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1.
Lakartidningen ; 1162019 Oct 08.
Artigo em Sueco | MEDLINE | ID: mdl-31593285

RESUMO

The recently documented high survival of extremely preterm infants in Sweden is related to a high degree of centralization of pre- and postnatal care and to recently issued national consensus guidelines providing recommendations for perinatal care at 22-24 gestational weeks. The prevalence of major neonatal morbidity remains high and exceeded 60 % in a recent study of extremely preterm infants born at < 27 gestational weeks delivered in Sweden in 2014-2016 and surviving to 1 year of age. Damage to immature organ systems inflicted during the neonatal period causes varying degrees of functional impairment with lasting effects in the growing child. There is an urgent need for evidence-based novel interventions aiming to prevent neonatal morbidity with a subsequent improvement of long-term outcome.


Assuntos
Lactente Extremamente Prematuro , Doenças do Prematuro , Nascimento Prematuro , Displasia Broncopulmonar/epidemiologia , Displasia Broncopulmonar/fisiopatologia , Displasia Broncopulmonar/prevenção & controle , Serviços Centralizados no Hospital , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/fisiopatologia , Hemorragia Cerebral/prevenção & controle , Ventrículos Cerebrais/irrigação sanguínea , Ventrículos Cerebrais/diagnóstico por imagem , Enterocolite Necrosante/epidemiologia , Enterocolite Necrosante/fisiopatologia , Enterocolite Necrosante/prevenção & controle , Feminino , Humanos , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido , Doenças do Prematuro/epidemiologia , Doenças do Prematuro/fisiopatologia , Doenças do Prematuro/prevenção & controle , Assistência Perinatal/organização & administração , Gravidez , Nascimento Prematuro/mortalidade , Retinopatia da Prematuridade/sangue , Retinopatia da Prematuridade/epidemiologia , Retinopatia da Prematuridade/fisiopatologia , Retinopatia da Prematuridade/prevenção & controle , Taxa de Sobrevida , Suécia/epidemiologia
2.
Turk J Pediatr ; 61(1): 13-19, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31559716

RESUMO

Akyüz-Ünsal AI, Key Ö, Güler D, Bekmez S, Sagus M, Akcan AB, Kurt-Omurlu I, Anik A, Oruç-Dündar S, Türkmen M. Retinopathy of prematurity risk factors: Does human milk prevent retinopathy of prematurity? Turk J Pediatr 2019; 61: 13-19. The aim of this study was to investigate the risk factors for Retinopathy of Prematurity (ROP) development and the potential effect of human breast milk among these factors. For this purpose, infants admitted to a tertiary referral clinic for ROP screening and treatment between April 2013 and May 2015, were included in this retrospective study. The demographic data, accompanying diseases, previous surgery, type of feeding and duration of human breast milk intake were recorded. According to the ROP screening examination results, infants were divided into two groups as those with ROP (infants at any stage of ROP) and those without ROP. Relationship between the risk factors and ROP were evaluated. The comparison of 221 infants without ROP and 99 infants with ROP; revealed that gestational age at birth, birth weight, mechanical ventilation support, bronchopulmonary and cardiac diseases, hydrocephaly, any previous surgery, infections, steroid treatment percentages were high and human breast milk intake percentage was low among infants with ROP. Mean breast feeding time for infants with ROP (3.81 ± 2.33 month) was shorter than the infants without ROP (5.51 ± 1.43 month) (p < 0.001). In logistic regression analysis, the duration of breast feeding was inversely related with ROP (OR 0.744; 95% CI 0.621-0.891; p < 0,001). These results suggest that gestational age at birth and accompanying diseases are the main risk factors for the development of ROP. As the duration of the breast feeding of the infants without ROP was longer than the infants with ROP; breast feeding may have a preventive effect on ROP development.


Assuntos
Aleitamento Materno , Retinopatia da Prematuridade/etiologia , Retinopatia da Prematuridade/prevenção & controle , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Leite Humano , Retinopatia da Prematuridade/diagnóstico , Estudos Retrospectivos , Fatores de Risco
3.
Cochrane Database Syst Rev ; 7: CD000366, 2019 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-31283839

