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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 33  |  Issue : 4  |  Page : 1246-1251

Retinopathy of prematurity in preterm children


1 Department of Ophthalmology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Ophthalmology, Kafr El Sheikh Old Ophthalmology Hospital, Kafr El Sheikh, Egypt

Date of Submission24-Jun-2020
Date of Decision04-Aug-2020
Date of Acceptance16-Aug-2020
Date of Web Publication24-Dec-2020

Correspondence Address:
Samah A Ibrahem Tolan
MBBCh, Al-Zahra, Kafr El Sheikh
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_207_20

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  Abstract 


Objectives
The aim of this work was to screen the incidence of retinopathy of prematurity (ROP) in preterm children.
Background
Screening of ROP in preterm infants is important to detect early stages and observation till complete retinal vascularization. Cases with late stages need early treatment to prevent retinal detachment and blindness.
Patients and methods
This study was conducted on 30 extremely preterm infants born at less than 32 weeks of gestational age and admitted to neonatal incubators unit from March 2019 to December 2019 at Menoufia University Hospital and Al Quds Hospital in Al Mahla Al Qubra, Egypt.
Results
A total of 30 were included in the study. Males constituted 14 of the candidates, with ROP present in eight (44.4%), and females represented 16 candidates, with ROP present in 10 (55.6%). The mean hemoglobin levels during the first week of life were significantly lower in infants who developed ROP that warranted treatment.
Conclusion
ROP screening is essential to decrease blindness and long-term visual morbidity in preterm infants. The guidelines of management should be updated for practicing ophthalmologists.

Keywords: anemia, preterm, retinopathy of prematurity


How to cite this article:
Khairy HA, Zaky MA, Ibrahem Tolan SA. Retinopathy of prematurity in preterm children. Menoufia Med J 2020;33:1246-51

How to cite this URL:
Khairy HA, Zaky MA, Ibrahem Tolan SA. Retinopathy of prematurity in preterm children. Menoufia Med J [serial online] 2020 [cited 2021 Apr 18];33:1246-51. Available from: http://www.mmj.eg.net/text.asp?2020/33/4/1246/304494




  Introduction Top


Retinopathy of prematurity (ROP) is a vasoproliferative retinal disorder unique to premature infants. As premature births increase in many areas of the world, ROP has become a leading cause of childhood blindness. A better understanding of the pathogenesis of ROP, adherence to strict screening guidelines, and evolution of treatment options have reduced the number of sight-threatening complications owing to ROP[1].

Without timely treatment, neovascularization can lead to retinal detachment and blindness. Phase one ROP occurs within the infants' first weeks of life, and phase two ROP develops weeks to months after birth. Prematurity and/or low birth weights (BW) are known risk factors for ROP. It has been suggested that the risk factors for ROP may be phase-dependent and that they only have an effect during the early or late postnatal period, or in both[2].

Globally, there are at least 50 000 children who are blind owing to ROP, which remains an important cause of childhood blindness in high-income countries and is also emerging as a major cause of childhood blindness in middle-income economies, such as Latin America, Eastern Europe, India, and China[3].

The incidence and severity of ROP are particularly correlated with low gestational age (GA) at birth, increased survival rate of extremely low BW infants, and the lack of an effective screening and treatment program based on the international guidelines[4].

Premature infants have avascular or incompletely vascularized retina at birth, and ROP evolves over 4–5 weeks after birth[5]. This relatively slow evolution gives a small window of opportunity to effectively conduct retinal examinations and timely interventions to improve visual outcome and avoid irreversible blindness owing to retinal detachment from progressive untreated ROP[6].

The incidence of ROP is influenced by several factors, including GA, BW, genetics, ethnicity, and level of neonatal care. GA is defined as the length of time of growth of the fetus in the uterus. Screening programs should be regionally tailored to account for these differences. Advances in prenatal and neonatal care have resulted in increasing rates of ROP in the developing world[7].

Anemia of prematurity is a common condition in preterm infants, especially in extremely preterm infants born before 28 weeks of gestation. It is caused by immaturity of the hematopoietic system and is due to inadequate production of erythropoietin and iatrogenic blood loss owing to frequent blood sampling[8].

Most extremely preterm infants receive blood transfusions for anemia at some point during their hospitalization, based on hemoglobin levels and clinical indications, including oxygen requirements. Whether anemia and blood transfusions are risk factors for ROP or not is unclear[9].

