Incidence and Risk Factors of Retinopathy of Prematurity in Southeast Iran: A Retrospective Cohort Study

Incidence and Risk Factors of Retinopathy of Prematurity in Southeast Iran: A Retrospective Cohort Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Incidence and Risk Factors of Retinopathy of Prematurity in Southeast Iran: A Retrospective Cohort Study Alireza Maleki, Meisam Sargazi, Ali Yousefian, Saeedeh Sarhadi, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3877019/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background and objectives: Retinopathy of prematurity (ROP) is a significant cause of preventable premature infant vision loss. Many studies have reported different risk factors depending on the region. In this study, we evaluated the incidence of ROP and associated risk factors in a referral eye hospital in southeast Iran. Methods This was a retrospective cohort study of preterm infants with birth weight (BW) ≤ 2000 grams or gestational age (GA) ≤ 34weeks and infants with 34 < GA < 37weeks or GA 2000 grams referred by their pediatricians to our center from March 2022 until March 2023. Results 920 infants met the inclusion criteria for the study, the incidence of ROP and severe ROP was 20.2% and 3.58% respectively. Results of logistic regression analysis showed higher GA and BW as protective factors against ROP occurrence. History of blood transfusion and phototherapy increased ROP development. Conclusion Lower GA, lower BW, history of blood transfusion, and phototherapy were associated with ROP development. Phototherapy decreased the need for treatment among ROP patients. Ophthalmology Retinopathy of Prematurity Infant vision loss phototherapy Introduction Retinopathy of prematurity (ROP) is a significant cause of preventable premature infant vision loss. The incidence of disease is increasing in middle-income countries because of advances in prenatal and neonatal care.(1, 2) When infants are born prematurely, the oxygen levels are increased when comparing extrauterine levels to in-utero. This relative increase leads to constriction of growing vessels. Subsequently, vascular obliteration ensues and retinal ischemia causes vessel endothelial growth factor upregulation. This leads to aberrant neovascularization and retinal detachment.(3–6) Many studies have reported different risk factors depending on the region. Low gestational age and low birth weight are the two major risk factors for ROP. Other risk factors associated with this condition include oxygen supplementation at birth, prolonged mechanical ventilation, multiple gestation, sepsis, anemia, history of blood transfusion, intraventricular hemorrhage, and bilirubin levels.(7–12) Laser photocoagulation is the main treatment for ROP due to its safety and predictable outcomes. Intravitreal anti-vascular endothelial growth factors (VEGF) injection is another treatment option for the disease and promising results have been reported.(5, 13, 14) There is no information available about the characteristics of ROP in Sistan and Baluchestan in the Southeast of Iran. In this study, we evaluated the incidence of ROP and its associated risk factors and provided a summary report of treatment results in a referral eye hospital. Methods This was a retrospective cohort study of 920 preterm infants referred to a referral eye hospital from March 2022 until March 2023. All infants with birth weight (BW) ≤ 2000 grams or gestational age (GA) ≤ 34 weeks and infants with 34 < GA < 37 weeks or GA 2000 grams referred by their pediatricians were included in this study. Patients who did not complete follow-up examinations and had incomplete medical and informational records were excluded. The following data were collected and recorded: gender, BW, GA, number of pregnancies, oxygen therapy with continuous positive airway pressure (CPAP) or mechanical ventilation (number of days), history of blood transfusions, occurrence of intraventricular hemorrhage (IVH), occurrence of sepsis, phototherapy, mother’s age, type of delivery (cesarean section versus vaginal delivery), history of hypertension during pregnancy, history of pre-eclampsia, eclampsia and hemolysis elevated liver enzyme levels and low platelet levels (HELLP) syndrome. The first examination was done between 4 and 6 weeks of chronological age or within the 31 and 33 weeks postmenstrual age, whichever was later. Two experienced retina subspecialists examined infants after the instillation of tropicamide 0.5% for pupillary dilation. After topical anesthesia, fundoscopy was performed using an indirect ophthalmoscope and a + 20 D or + 30 D lens, an infant eyelid speculum, and a pediatric scleral depressor. The zones and stages of ROP were recorded based on the International Classification of Retinopathy of Prematurity. (15, 16) The follow-up examination was done according to disease severity and continued until full vascularization of the retina. Treatment was done for patients categorized as threshold, type 1 pre-threshold ROP, aggressive ROP, and patients with stage 4 or stage 5 ROP.(15, 17) In this study, ROP patients who needed treatment were considered as severe ROP. We treated ROP patients with threshold, pre-threshold type 1, and aggressive ROP with intravitreal injection of bevacizumab 0.625 mg/0.025 milliliter. These patients were then re-examined on days 3 and 7 after injection and if the ROP stage, zone, and plus disease were improving, then we followed them every 1–2 weeks until the absence of neovascularization and improvement of plus disease. Then, we extended follow-up to every 3–4 weeks until 65 weeks. At this point, if retinal vascularization reached a border of less than 0.5 disc diameter away from the ora serrata in all quadrants, patients were considered to have “full retinal vascularization”, and no more follow-ups were scheduled. Retreatment with laser was done when there was sustained neovascularization and plus disease after initial IVB therapy, or when new extra-retinal neovascularization or development of plus disease occurred after the initial response to treatment as mentioned above. We treated patients when full retinal vascularization was not achieved at 65 weeks, with laser photocoagulation. Statistical Analysis: Normally distributed quantitative data were described as mean and standard deviation (SD). The median and interquartile range (IQR) values represented asymmetrically distributed variables. The Kolmogorov-Smirnov test investigated the state of the normal distribution of quantitative variables. ROP risk factors variables were compared using the Mann-Whitney U test, Chi-square, and Fisher exact tests. Additionally, a comparative analysis of risk factors was performed for the data gathered on retinopathy of prematurity patients. The Mann-Whitney U test, Chi-square, and Fisher exact tests were used for these comparisons. To show the strength of the relationship between the variables, the effect size was calculated. The effect size was expressed by z/√N for the Mann-Whitney U test. Effect size, r, was interpreted as r ≤ 0.3 representing a small effect, 0.3 < r < 0.5, representing a medium effect, and 0.5 ≤ r representing a large effect. Also, the odds ratio and confidence interval of 95% were used to express the intensity of the relationship regarding Chi-square and Fisher exact tests. An odds ratio greater than one meant increased odds of occurrence of ROP or treated ROP, and on the other hand, an odds ratio less than one was interpreted as lower odds of ROP or treated ROP compared to the non-occurrence of them. Finally, logistic regression analysis was used to determine the variables predicting the occurrence of retinopathy of prematurity and retinopathy of prematurity requiring treatment. Variables that were statistically significant in the univariate analysis were included in the regression analysis. In all comparison groups, the threshold of significance was 0.05. IBM SPSS Statistics for Windows version 27.0 (IBM Corp. 2013. Armonk, NY: IBM Corp) was employed to carry out the analysis. Results A total of 1143 newborn babies were referred to our hospital and screened for ROP. Of them, 920 infants met the inclusion criteria for the study. 172 infants did not complete follow-up visits and 51 infants had incomplete medical records. Of 920 infants who met the inclusion criteria 50.3% were male [n: 463]. The mean GA was 32.71 ± 2.11 weeks. Mean BW was 1809.45 ± 762.41 grams. Of all screened infants, 561 infants received oxygen by CPAP, 56 infants were under mechanical ventilation, 51 infants received red blood cell transfusion, five infants had a history of IVH, and 25 infants developed sepsis. 301 infants were the result of multiple births. The evaluation of risk factors and their relationship with ROP development is shown in Table 1 . Table 1 Comparison of risk factors of retinopathy of prematurity (ROP) between ROP and without ROP groups Variable Categories Total N = 920 ROP N = 186 Without ROP N = 734 p–value Effect size Gestational Age (week), Mean(SD) median(IQR) 32.7(2.11) 33.0(2) 30.4(2.1) 30.0(3) 33.2(1.6) 33.0(2) < 0.001 a 0.48 b Birth weight(gr), Mean(SD) median(IQR) 1809(762.4) 1800(500) 1447.8(354.8) 1425.0(525.0) 1901.0(809.5) 1900.0(471.2) < 0.001 a 0.41 b Gender, Male, N% 463(50.3%) 95(51.1%) 368(50.1%) 0.81 c 0.96(0.69–1.32) d Multiple births 301(32.7%) 57(30.6%) 244(33.2%) 0.5 c 0.88(0.62–1.25) CPAP, N (%) 561(61%) 156(83.9%) 405(55.2%) < 0.001 c 4.22(2.78–6.40) d Days on CPAP 1.18(1.8) 1.00(2.00) 1.83(2.70) 1.00(1.44) 1.02(1.44) 1.00(1.0) < 0.001 a 0.15 Mechanical ventilation, N (%) 56(6.1%) 23(12.4%) 33(4.5%) < 0.001 c 2.99(1.71–5.24) d Days on mechanical ventilation 0.10(0.54) 0.00(0.00) 0.14(0.67) 0.00(0.00) 0.09(0.5) 0.00(0.00) 0.053 a 0.06 Blood transfusion, N (%) 51(5.5%) 36(19.4%) 15(2%) < 0.001 c 11.5(6.14–21.54) d Intraventricular hemorrhage, N(%) 5(0.5%) 3(1.6%) 2(0.3%) 0.059 e 6.0(0.99–36.1) d Sepsis, N(%) 25(2.7%) 14(7.5%) 11(1.5%) < 0.001 c 5.34(2.38–11.9) d Phototherapy, N(%) 684(74.3%) 155(83.3%) 529(72.1%) 0.002 c 1.93(1.27–2.94) d Type of delivery, C/S, N(%) 606(65.9%) 104(55.9%) 502(68.4%) 0.001 c 1.7(1.22–2.37) d In vitro fertilization (IVF), N(%) 73(7.9%) 14(7.5%) 59(8%) 0.81 c 0.93(0.50–1.70) d Cause of premature Birth, N(%) Onset of labor pains 334(36.3%) 373(40.5%) 140(15.2%) 73(7.9%) 77(41.4%) 77(41.4%) 24(12.9%) 8(4.3%) 257(35%) 296(40.3%) 116(15.8%) 65(8.9%) 0.09 c ---- Rupture of the amniotic sac Hypertension Other (preeclampsia, eclampsia, doctor’s diagnosis, HELLP syndrome) Age of mother(year) Mean (SD) Median (IQR) 28.15(7.4) 29.0(11) 26.6(7.4) 25.0(11) 28.5(7.18) 29.0(11) < 0.001 a 0.10 b a Mann Whitney U test, b effect size measure for Mann-Whitney U analysis with r = z/√N, c chi-square test, d odds ratio ( 95% confidence interval ), e Fisher’s exact test, Abbreviations: SD; standard deviation, IQR; interquartile