Comparison of Vitamin D Levels in Premature Infants with and without Retinopathy of Prematurity.

BACKGROUND: Retinopathy of prematurity (RoP) is a cause of newborn blindness. Several predisposing factors have been reported to contribute to the disease process. The current study aimed to compare serum vitamin D levels in infants with and without RoP. METHODS: This case-control study was conducted on 154 very low birth weight (VLBW) infants admitted to Ghaem hospital, Mashhad, Iran, during 2016-2019. Retinal examination for RoP was done at the 32nd week of pregnancy and vitamin D level was determined using the infants' first-day serum samples. A researcher-made questionnaire including maternal, infant, laboratory, and retinal examination information was used as the data collection tool. RESULTS: Out of 154 infants in the study, 56 (36.4%) were normal while 98 (63.6%) had RoP. Based on the severity of retinopathy, 43 infants (43.9%) were at stage I, 48 (49%) at stage II, and 7 (7.1%) at stage III. Significant differences in neonatal (P<0.001) and maternal (P=0.015) vitamin D levels, first and fifth minute Apgar scores (P=0.034 and P=0.001, respectively), and weight (P=0.014) were found between the infants with and without RoP. CONCLUSION: The incidence of RoP was higher in infants with lower gestational age, lower birth weight, low first and fifth minutes Apgar scores, and male sex. Low serum levels of vitamin D in premature infants and their mothers were associated with incidence of RoP. The higher the stage of RoP, the greater was the severity of vitamin D deficiency. Thus, controlling the maternal vitamin D level during pregnancy, consumption of vitamin D supplements, and investigation of serum vitamin D levels in premature infants are recommended. Early correction of vitamin D deficiency may lead to reduction of RoP.

Intravitreal bevacizumab to treat retinopathy of prematurity in 865 eyes: a study to determine predictors of primary treatment failure and recurrence.

PURPOSE: This study aimed to evaluate the rate and risk factors for primary failure and recurrence after intravitreal anti-VEGF injection in retinopathy of prematurity (ROP). METHODS: This retrospective study was performed on 865 eyes from 441 patients with retinopathy of prematurity receiving intravitreal bevacizumab from 2012 to 2019. Medical records of patients were evaluated. RESULTS: Mean gestational age (GA) and birth weight of patients were 28 ± 2 weeks and 1121 ± 312 g, respectively. Thirty-five eyes (4.04%) had a primary failure, including 18 eyes from 187 eyes in zone 1 (9.6%) and 17 eyes from 678 eyes in zone 2 (2.5%). The mean time of retreatment was 16.64 ± 13.68 days in eyes without regression ROP. The remaining 830 eyes (95.95%) were included in recurrence analysis. The recurrence occurred in 33 eyes (3.97%) of them in 20 patients, with the meantime of 77.52 days after the first treatment (IVB). The presence of plus disease, history of oxygen therapy or phototherapy, and GA less than 32 were associated with significantly increased prevalence of treatment failure. The risk factors predicting recurrence are lower birth weight, zone 1 pretreatment, history of intubation, anemia, and sepsis. CONCLUSION: Intravitreal anti-VEGF is a successful treatment for ROP with a low rate of primary failure and recurrence. Awareness of risk factors for treatment failure and recurrence may help clinicians to schedule more vigilant approach in susceptible cases.

Oral Application of Colostrum and Mother's Own Milk in Preterm Infants-A Randomized, Controlled Trial.

OBJECTIVES: To evaluate the effects of oral application of mother's own milk (OMOM) on clinical outcomes in preterm infants of 260/7-306/7 wk gestation. METHODS: In this placebo-controlled randomized trial, subjects received either OMOM or sterile water, beginning at 24-72 h of life, until the infant reached 32 wk postmenstrual age or spoon-feeds were initiated, whichever was earlier. The primary outcome was a composite adverse health outcome, defined as the occurrence of either mortality, late-onset sepsis (LOS), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), or retinopathy of prematurity (ROP). Antibiotic usage and time to full enteral feed were secondary outcomes. Salivary IgA (sIgA) levels at baseline and after 7 d of application in a subset of infants were also compared. RESULTS: A total of 133 neonates (66 colostrum and 67 placebo) were analyzed for the primary outcome. OMOM group had lower incidence of composite adverse health outcome (43.9% vs. 61.2%, RR: 0.70; 95% CI: 0.50-0.99, p = 0.046) and LOS (22.7% vs. 43.3%, RR: 0.73; 95% CI: 0.57-0.93; p = 0.012). There were no significant differences in mortality, NEC, IVH, BPD, ROP, and time to full feeds. The effects were more pronounced in the 290/7-306/7 wk subgroup, in whom the colostrum group also achieved full feeds earlier. There were no differences in the change of sIgA levels from baseline to the seventh day of the application. No adverse effects related to the OMOM application were found. CONCLUSIONS: OMOM decreases the incidence of late-onset sepsis in preterm neonates (260/7-306/7 wk) and is safe. TRIAL REGISTRATION: Clinical Trials Registry-India CTRI/2017/03/008031.