RESUMO

BACKGROUND: Inositol is an essential nutrient required by human cells in culture for growth and survival. Inositol promotes maturation of several components of surfactant and may play a critical role in fetal and early neonatal life. A drop in inositol levels in infants with respiratory distress syndrome (RDS) can be a sign that their illness will be severe. OBJECTIVES: To assess the effectiveness and safety of supplementary inositol in preterm infants with or without respiratory distress syndrome (RDS) in reducing adverse neonatal outcomes including: death (neonatal and infant deaths), bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), intraventricular haemorrhage (IVH), periventricular leukomalacia (PVL), necrotizing enterocolitis (NEC) and sepsis. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 11), MEDLINE via PubMed (1966 to 5 November 2018), Embase (1980 to 5 November 2018), and CINAHL (1982 to 5 November 2018). We searched clinical trial databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCT) and quasi-randomised trials. SELECTION CRITERIA: We included all randomised controlled trials of inositol supplementation of preterm infants compared with a control group that received a placebo or no intervention. Outcomes included neonatal death, infant death, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), intraventricular haemorrhage (IVH), necrotizing enterocolitis (NEC) and sepsis. DATA COLLECTION AND ANALYSIS: The three review authors independently abstracted data on neonatal outcomes and resolved any disagreements through discussion and consensus. Outcomes were reported as typical risk ratio (RR), risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB) or number needed to treat for an additional harmful outcome (NNTH). We used the GRADE approach to assess the quality of evidence. MAIN RESULTS: Six published randomised controlled trials were identified, with a total of 1177 infants. Study quality varied for the comparison 'Inositol supplementation to preterm infants (repeat doses in any amount and any duration of treatment) versus control' and interim analyses had occurred in several trials for the outcomes of interest. In this comparison, neonatal death was found to be significantly reduced (typical RR 0.53, 95% CI 0.31 to 0.91; typical RD -0.09, 95% CI -0.16 to -0.01; NNTB 11, 95% CI 6 to 100; 3 trials, 355 neonates). Infant deaths were not reduced (typical RR 0.89, 95% CI 0.71 to 1.13; typical RD -0.02, 95% CI -0.07 to 0.02; 5 trials, 1115 infants) (low-quality evidence). ROP stage 2 or higher or stage 3 or higher was not significantly reduced (typical RR 0.89, 95% CI 0.75 to 1.06; typical RD -0.04, 95% CI -0.10 to 0.02; 3 trials, 810 infants) (moderate-quality evidence). There were no significant findings for ROP (any stage), NEC (suspected or proven), sepsis, IVH grade greater than II (moderate-quality evidence). For the comparison 'Inositol supplementation IV initially followed by enteral administration (repeat doses of 80 mg/kg/day) in preterm infants born at less than 30 weeks' postmenstrual age (PMA) compared to placebo for preterm infants at risk for or having respiratory distress syndrome' the results from two studies of high quality were included (N = 760 neonates). Recruitment to the larger study (N = 638) was terminated because of a higher rate of deaths in the inositol group. We did not downgrade the quality of the study. The meta-analyses of the outcomes of 'Type 1 ROP or death before determination of ROP outcome using the adjudicated ROP outcome', 'Type 1 ROP including adjudicated ROP outcome', 'All-cause mortality (outcome collected through first event: death, hospital discharge, hospital transfer, or 120 days after birth)' and 'Severe IVH (grade 3 or 4)' did not show significant findings (moderate-quality evidence). There were no significant findings for the outcomes 'BPD or death by it prior to 37 weeks' postmenstrual age (outcomes collected through first event: death, hospital discharge, hospital transfer, or 120 days after birth)', 'Late onset sepsis (> 72 hours of age)', and 'Suspected or proven NEC' (high-quality evidence). AUTHORS' CONCLUSIONS: Based on the evidence from randomised controlled trials to date, inositol supplementation does not result in important reductions in the rates of infant deaths, ROP stage 3 or higher, type 1 ROP, IVH grades 3 or 4, BPD, NEC, or sepsis. These conclusions are based mainly on two recent randomised controlled trials in neonates less than 30 weeks' postmenstrual age (N = 760), the most vulnerable population. Currently inositol supplementation should not be routinely instituted as part of the nutritional management of preterm infants with or without RDS. It is important that infants who have been enrolled in the trials included in this review are followed to assess any effects of inositol supplementation on long-term outcomes in childhood. We do not recommend any additional trials in neonates.


Assuntos
Inositol/uso terapêutico , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológico , Complexo Vitamínico B/uso terapêutico , Displasia Broncopulmonar/prevenção & controle , Suplementos Nutricionais , Enterocolite Necrosante/prevenção & controle , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Ensaios Clínicos Controlados Aleatórios como Assunto , Síndrome do Desconforto Respiratório do Recém-Nascido/mortalidade , Retinopatia da Prematuridade/prevenção & controle , Sepse/prevenção & controle
4.
BMC Ophthalmol ; 19(1): 135, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31238915

RESUMO

BACKGROUND: Inositol supplementation has been linked to beneficial effects on reducing the incidence of retinopathy of prematurity (ROP); however, it's controversial. The meta-analysis aimed to check out the efficacy and safety of inositol supplementation in preterm infants for preventing ROP. METHODS: We conducted searches through PubMed, EMBASE, Medline, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, ClinicalTrials.gov website and conference proceedings. Randomized controlled trials comparing inositol supplementation with placebo were included. Two independent reviewers performed screening, review, and extraction. Statistical analysis was performed using R Project. RESULTS: Six studies (1194 infants) were proved eligible. In comparison with placebo, inositol supplementation revealed no effect on the incidence of severe ROP (relative risk [RR] = 0.49, 95% confidence interval [CI], 0.18-1.32; heterogeneity, P = .02; I2 = 66%; low quality of evidence [QOE]), mortality (RR = 1.25, 95% CI, 0.82-1.90; heterogeneity, P = .07; I2 = 51%; low QOE), all stages of ROP (RR = 0.98, 95% CI, 0.87-1.11; heterogeneity, P = .41; I2 = 0%; moderate QOE) and other adverse events. Sensitivity analysis showed an increased mortality in the inositol group (RR = 1.55, 95% CI, 1.14-2.11; heterogeneity, P = .30; I2 = 18%) after removing the study Hallman 1986, and meta-regression showed a significant association between publication year and efficacy of inositol compared with placebo (ß = 0.1241; 95% CI, 0.0417-0.0026; z = 2.9527; p = .0032). CONCLUSIONS: Based on current evidence, inositol supplementation showed no significant effect on preventing severe ROP, and exploratory sensitivity analysis showed a trend toward an increase on mortality.


Assuntos
Suplementos Nutricionais , Inositol/uso terapêutico , Retinopatia da Prematuridade/prevenção & controle , Complexo Vitamínico B/uso terapêutico , Humanos , Recém-Nascido
5.
Cochrane Database Syst Rev ; 6: CD013163, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31158919

