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1.
Medicine (Baltimore) ; 99(8): e19084, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080082

RESUMO

BACKGROUND: Sustained Inflations (SI) and Intermittent Positive Pressure Ventilation (IPPV) are two interventions to prevent Bronchopulmonary dysplasia (BPD). The aim of this study is to assess the effect of these two interventions. METHODS: The databases of PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) will be comprehensively searched from inception to September 2019. All RCTs and quasi-RCTs which compare the efficacy of SI vs IPPV among preterm infants are eligible. We will assess the methodological quality using the Cochrane Handbook version 5.1.0. A meta-analysis will be performed using RevMan 5.3 software and the results will be presented using risk ratios (RRs) and 95% confidence intervals (CIs). CONCLUSIONS: This study will provide strong evidence for assessing the effect of SI and IPPV on BPD or death among preterm infants. PROSPERO REGISTRATION NUMBER: CRD42019135816.


Assuntos
Displasia Broncopulmonar/prevenção & controle , Insuflação/efeitos adversos , Ventilação com Pressão Positiva Intermitente/efeitos adversos , Lesão Pulmonar Induzida por Ventilação Mecânica/prevenção & controle , Peso ao Nascer , Displasia Broncopulmonar/mortalidade , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Insuflação/instrumentação , Ventilação com Pressão Positiva Intermitente/instrumentação , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Lesão Pulmonar Induzida por Ventilação Mecânica/mortalidade
3.
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
4.
Clin Drug Investig ; 39(11): 1093-1107, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31414269

RESUMO

BACKGROUND: Bronchopulmonary dysplasia (BPD) is the need for oxygen therapy at 36 weeks postmenstrual age (PMA). Sildenafil has been shown to enhance the lung alveolarization and vascularization in newborn animal models after lung injury and has possible therapeutic potential for the prevention of BPD. OBJECTIVE: To perform a proof-of-concept, Phase II, pilot randomized, double-blind, clinical trial to study the efficacy of sildenafil in preventing BPD, in postnatal (< 24 h), extremely and very preterm infants. METHODS: This Phase II, pilot randomized, double-blind, clinical trial was conducted in the Neonatal Intensive Care Unit of Women's Wellness and Research Center, Doha, Qatar during 2012-2014. Infants of 240/7-296/7 weeks' gestation were eligible if they needed respiratory or oxygen support ≥ 25% at randomization, and if they were at a postnatal age of < 24 h at randomization. Forty preterm infants were randomly assigned to receive off-label oral sildenafil (0.5 mg/kg every 6 h) or a placebo solution, for one week. The primary endpoints were the incidence of BPD and death at 36 weeks PMA, and the side effects. Secondary outcomes included the incidence of BPD and the respiratory support at day 28 of life, duration of oxygen use, fraction of inspired oxygen use at 36 weeks and 28 days of life, duration of hospitalization, and the incidence of significant retinopathy of prematurity, severe intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, patent ductus arteriosus, and late sepsis. RESULTS: No significant differences were observed between the sildenafil and placebo study groups in mortality at 36 weeks PMA (10% vs 20%, p = 1), respiratory support at 36 weeks (30% vs 25%, p = 0.57), and side effects (0% vs 0%). For all other secondary outcomes, no significant differences were detected. CONCLUSIONS: While not associated with side effects, off-label oral sildenafil did not demonstrate benefits in the prevention of BPD or death in the extreme and very preterm infants. Future studies of dosing and efficacy that target different regimens of sildenafil are warranted before sildenafil is recommended for the prevention of BPD.


