leading to the replacement of fetal haemoglobin with adult haemoglobin are also essential factors in ROP progression.

Contribution:
Dyumin I.I., Balakireva E.A. — the concept and design of the study;
Dyumin I.I., Nikolaenko I.V. — collection and processing of material;
Dyumin I.I., Sevostyanov A.I. — statistical processing;
Dyumin I.I., Sevostyanov A.I., Yaroshevich E.A. — writing text;
Balakireva E.A., Yaroshevich E.A. — editing.
All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.

Acknowledgment. The study had no sponsorship.

Conflict of interest. The authors declare no conflict of interest.

Received: May 31, 2021
Accepted: June 23, 2021
Published: July 16, 2021

1. Phelps D.L. Retinopathy of prematurity: history, classification, and pathophysiology. NeoReviews. 2001; 2(7): 153-66. https://doi.org/10.1542/neo.2-7-e153

2. Sharma M., VanderVeen D.K. Identification and treatment of retinopathy of prematurity: update 2017. NeoReviews. 2017; 18(2): 84-90. https://doi.org/10.1542/neo.18-2-e84

3. Quinn G.E. Challenges and future directions in the detection and treatment of retinopathy of prematurity. NeoReviews. 2017; 18(2): 91-9. https://doi.org/10.1542/neo.18-2-e91

4. Norman M., Hellström A., Hallberg B., Wallin A., Gustafson P., Tornqvist K., et al. Prevalence of severe visual disability among preterm children with retinopathy of prematurity and association with adherence to best practice guidelines. JAMA Netw. Open. 2019; 2(1): e186801. https://doi.org/10.1001/jamanetworkopen.2018.6801

5. Taner A., Tekle S., Hothorn T., Adams M., Bassler D., Gerth-Kahlert C. Higher incidence of retinopathy of prematurity in extremely preterm infants associated with improved survival rates. Acta Paediatr. 2020; 109(10): 2033-9. https://doi.org/10.1111/apa.15197

6. Saydasheva E.I., Gorelik Yu.V., Buyanovskaya S.V., Kovshov F.V. Retinopathy of prematurity: the course and results of treatment in children with gestational age less than 27 weeks. Rossiyskaya pediatricheskaya oftal’mologiya. 2015; 10(2): 2–32. (in Russian)

7. Tavassoli S., Wach R., Haynes R., Markham R., Williams C. Estimate of incidence of ROP requiring treatment in extreme preterms and impact on service-7 year review in tertiary unit. Eye (Lond.). 2019; 33(5): 845-9. https://doi.org/10.1038/s41433-018-0330-x

8. Freitas A.M., Mörschbächer R., Thorell M.R., Rhoden E.L. Incidence and risk factors for retinopathy of prematurity: a retrospective cohort study. Int. J. Retina Vitreous. 2018; 4: 20. https://doi.org/10.1186/s40942-018-0125-z

9. Lynch A.M., Wagner B.D., Hodges J.K., Thevarajah T.S., McCourt E.A., Cerda A.M., et al. The relationship of the subtypes of preterm birth with retinopathy of prematurity. Am. J. Obstet. Gynecol. 2017; 217(3): 354.e1-8. https://doi.org/10.1016/j.ajog.2017.05.029

10. Holm M., Morken T.S., Fichorova R.N., VanderVeen D.K., Allred E.N., Dammann O., et al. Systemic inflammation-associated proteins and retinopathy of prematurity in infants born before the 28th week of gestation. Invest. Ophthalmol. Vis. Sci. 2017; 58(14): 6419-28. https://doi.org/10.1167/iovs.17-21931

11. Quimson S.K. Retinopathy of prematurity: pathogenesis and current treatment options. Neonatal Netw. 2015; 34(5): 284-7. https://doi.org/10.1891/0730-0832.34.5.284

12. Hellström A., Hård A.L., Svensson E., Niklasson A. Ocular fundus abnormalities in children born before 29 weeks of gestation: a population-based study. Eye (Lond.). 2000; (Pt. 3A): 324-9. https://doi.org/10.1038/eye.2000.81

13. Shah P.K., Prabhu V., Ranjan R., Narendran V., Kalpana N. Retinopathy of prematurity: clinical features, classification, natural history, management and outcome. Indian Pediatr. 2016; 53(Suppl. 2): 118-22.

