Prevalence and Risk Factors of Retinopathy of Prematurity in Iran
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Azami et al. BMC Ophthalmology (2018) 18:83 https://doi.org/10.1186/s12886-018-0732-3 RESEARCHARTICLE Open Access Prevalence and risk factors of retinopathy of prematurity in Iran: a systematic review and meta-analysis Milad Azami1, Zahra Jaafari2, Shoboo Rahmati2, Afsar Dastjani Farahani3 and Gholamreza Badfar4* Abstract Background: Retinopathy of prematurity (ROP) refers to the developmental disorder of the retina in premature infants and is one of the most serious and most dangerous complications in premature infants. The prevalence of ROP in Iran is different in various parts of Iran and its prevalence is reported to be 1–70% in different regions. This study aims to determine the prevalence and risk factors of ROP in Iran. Methods: This review article was conducted based on the preferred reporting items for systematic review and meta-analysis (PRISMA) protocols. To find literature about ROP in Iran, a comprehensive search was done using MeSH keywords in several online databases such as PubMed, Ovid, Science Direct, EMBASE, Web of Science, CINAHL, EBSCO, Magiran, Iranmedex, SID, Medlib, IranDoc, as well as the Google Scholar search engine until May 2017. Comprehensive Meta-analysis Software (CMA) Version 2 was used for data analysis. Results: According to 42 studies including 18,000 premature infants, the prevalence of ROP was reported to be 23. 5% (95% CI: 20.4–26.8) in Iran. The prevalence of ROP stages 1, 2, 3, 4 and 5 was 7.9% (95% CI: 5.3–11.5), 9.7% (95% CI: 6.1–15.3), 2.8% (95% CI: 1.6–4.9), 2.9% (95% CI: 1.9–4.5) and 3.6% (95% CI: 2.4–5.2), respectively. The prevalence of ROP in Iranian girls and boys premature infants was 18.3% (95% CI: 12.8–25.4) and 18.9% (95% CI: 11.9–28.5), respectively. The lowest prevalence of ROP was in the West of Iran (12.3% [95% CI: 7.6–19.1]), while the highest prevalence was associated with the Center of Iran (24.9% [95% CI: 21.8–28.4]). The prevalence of ROP is increasing according to the year of study, and this relationship is not significant (p = 0.181). The significant risk factors for ROP were small gestational age (p < 0.001), low birth weight (p < 0.001), septicemia (p = 0.021), respiratory distress syndrome (p = 0.036), intraventricular hemorrhage (p = 0.005), continuous positive pressure ventilation (p = 0.023), saturation above 50% (p = 0.023), apnea (p = 0.002), frequency and duration of blood transfusion, oxygen therapy and phototherapy (p < 0.05), whereas pre-eclampsia decreased the prevalence of ROP (p = 0.014). Conclusion: Considering the high prevalence of ROP in Iran, screening and close supervision by experienced ophthalmologists to diagnose and treat the common complications of pre-maturity and prevent visual impairment or blindness is necessary. Keywords: Meta-analysis, Retinopathy of prematurity, Iran, Prevalence, Risk factor * Correspondence: [email protected] 4Department of Pediatrics, Behbahan Faculty of Medical Sciences, Behbahan, Iran Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Azami et al. BMC Ophthalmology (2018) 18:83 Page 2 of 14 Background reduced; therefore, the significance of statistical results in- Retinopathy of prematurity (ROP) refers to the develop- creases [16, 17]. This study aims to determine the inci- mental disorder of the retina in premature infants and is dence and risk factors for ROP in Iran. one of the most serious and most dangerous complica- tions in premature infants. Methods Embryonic retinal arteries start to grow in the third Study protocol month of pregnancy and their development ends at This review article was conducted based on the birth. Therefore, the stages of evolution of the eye are preferred reporting items for systematic review and defective in premature infants, and the growth of the meta-analysis (PRISMA) protocols [16]. The study was vessels is either stopped or unusual, and ultimately, the conducted in five stages: design and search strategy, a vessels become very fragile, which can lead to visual im- collection of articles and their systematic review, evalu- pairment in severe cases [1]. ation of inclusion and exclusion criteria, qualitative Despite considerable progress made in the treatment evaluation and statistical analysis of data. To avoid bias of ROP, it is still a common cause of reduced vision in in the study, each of the above steps was carried out by children in developed countries, and its prevalence is in- two researchers independently. In case of differences in creasing [2–4]. This is a preventable disease and re- the results obtained by the two researchers, a third re- sponds to treatments appropriately if diagnosed