RESUMO

BACKGROUND: Conventionally used soybean oil-based lipid emulsion (S-LE) have high polyunsaturated fatty acid (PUFA) content and phytosterols that may contribute to adverse effects in preterm infants. The newer lipid emulsions (LE) from different lipid sources are currently available for use in preterm infants. OBJECTIVES: To compare the safety and efficacy of all LE for parenteral nutrition (PN) in preterm infants (less than 37 weeks' gestation) including preterm infants with surgical conditions or parenteral nutrition-associated liver disease (PNALD)/cholestasis using direct comparisons and pair-wise meta-analyses. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 5), MEDLINE (1946 to 18 June 2018), Embase (1974 to 18 July 2018), CINAHL (1982 to 18 June 2018), MIDRIS (1971 to 31 May 2018), conference proceedings, trial registries (ClinicalTrials.gov and WHO's Trials Registry and Platform), and reference lists of retrieved articles. SELECTION CRITERIA: Randomised or quasi-randomised controlled studies in preterm infants with or without surgical conditions or PNALD within the first six months of life. DATA COLLECTION AND ANALYSIS: Data collection and analysis conformed to the methods of Cochrane Neonatal. We used the GRADE approach to assess the quality of evidence for important outcomes in addition to reporting statistical significance of results. MAIN RESULTS: We included 29 studies (n = 2037) in this review. LE were classified in three broad groups: 1. all fish oil-containing LE including pure fish oil-LE (F-LE) and multisource LE (e.g. medium-chain triglycerides (MCT)-olive-fish-soybean oil-LE (MOFS-LE), MCT-fish-soybean oil-LE (MFS-LE) and olive-fish-soybean oil-LE (OFS-LE); 2. conventional S-LE; 3. alternative-LE (e.g. MCT-soybean oil-LE (MS-LE), olive-soybean oil-LE and borage oil-based LE).We considered the following broad comparisons: fish oil LE versus non-fish oil LE; fish oil LE versus another fish oil LE; alternative-LE versus S-LE; alternative-LE versus another alternative-LE in preterm infants less than 37 weeks' gestation, preterm infants with surgical conditions and preterm infants with PNALD/cholestasis. Separate subgroup comparisons of each LE preparation were included within these broader groups.Most studies in preterm infants used PN for mean duration of four weeks or less and for longer duration in infants with cholestasis or surgical conditions.We defined the primary outcome of PNALD/cholestasis as conjugated bilirubin (Cbil) 2 mg/dL or greater and resolution of PNALD/cholestasis as Cbil less than 2 mg/dL. There was heterogeneity in definitions used by the included studies with Cbil cut-offs ranging from 17.1 µmol/L (1 mg/dL) up to 50 µmol/L (about 3 mg/dL).In preterm infants, meta-analysis found no evidence of a difference in the incidence of PNALD/cholestasis (Cbil cut-off: 2 mg/dl) between fish oil-LEs and all non-fish oil LEs (typical risk ratio (RR) 0.61, 95% confidence interval (CI) 0.24 to 1.56; typical risk difference (RD) -0.03, 95% CI -0.08 to 0.02; 4 studies; n = 328; low-quality evidence).We also considered an outcome allowing for any definition of PNALD (different Cbil cutoffs). In the meta-analysis for PNALD/cholestasis, using any definition and restricted to low or unclear risk of bias studies, there was no evidence of a difference between fish oil LE and all non-fish oil LE for incidence of cholestasis (typical RR 0.80, 95% CI 0.53 to 1.21; typical RD -0.02, 95% CI -0.05 to 0.02; 10 studies; n = 1024; low-quality evidence). There was no evidence of difference in subgroup meta-analyses of individual LE types in any comparison.In preterm infants with surgical conditions or cholestasis, there was only one small study each reporting no evidence of a difference in incidence or resolution of cholestasis respectively with use of a pure F-LE versus S-LE (using a Cbil cut-off of 2 mg/dL).In preterm infants with PNALD/cholestasis (using any definition), the meta-analysis showed significantly less cholestasis with the use of fish oil-LE compared to S-LE (typical RR 0.54, 95% CI 0.32 to 0.91; typical RD -0.39, 95% CI -0.65 to -0.12; number needed to treat for an additional beneficial outcome (NNTB) 3, 95% CI 2 to 9; 2 studies; n = 40; very low-quality evidence). However, this outcome had a very low number of participants from two small studies with methodological differences, one of which was terminated early, increasing the uncertainty about effect estimates.There were no differences between LE types in pair-wise meta-analyses for growth in preterm infants. There was paucity of studies in preterm infants with surgical conditions or cholestasis to perform meta-analyses for growth and most other outcomes.In the secondary outcomes for preterm infants, there was no difference between fish-oil LE and non-fish oil LE in meta-analysis for severe retinopathy of prematurity (ROP) (stage 3 or greater, or requiring surgery: typical RR 0.80, 95% CI 0.55 to 1.16; typical RD -0.03, 95% CI -0.07 to 0.02; 7 studies; n = 731; very low-quality evidence). There were no differences in the LE types in pair-wise meta-analyses for death, bronchopulmonary dysplasia (BPD), ventilation duration, patent ductus arteriosus, sepsis, necrotising enterocolitis, intraventricular haemorrhage, periventricular leukomalacia, jaundice, hyperglycaemia, hypertriglyceridaemia, intrahepatocellular lipid content and conjugated bilirubin levels in any comparison.In surgical infants, one study (n = 19) reported no differences in death, sepsis rates, Cbil and neurodevelopmental outcomes with pure F-LE versus S-LE.In infants with cholestasis, there were no evidence of differences in death or sepsis in meta-analyses between fish oil-LE and S-LE; (2 studies; n = 40; very low-quality evidence). AUTHORS' CONCLUSIONS: In the current review, we did not find any particular LE with or without fish oil to be better than another LE in preterm infants for prevention of PNALD/cholestasis, growth, mortality, ROP, BPD and other neonatal outcomes.In preterm infants with surgical conditions or cholestasis, there is currently insufficient evidence from randomised studies to determine with any certainty if fish oil LEs offer advantage in prevention or resolution of cholestasis or in any other clinical outcome.Further research, with larger well-designed trials, is warranted to evaluate the ideal composition of LE in preterm infants and the role of fish oil-containing and other LEs in the prevention and resolution of PNALD, ROP and other clinical outcomes.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Colestase/prevenção & controle , Óleos de Peixe/administração & dosagem , Recém-Nascido Prematuro , Nutrição Parenteral , Óleos Vegetais/administração & dosagem , Óleo de Soja/administração & dosagem , Ácido gama-Linolênico/administração & dosagem , Bilirrubina/sangue , Displasia Broncopulmonar/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Colestase/induzido quimicamente , Emulsões/administração & dosagem , Emulsões/química , Humanos , Recém-Nascido , Recém-Nascido Prematuro/crescimento & desenvolvimento , Nutrição Parenteral/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Retinopatia da Prematuridade/prevenção & controle , Óleo de Soja/efeitos adversos , Procedimentos Cirúrgicos Operatórios
6.
Med Sci Monit ; 25: 492-499, 2019 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-30652694

