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 Table of Contents  
Year : 2017  |  Volume : 110  |  Issue : 3  |  Page : 71-76

Incidence and risk factors of retinopathy of prematurity in neonatal intensive care units: Mansoura, Egypt

1 Department of Ophthalmology, Mansoura University, Mansoura, Egypt
2 Department of Opthalmology, Cairo University, Cairo, Egypt

Date of Submission02-Mar-2017
Date of Acceptance04-Apr-2017
Date of Web Publication6-Nov-2017

Correspondence Address:
Rania M.R. Bassiouny
El Gomhoria Street, Mansoura Ophthalmic Center, Mansoura, 35516
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ejos.ejos_25_17

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Retinopathy of prematurity ROP is a leading cause of blindness affecting ∼50 000 children worldwide. The incidence of the disease varies among different countries, it is influenced by the level of perinatal care, the existence of screening programs for early diagnosis. Low birth weight BW, small gestational age GA, other antenatal, postnatal risk factors have been identified with their relation to the severity of the disease.
The aim of this research was to study the incidence and risk factors of ROP in preterm babies at neonatal intensive care units, Mansoura city.
Patients and methods
This study included 402 preterm infants admitted to neonatal intensive care units in Mansoura city in the period from March 2013 to March 2015. Fundus examination was done using indirect ophthalmoscopy and a 28 D lens, and fundus images were captured using wide-field digital fundus camera (Retcam 3).
Out of the 402 screened preterm babies, 237 (59%) cases had ROP, among whom 101 (42.6%) had stage 1, 114 (48.1%) had stage 2, 12 (5.1%) had stage 3, 10 (4.2%) had aggressive posterior retinopathy, and 24 (10.1%) presented with plus disease. GA, BW, oxygen therapy, sepsis, multiple birth, and cesarean section were factors found to be significantly associated with the disease.
ROP occurred in 59% of all screened preterm babies. The main risk factors for the development of ROP were GA, BW, oxygen therapy, sepsis, multiple birth, and cesarean section.

Keywords: birth weight, gestational age, oxygen, preterm, retinopathy of prematurity

How to cite this article:
Bassiouny RM, Ellakkany RS, Aboelkhair SA, Mohsen TA, Othman IS. Incidence and risk factors of retinopathy of prematurity in neonatal intensive care units: Mansoura, Egypt. J Egypt Ophthalmol Soc 2017;110:71-6

How to cite this URL:
Bassiouny RM, Ellakkany RS, Aboelkhair SA, Mohsen TA, Othman IS. Incidence and risk factors of retinopathy of prematurity in neonatal intensive care units: Mansoura, Egypt. J Egypt Ophthalmol Soc [serial online] 2017 [cited 2023 Jan 31];110:71-6. Available from: http://www.jeos.eg.net/text.asp?2017/110/3/71/217696

  Introduction Top

Retinopathy of prematurity (ROP) is a leading cause of blindness in children because of abnormal vascular proliferation of the developing retina of preterm infants [1]. Most studies focused on low birth weight (BW) and small gestational age (GA) as risk factors for ROP [2],[3]. Currently, investigations are carried out for the identification of other risk factors to predict those stages that require treatment [4],[5]. Early diagnosis by proper screening could improve the success of treatment and reduce complications of the disease [6],[7],[8]. Therefore, the aim of this study was to identify the incidence of ROP and the associated risk factors in our region.

  Patients and methods Top

This prospective study was conducted on all preterm babies (GA <37 weeks) admitted in neonatal intensive care unit of Mansoura University Children Hospital (MUCH) or were referred from nearby hospitals for ROP screening from March 2013 to March 2015. They were subjected to neonatal history and clinical examination (data were collected from Egyptian Neonatal Network medical records), and possible risk factors such as sex, GA, BW, oxygen therapy, sepsis, jaundice, surfactant, respiratory distress syndrome, total parenteral nutrition, multiple birth, maternal age, antenatal steroid, and cesarean section (CS) were reviewed. The timing of the first examination was based on the GA at birth according to American Academy of Pediatrics guidelines [9]. Pupils of both eyes were dilated with combined cyclopentolate (100 mg/ml) and phenylephrine (10 mg/ml) drops half an hour before examination (one drop, 5–10 min apart). After pupillary dilatation, ophthalmological examination was performed using a sterile pediatric eye speculum (Barraquer wire speculum 9 mm blade; S1-500-00, PK], following instillation of benoxinate hydrochloride 0.4% eye drops for topical anesthesia. Fundus examination was performed using indirect ophthalmoscopy with 28 D lens and scleral depression, and fundus images were captured using wide-field digital fundus camera (Retcam III; Clarity Medical Systems, Inc., Pleasanton, CA). The ROP status of each infant was classified according to the International Classification of ROP, including stage, zone, and presence or absence of plus disease [10]. Infants with ROP were re-examined frequently depending on the zone and stage of the disease [9].