Lutein supplementation and retinopathy of prematurity: a meta-analysis.

BACKGROUND: Retinopathy of prematurity (ROP) is a multifactorial retinal disorder characterized by an abnormal vascular development of the retina of the preterm infants. Carotenoids are natural pigments that are synthesized by all plants and some microorganisms where they play a role in photoprotection and coloration. Lutein and zeaxanthin (L/Z) are two carotenoids identified as the major components of the macular pigment. Recently it has been suggested that lutein and its isomer zeaxanthin may act as antioxidant agents and that they may prevent ROP. OBJECTIVE: The primary objective of this study is to assess the safety and effectiveness of oral lutein in the prevention of retinopathy of prematurity in preterm neonates. STUDY DESIGN: We conducted a systematic search for randomized or quasi-randomized controlled trials without any language or publication year restriction. The studies have to recruit preterm neonates ≤32 completed weeks of gestation and to compare the administration of oral L/Z at any dosage or duration, versus placebo in order to prevent ROP. RESULT: Data from three RCT with a total of 406 participants failed to show any reduction in ROP incidence nor the risk of BPD, sepsis, NEC and mortality. It may reduce the number of transfusions but this result has to be assessed in a separate ad hoc trial.

Association of Docosahexaenoic Acid and Arachidonic Acid Serum Levels With Retinopathy of Prematurity in Preterm Infants.

Importance: Supplementing preterm infants with long-chain polyunsaturated fatty acids (LC-PUFA) has been inconsistent in reducing the severity and incidence of retinopathy of prematurity (ROP). Furthermore, few studies have measured the long-term serum lipid levels after supplementation. Objective: To assess whether ROP severity is associated with serum levels of LC-PUFA, especially docosahexaenoic acid (DHA) and arachidonic acid (AA), during the first 28 postnatal days. Design, Setting, and Participants: This cohort study analyzed the Mega Donna Mega study, a randomized clinical trial that provided enteral fatty acid supplementation at 3 neonatal intensive care units in Sweden. Infants included in this cohort study were born at a gestational age of less than 28 weeks between December 20, 2016, and August 6, 2019. Main Outcomes and Measures: Severity of ROP was classified as no ROP, mild or moderate ROP (stage 1-2), or severe ROP (stage 3 and type 1). Serum phospholipid fatty acids were measured through gas chromatography-mass spectrometry. Ordinal logistic regression, with a description of unadjusted odds ratio (OR) as well as gestational age- and birth weight-adjusted ORs and 95% CIs, was used. Areas under the curve were used to calculate mean daily levels of fatty acids during postnatal days 1 to 28. Blood samples were obtained at the postnatal ages of 1, 3, 7, 14, and 28 days. Results: A total of 175 infants were included in analysis. Of these infants, 99 were boys (56.6%); the median (IQR) gestational age was 25 weeks 5 days (24 weeks 3 days to 26 weeks 6 days), and the median (IQR) birth weight was 785 (650-945) grams. A higher DHA proportion was seen in infants with no ROP compared with those with mild or moderate ROP or severe ROP (OR per 0.5-molar percentage increase, 0.49 [95% CI, 0.36-0.68]; gestational age- and birth weight-adjusted OR, 0.66 [95% CI, 0.46-0.93]). The corresponding adjusted OR for AA levels per 1-molar percentage increase was 0.83 (95% CI, 0.66-1.05). The association between DHA levels and ROP severity appeared only in infants with sufficient AA levels, suggesting that a mean daily minimum level of 7.8 to 8.3 molar percentage of AA was necessary for a detectable association between DHA level and less severe ROP. Conclusions and Relevance: This cohort study found that higher mean daily serum levels of DHA during the first 28 postnatal days were associated with less severe ROP even after adjustment for known risk factors, but only in infants with sufficiently high AA levels. Further studies are needed to identify LC-PUFA supplementation strategies that may prevent ROP and other morbidities.

Individualized versus standard diet fortification for growth and development in preterm infants receiving human milk.