RESUMO

BACKGROUND Retinopathy of prematurity (ROP), or retrolental fibroplasia, affects premature infants who have undergone intensive care with oxygen therapy. This study aimed to investigate the inhibitory effect of the gamma-secretase inhibitor, DAPT, on neovascularization and its mechanism in a rat model of ROP. MATERIAL AND METHODS Sixty neonatal Sprague-Dawley (SD) rats included the control group (n=20), the model group (n=20), and the DAPT-treated group (n=20). The rat model of ROP was established using repeat cycles of oxygen inhalation. Enzyme-linked immunosorbent assay (ELISA) measured serum levels of vascular endothelial growth factor (VEGF), VEGF receptor-1 (VEGFR-1), and VEGFR-2. Histology of the retinal tissue included immunohistochemistry for the expression of Notch homolog-1 (Notch-1) and delta-like ligand 4 (DLL4). Retinal mRNA levels of DLL4, Notch-1, VEGF, VEGFR-1, and VEGFR-2 were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS The rat model of ROP showed increased serum levels of VEGF, VEGFR-1, and VEGFR-2 compared with the control group, which were decreased in the DAPT group. Histology of the retinal tissue in the model group showed degeneration of the retinal ganglion cells, and immunohistochemistry showed increased expression of Notch-1 and DLL4 compared with the control group and DAPT group. Retinal tissue in the model group had increased mRNA levels of DLL4, Notch-1, VEGF, VEGFR-1, and VEGFR-2 compared with the control group, and the DAPT group. CONCLUSIONS In a rat model, treatment with DAPT reduced the retinal changes associated with ROP with a mechanism that involved VEGF and its receptors through the DLL4/Notch-1 pathway.


Assuntos
Dipeptídeos/farmacologia , Retinopatia da Prematuridade/prevenção & controle , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Neovascularização Patológica/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor Notch1/metabolismo , Retinopatia da Prematuridade/sangue , Retinopatia da Prematuridade/enzimologia , Retinopatia da Prematuridade/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/sangue
7.
Thromb Haemost ; 119(3): 439-448, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30620991

RESUMO

The replication stress inflicted on retinal endothelial cells (ECs) in the context of hypoxia-induced pathological neovascularization during proliferative retinopathy is linked with activation of the deoxyribonucleic acid (DNA) repair response. Here, we studied the effect of deficiency of the DNA damage response adaptor 53BP1, which is an antagonist of homologous recombination (HR), in the context of proliferative retinopathy. In the model of retinopathy of prematurity (ROP), 53BP1-deficient mice displayed increased hypoxia-driven pathological neovascularization and tuft formation, accompanied by increased EC proliferation and reduced EC apoptosis, as compared with 53BP1-sufficient mice. In contrast, physiological retina angiogenesis was not affected by 53BP1 deficiency. Knockdown of 53BP1 in ECs in vitro also resulted in enhanced proliferation and reduced apoptosis of the cells under hypoxic conditions. Additionally, upon 53BP1 knockdown, ECs displayed increased HR rate in hypoxia. Consistently, treatment with an HR inhibitor reversed the hyper-proliferative angiogenic phenotype associated with 53BP1 deficiency in ROP. Thus, by unleashing HR, 53BP1 deletion increases pathological EC proliferation and neovascularization in the context of ROP. Our data shed light to a previously unknown interaction between the DNA repair response and pathological neovascularization in the retina.


Assuntos
Proliferação de Células , Células Endoteliais/metabolismo , Recombinação Homóloga , Neovascularização Retiniana/metabolismo , Vasos Retinianos/metabolismo , Retinopatia da Prematuridade/metabolismo , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/deficiência , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/metabolismo , Animais , Apoptose , Hipóxia Celular , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Predisposição Genética para Doença , Recombinação Homóloga/efeitos dos fármacos , Humanos , Camundongos Knockout , Morfolinas/farmacologia , Fenótipo , Pirróis/farmacologia , Neovascularização Retiniana/genética , Neovascularização Retiniana/patologia , Neovascularização Retiniana/prevenção & controle , Vasos Retinianos/efeitos dos fármacos , Vasos Retinianos/patologia , Retinopatia da Prematuridade/genética , Retinopatia da Prematuridade/patologia , Retinopatia da Prematuridade/prevenção & controle , Transdução de Sinais , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/genética
8.
J Pediatr ; 206: 56-65.e8, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30471715

RESUMO

OBJECTIVE: To investigate recombinant human insulin-like growth factor 1 complexed with its binding protein (rhIGF-1/rhIGFBP-3) for the prevention of retinopathy of prematurity (ROP) and other complications of prematurity among extremely preterm infants. STUDY DESIGN: This phase 2 trial was conducted from September 2014 to March 2016. Infants born at a gestational age of 230/7 weeks to 276/7 weeks were randomly allocated to rhIGF-1/rhIGFBP-3 (250 µg/kg/ 24 hours, continuous intravenous infusion from <24 hours of birth to postmenstrual age 296/7 weeks) or standard neonatal care, with follow-up to a postmenstrual age of 404/7 weeks. Target exposure was ≥70% IGF-1 measurements within 28-109 µg/L and ≥70% intended therapy duration. The primary endpoint was maximum severity of ROP. Secondary endpoints included time to discharge from neonatal care, bronchopulmonary dysplasia, intraventricular hemorrhage, and growth measures. RESULTS: Overall, 61 infants were allocated to rhIGF-1/rhIGFBP-3, 60 to standard care (full analysis set); 24 of 61 treated infants achieved target exposure (evaluable set). rhIGF-1/rhIGFBP-3 did not decrease ROP severity or ROP occurrence. There was, however, a 53% decrease in severe bronchopulmonary dysplasia in the full analysis set (21.3% treated vs 44.9% standard care), and an 89% decrease in the evaluable set (4.8% vs 44.9%; P = .04 and P = .02, respectively) for severity distribution between groups. There was also a nonsignificant trend toward decrease in grades 3-4 intraventricular hemorrhage in the full analysis set (13.1% vs 23.3%) and in the evaluable set (8.3% vs 23.3%). Fatal serious adverse events were reported in 19.7% of treated infants (12/61) and 11.7% of control infants (7/60). No effect was observed on time to discharge from neonatal care/growth measures. CONCLUSIONS: rhIGF-1/rhIGFBP-3 did not affect development of ROP, but decreased the occurrence of severe bronchopulmonary dysplasia, with a nonsignificant decrease in grades 3-4 intraventricular hemorrhage. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01096784.