range, CPAP; Continuous positive airway pressure, C/S; cesarean section. Table 2 shows the relationship between risk factors and severe ROP occurrence. Table 2 Comparison of risk factors of retinopathy of prematurity (ROP) between ROP with and without treatment groups Variable Categories Total N = 186 Treatment needed N = 33 Without treatment N = 153 p–value Effect size Gestational Age (week), Mean (SD) Median (IQR) 30.45(2.15) 30.0(3) 28.84(1.6) 29.0(3) 30.8(2.09) 31.0(3) < 0.001 a 0.35 b Birth weight (gr), Mean (SD) Median (IQR) 1447.8(354.8) 1425.0(525.0) 1185.6(294.8) 1115.0(315.0) 1504.4(341.7) 1500.0(512.5) < 0.001 a 0.35 b Gender, Male, N% 95(51.1%) 14(42.5%) 81(52.9%) 0.27 c 1.52(0.71–3.26) d Multiple births 57(30.6%) 14(42.4%) 43(28.1) 0.106 c 1.88(0.86–4.09) CPAP, N (%) 156(83.9%) 27(81.8%) 129(84.3%) 0.72 c 0.83(0.31–2.24) d Days on CPAP 1.8(2.7) 1(1.5) 1.96(2.88) 1.00(1.0) 1.81(2.67) 1.00(2.00) 0.45 a 0.05 Mechanical ventilation, N (%) 23(12.4%) 8(24.2%) 15(9.8%) 0.02 c 2.94(1.12–7.67) d Days on mechanical ventilation 0.14(0.67) 0.00(0.00) 0.12(0.33) 0.00(0.00) 0.15(0.73) 0.00(0.00) 0.55 a 0.04 Blood transfusion, N (%) 36(19.4%) 14(42.4%) 22(14.4%) < 0.001 c 4.38(1.92–10.1) d Intraventricular hemorrhage, N(%) 3(1.6%) 1(3%) 2(1.3%) 0.44 e 2.35(0.20–26.8) d Sepsis, N(%) 14(7.5%) 4(12.1%) 10(6.5%) 0.27 c 1.97(0.57–6.72) d Phototherapy, N(%) 155(83.3%) 22(66.7%) 133(86.9%) 0.005 c 0.30(0.12–0.71) d Type of delivery, C/S, N(%) 104(55.9%) 21(63.3%) 83(54.2%) 0.32 c 0.67(0.31–1.47) d In vitro fertilization (IVF), N(%) 14(7.5%) 4(12.1%) 10(6.5%) 0.27 c 1.97(0.57–6.72) d Cause of premature birth, N(%) Onset of labor pains 77(41.4%) 77(41.4%) 24(12.9%) 8(4.3%) 16(48.5%) 10(30.3%) 5(15.2%) 2(6.1%) 61(39.9%) 67(43.8%) 19(12.4%) 6(3.9%) 0.54 c ---- Rupture of the amniotic sac Hypertension Other (preeclampsia, eclampsia, doctor’s diagnosis, HELLP syndrome) Age of mother(year) Mean(SD) Median(IQR) 26.6(7.48) 25.0(11) 27.15(7.54) 25.0(11) 26.5(7.49) 24.0(12) 0.70 a 0.02 b a Mann Whitney U test, b effect size measure for Mann-Whitney U analysis with r = z/√N, c chi-square test, d odds ratio ( 95% confidence interval), e Fisher’s exact test, Abbreviations: SD; standard deviation, IQR; interquartile range, CPAP; Continuous positive airway pressure, C/S; cesarean section. Statistically significant relation between the gestational age, birth weight, being under Continuous Positive Airway Pressure (CPAP), number of days patients were under CPAP, being under mechanical ventilation, history of blood transfusion, history of sepsis, phototherapy, type of delivery (cesarean section) and lower mothers’ age and ROP occurrence were seen in univariate analysis. Table 1 results of multivariate logistic regression analysis showed higher GA and BW as protective factors against ROP occurrence. History of blood transfusion and phototherapy increased ROP development. Additionally, phototherapy had a significant effect on preventing severe ROP occurrence as shown in the logistic regression analysis in Table 3 Table 3. Risk factors for retinopathy of prematurity (ROP) and severe ROP: results of logistic regression analysis Risk factors for retinopathy of prematurity (ROP): results of logistic regression analysis Variables Wald Significance Odds Ratio 95%CI Gestational Age 54.85 <0.001 0.589 0.512-0.678 Birth weight 18.85 <0.001 0.998 0.998-0.999 Blood transfusion 15.476 <0.001 6.357 2.53-15.97 Phototherapy 7.459 0.006 2.172 1.24-3.78 Risk factors for severe retinopathy of prematurity (ROP): results of logistic regression analysis Phototherapy 4.46 0.035 0.349 0.131-0.927 Abbreviations: CI: confidence interval A total of 186 infants had ROP and the incidence of ROP in our study was 20.2%. The incidence of ROP and severe ROP development in different GA and BW groups is shown in Table 4. Twenty patients out of 33 patients with severe ROP were in the ≤30 weeks GA group. There were 15 ROP patients in ≤1000-grams BW group and 7 of them had severe ROP, although most severe ROP patients had 1000<BW≤1500 grams. Table 4 Incidence of ROP and severe ROP in different GA and BW groups Total N = 920 ROP N = 186 Without ROP N = 734 Severe ROP N = 33 ROP without treatment N = 153 Gestational Age category (week) , N(%) 34< 32<-≤34 30<-≤32 ≤ 30 172(18.7%) 526(57.2%) 151(16.4%) 71(7.7%) 4(2.2%) 56(30.1%) 65(34.9%) 61(32.8%) 168(22.9%) 470(64%) 86(11.7%) 10(1.4%) 0(0%) 2(6.1%) 11(33.3%) 20(60.6%) 4(2.6%) 54(35.3%) 54(35.3%) 41(26.8%) Weight category (gr),N(%) 2000< 1500<-≤2000 1000<-≤1500 ≤ 1000 222(24.1%) 499(54.2%) 179(19.5%) 20(2.2%) 9(4.8%) 77(41.1%) 85(45.7%) 15(8.1%) 213(29%) 422(57.5%) 94(12.8%) 5(0.7%) 0(0%) 6(18.2%) 20(60.6%) 7(21.2%) 9(5.9%) 71(46.4%) 65(42.5%) 8(5.2%) Of the 33 patients treated in our center, 22 patients had type 1 ROP and 6 patients had aggressive ROP. 19 patients received intravitreal bevacizumab injection, 5 patients were treated with laser retinal photocoagulation because of incomplete retinal vascularization at 65 weeks follow up, and 9 patients were treated with both laser and IVB injection. Discussion The incidence of ROP varies between different studies. Even in studies from various parts of Iran as shown in Table 5, screening programs, population heterogeneity, level of perinatal care and NICU care may influence the statistical differences.(18) Table 5. Incidence of ROP occurrence in different studies Author Year of publication country Study design Inclusion criteria Number of patients ROP Incidence (%) Risk factors Hu et al.(19) 2023 China retrospective case–control study BW1500 g or GA>32 weeks with an unstable clinical course 6115 27.0% lower BW, smaller GA, total days on oxygen, late-onset sepsis, frequency of red blood cell transfusions and relative weight gain Deb et al.(21) 2023 India prospective cohort study GA <35 weeks and BW 31 + 6 weeks to 36 + 6 weeks 4156 22% duration of hospital stay, BW and GA Freitas et al.(18) 2018 Brazil retrospective cohort study GA l< 32 weeks or BW <1500 g; or neonates born with 32-37 weeks' gestation or BW above 1500 g and any of the following associated: multiple gestation, respiratory distress syndrome, sepsis, blood transfusions or IVH 602 33.9% extremely low BW, pulmonary diseases, IVH, and low GA Al qahtani et al.(23) 2020 Saudi Arabia retrospective cohort study BW <1501 g or GA <32 weeks 581 38.6% BW, GA, Postnatal steroid, O2 THERAPY, IVH, RBC transfusion Dani et al.(24) 2021 italY cohort GA between 23 and 30 weeks 178 38% IVH, RBC transfusion Zarei et al.(25) 2019 Iran retrospective cohort study GA ≤ 37 weeks 1,990 27.28% GA, BW, and history of transfusion Abrishami et al.(26) 2013 Iran cross-sectional study <32 gestational weeks 122 26.2% GA, sex, BW, Apgar score, duration of parenteral nutrition, oxygen therapy, phototherapy, maximum PaO2 and minimum SpO2 (univariate analysis) Alizadeh et al.(27) 2015 Iran cross-sectional study BW ≤2500 g and/or GA ≤36 weeks 310 20.6% low GA and low BW Khorshidifar et al.(28) 2019 Iran cross-sectional study BW ≤2000 grams or GA <34 weeks and all other infants at risk of ROP admitted to the NICU or referred to our ROP clinic 207 33.3% BW, GA and blood transfusion GA; gestational age, IVH; intraventricular hemorrhage, NICU; neonatal intensive care unit. The incidence of ROP in our study was 20.2% among infants with BW≤2000 g or GA≤34 weeks or preterm infants with GA above 34 weeks or with BW above 2000 grams with unstable clinical conditions referred by neonatologists. 185 patients with ROP had BW≤2000-grams or GA≤34 weeks and only 1 patient did not fit in the previously mentioned inclusion criteria selected. This patient was directly referred for evaluation by a pediatrician. By implementing other criteria such as BW≤1500 gram or GA≤32 weeks, BW≤2000 gram or GA≤32 weeks, BW≤1500 gram or GA≤34 weeks, 27 ROP patients, 6 ROP patients, and 4 ROP patients would be missed, respectively. The mean GA and BW of infants who developed ROP were 30.4±2.1 weeks and 1447.8±354.8 grams, respectively. For patients with severe ROP, the mean GA and BW were 28.84±1.6 weeks and 1185.6±294.8 grams, respectively. The mean GA and BW for severe ROP in our study are within the range of GA 24-32 weeks and BW 700-1480 grams previously reported by Khorshidifar et al. in their study of ROP in Tehran, the capital of Iran.(28) Identifying risk factors for developing ROP helps set screening criteria, reduce unnecessary examinations, and may help prevent ROP occurrence or progression. Lower gestational age, lower birth weight, multiple births, red blood cell transfusions, phototherapy, intraventricular hemorrhage, supplemental oxygen therapy, sepsis occurrence, and pulmonary diseases are among the risk factors mentioned in the studies, as shown in Table 5. Like many other studies, lower BW and lower GA were correlated with ROP development. (18, 20, 22, 23, 25-28) Lower GA and lower BW suggest infants are more immature and are risk factors for developing ROP due to general immaturity.(29) Blood transfusion was a risk factor for ROP development in our study. A lower concentration of HbF has been associated with ROP development.(30) Blood transfusion replaces fetal hemoglobin (HbF) by adult hemoglobin (HbA) and may cause ROP development by increasing retinal oxygen delivery.(31, 32) Phototherapy increased the risk of ROP development in our study. Antioxidant effects of bilirubin can be protective against ROP.(33) However, in ROP patients, it reduced the need for treatment and was the only factor that had a protective effect against severe ROP occurrence in our study. Laser photocoagulation of avascular retina is the most common treatment of ROP, but it reduces the patient’s visual field significantly. In recent years intravitreal anti-VEGF injections have been implemented. Although higher recurrence is reported in some studies, there is controversy between studies about recurrence rate. Retinal tissue ablation, visual field reduction, and myopia occurrence are lower than laser photocoagulation.(5, 14, 34-36) In our study, the incidence of severe ROP was 3.58 %. 19 patients received IVB injections and retinal vascularization was completed in all of them. We followed up with the patients until 65 weeks gestation and none of them showed recurrence after ROP regression. 9 patients treated with IVB injection, needed laser retreatment, 6 of them had aggressive ROP and did not respond well to primary IVB treatment, and 3 patients had type 1 ROP which showed incomplete vascularization until 65 weeks follow-up visit. All patients who needed treatment in our study had GA≤34 weeks and BW≤2000 grams. One limitation of our study is the retrospective design, which decreased our control on evaluations. The strength of our study is the large number of patients evaluated in our center. Conclusion The incidence of ROP occurrence in our study was 20.2%. Lower GA, lower BW, history of blood transfusion, and phototherapy were associated with ROP development. The incidence of severe ROP occurrence was 3.58% and phototherapy decreased the need for treatment between ROP patients. Declarations Ethics: The Ethics Committee of Zahedan University of Medical Sciences approved the project and the ethical principles in the Declaration of Helsinki were followed. References Ludwig CA, Chen TA, Hernandez-Boussard T, Moshfeghi AA, Moshfeghi DM. The Epidemiology of Retinopathy of Prematurity in the United States. Ophthalmic Surg Lasers Imaging Retina. 