The overall health status of infants also affects the risk for ROP, and other complications of preterm birth, such as bronchopulmonary dysplasia, necrotizing enterocolitis, intraventricular hemorrhage, and sepsis, are often seen in association with ROP[10].

However, others have suggested that timely correction of anemia with blood transfusions may have initiated the regression of ROP. Anemia at birth has been associated with ROP development[11].

The aim of this study was to screen the incidence of preterm children with ROP.


  Patients and methods Top


This study was conducted on 30 extremely preterm infants born at less than 32 weeks of GA and admitted to neonatal incubators unit from March 2019 to December 2019 at Menoufia University Hospital and Al Quds Hospital in Al Mahla Al Qubra, Egypt.

Eligible patients were aged less than 32 weeks with the following inclusion criteria considered: preterm newborns (GA 23–32 weeks), with BW less than 1500 g diagnosed, and a signed informed consent from parents.

Patients were excluded from the study if they had ROP-like syndromes: familial exudative vitreoretinopathy and incontinentia pigmenti (Bloch–Sulzberger syndrome), retinal dysplasia, and other retinochorodial disorders, for example, retinitis pigmentosa, macular dystrophy, and choroidal dystrophy.

Methods

Informed consent was obtained from the patients according to medical ethics after explaining the research. Data collected from the patients included age, past ocular and medical history, medications, allergies, and family history of ocular diseases.

Patients underwent baseline assessment, such as complete blood counting with hemoglobin level, bilirubin level, oxygen saturation, and coagulation tests.

First examination was done at a postnatal age of 4 weeks, but in the most immature infants (GA 27 weeks), the first examination was postponed until a postnatal age of 31 weeks.

Maternal data including age, perinatal history, and systemic diseases were collected.

All associated systemic findings, including blood culture-proven sepsis, respiratory distress syndrome (RDS), apnea, necrotizing enterocolitis, intraventricular hemorrhage, blood product transfusion, and congenital heart diseases were recorded.

Pupils were dilated using three drops of a combination of cyclopentolate 0.1% and phenylephrine 1% at 10-min intervals, 60 min before examination.

Comfort care techniques (e.g., administering glucose 25% solution, and installation of local anesthetics –0.5% proparacaine eye drops – just before examination) during the screening examination were considered.

Pediatric eye speculum and pediatric scleral depressor were used and then indirect ophthalmoscopy was performed using a binocular indirect ophthalmoscope with a 28-D lens. Indirect ophthalmoscopy is necessary to perform a proper retinal examination. First the examiner should examine the anterior eye, noting pupil wideness, a possible tunica vasculosa lentis, or a rubeosis iridis. Moreover, RetCam documentation was done when available, which is a useful screening tool to detect treatable ROP and may safely reduce the overall number of indirect ophthalmoscopy examinations required. Screening for ROP with digital fundus imaging is associated with a significantly lower pain and stress.

Statistical analysis

The collected data were revised, coded, tabulated, and introduced to a PC using Statistical package for Social Science (IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 25.0.; IBM Corp., Armonk, New York, USA). Data were presented, and suitable analysis was done according to the type of data obtained for each parameter. Kolmogorov–Smirnov test was done to test the normality of data distribution. Significant data were considered to be nonparametric.


  Results Top


A total of 30 patients were included in the study. Males constituted 14 of the candidates, with ROP present in eight (44.4%), and females represented 16, with ROP present in 10 (55.6%). Regarding the relationship between GA and ROP, we found that two infants were aged 25–26 weeks, and both of them had ROP (11.2% from 18 infants with ROP), and this represents 100% of this age period [Table 1].
Table 1: Sex distribution in study infants and comparison of the studied groups according to gestational age categories

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Of 30 babies, 26 babies were singletons, and four babies were twins. Of 26 singletons, two babies developed ROP. None of the twins developed ROP. Type of gestation was not found to be significantly associated (P = 0.001) with ROP in the present study.

Of 30 infants screened, six had RDS. Of 18 ROP cases present, four (22.2%) of them had RDS, whereas of 12 non-ROP cases, two (16.7%) of them had RDS. P value was more than 0.001, with nonsignificant level [Table 2].
Table 2: The relationship between respiratory distress syndrome and retinopathy of prematurity

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Regarding the relationship between oxygen administration and ROP, we found that 25 infants received oxygen, comprising 18 (72%) infants with ROP and seven (28%) infants without ROP. The 18 infants who received oxygen all had ROP, and this represents 100% of infants [Table 3].
Table 3: The relationship between oxygen administration and retinopathy of prematurity

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The relationship between jaundice and ROP is shown in [Figure 1].
Figure 1: The relationship between jaundice and retinopathy of prematurity.