Assuntos
Hemorragia Cerebral/prevenção & controle , Fator de Crescimento Insulin-Like I/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Retinopatia da Prematuridade/prevenção & controle , Displasia Broncopulmonar/prevenção & controle , Hemorragia Cerebral/terapia , Feminino , Idade Gestacional , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Recém-Nascido Prematuro , Infusões Intravenosas , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/uso terapêutico , Masculino , Retinopatia da Prematuridade/mortalidade , Retinopatia da Prematuridade/terapia , Índice de Gravidade de Doença , Resultado do Tratamento
9.
Arch. argent. pediatr ; 116(6): 386-393, dic. 2018. graf
Artigo em Inglês, Espanhol | LILACS, BINACIS | ID: biblio-973682

RESUMO

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.


Assuntos
Humanos , Recém-Nascido , Retinopatia da Prematuridade/diagnóstico , Triagem Neonatal/métodos , Inibidores da Angiogênese/uso terapêutico , Argentina/epidemiologia , Índice de Gravidade de Doença , Retinopatia da Prematuridade/prevenção & controle , Retinopatia da Prematuridade/epidemiologia , Recém-Nascido Prematuro , Epidemiologia Descritiva , Incidência , Estudos Retrospectivos , Fatores de Risco , Acesso aos Serviços de Saúde , Programas Nacionais de Saúde/organização & administração
10.
Arch Argent Pediatr ; 116(6): 386-393, 2018 12 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30457716

RESUMO

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.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Triagem Neonatal/métodos , Retinopatia da Prematuridade/epidemiologia , Argentina/epidemiologia , Acesso aos Serviços de Saúde , Humanos , Incidência , Recém-Nascido , Recém-Nascido Prematuro , Programas Nacionais de Saúde/organização & administração , Retinopatia da Prematuridade/diagnóstico , Retinopatia da Prematuridade/prevenção & controle , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença
11.
JAMA ; 320(16): 1649-1658, 2018 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-30357297

RESUMO

Importance: Previous studies of myo-inositol in preterm infants with respiratory distress found reduced severity of retinopathy of prematurity (ROP) and less frequent ROP, death, and intraventricular hemorrhage. However, no large trials have tested its efficacy or safety. Objective: To test the adverse events and efficacy of myo-inositol to reduce type 1 ROP among infants younger than 28 weeks' gestational age. Design, Setting, and Participants: Randomized clinical trial included 638 infants younger than 28 weeks' gestational age enrolled from 18 neonatal intensive care centers throughout the United States from April 17, 2014, to September 4, 2015; final date of follow-up was February 12, 2016. The planned enrollment of 1760 participants would permit detection of an absolute reduction in death or type 1 ROP of 7% with 90% power. The trial was terminated early due to a statistically significantly higher mortality rate in the myo-inositol group. Interventions: A 40-mg/kg dose of myo-inositol was given every 12 hours (initially intravenously, then enterally when feeding; n = 317) or placebo (n = 321) for up to 10 weeks. Main Outcomes and Measures: Type 1 ROP or death before determination of ROP outcome was designated as unfavorable. The designated favorable outcome was survival without type 1 ROP. Results: Among 638 infants (mean, 26 weeks' gestational age; 50% male), 632 (99%) received the trial drug or placebo and 589 (92%) had a study outcome. Death or type 1 ROP occurred more often in the myo-inositol group vs the placebo group (29% vs 21%, respectively; adjusted risk difference, 7% [95% CI, 0%-13%]; adjusted relative risk, 1.41 [95% CI, 1.08-1.83], P = .01). All-cause death before 55 weeks' postmenstrual age occurred in 18% of the myo-inositol group and in 11% of the placebo group (adjusted risk difference, 6% [95% CI, 0%-11%]; adjusted relative risk, 1.66 [95% CI, 1.14-2.43], P = .007). The most common serious adverse events up to 7 days of receiving the ending dose were necrotizing enterocolitis (6% for myo-inositol vs 4% for placebo), poor perfusion or hypotension (7% vs 4%, respectively), intraventricular hemorrhage (10% vs 9%), systemic infection (16% vs 11%), and respiratory distress (15% vs 13%). Conclusions and Relevance: Among premature infants younger than 28 weeks' gestational age, treatment with myo-inositol for up to 10 weeks did not reduce the risk of type 1 ROP or death vs placebo. These findings do not support the use of myo-inositol among premature infants; however, the early termination of the trial limits definitive conclusions.