BACKGROUND: Human milk as compared to formula reduces morbidity in preterm infants but requires fortification to meet their nutritional needs and to reduce the risk of extrauterine growth failure. Standard fortification methods are not individualized to the infant and assume that breast milk is uniform in nutritional content. Strategies for individualizing fortification are available; however it is not known whether these are safe, or if they improve outcomes in preterm infants. OBJECTIVES: To determine whether individualizing fortification of breast milk feeds in response to infant blood urea nitrogen (adjustable fortification) or to breast milk macronutrient content as measured with a milk analyzer (targeted fortification) reduces mortality and morbidity and promotes growth and development compared to standard, non-individualized fortification for preterm infants receiving human milk at < 37 weeks' gestation or at birth weight < 2500 grams. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 9), in the Cochrane Library; Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions(R); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), on September 20, 2019. We also searched clinical trials databases and the reference lists of retrieved articles for pertinent randomized controlled trials (RCTs) and quasi-randomized trials. SELECTION CRITERIA: We considered randomized, quasi-randomized, and cluster-randomized controlled trials of preterm infants fed exclusively breast milk that compared a standard non-individualized fortification strategy to individualized fortification using a targeted or adjustable strategy. We considered studies that examined any use of fortification in eligible infants for a minimum duration of two weeks, initiated at any time during enteral feeding, and providing any regimen of human milk feeding. DATA COLLECTION AND ANALYSIS: Data were collected using the standard methods of Cochrane Neonatal. Two review authors evaluated the quality of the studies and extracted data. We reported analyses of continuous data using mean differences (MDs), and dichotomous data using risk ratios (RRs). We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: Data were extracted from seven RCTs, resulting in eight publications (521 total participants were enrolled among these studies), with duration of study interventions ranging from two to seven weeks. As compared to standard non-individualized fortification, individualized (targeted or adjustable) fortification of enteral feeds probably increased weight gain during the intervention (typical mean difference [MD] 1.88 g/kg/d, 95% confidence interval [CI] 1.26 to 2.50; 6 studies, 345 participants), may have increased length gain during the intervention (typical MD 0.43 mm/d, 95% CI 0.32 to 0.53; 5 studies, 242 participants), and may have increased head circumference gain during the intervention (typical MD 0.14 mm/d, 95% CI 0.06 to 0.23; 5 studies, 242 participants). Compared to standard non-individualized fortification, targeted fortification probably increased weight gain during the intervention (typical MD 1.87 g/kg/d, 95% CI 1.15 to 2.58; 4 studies, 269 participants) and may have increased length gain during the intervention (typical MD 0.45 mm/d, 95% CI 0.32 to 0.57; 3 studies, 166 participants). Adjustable fortification probably increased weight gain during the intervention (typical MD 2.86 g/kg/d, 95% CI 1.69 to 4.03; 3 studies, 96 participants), probably increased gain in length during the intervention (typical MD 0.54 mm/d, 95% CI 0.38 to 0.7; 3 studies, 96 participants), and increased gain in head circumference during the intervention (typical MD 0.36 mm/d, 95% CI 0.21 to 0.5; 3 studies, 96 participants). We are uncertain whether there are differences between individualized versus standard fortification strategies in the incidence of in-hospital mortality, bronchopulmonary dysplasia, necrotizing enterocolitis, culture-proven late-onset bacterial sepsis, retinopathy of prematurity, osteopenia, length of hospital stay, or post-hospital discharge growth. No study reported severe neurodevelopmental disability as an outcome. One study that was published after our literature search was completed is awaiting classification. AUTHORS' CONCLUSIONS: We found moderate- to low-certainty evidence suggesting that individualized (either targeted or adjustable) fortification of enteral feeds in very low birth weight infants increases growth velocity of weight, length, and head circumference during the intervention compared with standard non-individualized fortification. Evidence showing important in-hospital and post-discharge clinical outcomes was sparse and of very low certainty, precluding inferences regarding safety or clinical benefits beyond short-term growth.

Oral vitamin A supplementation for ROP prevention in VLBW preterm infants.

Vitamin A administration may decrease any stage of retinopathy of prematurity (ROP) in preterm infants. To evaluate whether vitamin A oral supplementation could be preventive in ROP incidence and severity in VLBW infants, we compared results from 31 preterm infants, (< 1500 g or < 32 weeks) who, during a previous investigation, prospectively received 3000 UI/kg/die oral retinol palmitate drops, for 28 days, with 31 matching preterm newborns hospitalized in our NICU the same period, as control group. Although ROP incidence was similar, in the supplemented group, we had 9 cases of ROP grade 1, no ROP grade ≥ 2, in the un-supplemented group, 4 cases of ROP grade 1 and 6 ROP grade ≥ 2 (p = 0.018). The percentage of babies requiring treatment for ROP was 0 in treated and 16.6 in the un-treated group (p = 0.020). Moreover, Vitamin A administration showed a protective effect with an 88% risk reduction of developing severe ROP. Since vitamin A parenteral/IM administration presents some awareness, the results of this investigation may be important to plan further trials to confirm the usefulness of oral administration in mitigating the ROP severity of VLBW infants.ClinicalTrials.gov NCT02102711; may 03/06/2014.

Retinopathy of prematurity treatment in the UK: trends in neonatal anaesthetic support and location of treatment from a national surveillance study.