14. Liegl R., Hellström A., Smith L.E. Retinopathy of prematurity: the need for prevention. Eye Brain. 2016; 8: 91-102. https://doi.org/10.2147/EB.S99038

15. Rocha G., Flor de Lima F., Riquito B., Guimarães H. Very preterm infant outcomes according to timing of birth. J. Neonatal. Perinatal. Med. 2020; 13(1): 97-104. https://doi.org/10.3233/NPM-180153

16. Wade K.C., Ying G.S., Baumritter A., Gong A., Kemper A.R., Quinn G.E., et al. Factors in premature infants associated with low risk of developing retinopathy of prematurity. JAMA Ophthalmol. 2019; 137(2): 160-6. https://doi.org/10.1001/jamaophthalmol.2018.5520

17. Hakeem A.H., Mohamed G.B., Othman M.F. Retinopathy of prematurity: a study of prevalence and risk factors. Middle East Afr. J. Ophthalmol. 2012; 19(3): 289-94. https://doi.org/10.4103/0974-9233.97927

18. Chang J.W. Risk factor analysis for the development and progression of retinopathy of prematurity. PLoS One. 2019; 14(7): e0219934. https://doi.org/10.1371/journal.pone.0219934

19. Kumawat D., Sachan A., Shah P., Chawla R., Chandra P. Aggressive posterior retinopathy of prematurity: a review on current understanding. Eye (Lond.). 2021; 35(4): 1140-58. https://doi.org/10.1038/s41433-021-01392-6

20. Chaves-Samaniego M.J., Chaves-Samaniego M.C., Muñoz Hoyos A., García Serrano J.L. New evidence on the protector effect of weight gain in retinopathy of prematurity. An. Pediatr. (Engl. Ed.). 2020; S1695-4033(20)30222-8. https://doi.org/10.1016/j.anpedi.2020.05.022 (in Spanish)

21. Gole G.A., Ells A.L., Katz X., Holmstrom G., Fielder A.R., Capone A., et al. The international classification of retinopathy of prematurity revisited. Arch. Ophthalmol. 2005; 123(7): 991-9. https://doi.org/10.1001/archopht.123.7.991

22. Choi Y.B., Lee J., Park J., Jun Y.H. Impact of prolonged mechanical ventilation in very low birth weight infants: results from a national cohort study. J. Pediatr. 2018; 194: 34-39.e3. https://doi.org/10.1016/j.jpeds.2017.10.042

23. Jain D., Bancalari E. New developments in respiratory support for preterm infants. Am. J. Perinatol. 2019; 36(S. 02): S13-7. https://doi.org/10.1055/s-0039-1691817

24. Bhattacharjee I., Das A., Collin M., Aly H. Predicting outcomes of mechanically ventilated premature infants using respiratory severity score. J. Matern. Fetal Neonatal Med. 2020; 1-8. https://doi.org/10.1080/14767058.2020.1858277

25. Girelli G., Antoncecchi S., Casadei A.M., Del Vecchio A., Isernia P., Motta M., et al. Recommendations for transfusion therapy in neonatology. Blood Transfus. 2015; 13(3): 484-97. https://doi.org/10.2450/2015.0113-15

26. New H.V. Transfusion in neonates and older children: Principles and updates. Transfus. Clin. Biol. 2019; 26(3): 195-6. https://doi.org/10.1016/j.tracli.2019.07.003

27. D’Amato G., Faienza M.F., Palladino V., Bianchi F.P., Natale M.P., Christensen R.D., et al. Red blood cell transfusions and potentially related morbidities in neonates under 32 weeks’ gestation. Blood Transfus. 2021; 19(2): 113-9. https://doi.org/10.2450/2020.0092-20

28. Pivodic A., Hård A.L., Löfqvist C., Smith L.E.H., Wu C., Bründer M.C., et al. Individual risk prediction for sight-threatening retinopathy of prematurity using birth characteristics. JAMA Ophthalmol. 2020; 138(1): 21-9. https://doi.org/10.1001/jamaophthalmol.2019.4502

29. Li Y., Li J., Zhang X., Peng J., Li J., Zhao P. Identification of gene mutations in atypical retinopathy of prematurity cases. J. Ophthalmol. 2020; 2020: 4212158. https://doi.org/10.1155/2020/4212158

