European Journal of Cardiovascular Medicine

ROP (retinopathy of prematurity) is a disease of the developing blood vessels in the retina in the infants that are born preterm. The vital pathological factor in ROP is the ischemia of the avascular retina which ultimately result in the neovascularization.1

Retinopathy of prematurity is one of the most vital and key factors for managing the preventable blindness in the child subjects. Despite the well-established records of birth weight and gestational age as the two main risk factors in causing the retinopathy of prematurity, however, anaemia is yet not established as an independent risk factor in causing the retinopathy of prematurity.2

Literature data is substantial concerning retinopathy of prematurity and the associated risk factors as gestational age and birth weight. However, existing literature data is scarce concerning the role of anaemia in causing retinopathy of prematurity.3,4

The present prospective observational study was aimed to comparatively assess the incidence of retinopathy of prematurity in anaemic and non-anaemic  infants in India to assess the role of anaemia in retinopathy. The study was done at Department of Ophthalmology of the tertiary care hospital in Rajasthan Institute. Verbal and written informed consent were taken from all the subjects and school authorities before study participation.

The study included 200 infants that met the inclusion criteria for the study. Following the standards of inclusion, all the premature infants in birth weight of 2 kg or lesser and the gestational age of <34 weeks. The exclusion criteria for the study were subjects with birth weight >2.5kgs, gestational age <34 weeks, with any congenital anomaly, and were not willing to participate in the study.

The gestational age and birth weight at the time of birth was noted in all the subjects. All the needed risk factors were recorded including the blood transfusion. In both the eyes of all the subjects, 2.5% phenylephrine and 0.5% diluted tropicamide was instilled thrice for nearly an hours before assessment of pupil dilatation. To decrease the discomfort while testing, 0.5% paracaine as topical anaesthetic was used after full dilation of the pupil. For keeping the eyelids apart, sterile eye speculum was inserted.

Indirect ophthalmoscope with a 20 D lens and scleral depressor was used for examination of peripheral retina. Findings of the fungus were documented including severity, stag, zone, and vascularity of the retinopathy of prematurity. Diagnosis was made using the guidelines of ICROP.5 Treatment was planned for subjects with type 1 ROP. Parents were counselled and explained for procedure concerning the importance of treatment and follow-up. Last follow-up visit was done at 41 weeks after the conception age. The variables assessed were exchange transfusion, blood transfusion, anaemia, birth weight, gestational age, twin pregnancy, and gender of the subjects.

The gathered data from the study subjected was assessed with statistical evaluation using the chi-square test, Fisher’s exact test, Mann Whitney U test, and SPSS (Statistical Package for the Social Sciences) software version 24.0 (IBM Corp., Armonk. NY, USA) using ANOVA, chi-square test, and student's t-test. The significance level was considered at a p-value of <0.05.

The present prospective observational study was aimed to comparatively assess the incidence of retinopathy of prematurity in anaemic and non-anaemic  infants in India to assess the role of anaemia in retinopathy. The present study assessed 200 premature infants with consecutive birth at the Institute within the defined study period with the gestational age at birth <34 weeks or birth weight <200 grams were assessed to study the retinopathy of prematurity. The incidence of ROP was also assessed in neonates with anaemia and non-anaemic  infants. Among 200 infants, there were 108 males and 92 females. The birth weight was in the range of 940-2000 grams and gestational age at birth was 28-34 weeks.

It was seen that for profile and prevalence assessment for ROP, ROP was seen in 48 subjects among total 200 infants included in the study. The remaining 152 subjects depicted 3A vascularized retina on subsequent three follow-ups. Stage 2 of ROP was most commonly seen in 24 infants, stage 1 ROP in 10 subjects, stage 3 in 8 subjects, and stage 4 in 2 infants of the study. APROP (Aggressive Posterior ROP) was seen in 2 infants. Stage 5 ROP was not seen in any study subject. In 48 subjects with ROP, 25% (n=12) babied needed treatment and other 75% (n=36) subjects showed spontaneous regression.

The study results showed that for association of ROP and anaemia, in 200 infants included and screened in the study, 32 subjects had anaemia. Among 32 infants, 50% (n=16) infants had ROP. Among remaining 168 subjects without anaemia, 19% (n=32) infants had ROP. On statistical assessment, a significant association was seen in incidence of ROP and anaemia in study subjects with p=0.006 (Table 1).

Concerning the assessment of ROP and blood transfusion in study subjects among 200 subjects included in the study subjects, 22 infants were given blood transfusion where 54.5% (n=12) infants had retinopathy of prematurity. In the remaining 178 infants that were not given blood transfusion, 20.2% (n=36) infants had retinopathy of prematurity (Table 2). On statistical assessment, significant association was seen in incidence of ROP and blood transfusion in study subjects with p=0.01.