Assuntos
Displasia Broncopulmonar/prevenção & controle , Recém-Nascido Prematuro , Profilaxia Pré-Exposição/métodos , Estudo de Prova de Conceito , Citrato de Sildenafila/administração & dosagem , Vasodilatadores/administração & dosagem , Displasia Broncopulmonar/diagnóstico , Método Duplo-Cego , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro/crescimento & desenvolvimento , Masculino , Projetos Piloto , Fatores de Risco
5.
Neonatal Netw ; 38(4): 242-249, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31470395

RESUMO

Bronchopulmonary dysplasia (BPD) is a morbidity of prematurity with implications for respiratory and neurologic health into adulthood. Multiple risk factors contribute to the development of BPD leading to examination of various prevention strategies. The roles of systemic corticosteroids and caffeine have been addressed by the American Academy of Pediatrics. The place in therapy of other agents commonly utilized in clinical practice remains unclear. Inhaled nitric oxide has been the subject of numerous large, randomized controlled trials in preterm infants. Despite sound rationale, these trials have largely failed to document benefit, suggesting a limited role for inhaled nitric oxide therapy in the preterm population. In contrast, intramuscular vitamin A has been documented to reduce the incidence of BPD in randomized trials. However, the invasiveness and the sporadic availability of this therapy have led to decreased utilization. All macrolide antibiotics do not appear to have a similar impact on the incidence of BPD; however, azithromycin administered to infants colonized with Ureaplasma may have impact. Questions remain about the optimal dosing approach and long-term safety of this intervention. Finally, diuretic therapy is widely used in clinical practice despite significant toxicities and limited data supporting a role in BPD prevention. Taken together, available data suggest that caffeine and selective use of corticosteroids remain the mainstays of pharmacologic BPD prevention.


Assuntos
Corticosteroides/uso terapêutico , Displasia Broncopulmonar/tratamento farmacológico , Displasia Broncopulmonar/prevenção & controle , Cafeína/uso terapêutico , Recém-Nascido Prematuro , Enfermagem Neonatal/normas , Guias de Prática Clínica como Assunto , Antibacterianos/uso terapêutico , Diuréticos/uso terapêutico , Feminino , Humanos , Macrolídeos/uso terapêutico , Masculino , Óxido Nítrico/uso terapêutico , Vitamina A/uso terapêutico
6.
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
7.
J Neonatal Perinatal Med ; 12(2): 161-171, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31256080

RESUMO

BACKGROUND: Pulmonary hemorrhage (PH) is occasionally seen in premature infants after surfactant treatment for respiratory distress syndrome (RDS). These infants receive frequent chest radiographs (CXR) during and after hospitalization enabling long-term radiographic-clinical correlation. OBJECTIVE: To chart the natural evolution of CXR findings of PH in RDS and correlate radiographic patterns to supplemental oxygen requirement. MATERIALS AND METHODS: Retrospective review of clinical notes for gestational age (GA), birth weight (BW), intraventricular hemorrhage (IVH) and oxygen requirement were performed. CXRs were reviewed at 4 time-points; during PH, 28 days postnatal age, 36 weeks and at farthest available clinical follow-up. RESULTS: 18 infants born (2003-2016), GA (24-30 weeks); BW (482-1590 grams) were included. Mean onset of PH was 1.94 (0-5) days. 9/18 (50%) had IVH. 3 died during PH; all had IVH. During PH, CXR showed whiteout 9/18 (50%); patchy opacities 5/18 (27%); diffuse haziness 1/18 (6%) and no change 3/18 (17%). At 28 days postnatal age, CXR showed fine-interstitial (FI) markings 14/15 (93%) and whiteout 1/15 (7%). At 36 weeks,12/14 (85%) had FI and 2/14 (15%) developed cystic-interstitial changes. At farthest follow-up, FI 3/13 (23%); coarse-interstitial 4/13 (30%); peri-bronchial cuffing 5/13 (38%); normal 1/13 (9%) and the majority had hyperinflation 9/13 (69%). At discharge, 9/14 (64%) required home-oxygen and 5/14 (36%) were on room-air. At farthest follow-up, 6/14 (42%) required home-oxygen and 8/14 (58%) were on room-air. CONCLUSION: Premature infants that survive PH may later develop chronic lung disease of prematurity with an evolving interstitial pattern on CXR that clears overtime as they outgrow the need for supplemental oxygen.