30. Helmo F.R., Alves E.A.R., Moreira R.A.A., Severino V.O., Rocha L.P., Monteiro M.L.G.D.R., et al. Intrauterine infection, immune system and premature birth. J. Matern. Fetal Neonatal Med. 2018; 31(9): 1227-33. https://doi.org/10.1080/14767058.2017.1311318

31. Humberg A., Leienbach V., Fortmann M.I., Rausch T.K., Buxmann H., Müller A., et al. Prevalence of congenital cmv infection and antiviral therapy in very-low-birth-weight infants: observations of the German neonatal network. Klin. Pediatr. 2018; 230(5): 257-62. https://doi.org/10.1055/a-0598-4748

32. Guo K., Wang X.Y., Feng G.S., Tian J., Zeng Y.P., Ma S.X., et al. The epidemiology of blood transfusion in hospitalized children: a national cross-sectional study in China. Transl. Pediatr. 2021; 10(4): 1055-62. https://doi.org/10.21037/tp-20-464

33. Kan I.G., Astasheva I.B., Guseva M.R., Degtyareva A.V., Ionov O.V. Medical risk factors and ways to reduce frequency and severity of retinopathy of prematurity in perinatal center modern conditions. experience of the V.I. Kulakov Obstetrics, Gynecology and Perinatology Research Center of Ministry of Healthсаre of the Russian Federation. Neonatologiya: novosti, mneniya, obuchenie. 2016; (4): 76–82. (in Russian)

34. Stoica F., Chirita-Emandi A., Andreescu N., Stanciu A., Zimbru C.G., Puiu M. Clinical relevance of retinal structure in children with laser-treated retinopathy of prematurity versus controls - using optical coherence tomography. Acta Ophthalmol. 2018; 96(2): 222-8. https://doi.org/10.1111/aos.13536

35. Kan I.G., Astasheva I.B., Degtyareva A.V., Ionov O.V., Tumasyan E.A. Time of retinopathy occurrence and features of its course in premature infants using new approaches to respiratory therapy at the stage of primary resuscitation of newborns. Rossiyskaya detskaya oftal’mologiya. 2020; (1): 29–34. https://doi.org/10.25276/2307-6658-2020-1-29-34 (in Russian)

36. Askie L.M., Darlow B.A., Finer N., Schmidt B., Stenson B., Tarnow-Mordi W., et al. Association between oxygen saturation targeting and death or disability in extremely preterm infants in the neonatal oxygenation prospective meta-analysis collaboration. JAMA. 2018; 319(21): 2190-201. https://doi.org/10.1001/jama.2018.5725

37. Gantz M.G., Carlo W.A., Finer N.N., Rich W., Faix R.G., Yoder B.A., et al. Achieved oxygen saturations and retinopathy of prematurity in extreme preterms. Arch. Dis. Child Fetal Neonatal Ed. 2020; 105(2): 138-44. https://doi.org/10.1136/archdischild-2018-316464

38. Stutchfield C.J., Jain A., Odd D., Williams C., Markham R. Foetal haemoglobin, blood transfusion, and retinopathy of prematurity in very preterm infants: a pilot prospective cohort study. Eye. 2017; 31(10): 1451-55. https://doi.org/10.1038/eye.2017.76

39. Shukla A., Sonnie C., Worley S., Sharma A., Howard D., Moore J., et al. Comparison of biphasic vs static oxygen saturation targets among infants with retinopathy of prematurity. JAMA Ophthalmol. 2019; 137(4): 417-23. https://doi.org/10.1001/jamaophthalmol.2018.7021

40. Mayock D.E., Xie Z., Comstock B.A., Heagerty P.J., Juul S.E. High-dose erythropoietin in extremely low gestational age neonates does not alter risk of retinopathy of prematurity. Neonatology. 2020; 117(5): 650-7. https://doi.org/10.1159/000511262

41. Chang J.W. Risk factor analysis for the development and progression of retinopathy of prematurity. PLoS One. 2019; 14(7): e0219934. https://doi.org/10.1371/journal.pone.0219934

42. AlRyalat S.A., Al Oweidat K., Al-Amer A., Khader A., Ajaj A., Alessa Z., et al. Perinatal events predicting retinopathy of prematurity in extremely pre-term infants. J. Neonatal. Perinatal. Med. 2020; 13(2): 261-6. https://doi.org/10.3233/NPM-190336