2017;48(7):553-62. Gilbert C. Retinopathy of prematurity: a global perspective of the epidemics, population of babies at risk and implications for control. Early Hum Dev. 2008;84(2):77-82. Hartnett ME, Penn JS. Mechanisms and management of retinopathy of prematurity. N Engl J Med. 2012;367(26):2515-26. Beharry KD, Valencia GB, Lazzaro DR, Aranda JV. 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Dani C, Coviello C, Panin F, Frosini S, Costa S, Purcaro V, et al. Incidence and risk factors of retinopathy of prematurity in an Italian cohort of preterm infants. Ital J Pediatr. 2021;47(1):64. Zarei M, Bazvand F, Ebrahimiadib N, Roohipoor R, Karkhaneh R, Farahani Dastjani A, et al. Prevalence and Risk Factors of Retinopathy of Prematurity in Iran. J Ophthalmic Vis Res. 2019;14(3):291-8. Abrishami M, Maemori GA, Boskabadi H, Yaeghobi Z, Mafi-Nejad S, Abrishami M. Incidence and risk factors of retinopathy of prematurity in mashhad, northeast iran. Iran Red Crescent Med J. 2013;15(3):229-33. Alizadeh Y, Zarkesh M, Moghadam RS, Esfandiarpour B, Behboudi H, Karambin MM, et al. Incidence and Risk Factors for Retinopathy of Prematurity in North of Iran. J Ophthalmic Vis Res. 2015;10(4):424-8. Khorshidifar M, Nikkhah H, Ramezani A, Entezari M, Daftarian N, Norouzi H, et al. Incidence and risk factors of retinopathy of prematurity and utility of the national screening criteria in a tertiary center in Iran. Int J Ophthalmol. 2019;12(8):1330-6. Fortes Filho JB, Eckert GU, Valiatti FB, Dos Santos PG, da Costa MC, Procianoy RS. The influence of gestational age on the dynamic behavior of other risk factors associated with retinopathy of prematurity (ROP). Graefes Arch Clin Exp Ophthalmol. 2010;248(6):893-900. Prasad N, Dubey A, Kumar K, Shrivastava J. Role of fetal hemoglobin in the development and progression of retinopathy of prematurity in preterm infants. Indian J Ophthalmol. 2023;71(11):3478-83. Villeneuve A, Arsenault V, Lacroix J, Tucci M. Neonatal red blood cell transfusion. Vox Sang. 2021;116(4):366-78. Stutchfield CJ, 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 (Lond). 2017;31(10):1451-5. Boskabadi H, Shoeibi N, Bagheri F, Pourbadakhshan N, Moradi A, Zakerihamidi M. Potential Role of Bilirubin in Preventing Retinopathy of Prematurity. Curr Pediatr Rev. 2023;19(2):197-202. Tsiropoulos GN, Seliniotaki AK, Haidich AB, Ziakas N, Mataftsi A. Comparison of adverse events between intravitreal anti-VEGF and laser photocoagulation for treatment-requiring retinopathy of prematurity: a systematic review. Int Ophthalmol. 2023;43(3):1027-62. Li Z, Zhang Y, Liao Y, Zeng R, Zeng P, Lan Y. Comparison of efficacy between anti-vascular endothelial growth factor (VEGF) and laser treatment in Type-1 and threshold retinopathy of prematurity (ROP). BMC Ophthalmol. 2018;18(1):19. Tomioka M, Murakami T, Okamoto F, Kinoshita T, Shinomiya K, Nishi T, et al. Five-year visual outcome of treatment for retinopathy of prematurity in infants weighing less than 500 g at birth: A multicenter cohort study from J-CREST. Retina. 2023. Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3877019","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":267931888,"identity":"0e79e3d4-5e1f-4f5b-926f-f988075dba39","order_by":0,"name":"Alireza Maleki","email":"","orcid":"","institution":"Zahedan University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Alireza","middleName":"","lastName":"Maleki","suffix":""},{"id":267931889,"identity":"585bf50d-33d8-4714-8f74-8f62c5f75cfd","order_by":1,"name":"Meisam Sargazi","email":"","orcid":"","institution":"Zahedan University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Meisam","middleName":"","lastName":"Sargazi","suffix":""},{"id":267931890,"identity":"cd7863b2-b1e1-4757-b41b-8e2e1271e66a","order_by":2,"name":"Ali Yousefian","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDElEQVRIiWNgGAWjYBACNnbGBgiL+SCQwcMmB2IfeIBHCz8zTAtbIpAhw2cM1pKAR4tkM9w+kDIbuUSwCfi0GBxmbmDmqThsz8/G3Pi5IMcsfX7Y4YdAW+zkdBtwaWEEajlzOHFmG2Oz9Iwzabkbb6cZALUkG5sdwKOFt+1wgsH9xgZp3p5juRtnJ4C0HEjchkOLPVSLvf0xxubfvP/+pxvOTv+AVwvMFsYNbIxt0jw8bAny0jn4bQFpOTjnTHrijGOMbdZALYYbpHMKDiQY4PHL8faHD95UWNvzt7E/vg3UIi8/O33zhw8VdnK4tIDAIR4UQ8AqDXArBwHGH8g8+Qb8qkfBKBgFo2DkAQAuT2AUFBlTFAAAAABJRU5ErkJggg==","orcid":"","institution":"Zahedan University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Ali","middleName":"","lastName":"Yousefian","suffix":""},{"id":267931891,"identity":"d301bd8b-2b3c-4a3a-8c10-19c69123fb81","order_by":3,"name":"Saeedeh Sarhadi","email":"","orcid":"","institution":"Zahedan University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Saeedeh","middleName":"","lastName":"Sarhadi","suffix":""},{"id":267931892,"identity":"35d30b64-801b-4899-88b1-ef2159a3ebe4","order_by":4,"name":"Maryam Mollaei","email":"","orcid":"","institution":"Zahedan University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Maryam","middleName":"","lastName":"Mollaei","suffix":""},{"id":267931893,"identity":"34a65a74-c4bf-4498-94dc-be507ae19acb","order_by":5,"name":"Seyed Omid Mohammadi","email":"","orcid":"","institution":"Texas Christian University","correspondingAuthor":false,"prefix":"","firstName":"Seyed","middleName":"Omid","lastName":"Mohammadi","suffix":""}],"badges":[],"createdAt":"2024-01-18 22:40:02","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-3877019/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3877019/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":50011566,"identity":"83c59bfb-c7e1-418a-a2d7-beef2a763b93","added_by":"auto","created_at":"2024-01-23 05:21:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":731772,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3877019/v1/ec18028d-ab4f-4a32-b0fa-4a336bdfbcd7.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eIncidence and Risk Factors of Retinopathy of Prematurity in Southeast Iran: A Retrospective Cohort Study\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eRetinopathy of prematurity (ROP) is a significant cause of preventable premature infant vision loss. The incidence of disease is increasing in middle-income countries because of advances in prenatal and neonatal care.(1, 2)\u003c/p\u003e \u003cp\u003eWhen infants are born prematurely, the oxygen levels are increased when comparing extrauterine levels to in-utero. This relative increase leads to constriction of growing vessels. Subsequently, vascular obliteration ensues and retinal ischemia causes vessel endothelial growth factor upregulation. This leads to aberrant neovascularization and retinal detachment.(3\u0026ndash;6)\u003c/p\u003e \u003cp\u003eMany studies have reported different risk factors depending on the region. Low gestational age and low birth weight are the two major risk factors for ROP. Other risk factors associated with this condition include oxygen supplementation at birth, prolonged mechanical ventilation, multiple gestation, sepsis, anemia, history of blood transfusion, intraventricular hemorrhage, and bilirubin levels.(7\u0026ndash;12)\u003c/p\u003e \u003cp\u003eLaser photocoagulation is the main treatment for ROP due to its safety and predictable outcomes. Intravitreal anti-vascular endothelial growth factors (VEGF) injection is another treatment option for the disease and promising results have been reported.(5, 13, 14)\u003c/p\u003e \u003cp\u003eThere is no information available about the characteristics of ROP in Sistan and Baluchestan in the Southeast of Iran. In this study, we evaluated the incidence of ROP and its associated risk factors and provided a summary report of treatment results in a referral eye hospital.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis was a retrospective cohort study of 920 preterm infants referred to a referral eye hospital from March 2022 until March 2023.\u003c/p\u003e \u003cp\u003eAll infants with birth weight (BW)\u0026thinsp;\u0026le;\u0026thinsp;2000 grams or gestational age (GA)\u0026thinsp;\u0026le;\u0026thinsp;34 weeks and infants with 34\u0026thinsp;\u0026lt;\u0026thinsp;GA\u0026thinsp;\u0026lt;\u0026thinsp;37 weeks or GA\u0026thinsp;\u0026lt;\u0026thinsp;37 weeks and BW\u0026thinsp;\u0026gt;\u0026thinsp;2000 grams referred by their pediatricians were included in this study. Patients who did not complete follow-up examinations and had incomplete medical and informational records were excluded.\u003c/p\u003e \u003cp\u003eThe following data were collected and recorded: gender, BW, GA, number of pregnancies, oxygen therapy with continuous positive airway pressure (CPAP) or mechanical ventilation (number of days), history of blood transfusions, occurrence of intraventricular hemorrhage (IVH), occurrence of sepsis, phototherapy, mother\u0026rsquo;s age, type of delivery (cesarean section versus vaginal delivery), history of hypertension during pregnancy, history of pre-eclampsia, eclampsia and hemolysis elevated liver enzyme levels and low platelet levels (HELLP) syndrome.\u003c/p\u003e \u003cp\u003eThe first examination was done between 4 and 6 weeks of chronological age or within the 31 and 33 weeks postmenstrual age, whichever was later. Two experienced retina subspecialists examined infants after the instillation of tropicamide 0.5% for pupillary dilation. After topical anesthesia, fundoscopy was performed using an indirect ophthalmoscope and a\u0026thinsp;+\u0026thinsp;20 D or +\u0026thinsp;30 D lens, an infant eyelid speculum, and a pediatric scleral depressor. The zones and stages of ROP were recorded based on the International Classification of Retinopathy of Prematurity. (15, 16) The follow-up examination was done according to disease severity and continued until full vascularization of the retina.\u003c/p\u003e \u003cp\u003eTreatment was done for patients categorized as threshold, type 1 pre-threshold ROP, aggressive ROP, and patients with stage 4 or stage 5 ROP.(15, 17)\u003c/p\u003e \u003cp\u003eIn this study, ROP patients who needed treatment were considered as severe ROP.