Assuntos
Displasia Broncopulmonar/epidemiologia , Hemorragia/diagnóstico por imagem , Pneumopatias/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológico , Administração Tópica , Displasia Broncopulmonar/prevenção & controle , Hemorragia Cerebral Intraventricular/epidemiologia , Criança , Pré-Escolar , Comorbidade , Progressão da Doença , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Surfactantes Pulmonares/uso terapêutico , Radiografia Torácica , Síndrome do Desconforto Respiratório do Recém-Nascido/epidemiologia , Estudos Retrospectivos
8.
Pediatrics ; 144(1)2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31164440

RESUMO

CONTEXT: Previous studies have suggested that intervention with omega-3 long-chain polyunsaturated fatty acids (N-3 LCPUFAs), especially docosahexaenoic acid, can reduce the incidence of bronchopulmonary dysplasia (BPD) in preterm infants. However, conflicting results have been reported. OBJECTIVE: We conducted this meta-analysis to investigate the effect of intervention with N-3 LCPUFAs on the incidence of BPD in preterm infants. DATA SOURCES: PubMed, Embase, and the Cochrane Library were searched for articles published from database inception to October 1, 2018. STUDY SELECTION: We included randomized controlled trials (RCTs) in which the effect of intervention with N-3 LCPUFAs on the incidence of BPD was examined. DATA EXTRACTION: Two independent authors conducted the literature search and data extraction. The risk ratio was determined, and subgroup analyses were performed. RESULTS: After applying the inclusion criteria, 14 RCTs with 3531 preterm infants were included in the study. Intervention with N-3 LCPUFAs revealed no significant effect on the incidence of BPD in preterm infants (risk ratio: 0.99; 95% confidence interval: 0.84-1.18; Z = 0.08; P = .93). Our secondary subgroup analysis, which was stratified by gestational age, birth weight, dosage of docosahexaenoic acid, and duration of intervention, also revealed no significant effects. LIMITATIONS: The populations, protocols, and pharmaceutical ingredients of N-3 LCPUFAs vary among the included RCTs. CONCLUSIONS: The results of our meta-analysis indicate that intervention with N-3 LCPUFAs cannot prevent BPD in preterm infants. These findings provide no support for intervention with N-3 LCPUFAs in preterm infants.


Assuntos
Anti-Inflamatórios/uso terapêutico , Displasia Broncopulmonar/prevenção & controle , Ácidos Graxos Ômega-3/uso terapêutico , Displasia Broncopulmonar/epidemiologia , Humanos , Incidência , Recém-Nascido , Recém-Nascido Prematuro , Resultado do Tratamento
9.
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
10.
Curr Med Sci ; 39(3): 493-499, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31209823