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The relationship between sepsis and ROP is shown in [Figure 2].
Figure 2: The relationship between sepsis and retinopathy of prematurity.

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Maternal age for infants with ROP was 25.9 ± 5.2 years, whereas for those without ROP was 26.7 ± 4.8, with a P value of 0.11, which is not statistically significant.

Regarding delivery mode as a risk factor, we found that of 18 infants with ROP, five (27.8%) of their mothers had vaginal mode of delivery, whereas 13 (72.2%) had cesarean section mode of delivery. P value was 0.04, being statistically significant.

The mean hemoglobin levels during the first week of life were significantly lower in infants who developed ROP that warranted treatment. The total number and timing of blood transfusions during the first 4 weeks of life were found to be independent risk factors for ROP warranting treatment in our study, as well when the data were adjusted for GA. Our findings suggest that anemia and blood transfusions may be risk factors for ROP warranting treatment.


  Discussion Top


ROP is a sight-threatening and vasoproliferative disease that occurs only in premature infants. ROP is one of the leading causes of preventable blindness in both developed and developing countries[12].

ROP is diagnosed only in a minority of premature infants, with a smaller subset requiring intervention. As a result, better understanding of risk factors of progression to ROP, especially in those cases requiring treatment, would allow for more effective screening programs[13].

Anemia of prematurity is a common condition in preterm infants, especially in extremely preterm infants born before 28 weeks of gestation[14]. It is caused by immaturity of the hematopoietic system and is due to inadequate production of erythropoietin and iatrogenic blood loss owing to frequent blood sampling[15].

No screening criteria have been published for Egypt. Thus, our inclusion criteria were all preterm babies (GA <32 weeks). In the present study the overall prevalence of positive population for ROP was 60% while previous studies national prevalence that report 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%[16],[17]. However, other studies revealed higher incidence ranging from 64.7 to 71%[18],[19].

Different studies were conducted in different regions in Egypt. A study in a neonatal ICU owned by a nongovernmental society in Cairo revealed an incidence of 23%[19]. Another study in Alexandria revealed an incidence of 34.4%[20].

In the current study, among patients with ROP, 38.9% had stage 1 ROP and 38.9% 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. [21], who reported an incidence of 45.5% for both stages 1 and 2. Celebi et al.[22] reported an incidence of 25.9 and 11.06% for stages 1 and 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%[23]. This was also found by Singh et al. [17], who reported 14.28 and 64.28% for stages 1 and 2, respectively.

In the current study, the mean GA and BW of infants with ROP were 29.5 ± 2.3 weeks and 1514 ± 391 g, respectively, which were significantly lower than those in the non-ROP group. This was consistent with other studies[16],[24]. However, some researchers reported lower values compared with the present study, suggesting that more mature infants develop ROP in low/middle-income countries[25].

A significant negative correlation between ROP severity with GA and BW was recorded in this study. Celebi et al.[22] 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[22].

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[17],[26].

Moreover, there was a significant relationship between duration of oxygen therapy, high oxygen pressure, and retinopathy[27].

However, in the present study, no data are available about the duration of administration of oxygen and its concentration. On the contrary, some studies proved no significant relationship between oxygen and occurrence of ROP[28].

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[17].

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[22],[29]. Weintraub et al.[30] 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[17].

However, many other researchers postulated that sepsis has no clinical significance[16],[31],[32].

In the current study, a high incidence of ROP was found to be associated with multiple births. The relationship between ROP and multiple births is still debated in the literature. Some researchers did not find any significant association between ROP development and multiple pregnancies[33].

The results of studies evaluating anemia as a risk factor for ROP have been inconsistent. Bossi et al.[34] reported no association between hemoglobin levels and any stage of ROP in their cohort of 639 infants. Englert et al.[35] reported that infants with prolonged severe anemia, with a hemoglobin of less than 8 g/ml, developed milder ROP than those infants with anemia with shorter duration who received frequent blood transfusions.

That study showed that severe anemia was associated with ROP severity. However, Banerjee et al.[11] found that low hemoglobin levels at birth were associated with increased morbidities, including ROP. In a retrospective case series of 82 eyes who had milder ROP not warranting treatment, anemia was found to be one of the predictive risk factor for delayed involution of ROP[36] and timely blood transfusions have been suggested as a way of initiating the regression of ROP[37].


  Conclusion and recommendations Top


ROP screening of preterm infants 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

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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