Assuntos
Lactente Extremamente Prematuro , Doenças do Recém-Nascido/mortalidade , Inositol/uso terapêutico , Retinopatia da Prematuridade/prevenção & controle , Hemorragia Cerebral Intraventricular/prevenção & controle , Método Duplo-Cego , Feminino , Seguimentos , Idade Gestacional , Humanos , Recém-Nascido , Inositol/efeitos adversos , Terapia Intensiva Neonatal , Masculino , Retinopatia da Prematuridade/mortalidade , Falha de Tratamento
12.
J Perinatol ; 38(10): 1295-1300, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30046180

RESUMO

The risk of developing treatment-warranted Type 1 retinopathy of prematurity (ROP) might be reduced in preterm infants by modifying certain systemic factors. There are steps that can be taken both early and late in the course of retinal vascular maturation that may potentially reduce an infant's risk of developing Type 1 ROP. In prethreshold stage 2-3 ROP without plus disease, a combination of supplemental oxygen, correction of severe anemia, and light adaptation to reduce rod photoreceptor oxygen consumption helped us to reduce ROP severity, and encouraged a return to a more physiologic retinal vascular maturation pattern. Thus, it may be possible to reduce the risk of developing Type 1 ROP by making adjustments in certain systemic parameters aimed at reducing retinal hypoxia, thereby gently lowering pathologically elevated levels of vascular endothelial growth factor (VEGF) within the eye.


Assuntos
Adaptação Ocular , Anemia/terapia , Oxigênio/administração & dosagem , Oxigênio/sangue , Retinopatia da Prematuridade/prevenção & controle , Fator A de Crescimento do Endotélio Vascular/sangue , Cegueira/prevenção & controle , Humanos , Lactente , Recém-Nascido , Estado Nutricional , Consumo de Oxigênio , Oxigenoterapia/efeitos adversos , Retinopatia da Prematuridade/terapia , Fatores de Tempo
13.
BMJ Open ; 8(7): e021749, 2018 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-29982217

RESUMO

INTRODUCTION: Retinopathy of prematurity (ROP) is a disease observed in extremely premature infants characterised by visioning-threatening retinal vessel proliferation. Propranolol, a drug used for decades in newborn infants with heart diseases, hypertension and thyrotoxicosis and licenced for infantile haemangiomas, may be effective in halting progression of ROP to severe stages, as suggested by preliminary data from small studies. METHODS AND ANALYSIS: ROPROP is an investigator-initiated, multicentre, placebo-controlled double-blind, randomised controlled trial aiming to assess the safety and efficacy of orally administered propranolol to reduce the risk of threshold ROP (stage 3) in extremely preterm infants at 48 weeks postmenstrual age (primary objective) and the rate of infants requiring local interventions for severe ROP (secondary objective). Key inclusion criteria: gestational age <28 weeks, birth weight <1250 g, postmenstrual age ≥31 and <37 weeks, incipient ROP (stage 1 or 2, with or without plus disease) and written informed consent by parents or legal guardian. Key exclusion criteria: requirement for open-label propranolol treatment, major congenital malformations (including those with cerebrovascular malformations), known chromosomal anomalies, colobomas and other eye malformations, atrioventricular block grade 2 or 3 and comedication with antiarrhythmics, clonidine, insulin (pharmacodynamic interaction), phenobarbital or rifampicin (pharmacokinetic interaction). The intervention consists of oral propranolol-hydrochloride (1.6 mg/kg/day in three to four divided dosages) or placebo until discharge, for a maximum of 10 weeks. Analysis is by intention to treat. ETHICS AND DISSEMINATION: The protocol has received ethical and regulatory approval. Results will be published after peer review irrespective of the study outcome. TRIAL REGISTRATION NUMBERS: NCT03083431 , EudraCT# 2017-002124-24 (EUCTR), 00013730 (DRKS); Pre-results.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Propranolol/administração & dosagem , Retinopatia da Prematuridade/prevenção & controle , Administração Oral , Progressão da Doença , Método Duplo-Cego , Idade Gestacional , Humanos , Lactente , Lactente Extremamente Prematuro , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
14.
Exp Cell Res ; 369(2): 243-250, 2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-29803741

RESUMO

Endoplasmic reticulum (ER) stress signaling is activated in retinal degeneration disease. Activating transcription factor 4 (ATF4), an important mediator of the unfolded protein response (UPR), is a key element that maintains cell survival and proliferation in hypoxic conditions. Our previous studies showed that a small ribosomal protein L41 (RPL41) inhibits ATF4 by inducing its phosphorylation and degradation. In the present study, the effects of mini-peptide RPL41 on retinal neovascularization (RNV) in oxygen-induced retinopathy (OIR) mice was investigated. We induced OIR in C57BL/6 mice and obtained retinas from normoxia, OIR, OIR control (treated with PBS), and OIR treated (treated with RPL41) mice. Our results showed that ER stress signaling was activated and ATF4 was overexpressed in the retinas of OIR mice. After intravitreal injection of RPL41, the size of RNV and vaso-obliteration, and the number of preretinal neovascular cell nuclei in the retinas of OIR mice were significantly decreased. Western blot analysis and quantitative real-time polymerase chain reaction (qPCR) showed ATF4 and VEGF expression decreased after intravitreal injection of RPL41. Furthermore, the expression levels of inflammatory genes including TNF-α, IL-1ß, and IL-6 were significantly decreased compared with the OIR control mice. In conclusion, RPL41 prevented pathologic neovascularization and exerted anti-inflammatory effects by degrading the important ER stress factor ATF4, thus, RPL41 could be a promising therapeutic agent for the treatment of neovascular eye diseases, especially retinopathy of prematurity (ROP).


Assuntos
Fator 4 Ativador da Transcrição/metabolismo , Peptídeos/farmacologia , Neovascularização Retiniana/metabolismo , Neovascularização Retiniana/prevenção & controle , Proteínas Ribossômicas/metabolismo , Fator 4 Ativador da Transcrição/genética , Sequência de Aminoácidos , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático , Fator de Iniciação 2 em Eucariotos/genética , Fator de Iniciação 2 em Eucariotos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Oxigênio/metabolismo , Peptídeos/metabolismo , Proteólise , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Retina/metabolismo , Retina/patologia , Neovascularização Retiniana/patologia , Retinopatia da Prematuridade/genética , Retinopatia da Prematuridade/metabolismo , Retinopatia da Prematuridade/prevenção & controle , Proteínas Ribossômicas/genética , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
15.
Arq Bras Oftalmol ; 81(2): 102-109, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29846422