RESUMO

There is uncertain result with regard to the use of inhalation or instillation steroids to prevent bronchopulmonary dysplasia in preterm infants. This meta-analysis was designed to evaluate the efficacy and safety of early airway administration (within 2 days after birth) of corticosteroids and pulmonary surfactant (PS) for preventing bronchopulmonary dysplasia (BPD) in premature infants with neonatal respiratory distress syndrome (NRDS). The related studies were retrieved in PubMed, EMBASE, the Cochrane Library, Clinical Trial, CNKI, Wanfang and VIP Database from inception to August 2018. Two reviewers independently screened the studies to ensure that all patients with diagnosis of NRDS were enrolled to studies within 1 day after birth, assessed the quality of included studies by GRADEpro system and extracted the data for review. The meta-analysis was performed by RevMan 5.2 software. A subgroup analysis about inhaled corticosteroid (ICS) delivery method was made between ICS inhalation subgroup [inhalation of ICS by nebulizer or metered dose inhaler (MDI)] and ICS intratracheal instillation subgroup (PS used as a vehicle). Eight randomized controlled trials were enrolled in the meta-analysis, 5 trials of which stated the randomized method, grouping and blinded method, and the follow-up procedures were reported. GRADEpro system showed high quality of 4 trials (5 articles), and the rest 4 trials had moderate quality. Meta-analysis showed that the incidence of BPD was decreased in ICS group, the relative risk (RR) was 0.56 (95% CI: 0.42-0.76), and similar trends were found in ICS inhalation subgroup and ICS intratracheal instillation subgroup, with the corresponding RR being 0.58 (95% CI: 0.41-0.82) and 0.47 (95% CI: 0.24-0.95) respectively. ICS could also significantly reduce the mortality risk as compared with placebo control group (RR: 0.67; 95% CI: 0.45-0.99), with RR of ICS inhalation subgroup and ICS intratracheal instillation subgroup being 0.81 (95% CI: 0.34-1.94) and 0.64 (95% CI: 0.41-0.99) respectively. Moreover, the percentage of infants using PS more than one time was lower in ICS group than in the placebo control group, with the RR and 95% CI being 0.55 (95% CI: 0.45-0.67), and that in ICS intratracheal instillation subgroup lower than in ICS inhalation subgroup (RR: 0.56; 95% CI: 0.45-0.69, and RR: 0.35; 95% CI: 0.08-1.52 respectively). There was no significant difference in the incidence of infection or retinopathy of prematurity and neuro-motor system impairment between ICS group and placebo control group, with the corresponding RR being 0.95 (95% CI: 0.59-1.52), 0.92 (95% CI: 0.62-1.38) and 1.13 (95% CI: 0.92-1.39), respectively. It was concluded that early administration of ICS and PS is an effective and safe option for preterm infants with NRDS in preventing BPD and reducing mortality, decreasing the additional PS usage, especially for the ICS intratracheal instillation subgroup. Furthermore, the appropriate dose and duration of ICS, combined use of inhalation or instillation of ICS with PS and the long-term safety of airway administration of corticosteroids need to be assessed in large trials.


Assuntos
Corticosteroides/uso terapêutico , Displasia Broncopulmonar/prevenção & controle , Surfactantes Pulmonares/uso terapêutico , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológico , Fármacos do Sistema Respiratório/uso terapêutico , Administração por Inalação , Displasia Broncopulmonar/complicações , Displasia Broncopulmonar/mortalidade , Displasia Broncopulmonar/fisiopatologia , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Ensaios Clínicos Controlados Aleatórios como Assunto , Síndrome do Desconforto Respiratório do Recém-Nascido/complicações , Síndrome do Desconforto Respiratório do Recém-Nascido/mortalidade , Síndrome do Desconforto Respiratório do Recém-Nascido/fisiopatologia , Prevenção Secundária/métodos , Análise de Sobrevida , Traqueia
11.
Eur J Pediatr ; 178(8): 1171-1184, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31144162

RESUMO

Early lung inflammation has been implicated in the pathogenesis of bronchopulmonary dysplasia (BPD). We aimed to establish the efficacy and safety of systemic hydrocortisone for the prevention of BPD. A systematic review and meta-analysis were undertaken, with a detailed electronic literature search. Trials involving preterm infants were included if they were randomised to receive systemic hydrocortisone or a placebo. The primary outcome was the composite of survival without BPD at 36-week postmenstrual age (PMA). Results are presented as relative risk (RR) or risk difference (RD) with 95% confidence intervals (CIs), along with numbers needed to treat (NNT) or harm (NNH). After filtering, 12 studies using early (within 1 week of birth) and two using late hydrocortisone were identified. Early systemic hydrocortisone significantly increased the chances of survival without BPD (RR 1.13, 95% CI [1.01, 1.26], NNT 18), and survival without moderate-to-severe neurodevelopmental impairment (1.13 [1.02, 1.26], NNT 14). Infants who received hydrocortisone had a higher risk of intestinal perforation (1.69 [1.07, 2.68], NNH 30), primarily with concurrent treatment for patent ductus arteriosus.Conclusion: Early systemic hydrocortisone is a modestly effective therapy for the prevention of BPD in preterm infants, although some safety concerns remain. No conclusions could be drawn for late hydrocortisone due to the paucity of studies. What is Known: • Preterm infants are at high risk of developing bronchopulmonary dysplasia (BPD) and early lung inflammation plays a significant role in its pathogenesis. • Both early and late systemic dexamethasone seems to reduce the incidence of BPD, but its use is associated with serious neurodevelopmental impairment at follow-up. What is New: • Early systemic hydrocortisone significantly improved survival without BPD at 36 weeks and survival without moderate to severe neurodevelopmental impairment on follow up. • Incidence of gastrointestinal perforation associated with concurrent treatment for PDA was significantly higher, although early systemic hydrocortisone reduced the need for treatment of PDAs.