The aim of this study is to evaluate current anaesthetic practice for retinopathy of prematurity (ROP) interventions in the UK. We collected the data from the 12-month prospective British Ophthalmic Surveillance Unit study carried out in 2013/2014 that were analysed with regard to type of anaesthesia used for primary ROP procedures and the hospital department in which treatment took place. A total of 327 cases of treated ROP from 55 different UK units were reported in the study. Type of anaesthesia used during treatment was available for 324 (99.1%) cases and the treatment location in 316 (96.6%). Overall, 266 (89.3%) laser treatments and 13 (50.0%) of primary intravitreal injections were performed with the neonate intubated, using intravenous sedation (IVS) in 158 (59.4%) and the remainder, under general anaesthesia (GA). Two hundred thirteen (67.4%) of all ROP procedures took place in the neonatal unit. GA was used in 98 (95.1%) of theatre cases compared with 19 (8.9%) of cases treated in the neonatal unit. Three (0.9%) neonates suffered significant respiratory distress during or immediately after laser treatment.Conclusion: This survey suggests that the preference in UK units is to undertake ROP laser treatment in the neonatal unit with the neonate intubated and sedated intravenously. Those babies treated in the operating theatre are more likely to receive GA. In the surveyed year, half of the neonates receiving intravitreal injections as sole primary therapy was intubated; the reason for this could not be elucidated from the responses. Adverse respiratory reactions during or after laser treatment affected fewer than 1% of the neonates in this study. What is Known: • Prior to the introduction of intravitreal anti-VEGF, almost all ROP treatments in the UK were performed under general anaesthetic (GA). • The technique of intravitreal injection is described using topical anaesthesia and was thought to be changing anaesthesia preferences for ROP treatment. What is New: • Half of the neonates receiving primary anti-VEGF injection in the UK were treated under intravenous sedation or GA. • The increasing use of primary anti-VEGF treatment has not influenced trends in anaesthetic practice in the UK since the last review 10 years ago.

Retinopathy of prematurity: Overview and highlights of an initiative to integrate prevention, screening, and management into the public health system in India.

Purpose: In India, more than 800 special newborn care units (SNCUs) have been established since 2008 in government facilities. More preterm infants are now surviving and blindness from retinopathy of prematurity (ROP) is increasing. The aim of the Queen Elizabeth Diamond Jubilee Trust's initiative (2012-1019) was to improve the quality of neonatal care and integrate ROP services into the government health system using expertise in the government and nongovernment sector in four states in a sustainable and scalable manner. Methods: State Ministries of Health were engaged and collaboration was established between three government programs (Ministry of Health and Family Welfare, Rashtriya Bal Swasthya Karyakram, and blindness prevention) and relevant professionals. Extensive training took place and equipment was provided. Implementation was guided by a multidisciplinary National Task Force and was monitored by state coordination committees. The Task Force appointed technical expert groups to support implementation through advocacy, information, education and communication materials, operational guidelines, a competency-based training curriculum, and an online database and website. Results: Twenty-two ophthalmologists in government facilities were trained to screen for ROP and nine to treat ROP. Almost 13,500 preterm infants were screened in 17 SNCUs and 86% of the 456 infants with sight-threatening ROP were treated. An educational resource using latest pedagogy based on key domain areas for best practices for small and preterm neonates including ROP has been developed and pilot tested and is being evaluated and scaled up. Conclusion: All four states are scaling up services or have plans to scale up, and several other states have started the initiatives.

Effects of fish oil-containing lipid emulsions on retinopathy of prematurity in very low birth weight infants.

BACKGROUND: The aim of the study was to assess the impact of different types of parenteral emulsions on retinopathy of prematurity (ROP) in very low birth weight (VLBW, birth body weight < 1500 g) infants by comparing fish oil-containing and soy-based parenteral emulsions. METHODS: Data of preterm infants with body weights below 1500 gm at birth and receiving total parenteral nutrition (TPN) for a minimum of 7 days during the period between January 2009 and November 2017 were analyzed in this retrospective study. We compared clinical outcomes in two epochs using different lipid emulsions: epoch 1 (soybean-based lipid emulsions, January 2009-February 2014) versus epoch 2 (fish oil-containing lipid emulsions, January 2015-November 2017). The primary outcomes measured were the incidence of ROP and the number of ROP cases requiring bevacizumab therapy. RESULTS: A total of 396 infants were enrolled in this study (203 in epoch 1 and 193 in epoch 2). A lower incidence of any stage ROP (24.1 vs. 11.4%, p < 0.001) and lower requirement of bevacizumab therapy (12.8 vs. 5.2%, p = 0.001) were observed in epoch 2. Gestational age, glutamic-pyruvic transaminase, total bilirubin, and alkaline phosphatase levels, and type of lipid emulsion in TPN were associated with higher ROP incidence. Multivariate logistic regression analysis revealed that parenteral nutrition in the form of lipid emulsions containing fish oil was associated with a lower risk of development of ROP [Odds Ratio: 0.178, 95% confidence interval (CI): 0.095-0.330, p < 0.001]. CONCLUSIONS: Compared with soybean-based lipid solutions, the use of fish oil-containing lipid solutions may be associated with a lower incidence of ROP and decreased need for bevacizumab treatment in preterm infants.