Statistical analysis

Data were analyzed using Statistical Package for the Social Sciences (version 21.0, SPSS Inc., Chicago, Illinois, USA). Qualitative data were described using number and percentage. Association between categorical variables was tested using χ2-tests or Fisher’s exact test. Continuous variables were presented as mean±SD for parametric data and were tested using independent t-test. A value of P less than or equal to 0.05 was considered statistically significant. A logistic regression model using a backward stepwise method was used for significant variables. The odds ratio and 95% confidence interval for each possible risk factor were also calculated.

  Results Top

A total of 402 preterm infants were screened for ROP [207 (51.5%) preterm infants referred from MUCH and 195 (48.5%) infants referred from other hospitals]. Male sex represented 52.7%. Their mean GA was 31.5±2.3 weeks (range: 24–36 weeks). The mean BW was 1514±391 g (range: 600–2860 g). One hundred and seventy babies (42.3%) were an outcome of multiple birth. The mean age of the mothers was 26.2±5.0 years. Two hundred and four mothers (50.7%) received antenatal steroids. The incidence of CS was 76.1%. Among all screened preterm, 237 (59%) patients developed ROP.

The incidence of ROP was increased with the decrease of GA and BW ([Figure 1] and [Figure 2]) and both were significantly lower in the ROP group (P<0.001) compared with the non-ROP group ([Table 1] and [Table 2]).
Figure 1 Incidence of retinopathy of prematurity according to gestational age categories.

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Figure 2 Incidence of retinopathy of prematurity according to birth weight categories.

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Table 1 Comparison of the studied groups according to gestational age categories

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Table 2 Comparison of the studied groups according to birth weight categories

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ROP risk factors (neonatal and maternal factors) were analyzed by univariate analysis and logistic regression analysis. There were statistically significant differences (P≤0.05) between the ROP group and the non-ROP group as regards GA, BW, oxygen therapy, sepsis, multiple birth, and delivery by CS ([Table 3]).
Table 3 Univariate analysis of risk factors of retinopathy of prematurity

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Preterm babies with mean BW of 1414±338 g and who received oxygen therapy after birth were predicted to be at risk for development of ROP ([Table 4]). There was a significant negative correlation between ROP severity, both with GA and BW, as shown in [Table 5].
Table 4 Logistic regression analysis of risk factors of retinopathy of prematurity

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Table 5 Correlation between retinopathy of prematurity severity and gestational age and birth weight

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According to the International Committee for the Classification of ROP [10], 101 (42.6%) patients had stage 1 ([Figure 3]), 114 (48.1%) had stage 2 ([Figure 4]), 12 (5.1%) had stage 3 ([Figure 5]), 10 (4.2%) had aggressive posterior ROP ([Figure 6]), and 24 (10.1%) presented with plus disease ([Figure 7]).
Figure 3 Stage 1: demarcation line.

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Figure 4 Stage 2: ridge.

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Figure 5 Stage 3: extraretinal fibrovascular proliferation.

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Figure 6 Aggressive posterior retinopathy of prematurity.

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Figure 7 Plus disease.

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Regarding retinal zone finding, 12 (5.1%) were in zone 1, 64 (27%) were in zone 2, and 161 (67.9%) were in zone 3 ([Table 6]).
Table 6 Distribution of stage and zone among the retinopathy of prematurity group at first visit

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Eleven (4.6%) ROP patients were classified as threshold ROP. In addition, according to early treatment ROP prethreshold classification, 13 (5.5%) patients of the ROP group were identified as type I, whereas two (0.84%) patients were identified as type II.

  Discussion Top

ROP represents a major cause of preventable blindness of children in the developing and developed world. The incidence of the disease has increased with the improvement of neonatal care. Several countries have adopted their screening protocol for early detection and management of those preterm infants suffering from this blinding disease. However, ROP screening in preterms in Egypt is still in early stage.

No screening criteria have been published for Egypt. Thus, our inclusion criteria were all preterm babies (GA <37 weeks). The present study revealed an incidence of ROP of 59%. The incidence of the disease had been varied in different studies from 12.4 to 71%. Lower incidence was reported in developed countries ranging from 12.4 to 29.2% [3],[11],[12],[13],[14],[15],[16],[17]. However, other studies revealed higher incidence ranging from 64.7 to 71% [18],[19],[20],[21],[22],[23].