\u003c/p\u003e \u003cp\u003eWe treated ROP patients with threshold, pre-threshold type 1, and aggressive ROP with intravitreal injection of bevacizumab 0.625 mg/0.025 milliliter. These patients were then re-examined on days 3 and 7 after injection and if the ROP stage, zone, and plus disease were improving, then we followed them every 1\u0026ndash;2 weeks until the absence of neovascularization and improvement of plus disease. Then, we extended follow-up to every 3\u0026ndash;4 weeks until 65 weeks. At this point, if retinal vascularization reached a border of less than 0.5 disc diameter away from the ora serrata in all quadrants, patients were considered to have \u0026ldquo;full retinal vascularization\u0026rdquo;, and no more follow-ups were scheduled.\u003c/p\u003e \u003cp\u003eRetreatment with laser was done when there was sustained neovascularization and plus disease after initial IVB therapy, or when new extra-retinal neovascularization or development of plus disease occurred after the initial response to treatment as mentioned above. We treated patients when full retinal vascularization was not achieved at 65 weeks, with laser photocoagulation.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis:\u003c/h2\u003e \u003cp\u003eNormally distributed quantitative data were described as mean and standard deviation (SD). The median and interquartile range (IQR) values represented asymmetrically distributed variables. The Kolmogorov-Smirnov test investigated the state of the normal distribution of quantitative variables. ROP risk factors variables were compared using the Mann-Whitney U test, Chi-square, and Fisher exact tests. Additionally, a comparative analysis of risk factors was performed for the data gathered on retinopathy of prematurity patients. The Mann-Whitney U test, Chi-square, and Fisher exact tests were used for these comparisons. To show the strength of the relationship between the variables, the effect size was calculated. The effect size was expressed by z/\u0026radic;N for the Mann-Whitney U test. Effect size, r, was interpreted as r\u0026thinsp;\u0026le;\u0026thinsp;0.3 representing a small effect, 0.3\u0026thinsp;\u0026lt;\u0026thinsp;r\u0026thinsp;\u0026lt;\u0026thinsp;0.5, representing a medium effect, and 0.5\u0026thinsp;\u0026le;\u0026thinsp;r representing a large effect. Also, the odds ratio and confidence interval of 95% were used to express the intensity of the relationship regarding Chi-square and Fisher exact tests. An odds ratio greater than one meant increased odds of occurrence of ROP or treated ROP, and on the other hand, an odds ratio less than one was interpreted as lower odds of ROP or treated ROP compared to the non-occurrence of them. Finally, logistic regression analysis was used to determine the variables predicting the occurrence of retinopathy of prematurity and retinopathy of prematurity requiring treatment. Variables that were statistically significant in the univariate analysis were included in the regression analysis. In all comparison groups, the threshold of significance was 0.05. IBM SPSS Statistics for Windows version 27.0 (IBM Corp. 2013. Armonk, NY: IBM Corp) was employed to carry out the analysis.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 1143 newborn babies were referred to our hospital and screened for ROP. Of them, 920 infants met the inclusion criteria for the study. 172 infants did not complete follow-up visits and 51 infants had incomplete medical records. Of 920 infants who met the inclusion criteria 50.3% were male [n: 463].\u003c/p\u003e\n\u003cp\u003eThe mean GA was 32.71\u0026thinsp;\u0026plusmn;\u0026thinsp;2.11 weeks. Mean BW was 1809.45\u0026thinsp;\u0026plusmn;\u0026thinsp;762.41 grams.\u003c/p\u003e\n\u003cp\u003eOf all screened infants, 561 infants received oxygen by CPAP, 56 infants were under mechanical ventilation, 51 infants received red blood cell transfusion, five infants had a history of IVH, and 25 infants developed sepsis. 301 infants were the result of multiple births.\u003c/p\u003e\n\u003cp\u003eThe evaluation of risk factors and their relationship with ROP development is shown in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u0026nbsp;\u003c/p\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eComparison of risk factors of retinopathy of prematurity (ROP) between ROP and without ROP groups\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCategories\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;920\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eROP\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;186\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eWithout ROP\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;734\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep\u0026ndash;value\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eEffect size\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eGestational Age (week),\u003c/p\u003e\n \u003cp\u003eMean(SD)\u003c/p\u003e\n \u003cp\u003emedian(IQR)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e32.7(2.11)\u003c/p\u003e\n \u003cp\u003e33.0(2)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e30.4(2.1)\u003c/p\u003e\n \u003cp\u003e30.0(3)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e33.2(1.6)\u003c/p\u003e\n \u003cp\u003e33.0(2)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e0.48\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eBirth weight(gr),\u003c/p\u003e\n \u003cp\u003eMean(SD)\u003c/p\u003e\n \u003cp\u003emedian(IQR)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e1809(762.4)\u003c/p\u003e\n \u003cp\u003e1800(500)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e1447.8(354.8)\u003c/p\u003e\n \u003cp\u003e1425.0(525.0)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e1901.0(809.5)\u003c/p\u003e\n \u003cp\u003e1900.0(471.2)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e0.41\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender, Male, N%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e463(50.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e95(51.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e368(50.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.81\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.96(0.69\u0026ndash;1.32)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eMultiple births\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e301(32.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57(30.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e244(33.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.5 \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.88(0.62\u0026ndash;1.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eCPAP, N (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e561(61%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e156(83.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e405(55.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.22(2.78\u0026ndash;6.40)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eDays on CPAP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.18(1.8)\u003c/p\u003e\n \u003cp\u003e1.00(2.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.83(2.70)\u003c/p\u003e\n \u003cp\u003e1.00(1.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.02(1.44)\u003c/p\u003e\n \u003cp\u003e1.00(1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eMechanical ventilation, N (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56(6.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23(12.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33(4.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.99(1.71\u0026ndash;5.24)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eDays on mechanical ventilation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.10(0.54)\u003c/p\u003e\n \u003cp\u003e0.00(0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.14(0.67)\u003c/p\u003e\n \u003cp\u003e0.00(0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.09(0.5)\u003c/p\u003e\n \u003cp\u003e0.00(0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.053 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eBlood transfusion, N (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51(5.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36(19.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15(2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.5(6.14\u0026ndash;21.54)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eIntraventricular hemorrhage, N(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(0.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(1.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(0.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.059\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.0(0.99\u0026ndash;36.1)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eSepsis, N(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25(2.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14(7.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11(1.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.34(2.38\u0026ndash;11.9)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003ePhototherapy, N(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e684(74.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e155(83.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e529(72.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.002\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.93(1.27\u0026ndash;2.94)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of delivery, C/S, N(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e606(65.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e104(55.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e502(68.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.001\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.7(1.22\u0026ndash;2.37)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eIn vitro fertilization (IVF), N(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73(7.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14(7.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59(8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.81\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.93(0.50\u0026ndash;1.70)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003e\u003cstrong\u003eCause of premature\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eBirth, N(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOnset of labor pains\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003e334(36.3%)\u003c/p\u003e\n \u003cp\u003e373(40.5%)\u003c/p\u003e\n \u003cp\u003e140(15.2%)\u003c/p\u003e\n \u003cp\u003e73(7.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003e77(41.4%)\u003c/p\u003e\n \u003cp\u003e77(41.4%)\u003c/p\u003e\n \u003cp\u003e24(12.9%)\u003c/p\u003e\n \u003cp\u003e8(4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003e257(35%)\u003c/p\u003e\n \u003cp\u003e296(40.3%)\u003c/p\u003e\n \u003cp\u003e116(15.8%)\u003c/p\u003e\n \u003cp\u003e65(8.