Assuntos
Anti-Inflamatórios/uso terapêutico , Displasia Broncopulmonar/prevenção & controle , Hidrocortisona/uso terapêutico , Esquema de Medicação , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Resultado do Tratamento
12.
Neonatology ; 115(4): 384-391, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30974430

RESUMO

Bronchopulmonary dysplasia (BPD) is one of the few diseases in neonatal medicine that has continued to evolve since its first description about 50 years ago. Over these years, advancements in neonatal medicine such as antenatal steroids and exogenous surfactant therapy have significantly reduced neonatal mortality and lowered the limits of viability for preterm infants. Although the incidence of BPD continues to be high, especially in extremely low birth weight infants, the clinical picture has evolved into a milder disease with low mortality or significant morbidities. This new BPD is the result of complex interactions between altered alveolar and vascular development, injury by ante- and postnatal pathogenic factors, and reparative processes in the lung. There has been significant progress in our understanding of risk factors for BPD, but challenges persist in its definition, and in finding effective preventive strategies. There are promising developments with newer preventive interventions such as mesenchymal stem cells, exosomes, immunomodulators, and growth factors, but they are still in preclinical stage. The future challenges include finding ways to define BPD based on the severity of lung pathology, which can better predict long-term outcomes, development of early predictors of lung disease, and finding innovative and evidence-based preventive and management strategies.


Assuntos
Displasia Broncopulmonar/patologia , Displasia Broncopulmonar/prevenção & controle , Displasia Broncopulmonar/terapia , Recém-Nascido Prematuro , Prática Clínica Baseada em Evidências , Humanos , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Recém-Nascido , Alvéolos Pulmonares/patologia , Surfactantes Pulmonares/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração Artificial , Fatores de Risco , Esteroides/uso terapêutico
13.
Neonatology ; 115(4): 411-422, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30974437

RESUMO

Traditionally, surfactant has been administered to preterm infants with respiratory distress syndrome via an endotracheal tube and in conjunction with mechanical ventilation. However, negative consequences of mechanical ventilation such as pneumothorax and bronchopulmonary dysplasia are well known. In order to provide the benefits of surfactant administration without the negative effects of mechanical ventilation, several methods of less invasive surfactant administration have been developed. These methods include InSurE (intubate, surfactant, extubate), pharyngeal administration, laryngeal mask administration, aerosolized surfactant administration, and thin catheter administration (TCA). Of these, TCA has been studied most extensively and holds the most promise as a less invasive and effective mode of surfactant administration to preterm infants. Further studies will aid in determining which patients would benefit most from less invasive surfactant administration.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas/métodos , Intubação Intratraqueal/métodos , Surfactantes Pulmonares/administração & dosagem , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Displasia Broncopulmonar/prevenção & controle , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Pneumotórax/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Pediatr Ann ; 48(4): e148-e153, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30986315

RESUMO

Bronchopulmonary dysplasia (BPD) is a chronic lung disease most commonly seen in premature infants who require mechanical ventilation and oxygen therapy. Despite advances in neonatal care resulting in improved survival and decreased morbidity, limited progress has been made in reducing rates of BPD. Therapeutic options to protect the vulnerable developing lung are limited as are strategies to treat lung injury, resulting in ongoing concerns for long-term pulmonary morbidity after preterm birth. Lung protective strategies and optimal nutrition are recognized to improve pulmonary outcomes. However, characterization of late outcomes is challenged by rapid advances in neonatal care. As a result, current adult survivors reflect outdated medical practices. Although neonatal pulmonary disease tends to improve with growth, compromised respiratory health has been documented in young adult survivors of BPD. With improved survival of premature infants but limited progress in reducing rates of disease, BPD represents a growing burden on health care systems. [Pediatr Ann. 2019;48(4):e148-e153.].