Table 1: Distribution of anaemia and ROP in study subjects

Table 2: ROP and blood transfusion in study subjects

The present study assessed 200 premature infants with consecutive birth at the Institute within the defined study period with the gestational age at birth <34 weeks or birth weight <200 grams were assessed to study the retinopathy of prematurity. The incidence of ROP was also assessed in neonates with anaemia and non-anaemic  infants. Among 200 infants, there were 108 males and 92 females. The birth weight was in the range of 940-2000 grams and gestational age at birth was 28-34 weeks. These data were comparable to the previous studies of Hellgren G et al6 in 2021 and Cakir B et al7 in 2018 where authors assessed subjects with demographic data comparable to the present study in their respective studies.

The study results showed that for profile and prevalence assessment for ROP, ROP was seen in 48 subjects among total 200 infants included in the study. The remaining 152 subjects depicted 3A vascularized retina on subsequent three follow-ups. Stage 2 of ROP was most commonly seen in 24 infants, stage 1 ROP in 10 subjects, stage 3 in 8 subjects, and stage 4 in 2 infants of the study. APROP (Aggressive Posterior ROP) was seen in 2 infants. Stage 5 ROP was not seen in any study subject. In 48 subjects with ROP, 25% (n=12) babied needed treatment and other 75% (n=36) subjects showed spontaneous regression. These results were consistent with the findings of Parrozzani R et al8 in 2021 and Bishnoi K et al9 in 2024 where for profile and prevalence assessment for ROP reported by the authors in their studies were comparable to the present study.

It was seen that for association of ROP and anaemia, in 200 infants included and screened in the study, 32 subjects had anaemia. Among 32 infants, 50% (n=16) infants had ROP. Among remaining 168 subjects without anaemia, 19% (n=32) infants had ROP. On statistical assessment, a significant association was seen in incidence of ROP and anaemia in study subjects with p=0.006. These findings were in agreement with the results of Tang W et al10 in 2024 and Erdöl H et al11 in 2017 where association of ROP and anaemia similar to the present study was also reported by the authors in their respective studies.

On assessing the ROP and blood transfusion in study subjects among 200 subjects included in the study subjects, 22 infants were given blood transfusion where 54.5% (n=12) infants had retinopathy of prematurity. In the remaining 178 infants that were not given blood transfusion, 20.2% (n=36) infants had retinopathy of prematurity (Table 2). On statistical assessment, significant association was seen in incidence of ROP and blood transfusion in study subjects with p=0.01. These results correlated with the findings of Prasad N et al12 in 2023 and Pinheiro AM et al13 in 2009 where ROP and blood transfusion results reported by the authors was comparable to the present study.

Considering its limitations, the present study concludes that anaemia is a vital risk factor that affects the incidence of ROP. Anaemia must be hence, managed and avoided in premature infants for management of retinopathy of prematurity. Further longitudinal studies with larger sample size and longer monitoring are needed to reach a definitive conclusion.

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4.       Coats DK, Aaron MM, Mohamed AH. Involution of retinopathy of prematurity after laser treatment: Factors associated with development of retinal detachment. Am J Ophthalmol. 2005;140:214–22.

5.       International Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity revisited. Arch Ophthalmol. 2005;123:991–9.

6.       Hellgren G, Lundgren P, Pivodic A, Löfqvist C, Nilsson AK, Ley D, et al. Decreased Platelet Counts and Serum Levels of VEGF-A, PDGF-BB, and BDNF in Extremely Preterm Infants Developing Severe ROP. Neonatology. 2021;118:18–27.

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8.       Parrozzani R, Marchione G, Fantin A, Frizziero L, Salvadori S, Nardo D, et al. Thrombocytopenia as Type 1 ROP Biomarker: A Longitudinal Study. J Pers Med. 2021;11:1120.

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10.    Tang W, Zhang Y, Zhang H, Li K, Zhao Z, Ma H, et al. Progress in the study of association between hematological indicators and retinopathy of prematurity (Review). Biomed Rep. 2024;21:111.

11.    Erdöl H, Hacioglu D, Kola M, Türk A, Aslan Y. Investigation of the effect of hemoglobin F and A levels on development of retinopathy of prematurity. J AAPOS. 2017;21:136–40.

12.    Prasad N, Kumar K, Dubey A. Fetal hemoglobin, blood transfusion, and retinopathy of prematurity in preterm infants: An observational, prospective study. Indian J Ophthalmol. 2023;71:2803–7.

13.    Pinheiro AM, Silva WA, Bessa CGF, Cunha HM, Ferreira MAF, Gomes AHB. [Incidence and risk factors of retinopathy of prematurity in University Hospital Onofre Lopes, Natal (RN)- Brazil]. Arq Bras Oftalmol. 2009;72:451–6.