These variations among different studies might be because of different GA, BW survival rate of neonates, and level of perinatal care. It also varied among different races, geographical areas, and countries. In addition, late starting of retinal screening in developing countries may have missed the diagnosis of ROP [4]. Socioeconomic status and differences in resources might influence care protocols and the ability to screen patients, which in turn influence outcomes and reported incidences [22].

There is no previous similar research reporting the incidence of ROP in Mansoura or Dakahlia governorate. However, different studies were conducted in different regions in Egypt. A study in an neonatal ICU owned by a nongovernmental society in Cairo revealed an incidence of 23% [23]. Another study in Alexandria revealed an incidence of 34.4% [24].

In the current study, among ROP patients, 42.6% had stage 1 ROP and 48.1% had stage 2 ROP. The high percentage of stages 1 and 2 might indicate that more cases of earlier ROP stages were documented by early screening and this might explain the overall incidence found in this study. This was in agreement with Babaei et al. [25], who reported an incidence of 45.5% for both stage 1 and stage 2. Celebi et al. [26] reported an incidence of 25.9% and 11.06% for stage 1 and stage 2, respectively, in extremely low BW infants, which were lower values than in the current study. Another study conducted in Iran described the majority of cases as stage 2 (63.07%), whereas the percentage of cases at stage 1 was 16.99% [27]. This was also found by Singh et al. [15], who reported 14.28 and 64.28% for stage 1 and stage 2, respectively.

Regarding retinal zone findings, 5.1% were in zone 1, 27% were in zone 2, and 67.9% were in zone 3. This was similar to the study by Waheeb and Alshehri [28], who found that the majority of cases (64.5%) were in zone 3 and the fewest cases were in zone 1 (6.5%).

In the current study, the mean GA and BW of infants with ROP were 30.9±2.1 weeks and 1414±339 g, respectively, which were significantly lower than those in the non-ROP group. This was consistent with other studies [14],[22]. However, some researchers reported lower values compared with the present study, suggesting that more mature infants develop ROP in low/middle-income countries [6].

A significant negative correlation between ROP severity with GA and BW was recorded in this study. Celebi et al. [26] added that the severity of ROP was negatively correlated with BW and GA at birth. This might be because of immature vascularization that increases susceptibility of the retina to oxidative damage and to a number of perinatal factors that include hyperoxia and hypoxia, as well as sepsis [26].

Our study revealed a strong association between oxygen delivery and ROP. This association had already been described in other studies in which oxygen was reported as a risk factor [15],[29]. Moreover, there was a significant relationship between duration of oxygen therapy, high oxygen pressure, and retinopathy [30]. However, in the present study, no data are available about the duration of administration of oxygen and its concentration. On the other hand, some studies proved no significant relationship between oxygen and occurrence of ROP [31]. Some authors revealed that the duration of oxygen therapy was directly proportional to ROP development. In addition, the fluctuation in oxygen exposure resulting in hyperoxia (>3 episodes) and hypoxia (2–3 episodes) was known to be a significant risk factor for the disease [15].

In the current work, sepsis was proved to be a significant risk factor for ROP on univariate analysis. This was matched with other studies that reported sepsis as an important and significant predictor of developing severe ROP. They proved that early detection and prevention of sepsis may decrease the incidence of ROP requiring treatment [26],[32]. Weintraub et al. [33] noted that sepsis increases the risk of developing ROP 12-fold, as it might increase oxygen demand and interfere with oxygen tension, which increases retinal ischemia, resulting in ROP. A probable cause behind that is endotoxin-induced retinitis with increased active leukocyte adhesion to the vascular endothelium of retinal blood vessels, leading to inflammation and leakage [15]. However, many other researchers postulated that sepsis has no clinical significance [14],[28],[34]. In the current study, a high incidence of ROP was found to be associated with multiple birth. The relationship between ROP and multiple birth is still debated in the literature. Some researchers did not find any significant association between ROP development and multiple pregnancies [35].

The current study did not identify jaundice, antenatal steroid, maternal age surfactant, respiratory distress syndrome, and total parenteral nutrition as risk factors. However, other researchers recorded their association with ROP [5],[14],[15],[36],[37].

The most common widespread ROP screening guidelines are those of the USA and the UK. These guidelines have been shown to be inadequate for screening in low/middle-income countries [38],[39]. It is recommended that each country should develop and use its own specific screening criteria that are appropriate for its population [7].

In conclusion, ROP screening of preterms is essential to decrease blindness, as well as long-term visual morbidity, in these infants. More efforts are needed to reduce the incidence of ROP, avoid risk factors, and improve the guidelines to ensure that all babies at risk receive a timely screening examination.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]

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