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003e0.09\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003e----\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eRupture of the amniotic sac\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eHypertension\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOther (preeclampsia, eclampsia, doctor\u0026rsquo;s diagnosis, HELLP syndrome)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge of mother(year)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003cp\u003eMedian (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.15(7.4)\u003c/p\u003e\n \u003cp\u003e29.0(11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.6(7.4)\u003c/p\u003e\n \u003cp\u003e25.0(11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.5(7.18)\u003c/p\u003e\n \u003cp\u003e29.0(11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.10\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003ea\u003c/sup\u003eMann Whitney U test, \u003csup\u003eb\u003c/sup\u003e effect size measure for Mann-Whitney U analysis with r\u0026thinsp;=\u0026thinsp;z/\u0026radic;N, \u003csup\u003ec\u003c/sup\u003e chi-square test, \u003csup\u003ed\u003c/sup\u003e odds ratio ( 95% confidence interval ), \u003csup\u003ee\u003c/sup\u003e Fisher\u0026rsquo;s exact test, Abbreviations: SD; standard deviation, IQR; interquartile range, CPAP; Continuous positive airway pressure, C/S; cesarean section.\u003c/p\u003e\n\u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eshows the relationship between risk factors and severe ROP occurrence.\u0026nbsp;\u003c/p\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eComparison of risk factors of retinopathy of prematurity (ROP) between ROP with and without treatment groups\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCategories\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;186\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTreatment\u003c/p\u003e\n \u003cp\u003eneeded\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;33\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eWithout treatment\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;153\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep\u0026ndash;value\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eEffect size\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eGestational Age (week),\u003c/p\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003cp\u003eMedian (IQR)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e30.45(2.15)\u003c/p\u003e\n \u003cp\u003e30.0(3)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e28.84(1.6)\u003c/p\u003e\n \u003cp\u003e29.0(3)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e30.8(2.09)\u003c/p\u003e\n \u003cp\u003e31.0(3)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e0.35\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eBirth weight (gr),\u003c/p\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003cp\u003eMedian (IQR)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e1447.8(354.8)\u003c/p\u003e\n \u003cp\u003e1425.0(525.0)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e1185.6(294.8)\u003c/p\u003e\n \u003cp\u003e1115.0(315.0)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e1504.4(341.7)\u003c/p\u003e\n \u003cp\u003e1500.0(512.5)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e0.35\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender, Male, N%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e95(51.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14(42.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e81(52.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.27\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.52(0.71\u0026ndash;3.26)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eMultiple births\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57(30.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14(42.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43(28.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.106 \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.88(0.86\u0026ndash;4.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eCPAP, N (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e156(83.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27(81.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e129(84.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.72\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.83(0.31\u0026ndash;2.24)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eDays on CPAP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.8(2.7)\u003c/p\u003e\n \u003cp\u003e1(1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.96(2.88)\u003c/p\u003e\n \u003cp\u003e1.00(1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.81(2.67)\u003c/p\u003e\n \u003cp\u003e1.00(2.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.45 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eMechanical ventilation, N (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23(12.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8(24.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15(9.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.02\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.94(1.12\u0026ndash;7.67)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eDays on mechanical ventilation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.14(0.67)\u003c/p\u003e\n \u003cp\u003e0.00(0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.12(0.33)\u003c/p\u003e\n \u003cp\u003e0.00(0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.15(0.73)\u003c/p\u003e\n \u003cp\u003e0.00(0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.55 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eBlood transfusion, N (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36(19.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14(42.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22(14.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.38(1.92\u0026ndash;10.1)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eIntraventricular hemorrhage, N(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(1.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(1.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.44\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.35(0.20\u0026ndash;26.8)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eSepsis, N(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14(7.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(12.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10(6.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.27\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.97(0.57\u0026ndash;6.72)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003ePhototherapy, N(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e155(83.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22(66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e133(86.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.005\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.30(0.12\u0026ndash;0.71)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of delivery, C/S, N(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e104(55.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21(63.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e83(54.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.32\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.67(0.31\u0026ndash;1.47)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eIn vitro fertilization (IVF), N(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14(7.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(12.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10(6.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.27\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.97(0.57\u0026ndash;6.72)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003e\u003cstrong\u003eCause of premature birth, N(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOnset of labor pains\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003e77(41.4%)\u003c/p\u003e\n \u003cp\u003e77(41.4%)\u003c/p\u003e\n \u003cp\u003e24(12.9%)\u003c/p\u003e\n \u003cp\u003e8(4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003e16(48.5%)\u003c/p\u003e\n \u003cp\u003e10(30.3%)\u003c/p\u003e\n \u003cp\u003e5(15.2%)\u003c/p\u003e\n \u003cp\u003e2(6.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003e61(39.9%)\u003c/p\u003e\n \u003cp\u003e67(43.8%)\u003c/p\u003e\n \u003cp\u003e19(12.4%)\u003c/p\u003e\n \u003cp\u003e6(3.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003e0.54\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003e----\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eRupture of the amniotic sac\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eHypertension\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOther (preeclampsia, eclampsia, doctor\u0026rsquo;s diagnosis, HELLP syndrome)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge of mother(year)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean(SD)\u003c/p\u003e\n \u003cp\u003eMedian(IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.6(7.48)\u003c/p\u003e\n \u003cp\u003e25.0(11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27.15(7.54)\u003c/p\u003e\n \u003cp\u003e25.0(11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.5(7.49)\u003c/p\u003e\n \u003cp\u003e24.0(12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.70\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.02\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ea\u003c/sup\u003eMann Whitney U test, \u003csup\u003eb\u0026nbsp;\u003c/sup\u003eeffect size measure for Mann-Whitney U analysis with r = z/\u0026radic;N, \u003csup\u003ec\u0026nbsp;\u003c/sup\u003echi-square test, \u003csup\u003ed\u0026nbsp;\u003c/sup\u003eodds ratio ( 95% confidence interval), \u003csup\u003ee\u003c/sup\u003e Fisher\u0026rsquo;s exact test, Abbreviations: SD; standard deviation, IQR; interquartile range,\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eCPAP; Continuous positive airway pressure,\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eC/S; cesarean section.\u003c/p\u003e\n\u003cp\u003eStatistically significant relation between the gestational age, birth weight, being under Continuous Positive Airway Pressure (CPAP), number of days patients were under CPAP, being under mechanical ventilation, history of blood transfusion, history of sepsis, phototherapy, type of delivery (cesarean section) and lower mothers\u0026rsquo; age and ROP occurrence were seen in univariate analysis. Table 1\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eresults of multivariate logistic regression analysis showed higher GA and BW as protective factors against ROP occurrence. History of blood transfusion and phototherapy increased ROP development. Additionally, phototherapy had a significant effect on preventing severe ROP occurrence as shown in the logistic regression analysis in Table 3\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3.