Assuntos
Displasia Broncopulmonar/complicações , Pulmão/fisiopatologia , Displasia Broncopulmonar/prevenção & controle , Displasia Broncopulmonar/terapia , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro
15.
Clin Perinatol ; 46(2): 291-310, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31010561

RESUMO

Rates of bronchopulmonary dysplasia (BPD) are increasing. After preterm birth, there are important developmental periods in which neonates are more vulnerable to stressful events. These periods are opportunities for pharmacologic interventions. Many drugs remain inadequately tested and no new drugs have been approved in more than 25 years for BPD prevention or therapy. More progress is needed in defining appropriate end points based on the pathophysiology of BPD and postdischarge chronic pulmonary insufficiency of prematurity and to develop effective new drugs. In addition, much work is needed to better define perinatal factors, early postnatal findings, and physiologic phenotypes or endotypes.


Assuntos
Displasia Broncopulmonar/tratamento farmacológico , Displasia Broncopulmonar/prevenção & controle , Administração por Inalação , Corticosteroides/uso terapêutico , Broncodilatadores/uso terapêutico , Cafeína/uso terapêutico , Diuréticos/uso terapêutico , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Fator de Crescimento Insulin-Like I/uso terapêutico , Transplante de Células-Tronco Mesenquimais , Óxido Nítrico/uso terapêutico , Oxigenoterapia , Inibidores da Fosfodiesterase 5/uso terapêutico , Inibidores de Fosfodiesterase/uso terapêutico , Gravidez , Cuidado Pré-Natal , Progesterona/uso terapêutico , Progestinas/uso terapêutico , Surfactantes Pulmonares/uso terapêutico , Citrato de Sildenafila/uso terapêutico , Vitamina A/uso terapêutico , Vitaminas/uso terapêutico
16.
Am J Physiol Cell Physiol ; 316(6): C815-C827, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30917030

RESUMO

We studied the role of bone marrow mesenchymal stem cells (MSCs) in our established model of bronchopulmonary dysplasia (BPD) induced by intrauterine hypoxia in the rat. First, we found that intrauterine hypoxia can reduce the number of MSCs in lungs and bone marrow of rat neonates, whereas the administration of granulocyte colony-stimulating factor or busulfan to either motivate or inhibit bone marrow MSCs to lungs altered lung development. Next, in vivo experiments, we confirmed that intrauterine hypoxia also impaired bone marrow MSC proliferation and decreased cell cycling activity. In vitro, by using the cultured bone marrow MSCs, the proliferation and the cell cycling activity of MSCs were also reduced when N-methyl-d-aspartic acid (NMDA) was used as an NMDA receptor (NMDAR) agonist. When MK-801 or memantine as NMDAR antagonists in vitro or in vivo was used, the reduction of cell cycling activity and proliferation were partially reversed. Furthermore, we found that intrauterine hypoxia could enhance the concentration of glutamate, an amino acid that can activate NMDAR, in the bone marrow of neonates. Finally, we confirmed that the increased concentration of TNF-ɑ in the bone marrow of neonatal rats after intrauterine hypoxia induced the release of glutamate and reduced the cell cycling activity of MSCs, and the latter could be partially reversed by MK-801. In summary, intrauterine hypoxia could decrease the number of bone marrow MSCs that could affect lung development and lung function through excessive activation of NMDAR that is partially caused by TNF-ɑ.