Multi-component lipid emulsion vs soy-based lipid emulsion for very low birth weight preterm neonates: A pre-post comparative study.

OBJECTIVE: To examine the effectiveness of soybean oil-medium chain triglycerides-olive oil-fish oil lipid emulsion (SMOF-LE) on clinical outcomes of very-low-birth-weight neonates. STUDY DESIGN: We conducted a pre-post comparative study of very-low-birth-weight neonates, dividing them according to lipid emulsion received: Intralipid (soy-based; n = 680) or SMOF-LE (n = 617). Primary outcomes were mortality, chronic lung disease, severe retinopathy, infection, and necrotising enterocolitis. Secondary outcomes were cholestasis, osteopenia, time to full feeds, and time to regain birthweight. RESULTS: Baseline characteristics between groups were comparable. Primary outcomes did not differ significantly between groups, although any retinopathy was significantly lower in the SMOF-LE group. SMOF-LE group had lower odds of cholestasis, osteopenia, and lipid interruption, and reduced times to full feeds and to regain birthweight. CONCLUSIONS: Compared with Intralipid, SMOF-LE was not associated with differences in mortality and major morbidities but was associated with lower odds of any retinopathy, cholestasis, and osteopenia; and improved lipid tolerance.

Effects of two different lipid emulsions on antioxidant status, lipid peroxidation and parenteral nutrition- related cholestasis in premature babies, a randomized-controlled study.

BACKGROUND: Olive oil-soybean oil (OO/SO) based lipid emulsions (LE) lack ω-3 PUFAs eicosapentaenoic acid -EPA and docosahexaenoic acid- DHA, which have clinical benefits on inflammatory processes. Fish oil based LEs are good sources of DHA and EPA. Fish oil, MCT, Olive oil and Soya oil (FMOS) lipid is one of the fish oil containing LEs supplemented with high levels of α-tocopherol and lower levels of phytosterol compared to OO/SO lipid emulsions. We investigated the effects of OO/SO and FMOS lipid preparations on cholestasis, levels of antioxidant enzymes and lipid peroxidation. METHODS: Preterm neonates ≤32 gestational weeks age and/or ≤1500 g were randomly assigned to receive either FMOS or OO/SO in the first day of life. Catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx) and thiobarbituric acid reactive substances (TBARS) levels in the first day of life, 7th day of lipid use and 28th day of life were measured and cholestasis during parenteral nutrition was recorded. RESULTS: 34 and 33 patients were in FMOS and OO/SO lipid groups respectively. Although the TBARS levels were higher in the first day of life and 7th day of LEs in OO/SO lipid group (p=0.014 and p=0.022), on the 28th day of life TBARS level was similar and SOD level was higher (p=0.014) in OO/SO group. Cholestasis was significantly lower in FMOS lipid group (0% vs. 18.2%), (p=0.011) and neonates regained birth weight earlier (p=0.006). There was no significant difference in other morbidities. CONCLUSIONS: FMOS and OO/SO lipid emulsions have similar effects on lipid peroxidation on 28th day of life and on morbidities in short term period except for cholestasis.

Resultados del Programa Nacional de Prevención de la Ceguera en la Infancia por Retinopatía del Prematuro en Argentina (2004-2016) / Results of the National Program for the Prevention of Blindness in Childhood by Retinopathy of Prematurity in Argentina (2004-2016)

Introducción. El Grupo ROP Argentina,a cargo del "Programa Nacional para la Prevención de la Ceguera en la Infancia por Retinopatía del Prematuro" (ROP), se creó en 2003. Objetivos. Describir la implementación y resultados alcanzados por el programa en la efectividad, acceso y calidad en la atención de la ROP (2004-2016). Población y métodos. Estudio descriptivo, retrospectivo, de una cohorte dinámica, en instituciones adheridas al registro. Población elegible: la totalidad de recién nacidos prematuros con factores de riesgo para desarrollar ROP. Resultados. Los servicios incorporados aumentaron de 14 a 98; cubrieron 24 provincias. Los niños < 1500 g registrados en 2004fueron 956, y 2739 en 2016. El 22,7 % de estos presentó algún grado de ROP y el 7,8 % requirió tratamiento (ROP grave). La pesquisa superó el 90 % y aumentaron los tratamientos en el lugar de origen (57 %-92 %). La incidencia de casos inusuales sigue siendo elevada (17,3 % de los tratados) y aún se registran oportunidades perdidas. El uso de drogas antiangiogénicas se triplicó desde su inicio en 2011. Conclusiones. Se observan logros significativos en términos de representatividad, alcance y adherencia al programa, también en el acceso a la pesquisa y tratamiento en el lugar de origen; sin embargo, la incidencia de ROP es aún elevada. La subraya la necesidad de fortalecer aún más las acciones del programa en cuanto a servicios.