\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eRisk factors for retinopathy of prematurity (ROP) and severe ROP: results of logistic regression analysis\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRisk factors for retinopathy of prematurity (ROP): results of logistic regression analysis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eWald\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSignificance\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;Odds Ratio\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;95%CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGestational Age\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e54.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e0.589\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e0.512-0.678\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBirth weight\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e18.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e0.998\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e0.998-0.999\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBlood transfusion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e15.476\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e6.357\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e2.53-15.97\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePhototherapy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e7.459\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e2.172\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e1.24-3.78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRisk factors for severe retinopathy of prematurity (ROP): results of logistic regression analysis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePhototherapy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e4.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e0.035\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e0.349\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e0.131-0.927\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations: CI: confidence interval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 186 infants had ROP and the incidence of ROP in our study was 20.2%.\u003c/p\u003e\n\u003cp\u003eThe incidence of ROP and severe ROP development in different GA and BW groups is shown in Table 4. Twenty patients out of 33 patients with severe ROP were in the \u0026le;30 weeks GA group. There were 15 ROP patients in \u0026le;1000-grams BW group and 7 of them had severe ROP, although most severe ROP patients had 1000\u0026lt;BW\u0026le;1500 grams.\u003c/p\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eIncidence of ROP and severe ROP in different GA and BW groups\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;920\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eROP\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;186\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eWithout ROP\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;734\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSevere ROP\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;33\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eROP without treatment\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;153\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGestational Age\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ecategory (week)\u003c/strong\u003e,\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eN(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34\u0026lt;\u003c/p\u003e\n \u003cp\u003e32\u0026lt;-\u0026le;34\u003c/p\u003e\n \u003cp\u003e30\u0026lt;-\u0026le;32\u003c/p\u003e\n \u003cp\u003e\u0026le;\u0026thinsp;30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e172(18.7%)\u003c/p\u003e\n \u003cp\u003e526(57.2%)\u003c/p\u003e\n \u003cp\u003e151(16.4%)\u003c/p\u003e\n \u003cp\u003e71(7.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(2.2%)\u003c/p\u003e\n \u003cp\u003e56(30.1%)\u003c/p\u003e\n \u003cp\u003e65(34.9%)\u003c/p\u003e\n \u003cp\u003e61(32.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e168(22.9%)\u003c/p\u003e\n \u003cp\u003e470(64%)\u003c/p\u003e\n \u003cp\u003e86(11.7%)\u003c/p\u003e\n \u003cp\u003e10(1.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0%)\u003c/p\u003e\n \u003cp\u003e2(6.1%)\u003c/p\u003e\n \u003cp\u003e11(33.3%)\u003c/p\u003e\n \u003cp\u003e20(60.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(2.6%)\u003c/p\u003e\n \u003cp\u003e54(35.3%)\u003c/p\u003e\n \u003cp\u003e54(35.3%)\u003c/p\u003e\n \u003cp\u003e41(26.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeight category\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(gr),N(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2000\u0026lt;\u003c/p\u003e\n \u003cp\u003e1500\u0026lt;-\u0026le;2000\u003c/p\u003e\n \u003cp\u003e1000\u0026lt;-\u0026le;1500\u003c/p\u003e\n \u003cp\u003e\u0026le;\u0026thinsp;1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e222(24.1%)\u003c/p\u003e\n \u003cp\u003e499(54.2%)\u003c/p\u003e\n \u003cp\u003e179(19.5%)\u003c/p\u003e\n \u003cp\u003e20(2.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(4.8%)\u003c/p\u003e\n \u003cp\u003e77(41.1%)\u003c/p\u003e\n \u003cp\u003e85(45.7%)\u003c/p\u003e\n \u003cp\u003e15(8.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e213(29%)\u003c/p\u003e\n \u003cp\u003e422(57.5%)\u003c/p\u003e\n \u003cp\u003e94(12.8%)\u003c/p\u003e\n \u003cp\u003e5(0.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0%)\u003c/p\u003e\n \u003cp\u003e6(18.2%)\u003c/p\u003e\n \u003cp\u003e20(60.6%)\u003c/p\u003e\n \u003cp\u003e7(21.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(5.9%)\u003c/p\u003e\n \u003cp\u003e71(46.4%)\u003c/p\u003e\n \u003cp\u003e65(42.5%)\u003c/p\u003e\n \u003cp\u003e8(5.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eOf the 33 patients treated in our center, 22 patients had type 1 ROP and 6 patients had aggressive ROP. 19 patients received intravitreal bevacizumab injection, 5 patients were treated with laser retinal photocoagulation because of incomplete retinal vascularization at 65 weeks follow up, and 9 patients were treated with both laser and IVB injection.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe incidence of ROP varies between different studies. Even in studies from various parts of Iran as shown in Table 5, screening programs, population heterogeneity, level of perinatal care and NICU care may influence the statistical differences.(18)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5. Incidence of ROP occurrence in different studies\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"636\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"16.037735849056602%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAuthor\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eYear of publication\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ecountry\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.20754716981132%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy design\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.79874213836478%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eInclusion criteria\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.018867924528301%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of patients\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.433962264150944%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eROP Incidence\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.50314465408805%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;Risk factors\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"16.037735849056602%\" valign=\"top\"\u003e\n \u003cp\u003eHu et al.(19)\u003c/p\u003e\n \u003cp\u003e2023\u003c/p\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.20754716981132%\" valign=\"top\"\u003e\n \u003cp\u003eretrospective case\u0026ndash;control study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.79874213836478%\" valign=\"top\"\u003e\n \u003cp\u003eBW\u0026lt;1500 grams\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.018867924528301%\" valign=\"top\"\u003e\n \u003cp\u003e611\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.433962264150944%\" valign=\"top\"\u003e\n \u003cp\u003e40.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.50314465408805%\" valign=\"top\"\u003e\n \u003cp\u003eLower GA, twin birth, moderate to severe bronchopulmonary disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"16.037735849056602%\" valign=\"top\"\u003e\n \u003cp\u003eBas et al.(20)\u003c/p\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003cp\u003eTurkey\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.20754716981132%\" valign=\"top\"\u003e\n \u003cp\u003eprospective cohort study\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.79874213836478%\" valign=\"top\"\u003e\n \u003cp\u003eBW \u0026le;1500 g or GA\u0026le;32 weeks and those with a BW\u0026gt;1500 g or GA\u0026gt;32 weeks with an unstable clinical course\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.018867924528301%\" valign=\"top\"\u003e\n \u003cp\u003e6115\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.433962264150944%\" valign=\"top\"\u003e\n \u003cp\u003e27.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.50314465408805%\" valign=\"top\"\u003e\n \u003cp\u003elower BW, smaller GA, total days on oxygen, late-onset sepsis, frequency of red blood cell transfusions and relative weight gain\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"16.037735849056602%\" valign=\"top\"\u003e\n \u003cp\u003eDeb et al.(21)\u003c/p\u003e\n \u003cp\u003e2023\u003c/p\u003e\n \u003cp\u003eIndia \u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.20754716981132%\" valign=\"top\"\u003e\n \u003cp\u003eprospective cohort study\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.79874213836478%\" valign=\"top\"\u003e\n \u003cp\u003eGA \u0026lt;35 weeks and BW \u0026lt;2500 grams\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.018867924528301%\" valign=\"top\"\u003e\n \u003cp\u003e574\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.433962264150944%\" valign=\"top\"\u003e\n \u003cp\u003e28.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.50314465408805%\" valign=\"top\"\u003e\n \u003cp\u003elower BW, acyanotic heart disease, sepsis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"16.037735849056602%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026Ccedil;\u0026ouml;mez et al.