Assuntos
Displasia Broncopulmonar/metabolismo , Displasia Broncopulmonar/prevenção & controle , Citoproteção/fisiologia , Células-Tronco Mesenquimais/metabolismo , Alvéolos Pulmonares/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Animais , Animais Recém-Nascidos , Células da Medula Óssea/metabolismo , Displasia Broncopulmonar/patologia , Células Cultivadas , Feminino , Hipóxia Fetal/complicações , Hipóxia Fetal/metabolismo , Hipóxia Fetal/patologia , Masculino , Gravidez , Alvéolos Pulmonares/crescimento & desenvolvimento , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
17.
J Pharm Biomed Anal ; 167: 7-14, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30738243

RESUMO

Budesonide is a potential therapeutic option for the prevention of bronchopulmonary dysplasia in mechanically ventilated premature neonates. The dose and concentrations of budesonide that drive effective prophylaxis are unknown, due in part to the difficulty in obtaining serial blood samples from this fragile population. Of primary concern is the limited total blood volume available for collection for the purposes of a pharmacokinetic study. Dried blood spots (DBS), which require the collection of <200 µL whole blood to fill an entire card, are an attractive low-blood volume alternative to traditional venipuncture sampling. We describe a simple and sensitive method for determining budesonide concentrations in DBS using an ultra-high-performance liquid chromatography - tandem mass spectrometry assay. Budesonide was liberated from a single 6 mm punch using a basified methyl tert-butyl ether extraction procedure. The assay was determined to be accurate and precise in the dynamic range of 1 to 50 ng/mL. The validated assay was then successfully applied to DBS collected as part of a multi-center, dose-escalation study of budesonide administered in surfactant via intra-tracheal instillation to premature neonates between 23 and 28 weeks gestational age. These findings show that DBS are a useful technique for collecting pharmacokinetic samples in premature neonates and other pediatric populations.


Assuntos
Budesonida/sangue , Teste em Amostras de Sangue Seco/métodos , Monitoramento de Medicamentos/métodos , Lactente Extremamente Prematuro/sangue , Bioensaio , Displasia Broncopulmonar/sangue , Displasia Broncopulmonar/prevenção & controle , Calibragem , Cromatografia Líquida de Alta Pressão , Teste em Amostras de Sangue Seco/instrumentação , Monitoramento de Medicamentos/instrumentação , Idade Gestacional , Humanos , Recém-Nascido , Limite de Detecção , Padrões de Referência , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem
18.
JAMA ; 321(4): 354-363, 2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30694322

RESUMO

Importance: Dexamethasone initiated after the first week of life reduces the rate of death or bronchopulmonary dysplasia (BPD) but may cause long-term adverse effects in very preterm infants. Hydrocortisone is increasingly used as an alternative, but evidence supporting its efficacy and safety is lacking. Objective: To assess the effect of hydrocortisone initiated between 7 and 14 days after birth on death or BPD in very preterm infants. Design, Setting, and Participants: Double-blind, placebo-controlled randomized trial conducted in 19 neonatal intensive care units in the Netherlands and Belgium from November 15, 2011, to December 23, 2016, among preterm infants with a gestational age of less than 30 weeks and/or birth weight of less than 1250 g who were ventilator dependent between 7 and 14 days of life, with follow-up to hospital discharge ending December 12, 2017. Interventions: Infants were randomly assigned to receive a 22-day course of systemic hydrocortisone (cumulative dose, 72.5 mg/kg) (n = 182) or placebo (n = 190). Main Outcomes and Measures: The primary outcome was a composite of death or BPD assessed at 36 weeks' postmenstrual age. Twenty-nine secondary outcomes were analyzed up to hospital discharge, including death and BPD at 36 weeks' postmenstrual age. Results: Among 372 patients randomized (mean gestational age, 26 weeks; 55% male), 371 completed the trial; parents withdrew consent for 1 child treated with hydrocortisone. Death or BPD occurred in 128 of 181 infants (70.7%) randomized to hydrocortisone and in 140 of 190 infants (73.7%) randomized to placebo (adjusted risk difference, -3.6% [95% CI, -12.7% to 5.4%]; adjusted odds ratio, 0.87 [95% CI, 0.54-1.38]; P = .54). Of 29 secondary outcomes, 8 showed significant differences, including death at 36 weeks' postmenstrual age (15.5% with hydrocortisone vs 23.7% with placebo; risk difference, -8.2% [95% CI, -16.2% to -0.1%]; odds ratio, 0.59 [95% CI, 0.35-0.995]; P = .048). Twenty-one outcomes showed nonsignificant differences, including BPD (55.2% with hydrocortisone vs 50.0% with placebo; risk difference, 5.2% [95% CI, -4.9% to 15.2%]; odds ratio, 1.24 [95% CI, 0.82-1.86]; P = .31). Hyperglycemia requiring insulin therapy was the only adverse effect reported more often in the hydrocortisone group (18.2%) than in the placebo group (7.9%). Conclusions and Relevance: Among mechanically ventilated very preterm infants, administration of hydrocortisone between 7 and 14 days after birth, compared with placebo, did not improve the composite outcome of death or BPD at 36 weeks' postmenstrual age. These findings do not support the use of hydrocortisone for this indication. Trial Registration: Netherlands National Trial Register Identifier: NTR2768.