Introduction. The ROP Argentina Group was created in 2003 and is responsible for the National Program for the Prevention of Blindness in Childhood by Retinopathy of Prematurity (ROP) in Argentina. Objectives. To describe the program implementation and results achieved in relation to ROP care in terms of effectiveness, access, and quality (2004-2016). Population and methods. Descriptive, retrospective study with a dynamic cohort carried out in facilities that are part of the registry. Eligible population: All preterm newborn infants with risk factors for ROP. Results. Participating health care services increased from 14 to 98 and covered the 23 provinces and the Autonomous City of Buenos Aires. A total of 956 infants were born with < 1500 g in 2004 and 2739, in 2016. Of these, 22.7 % had some degree of ROP and 7.8 % required treatment (severe ROP). Vision screening exceeded 90 %, and treatments at the place of origin increased (57 %-92 %). The incidence of unusual cases is still high (17.3 % of treated cases), and missed opportunities are still recorded. The use of anti-angiogenic drugs trebled since 2011, when they started to be used. Conclusions. Significant achievements were observed in terms of program representativeness, scope, and adherence, and also in relation to screening access and treatment at the place of origin; however, the incidence of ROP is still high. The persistence of unusual cases and missed opportunities evidences deficiencies in the quality of health care and outpatient followup and underlines the need to strengthen the program actions in relation to services.

Results of the National Program for the Prevention of Blindness in Childhood by Retinopathy of Prematurity in Argentina (2004-2016). / Resultados del Programa Nacional de Prevención de la Ceguera en la Infancia por Retinopatía del Prematuro en Argentina (2004-2016).

INTRODUCTION: The ROP Argentina Group was created in 2003 and is responsible for the National Program for the Prevention of Blindness in Childhood by Retinopathy of Prematurity (ROP) in Argentina. OBJETIVES: To describe the program implementation and results achieved in relation to ROP care in terms of effectiveness, access, and quality (2004-2016). POPULATION AND METHODS: Descriptive, retrospective study with a dynamic cohort carried out in facilities that are part of the registry. Eligible population: All preterm newborn infants with risk factors for ROP. RESULTS: Participating health care services increased from 14 to 98 and covered the 23 provinces and the Autonomous City of Buenos Aires. A total of 956 infants were born with < 1500 g in 2004 and 2739, in 2016. Of these, 22.7 % had some degree of ROP and 7.8 % required treatment (severe ROP). Vision screening exceeded 90 %, and treatments at the place of origin increased (57 %-92 %). The incidence of unusual cases is still high (17.3 % of treated cases), and missed opportunities are still recorded. The use of anti-angiogenic drugs trebled since 2011, when they started to be used. CONCLUSIONS: Significant achievements were observed in terms of program representativeness, scope, and adherence, and also in relation to screening access and treatment at the place of origin; however, the incidence of ROP is still high. The persistence of unusual cases and missed opportunities evidences deficiencies in the quality of health care and outpatient followup and underlines the need to strengthen the program actions in relation to services.

Introducción. El Grupo ROP Argentina,a cargo del "Programa Nacional para la Prevención de la Ceguera en la Infancia por Retinopatía del Prematuro" (ROP), se creó en 2003. Objetivos. Describir la implementación y resultados alcanzados por el programa en la efectividad, acceso y calidad en la atención de la ROP (2004-2016). Población y métodos. Estudio descriptivo, retrospectivo, de una cohorte dinámica, en instituciones adheridas al registro. Población elegible: la totalidad de recién nacidos prematuros con factores de riesgo para desarrollar ROP. Resultados. Los servicios incorporados aumentaron de 14 a 98; cubrieron 24 provincias. Los niños < 1500 g registrados en 2004fueron 956, y 2739 en 2016. El 22,7 % de estos presentó algún grado de ROP y el 7,8 % requirió tratamiento (ROP grave). La pesquisa superó el 90 % y aumentaron los tratamientos en el lugar de origen (57 %-92 %). La incidencia de casos inusuales sigue siendo elevada (17,3 % de los tratados) y aún se registran oportunidades perdidas. El uso de drogas antiangiogénicas se triplicó desde su inicio en 2011. Conclusiones. Se observan logros significativos en términos de representatividad, alcance y adherencia al programa, también en el acceso a la pesquisa y tratamiento en el lugar de origen; sin embargo, la incidencia de ROP es aún elevada. La subraya la necesidad de fortalecer aún más las acciones del programa en cuanto a servicios.