at early searcher intervened to reach an agreement. stages, but in case of delayed diagnosis and treatment, it may lead to blindness [5]. Search strategy The first incidences of ROP were reported in the 1940s To find literature about ROP in Iran, a comprehensive and 1950s, mainly as a result of the use of supplemental search was done using the terms (Retinopathy of Prema- oxygen without supervision (first epidemic). Although the turity [MeSH]) AND (“Incidence” [MeSH] OR “Epidemi- survival of premature infants improved in the following ology” [MeSH]), OR (“Prevalence” [MeSH]) AND (“Iran” decades, and despite improved monitoring methods for [MeSH]) in 7 international databases including PubMed, oxygen supplements, ROP emerged with an increasing in- Ovid, Science Direct, EMBASE, Web of Science, cidence (second epidemic) [6]. Over the past decade, the CINAHL, EBSCO, and 5 national databases including increasing incidence of ROP blindness has been recorded Magiran, Iranmedex, SID, Medlib, IranDoc, as well as in low-income countries. Studies show that ROP is the Google Scholar search engine until May 2017. Refer- leading cause of blindness in China, Southeast Asia, South ences to all relevant articles were reviewed. Due to the America, Latin America, and Eastern Europe, especially in inability of Iranian databases to search using Boolean urban centers of newly industrialized countries, and this is operators (AND, OR and NOT), searches on these data- referred to as the “third epidemic” [7]. bases were only performed using the keywords. ROP is a multifactorial disease and the most important risk factors are preterm delivery, especially before the 32nd Inclusion and exclusion criteria week of gestation and birth weight less than 1500 g. Apnea, Articles with the following characteristics were chosen intraventricular hemorrhage, various maternal factors (dia- for meta-analysis: 1. Original research papers published betes, preeclampsia, mother’s smoking), respiratory disor- either in Persian or English; 2. Medical dissertations; 3. ders, infection, vitamin E deficiency, heart disease, Review of the prevalence or risk factors for ROP. The increased blood carbon dioxide, increased oxygen (O2)con- exclusion criteria were: 1. Non-random sample for esti- sumption, decreased PH, decreased blood O2, bradycardia, mating the prevalence; 2. Being irrelevant to the topic; 3. transfusion, amount of received oxygen and duration of Congress papers; 4. Sample size other than premature ventilation are other risk factors for ROP [8–10]. infants; 5. Non-Iranian studies; 6. Review articles, case The prevalence of ROP in different regions of Iran is dif- reports, editorials; 7. Duplicate studies and 8. Low- ferent and its prevalence is reported to be 1–70% in differ- quality studies. ent regions [11–14]. Considering the abovementioned issues and the importance of the subject, as well as the di- ROP detection criteria versity of reports in Iranian studies, it is necessary to carry ROP was diagnosed by an expert through examination out more extensive and precise studies. Meta-analysis is a of retinas of infants using indirect ophthalmoscope. method that collects and analyzes multiple research data with a common purpose to provide a reliable estimate of Selection of studies the impact of some interventions or observations in medi- First, all related articles (articles with affiliations containing cine [15, 16]. Obviously, the sample size in meta-analysis Iranian authors) were collected and a list of titles was pre- becomes larger by collecting data from several studies and pared at the end of the search and removal of duplicates. therefore the range of changes and probabilities will be After blinding the specifications of the articles by on Azami et al. BMC Ophthalmology (2018) 18:83 Page 3 of 14 researcher (Milad Azami), including the name of the journal Statistical analysis and the name of the author, the full text of the articles was In each study, the prevalence of ROP was considered presented to the researchers. Each article was studied by two as the probability of binomial distribution. To evalu- researchers independently (Gholamreza Badfar, Afsar Dast- ate the heterogeneity of the studies, Cochran’sQtest jani Farahani). If the article was rejected, the reason for this and I2 index were used [19]. There are three cat- rejection was mentioned. In case of disagreement between egories for the I2 index: heterogeneity lower than the two authors, the article was judged by the team of 25%, heterogeneity between 25% and 75% and het- researchers. erogeneity more than 75%. Considering the hetero- geneity of the studies, a random effects model was Quality of studies used to combine ROP prevalence.