RESUMO

PURPOSE: To evaluate the possible protective effect of breast milk against retinopathy of prematurity by comparing the amount of breast milk received by patients who developed retinopathy of prematurity and those who did not and to determine both the required minimum amount of breast milk and the time of life during which neonates need to receive breast milk for this effect to be significant. METHODS: Cohort study of newborns with a birth weight of <1500 g or gestational age of <32 weeks, or both, born between January 2011 and October 2014 and hospitalized within the first 24 h of life in the Hospital Criança Conceição Neonatal Intensive Care Unit in Porto Alegre, RS, Brazil. RESULTS: The prevalence of retinopathy of prematurity of any degree was 31% (100 of 323 patients) and that of severe retinopathy of prematurity was of 9% (29 of 323 patients). The median amounts of breast milk received daily by patients with and without retinopathy of prematurity were 4.9 mL/kg (interquartile range, 0.3-15.4) and 10.2 mL/kg (1.5-25.5), respectively. The amount of breast milk received in the first 6 weeks of life was inversely associated with the incidence of both retinopathy of prematurity of any degree and severe retinopathy of prematurity in the univariate analyses. However, the statistical significance was maintained only during the sixth week of life in a per-period multivariate analysis controlling for confounding factors. CONCLUSIONS: Small amounts of breast milk are inadequate to prevent retinopathy of prematurity in premature newborns at risk for the disease.


Assuntos
Recém-Nascido Prematuro/fisiologia , Leite Humano/fisiologia , Retinopatia da Prematuridade/epidemiologia , Retinopatia da Prematuridade/prevenção & controle , Peso ao Nascer , Brasil/epidemiologia , Aleitamento Materno , Métodos Epidemiológicos , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Retinopatia da Prematuridade/fisiopatologia , Fatores de Tempo
16.
Adv Nutr ; 9(3): 238-246, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29767696

RESUMO

Erythropoietin (EPO) plays an important role in the development and maturation of the gastrointestinal tract. Recombinant EPO (rEPO) has been used to prevent anemia of prematurity. The gastrointestinal trophic effects of EPO may reduce feeding intolerance and necrotizing enterocolitis (NEC) in preterm neonates. The aim of this systematic review of randomized controlled trials (RCTs) was to evaluate the effects of rEPO on clinical outcomes such as feeding intolerance, stage II or higher NEC, any stage NEC, sepsis, retinopathy of prematurity, and bronchopulmonary dysplasia in preterm neonates. Twenty-five RCTs (intravenous: 13; subcutaneous: 10; enteral: 2; n = 4025) were eligible for inclusion. Meta-analysis of data from 17 RCTs (rEPO compared with placebo) with the use of a fixed-effects model showed no significant effect of rEPO on stage II or higher NEC (RR: 0.87; 95% CI: 0.64, 1.19; P = 0.39). Meta-analysis of data from 25 RCTs (rEPO compared with placebo) showed that rEPO significantly decreased the risk of any stage NEC [cases/total sample: 120/2058 (5.83%) compared with 146/1967 (7.42%); RR: 0.77; 95% CI: 0.61, 0.97; P = 0.03]. Only one RCT reported on time to full feedings. Meta-analysis of data from 15 RCTs showed a significant reduction in late-onset sepsis after rEPO administration (RR: 0.81; 95% CI: 0.71, 0.94; P = 0.004). Meta-analysis of 13 RCTs showed no significant effect of rEPO on mortality, retinopathy of prematurity, and bronchopulmonary dysplasia. Prophylactic rEPO had no effect on stage II or higher NEC, but it reduced any stage NEC, probably by reducing feeding intolerance, which is often labeled as stage I NEC. Adequately powered RCTs are required to confirm these findings.


Assuntos
Enterocolite Necrosante/prevenção & controle , Eritropoetina/uso terapêutico , Trato Gastrointestinal/efeitos dos fármacos , Recém-Nascido de Baixo Peso , Doenças do Prematuro/prevenção & controle , Recém-Nascido Prematuro , Sepse/prevenção & controle , Displasia Broncopulmonar/prevenção & controle , Eritropoetina/farmacologia , Humanos , Recém-Nascido , Retinopatia da Prematuridade/prevenção & controle
17.
Neonatology ; 114(1): 69-75, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29669357

RESUMO

BACKGROUND: For 70 years, there has been a search for the optimal oxygenation of premature infants. In spite of the lack of evidence, guidelines have successively reduced oxygenation targets during these years. OBJECTIVES: (1) To present a summary of previously published meta-analyses of 5 randomized studies (NeOProM) which tested a low (85-89%) versus a high (91-95%) oxygen saturation target the first weeks after birth on outcome of immature newborn infants. (2) To present international recommendations for oxygenation the first weeks after birth. METHODS: Data were retrieved from meta-analyses and reviews of these studies. RESULTS: Mortality and necrotizing enterocolitis (NEC) are significantly higher in patients with a low saturation target (relative risk, RR 1.16 and 1.24, respectively), while severe retinopathy of prematurity (ROP) is reduced (RR 0.74), fortunately without a change in the rate of blindness. Severe intraventricular hemorrhage, patent ductus arteriosus, and bronchopulmonary dysplasia (defined physiologically) were not significantly affected by the oxygen targets in the range of these studies. Based on these data, it is recommended that SpO2 targets from birth to 36 weeks postconceptional age for infants < 28 weeks gestational age (GA) should be between 90 and 94% (with alarm limits of 89 and 95%), respectively. It is recommended to keep infants small for GA well oxygenated within the suggested targets avoiding fluctuations. CONCLUSIONS: The ideal oxygen saturation targets for infants < 28 weeks GA are not known. Mortality, ROP, and NEC seem to be particularly oxygen-sensitive outcome variables. The optimal oxygen saturation for premature infants > 28 weeks GA has not been carefully studied.