Prevalence and risk factors of retinopathy of prematurity in Iran: a systematic review and meta-analysis.

BACKGROUND: Retinopathy of prematurity (ROP) refers to the developmental disorder of the retina in premature infants and is one of the most serious and most dangerous complications in premature infants. The prevalence of ROP in Iran is different in various parts of Iran and its prevalence is reported to be 1-70% in different regions. This study aims to determine the prevalence and risk factors of ROP in Iran. METHODS: This review article was conducted based on the preferred reporting items for systematic review and meta-analysis (PRISMA) protocols. To find literature about ROP in Iran, a comprehensive search was done using MeSH keywords in several online databases such as PubMed, Ovid, Science Direct, EMBASE, Web of Science, CINAHL, EBSCO, Magiran, Iranmedex, SID, Medlib, IranDoc, as well as the Google Scholar search engine until May 2017. Comprehensive Meta-analysis Software (CMA) Version 2 was used for data analysis. RESULTS: According to 42 studies including 18,000 premature infants, the prevalence of ROP was reported to be 23.5% (95% CI: 20.4-26.8) in Iran. The prevalence of ROP stages 1, 2, 3, 4 and 5 was 7.9% (95% CI: 5.3-11.5), 9.7% (95% CI: 6.1-15.3), 2.8% (95% CI: 1.6-4.9), 2.9% (95% CI: 1.9-4.5) and 3.6% (95% CI: 2.4-5.2), respectively. The prevalence of ROP in Iranian girls and boys premature infants was 18.3% (95% CI: 12.8-25.4) and 18.9% (95% CI: 11.9-28.5), respectively. The lowest prevalence of ROP was in the West of Iran (12.3% [95% CI: 7.6-19.1]), while the highest prevalence was associated with the Center of Iran (24.9% [95% CI: 21.8-28.4]). The prevalence of ROP is increasing according to the year of study, and this relationship is not significant (p = 0.181). The significant risk factors for ROP were small gestational age (p < 0.001), low birth weight (p < 0.001), septicemia (p = 0.021), respiratory distress syndrome (p = 0.036), intraventricular hemorrhage (p = 0.005), continuous positive pressure ventilation (p = 0.023), saturation above 50% (p = 0.023), apnea (p = 0.002), frequency and duration of blood transfusion, oxygen therapy and phototherapy (p < 0.05), whereas pre-eclampsia decreased the prevalence of ROP (p = 0.014). CONCLUSION: Considering the high prevalence of ROP in Iran, screening and close supervision by experienced ophthalmologists to diagnose and treat the common complications of pre-maturity and prevent visual impairment or blindness is necessary.

Effects of two different lipid emulsions on morbidities and oxidant stress statuses in preterm infants: an observational study.

OBJECTIVE: We examined the morbidities and oxidative stress statuses in preterms receiving either SMOFlipid or ClinOleic. STUDY DESIGN: This observational study was performed in Etlik Zubeyde Hanim Hospital, Turkey. Infants received SMOFlipid (5 months) or ClinOleic (7 months). Two hundred and twenty seven infants (SMOFlipid: 93, ClinOleic: 134) very low birth weighted infants were included. The oxidative stress status was evaluated in infants at low risk of oxidative stress by total antioxidant capacity (TAC) and total oxidant status (TOS) and oxidative stress index (OSI; TAC/TOS/100) at baseline, first week and third week. RESULTS: Parenteral nutrition was given for a median of 7 days in both groups. There were statistically insignificantly higher rates of retinopathy of prematurity (9.4 versus 11.7%) and chronic lung disease (4.7 versus 6.7%) in ClinOleic group compared with SMOFlipid group. The TAC, TOS and OSI decreased significantly in ClinOleic group after 1 week, and although the results were not statistically significant, the TAC increased while the TOS and OSI decreased in SMOFlipid group. In both groups, the TAC, TOS and OSI were lower than baseline after 3 weeks. CONCLUSION: SMOFlipid and ClinOleic result in similar oxidative stress statuses after they were stopped, and we detected no statistically significant differences in morbidity rates.

Probiotic supplementation in preterm infants does not affect the risk of retinopathy of prematurity: a meta-analysis of randomized controlled trials.