(22)\u003c/p\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003cp\u003eTurkey\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.20754716981132%\" valign=\"top\"\u003e\n \u003cp\u003eRetrospective\u003c/p\u003e\n \u003cp\u003eCohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.79874213836478%\" valign=\"top\"\u003e\n \u003cp\u003eGA \u0026gt;31 + 6 weeks to 36 + 6 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.018867924528301%\" valign=\"top\"\u003e\n \u003cp\u003e4156\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.433962264150944%\" valign=\"top\"\u003e\n \u003cp\u003e22%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.50314465408805%\" valign=\"top\"\u003e\n \u003cp\u003eduration of hospital stay, BW and GA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"16.037735849056602%\" valign=\"top\"\u003e\n \u003cp\u003eFreitas et al.(18)\u003c/p\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003cp\u003eBrazil\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\u003cbr\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.20754716981132%\" valign=\"top\"\u003e\n \u003cp\u003eretrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.79874213836478%\" valign=\"top\"\u003e\n \u003cp\u003eGA l\u0026lt; 32 weeks or BW \u0026lt;1500 g; or neonates born with 32-37 weeks\u0026apos; gestation or BW above 1500 g and any of the following associated: multiple gestation, respiratory distress syndrome, sepsis, blood transfusions or IVH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.018867924528301%\" valign=\"top\"\u003e\n \u003cp\u003e602\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.433962264150944%\" valign=\"top\"\u003e\n \u003cp\u003e33.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.50314465408805%\" valign=\"top\"\u003e\n \u003cp\u003eextremely low BW, pulmonary diseases, IVH, and low GA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"16.037735849056602%\" valign=\"top\"\u003e\n \u003cp\u003eAl qahtani et al.(23)\u003c/p\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003cp\u003eSaudi Arabia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.20754716981132%\" valign=\"top\"\u003e\n \u003cp\u003eretrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.79874213836478%\" valign=\"top\"\u003e\n \u003cp\u003eBW \u0026lt;1501 g or GA \u0026lt;32 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.018867924528301%\" valign=\"top\"\u003e\n \u003cp\u003e581\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.433962264150944%\" valign=\"top\"\u003e\n \u003cp\u003e38.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.50314465408805%\" valign=\"top\"\u003e\n \u003cp\u003eBW, GA,\u0026nbsp;Postnatal steroid, O2 THERAPY, IVH, RBC transfusion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"16.037735849056602%\" valign=\"top\"\u003e\n \u003cp\u003eDani et al.(24)\u003c/p\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003cp\u003eitalY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.20754716981132%\" valign=\"top\"\u003e\n \u003cp\u003ecohort\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.79874213836478%\" valign=\"top\"\u003e\n \u003cp\u003eGA between 23\u0026nbsp;and 30\u0026nbsp;weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.018867924528301%\" valign=\"top\"\u003e\n \u003cp\u003e178\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.433962264150944%\" valign=\"top\"\u003e\n \u003cp\u003e38%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.50314465408805%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;IVH, RBC transfusion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"16.037735849056602%\" valign=\"top\"\u003e\n \u003cp\u003eZarei et al.(25)\u003c/p\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003cp\u003eIran\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.20754716981132%\" valign=\"top\"\u003e\n \u003cp\u003eretrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.79874213836478%\" valign=\"top\"\u003e\n \u003cp\u003eGA\u0026nbsp;\u0026le;\u003c/p\u003e\n \u003cp\u003e37 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.018867924528301%\" valign=\"top\"\u003e\n \u003cp\u003e1,990\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.433962264150944%\" valign=\"top\"\u003e\n \u003cp\u003e27.28%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.50314465408805%\" valign=\"top\"\u003e\n \u003cp\u003eGA, BW, and history of transfusion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"16.037735849056602%\" valign=\"top\"\u003e\n \u003cp\u003eAbrishami et al.(26)\u003c/p\u003e\n \u003cp\u003e2013\u003c/p\u003e\n \u003cp\u003eIran\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.20754716981132%\" valign=\"top\"\u003e\n \u003cp\u003ecross-sectional study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.79874213836478%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;32 gestational weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.018867924528301%\" valign=\"top\"\u003e\n \u003cp\u003e122\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.433962264150944%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;26.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.50314465408805%\" valign=\"top\"\u003e\n \u003cp\u003eGA, sex, BW, Apgar score, duration of parenteral nutrition, oxygen therapy, phototherapy, maximum PaO2 and minimum SpO2 (univariate analysis)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"16.037735849056602%\" valign=\"top\"\u003e\n \u003cp\u003eAlizadeh et al.(27)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2015\u003c/p\u003e\n \u003cp\u003eIran\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.20754716981132%\" valign=\"top\"\u003e\n \u003cp\u003ecross-sectional study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.79874213836478%\" valign=\"top\"\u003e\n \u003cp\u003eBW \u0026le;2500 g and/or GA \u0026le;36 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.018867924528301%\" valign=\"top\"\u003e\n \u003cp\u003e310\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.433962264150944%\" valign=\"top\"\u003e\n \u003cp\u003e20.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.50314465408805%\" valign=\"top\"\u003e\n \u003cp\u003elow GA and low BW\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"16.037735849056602%\" valign=\"top\"\u003e\n \u003cp\u003eKhorshidifar et al.(28)\u003c/p\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003cp\u003eIran\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.20754716981132%\" valign=\"top\"\u003e\n \u003cp\u003ecross-sectional study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.79874213836478%\" valign=\"top\"\u003e\n \u003cp\u003eBW \u0026le;2000 grams or GA \u0026lt;34 weeks and all other infants at risk of ROP admitted to the NICU or referred to our ROP clinic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.018867924528301%\" valign=\"top\"\u003e\n \u003cp\u003e207\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.433962264150944%\" valign=\"top\"\u003e\n \u003cp\u003e33.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.50314465408805%\" valign=\"top\"\u003e\n \u003cp\u003eBW, GA and blood transfusion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eGA; gestational age, IVH; intraventricular hemorrhage, NICU; neonatal intensive care unit.\u003c/p\u003e\n\u003cp\u003eThe incidence of ROP in our study was 20.2% among infants with BW\u0026le;2000 g or GA\u0026le;34 weeks or preterm infants with GA above 34 weeks or with BW above 2000 grams with unstable clinical conditions referred by neonatologists.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e185 patients with ROP had BW\u0026le;2000-grams or GA\u0026le;34 weeks and only 1 patient did not fit in the previously mentioned inclusion criteria selected. This patient was directly referred for evaluation by a pediatrician.\u003c/p\u003e\n\u003cp\u003eBy implementing other criteria such as BW\u0026le;1500 gram or GA\u0026le;32 weeks, BW\u0026le;2000 gram or GA\u0026le;32 weeks, BW\u0026le;1500 gram or GA\u0026le;34 weeks, 27 ROP patients, 6 ROP patients, and 4 ROP patients would be missed, respectively.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe mean GA and BW of infants who developed ROP were 30.4\u0026plusmn;2.1 weeks and 1447.8\u0026plusmn;354.8 grams, respectively. For patients with severe ROP, the mean GA and BW were 28.84\u0026plusmn;1.6 weeks and 1185.6\u0026plusmn;294.8 grams, respectively.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe mean GA and BW for severe ROP in our study are within the range of GA 24-32 weeks and BW 700-1480 grams previously reported by Khorshidifar et al. in their study of ROP in Tehran, the capital of Iran.(28)\u003c/p\u003e\n\u003cp\u003eIdentifying risk factors for developing ROP helps set screening criteria, reduce unnecessary examinations, and may help prevent ROP occurrence or progression.\u003c/p\u003e\n\u003cp\u003eLower gestational age, lower birth weight,\u0026nbsp;multiple births, red blood cell transfusions, phototherapy, intraventricular hemorrhage, supplemental oxygen therapy, sepsis occurrence, and pulmonary diseases are among the risk factors mentioned in the studies, as shown in Table 5.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLike many other studies, lower BW and lower GA were correlated with ROP development.\u0026nbsp;(18, 20, 22, 23, 25-28)\u003c/p\u003e\n\u003cp\u003eLower GA and lower BW suggest infants are more immature and are risk factors for developing ROP due to general immaturity.(29)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBlood transfusion was a risk factor for ROP development in our study. A lower\u0026nbsp;concentration of HbF has been associated with ROP development.(30)\u0026nbsp;Blood transfusion replaces fetal hemoglobin (HbF) by adult hemoglobin (HbA) and may cause ROP development by increasing retinal\u0026nbsp;oxygen delivery.(31, 32)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePhototherapy increased the risk of ROP development in our study. Antioxidant effects of bilirubin can be protective against ROP.(33)\u0026nbsp;However, in ROP patients, it reduced the need for treatment and was the only factor that had a protective effect against severe ROP occurrence in our study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLaser photocoagulation of avascular retina is the most common treatment of ROP, but it reduces the patient\u0026rsquo;s visual field significantly. In recent years intravitreal anti-VEGF injections have been implemented. Although higher recurrence is reported in some studies, there is controversy between studies about recurrence rate. Retinal tissue ablation, visual field reduction, and myopia occurrence are lower than laser photocoagulation.(5, 14, 34-36)\u003c/p\u003e\n\u003cp\u003eIn our study, the incidence of severe ROP was 3.58 %. 19 patients received IVB injections and retinal vascularization was completed in all of them. We followed up with the patients until 65 weeks gestation and none of them showed recurrence after ROP regression.