Assuntos
Anti-Inflamatórios/administração & dosagem , Displasia Broncopulmonar/prevenção & controle , Hidrocortisona/administração & dosagem , Doenças do Prematuro/mortalidade , Recém-Nascido de muito Baixo Peso , Anti-Inflamatórios/efeitos adversos , Método Duplo-Cego , Humanos , Hidrocortisona/efeitos adversos , Incidência , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/prevenção & controle , Unidades de Terapia Intensiva Neonatal , Respiração Artificial , Tempo para o Tratamento , Falha de Tratamento
19.
J Obstet Gynaecol Res ; 45(5): 967-973, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30687995

RESUMO

AIM: The optimal antibiotic regimen for preterm premature rupture of membrane (pPROM) is still unclear. This study aimed to determine the effects of ampicillin-sulbactam (SBT/ABPC) and azithromycin (AZM) on the incidence of bronchopulmonary dysplasia (BPD). METHODS: This retrospective study included women with singleton gestations and a diagnosis of pPROM between 22 and 27 weeks of gestation. In patients presenting with a high risk of intra-amniotic infection between January 2011 and May 2013, piperacillin or cefmetazole + clindamycin (regimen 1 group; n = 11) was administered, whereas SBT/ABPC and AZM (regimen 2 group; n = 11) were administered in patients presenting a similar risk between June 2013 and May 2016. RESULTS: The incidence of moderate or severe infant BPD in the regimen 2 group was significantly lower than that in the regimen 1 group, even when adjusted for gestational age at the time of rupture of membrane, with an odds ratio (95% confidence interval) of 0.02 (1.8 × 10-5 -0.33). The incidence of BPD and total days on mechanical ventilation were significantly lower in the regimen 2 group than in the regimen 1 group. No significant differences were seen in other morbidities. CONCLUSION: In patients with pPROM between 22 and 27 weeks of gestation, the administration of SBT/ABPC and AZM may improve the perinatal outcomes.


Assuntos
Antibacterianos/farmacologia , Azitromicina/farmacologia , Displasia Broncopulmonar/prevenção & controle , Ruptura Prematura de Membranas Fetais/tratamento farmacológico , Adulto , Ampicilina/administração & dosagem , Ampicilina/farmacologia , Antibacterianos/administração & dosagem , Azitromicina/administração & dosagem , Displasia Broncopulmonar/epidemiologia , Cefmetazol/farmacologia , Clindamicina/farmacologia , Quimioterapia Combinada , Feminino , Ruptura Prematura de Membranas Fetais/epidemiologia , Humanos , Incidência , Piperacilina/farmacologia , Gravidez , Estudos Retrospectivos , Sulbactam/administração & dosagem , Sulbactam/farmacologia
20.
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
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