Retinopathy of prematurity (ROP) is a vascular disorder of the developing retina in preterm infants and is a leading cause of childhood blindness. Perinatal infection plays a pathogenic role in ROP. Probiotic supplementation reduces the risk of late onset sepsis (LOS) in preterm infants but it remains to be determined whether this reduction translates into a reduction of other complications. We conducted a systematic review and meta-analysis to evaluate the possible role of probiotics in altering the risk of ROP. Eleven randomized controlled trials (4250 infants; probiotics: 2121) were included in the meta-analysis that showed a significantly decreased rate of LOS with a risk ratio (RR) of 0.807 and a 95% confidence interval (CI) of 0.705 to 0.924 (P = 0.010; fixed effects model) but could not demonstrate a significant effect of probiotics on any stage ROP (RR 1.053, 95% CI 0.903 to 1.228, P = 0.508, 4 studies), or severe ROP (RR 0.841, 95% CI 0.666 to 1.063, P = 0.148, 9 studies). Meta-regression did not show any significant association between the RR for LOS and the RR for severe ROP. In conclusion, our results suggest that infection prevention by probiotics does not affect the risk of developing ROP in preterm infants.

Relationship between serum 25-hydroxy vitamin D levels and retinopathy of prematurity.

Aim To evaluate the relationship between serum 25-hydroxy vitamin D, 25 (OH) D, levels and retinopathy of prematurity. Methods and Results Serum 25 (OH) D levels were measured in 97 very low birth weight infants, prior to vitamin D supplementation. The development of retinopathy of prematurity and its treatment requirement were evaluated. At follow-up, retinopathy of prematurity developed in 71 (73.2%) infants. Serum 25 (OH) D levels were significantly lower in infants with retinopathy of prematurity than ones without retinopathy of prematurity ( P < 0.001). The infants who required treatment had lower 25 (OH) D levels compared with the infants who did not required treatment (7.1 ± 5.2 ng/ml vs. 11.9 ± 6.5 ng/ml; P = 0.003). Multivariate analysis showed that lower serum 25 (OH) D levels may be a risk factor for retinopathy of prematurity development [OR: 1.14, 95% CI (1.02-1.27), P = 0.02]. Conclusion Lower 25 (OH) D levels in the first days of life may be related to retinopathy of prematurity development and treatment requirement in premature infants.

Parenteral Fish-Oil Lipid Emulsions in the Prevention of Severe Retinopathy of Prematurity: A Systematic Review and Meta-Analysis.

Objective Omega-3 fatty acids are vital for brain and retinal maturation. It is not clear if early use of ω-3 fatty acids in the form of fish-oil lipid emulsions (FLEs) prevents retinopathy of prematurity (ROP) in preterm infants. The aim of this meta-analysis is to evaluate whether early administration of parenteral FLEs reduces ROP requiring laser therapy or severe ROP ≥stage 3 in preterm infants. Methods A literature search was performed to identify studies comparing parenteral FLEs with soybean-based lipid emulsions (SLEs) in preventing ROP. The main outcome was incidence of severe ROP or ROP requiring laser therapy. Results Studies met the inclusion criteria (four RCTs and two observational studies). The pooled relative risk of ROP requiring laser therapy or severe ROP ≥ stage 3 in FLEs group was 0.47 [95% CI: 0.24-0.90] and 0.40 [95% CI: 0.22-0.76] in RCTs and observational studies, respectively. FLEs also reduced cholestasis; however, other secondary outcomes of bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), sepsis, intraventricular hemorrhage (IVH), and mortality were similar. Conclusion The use of FLEs may reduce the incidence of severe ROP or need for laser therapy in preterm infants. A large multicenter RCT is required to confirm this.

Adequacy of published screening criteria for retinopathy of prematurity.

BACKGROUND: Criteria for screening preterm infants for retinopathy of prematurity vary around the world. We aimed to analyse the efficacy of alternative screening criteria. DESIGN: We collected retrospective data at a tertiary level neonatal nursery. PARTICIPANTS: Our participants were 1007 babies, born between 1997 and 2011, at <32 weeks gestational age or <1500 g birth weight (as recommended by the National Health and Medical Research Council in 1996), who had completed follow-up to full retinal vascularization, with defined presence or absence of retinopathy of prematurity. METHODS: We determined whether disease would be detected using an alternative Australian screening model (gestational age <30 weeks or birth weight <1250 g) or screening criteria utilized in developed countries with similar standards of neonatal care. MAIN OUTCOME MEASURES: Detection of retinopathy of prematurity is our main outcome. RESULTS: Using several of the alternative criteria, two neonates with clinically significant retinopathy of prematurity, one of whom required laser treatment to preserve sight, would not have been screened, and their disease may have gone undetected. Use of <30 weeks gestational age or <1500 g birth weight as the criteria would still have screened these infants but would have reduced the number of infants screened by 24.9%. CONCLUSIONS: Some commonly utilized international screening criteria for retinopathy of prematurity may risk clinically significant cases being missed and others may screen babies unnecessarily. Alternative criteria should be considered and '<30 weeks gestational age and/or <1500 g birth weight' appears a viable option.