Assuntos
Enterocolite Necrosante/prevenção & controle , Lactente Extremamente Prematuro , Oxigênio/uso terapêutico , Retinopatia da Prematuridade/prevenção & controle , Enterocolite Necrosante/epidemiologia , Idade Gestacional , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Metanálise como Assunto , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Retinopatia da Prematuridade/epidemiologia , Revisão Sistemática como Assunto
18.
Kennedy Inst Ethics J ; 28(1): 85-118, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29628452

RESUMO

The SUPPORT trial highlights ethical challenges raised by comparative effectiveness randomized controlled trials (ceRCTs) involving one or more usual care interventions. Debate about the SUPPORT trial has focused on whether study interventions posed "reasonably foreseeable risks" to enrolled infants and, thereby, reflects a preoccupation with U.S. regulations. As ceRCTs are conducted globally, our analysis of the SUPPORT trial is grounded in internationally accepted ethical principles. We argue that the central ethical issue raised by the SUPPORT trial is the following: should the SUPPORT trial interventions be conceptualized as practice, or research? The answer to this question has important implications for "downstream" ethical requirements-including whether the usual care interventions in ceRCTs require research ethics committee review, undergo harm-benefit analysis, and are included in informed consent documents-and it is antecedent to the development of ethical guidance for ceRCTs.


Assuntos
Pesquisa Comparativa da Efetividade/ética , Oxigenoterapia/efeitos adversos , Oxigenoterapia/métodos , Ensaios Clínicos Pragmáticos como Assunto/ética , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Consentimento Livre e Esclarecido , Oximetria , Oxigênio/sangue , Síndrome do Desconforto Respiratório do Recém-Nascido/mortalidade , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Retinopatia da Prematuridade/etiologia , Retinopatia da Prematuridade/prevenção & controle
19.
Br J Ophthalmol ; 102(10): 1336-1341, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29632000

RESUMO

BACKGROUND: Retinopathy of prematurity (ROP) is one of the leading causes of childhood blindness. Use of antenatal steroid can reduce neonatal morbidity and mortality in preterm births, but its effect on ROP remained controversial. We aim to determine the association between antenatal steroid and risk of ROP by a systematic review and meta-analysis. METHODS: Reported studies on the association between antenatal steroid and risk of ROP or severe ROP were identified from MEDLINE and Embase databases from their inception to November 2016. Outcome measures were ORs with 95% CIs. Extracted data were pooled using a random-effect model or fixed-effect model where appropriate. Heterogeneity was assessed, and sensitivity analysis was performed. RESULTS: A total of 434 relevant studies were identified, and 28 studies were eligible for the meta-analysis, involving 20 731 neonates with 4202 cases of ROP. Among the 28 studies included, 13 studies provided data evaluating the association between antenatal steroid use and severe ROP, involving 4999 neonates with 792 cases of severe ROP. Antenatal steroid administration was associated with a reduced risk of ROP development (ORunadjusted=0.82, 95% CI 0.68 to 0.98; ORadjusted=0.67, 95% CI 0.47 to 0.94) and progression to severe ROP (ORunadjusted=0.58, 95% CI 0.40 to 0.86). CONCLUSION: Antenatal steroid administration is associated with a reduced risk of ROP development and progression to severe ROP. Our results strengthened the indications of antenatal steroid therapy to high-risk mothers giving preterm births, especially in low-income and middle-income countries where antenatal steroid are not yet widely used.


Assuntos
Cuidado Pré-Natal/métodos , Retinopatia da Prematuridade/prevenção & controle , Esteroides/administração & dosagem , Feminino , Saúde Global , Humanos , Recém-Nascido , Morbidade/tendências , Gravidez , Retinopatia da Prematuridade/epidemiologia
20.
Invest Ophthalmol Vis Sci ; 59(2): 858-869, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29490339

RESUMO

Purpose: Low levels of the long chain polyunsaturated fatty acid (LCPUFA) docosahexaenoic acid (DHA) have been implicated in retinopathy of prematurity (ROP). However, oral DHA suffers from poor palatability and is associated with increased bleeding in premature infants. We asked whether oral administration of the neutraceutical arginine-glutamine (Arg-Glu) could increase retinal DHA and improve outcomes in a mouse model of oxygen-induced retinopathy (OIR). Methods: Postnatal day 7 (P7) pups were maintained at 75% oxygen for 5 days and then returned to room air on P12. Pups were gavaged twice daily with Arg-Gln or vehicle from P12 to P17 and eyes were harvested for analysis on P17. Vaso-obliteration and vascular density were assessed on retinal flat mounts and preretinal neovascularization was assessed on retinal cross sections. Retinas were used for measurement of DHA and 10,17S-docosatriene (neuroprotectin D1, NPD1), a key DHA-derived lipid, and for analysis by reverse-phase protein array (RPPA). Results: With Arg-Gln treatment, retinal DHA and NPD1 levels were increased in OIR pups. Arg-Gln reduced preretinal neovascularization by 39 ± 6% (P < 0.05) relative to vehicle control. This was accompanied by a restoration of vascular density of the retina in the pups treated with Arg-Gln (73.0 ± 3.0%) compared to vehicle (53.1 ± 3.4%; P < 0.05). Arg-Gln dipeptide restored OIR-induced signaling changes toward normoxia and was associated with normalization of insulin-like growth factor receptor 1 signaling and reduction of apoptosis and an increase in anti-apoptosis proteins. Conclusions: Arg-Gln may serve as a safer and easily tolerated nutraceutical agent for prevention or treatment of ROP.


Assuntos
Dipeptídeos/administração & dosagem , Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos/metabolismo , Retina/metabolismo , Neovascularização Retiniana/prevenção & controle , Retinopatia da Prematuridade/prevenção & controle , Administração Oral , Animais , Animais Recém-Nascidos , Cromatografia Líquida de Alta Pressão , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oxigênio/toxicidade , Gravidez , Neovascularização Retiniana/induzido quimicamente , Neovascularização Retiniana/metabolismo , Vasos Retinianos/efeitos dos fármacos , Vasos Retinianos/patologia , Retinopatia da Prematuridade/induzido quimicamente , Retinopatia da Prematuridade/metabolismo
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