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e9 patients treated with IVB injection, needed laser retreatment, 6 of them had aggressive ROP and did not respond well to primary IVB treatment, and 3 patients had type 1 ROP which showed incomplete vascularization until 65 weeks follow-up visit.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll patients who needed treatment in our study had GA\u0026le;34 weeks and BW\u0026le;2000 grams. One limitation of our study is the retrospective design, which decreased our control on evaluations. The strength of our study is the large number of patients evaluated in our center.\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe incidence of ROP occurrence in our study was 20.2%. Lower GA, lower BW, history of blood transfusion, and phototherapy were associated with ROP development. The incidence of severe ROP occurrence was 3.58% and phototherapy decreased the need for treatment between ROP patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe Ethics Committee of Zahedan University of Medical Sciences approved the project and the ethical principles in the Declaration of Helsinki were followed.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLudwig CA, Chen TA, Hernandez-Boussard T, Moshfeghi AA, Moshfeghi DM. The Epidemiology of Retinopathy of Prematurity in the United States. Ophthalmic Surg Lasers Imaging Retina. 2017;48(7):553-62.\u003c/li\u003e\n\u003cli\u003eGilbert C. Retinopathy of prematurity: a global perspective of the epidemics, population of babies at risk and implications for control. Early Hum Dev. 2008;84(2):77-82.\u003c/li\u003e\n\u003cli\u003eHartnett ME, Penn JS. Mechanisms and management of retinopathy of prematurity. N Engl J Med. 2012;367(26):2515-26.\u003c/li\u003e\n\u003cli\u003eBeharry KD, Valencia GB, Lazzaro DR, Aranda JV. Pharmacologic interventions for the prevention and treatment of retinopathy of prematurity. Semin Perinatol. 2016;40(3):189-202.\u003c/li\u003e\n\u003cli\u003eHellstrom A, Hard AL. Screening and novel therapies for retinopathy of prematurity - A review. Early Hum Dev. 2019;138:104846.\u003c/li\u003e\n\u003cli\u003eSmith LE. Pathogenesis of retinopathy of prematurity. 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Chin Med J (Engl). 2015;128(7):914-8.\u003c/li\u003e\n\u003cli\u003eSood V, Chellani H, Arya S, Guliani BP. Changing spectrum of retinopathy of prematurity (ROP) and variations among siblings of multiple gestation. Indian J Pediatr. 2012;79(7):905-10.\u003c/li\u003e\n\u003cli\u003eLiegl R, Hellstrom A, Smith LE. Retinopathy of prematurity: the need for prevention. Eye Brain. 2016;8:91-102.\u003c/li\u003e\n\u003cli\u003eGood WV, Early Treatment for Retinopathy of Prematurity Cooperative G. The Early Treatment for Retinopathy Of Prematurity Study: structural findings at age 2 years. Br J Ophthalmol. 2006;90(11):1378-82.\u003c/li\u003e\n\u003cli\u003eFrosini S, Franco F, Vicini G, Nicolosi C, Varriale G, Dani C, et al. Efficacy and safety of intravitreal bevacizumab for the treatment of retinopathy of prematurity: a single-center retrospective review. J Matern Fetal Neonatal Med. 2022;35(17):3337-42.\u003c/li\u003e\n\u003cli\u003eChiang MF, Quinn GE, Fielder AR, Ostmo SR, Paul Chan RV, Berrocal A, et al. International Classification of Retinopathy of Prematurity, Third Edition. Ophthalmology. 2021;128(10):e51-e68.\u003c/li\u003e\n\u003cli\u003eInternational Committee for the Classification of Retinopathy of P. The International Classification of Retinopathy of Prematurity revisited. Arch Ophthalmol. 2005;123(7):991-9.\u003c/li\u003e\n\u003cli\u003eEarly Treatment For Retinopathy Of Prematurity Cooperative G. Revised indications for the treatment of retinopathy of prematurity: results of the early treatment for retinopathy of prematurity randomized trial. Arch Ophthalmol. 2003;121(12):1684-94.\u003c/li\u003e\n\u003cli\u003eFreitas AM, Morschbacher R, Thorell MR, Rhoden EL. Incidence and risk factors for retinopathy of prematurity: a retrospective cohort study. Int J Retina Vitreous. 2018;4:20.\u003c/li\u003e\n\u003cli\u003eHu X, Zhang J, Zhang M, Chen X, Han S, Zhu J. Incidence and Risk Factors for Retinopathy of Prematurity in a Tertiary Hospital in China. Clin Ophthalmol. 2023;17:3189-94.\u003c/li\u003e\n\u003cli\u003eBas AY, Demirel N, Koc E, Ulubas Isik D, Hirfanoglu IM, Tunc T, et al. Incidence, risk factors and severity of retinopathy of prematurity in Turkey (TR-ROP study): a prospective, multicentre study in 69 neonatal intensive care units. Br J Ophthalmol. 2018;102(12):1711-6.\u003c/li\u003e\n\u003cli\u003eDeb D, Annamalai R, Muthukumar M. Incidence, risk factors, progression, and involution in retinopathy of prematurity at a tertiary care center in South India. Oman J Ophthalmol. 2023;16(3):452-60.\u003c/li\u003e\n\u003cli\u003eComez A, Celemler P, Ozmen MC, Yurttutan S, Akkececi NS, Gungor K, et al. Retinopathy of prematurity incidence and treatment modalities in moderate and late preterm infants: a study from two tertiary centers. Can J Ophthalmol. 2022;57(3):195-200.\u003c/li\u003e\n\u003cli\u003eAl-Qahtani B, Al-Otaibi M, Alabdulajabbar K, Selayem NB, Alshehri W, Omair A, et al. Retinopathy of Prematurity Incidence and Risk Factors in a Tertiary Hospital in Riyadh, Saudi Arabia. Middle East Afr J Ophthalmol. 2019;26(4):235-9.\u003c/li\u003e\n\u003cli\u003eDani C, Coviello C, Panin F, Frosini S, Costa S, Purcaro V, et al. Incidence and risk factors of retinopathy of prematurity in an Italian cohort of preterm infants. Ital J Pediatr. 2021;47(1):64.\u003c/li\u003e\n\u003cli\u003eZarei M, Bazvand F, Ebrahimiadib N, Roohipoor R, Karkhaneh R, Farahani Dastjani A, et al. Prevalence and Risk Factors of Retinopathy of Prematurity in Iran. J Ophthalmic Vis Res. 2019;14(3):291-8.\u003c/li\u003e\n\u003cli\u003eAbrishami M, Maemori GA, Boskabadi H, Yaeghobi Z, Mafi-Nejad S, Abrishami M. Incidence and risk factors of retinopathy of prematurity in mashhad, northeast iran. Iran Red Crescent Med J. 2013;15(3):229-33.\u003c/li\u003e\n\u003cli\u003eAlizadeh Y, Zarkesh M, Moghadam RS, Esfandiarpour B, Behboudi H, Karambin MM, et al. Incidence and Risk Factors for Retinopathy of Prematurity in North of Iran. J Ophthalmic Vis Res. 2015;10(4):424-8.\u003c/li\u003e\n\u003cli\u003eKhorshidifar M, Nikkhah H, Ramezani A, Entezari M, Daftarian N, Norouzi H, et al. Incidence and risk factors of retinopathy of prematurity and utility of the national screening criteria in a tertiary center in Iran. Int J Ophthalmol. 2019;12(8):1330-6.\u003c/li\u003e\n\u003cli\u003eFortes Filho JB, Eckert GU, Valiatti FB, Dos Santos PG, da Costa MC, Procianoy RS. The influence of gestational age on the dynamic behavior of other risk factors associated with retinopathy of prematurity (ROP). Graefes Arch Clin Exp Ophthalmol. 2010;248(6):893-900.\u003c/li\u003e\n\u003cli\u003ePrasad N, Dubey A, Kumar K, Shrivastava J. Role of fetal hemoglobin in the development and progression of retinopathy of prematurity in preterm infants. Indian J Ophthalmol. 2023;71(11):3478-83.\u003c/li\u003e\n\u003cli\u003eVilleneuve A, Arsenault V, Lacroix J, Tucci M. Neonatal red blood cell transfusion. Vox Sang. 2021;116(4):366-78.\u003c/li\u003e\n\u003cli\u003eStutchfield CJ, 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 (Lond). 2017;31(10):1451-5.\u003c/li\u003e\n\u003cli\u003eBoskabadi H, Shoeibi N, Bagheri F, Pourbadakhshan N, Moradi A, Zakerihamidi M. Potential Role of Bilirubin in Preventing Retinopathy of Prematurity. Curr Pediatr Rev. 2023;19(2):197-202.\u003c/li\u003e\n\u003cli\u003eTsiropoulos GN, Seliniotaki AK, Haidich AB, Ziakas N, Mataftsi A. Comparison of adverse events between intravitreal anti-VEGF and laser photocoagulation for treatment-requiring retinopathy of prematurity: a systematic review. Int Ophthalmol. 2023;43(3):1027-62.\u003c/li\u003e\n\u003cli\u003eLi Z, Zhang Y, Liao Y, Zeng R, Zeng P, Lan Y. Comparison of efficacy between anti-vascular endothelial growth factor (VEGF) and laser treatment in Type-1 and threshold retinopathy of prematurity (ROP). BMC Ophthalmol. 2018;18(1):19.\u003c/li\u003e\n\u003cli\u003eTomioka M, Murakami T, Okamoto F, Kinoshita T, Shinomiya K, Nishi T, et al. Five-year visual outcome of treatment for retinopathy of prematurity in infants weighing less than 500 g at birth: A multicenter cohort study from J-CREST. Retina. 2023.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Retinopathy of Prematurity, Infant vision loss, phototherapy","lastPublishedDoi":"10.21203/rs.3.rs-3877019/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3877019/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground and objectives:\u003c/h2\u003e \u003cp\u003eRetinopathy of prematurity (ROP) is a significant cause of preventable premature infant vision loss. Many studies have reported different risk factors depending on the region. In this study, we evaluated the incidence of ROP and associated risk factors in a referral eye hospital in southeast Iran.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis was a retrospective cohort study of preterm infants with birth weight (BW)\u0026thinsp;\u0026le;\u0026thinsp;2000 grams or gestational age (GA)\u0026thinsp;\u0026le;\u0026thinsp;34weeks and infants with 34\u0026thinsp;\u0026lt;\u0026thinsp;GA\u0026thinsp;\u0026lt;\u0026thinsp;37weeks or GA\u0026thinsp;\u0026lt;\u0026thinsp;37weeks and BW\u0026thinsp;\u0026gt;\u0026thinsp;2000 grams referred by their pediatricians to our center from March 2022 until March 2023.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003e920 infants met the inclusion criteria for the study, the incidence of ROP and severe ROP was 20.2% and 3.58% respectively. Results of logistic regression analysis showed higher GA and BW as protective factors against ROP occurrence. History of blood transfusion and phototherapy increased ROP development.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eLower GA, lower BW, history of blood transfusion, and phototherapy were associated with ROP development. Phototherapy decreased the need for treatment among ROP patients.\u003c/p\u003e","manuscriptTitle":"Incidence and Risk Factors of Retinopathy of Prematurity in Southeast Iran: A Retrospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-23 05:13:08","doi":"10.21203/rs.3.rs-3877019/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"245a715f-45ed-460e-bdc2-fb329e56d40f","owner":[],"postedDate":"January 23rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":28233901,"name":"Ophthalmology"}],"tags":[],"updatedAt":"2024-01-23T05:13:08+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-23 05:13:08","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3877019","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3877019","identity":"rs-3877019","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}