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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.
Pediatr Rev ; 40(10): 517-527, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31575803

RESUMO

Necrotizing enterocolitis (NEC) has been recognized for well over 5 decades yet remains the most common life-threatening surgical emergency in the newborn. The incidence of NEC has decreased steadily in preterm and very-low-birthweight infants over several decades and is typically uncommon in term newborns and infants with a birthweight greater than 2,500 g. Evidence accumulating during the past decade, however, suggests that practitioners should consider NEC in this broader subset of term infants with chromosomal and congenital anomalies complicated by heart or gastrointestinal defects when signs and symptoms of feeding intolerance, abdominal illness, or sepsis are present. The short- and long-term consequences of NEC are devastating in all infants, and although early disease recognition and treatment are essential, promoting human milk feeding as a primary modality in prevention is critical. This article highlights our current understanding of the pathophysiology, the clinical presentation, the risk factors for NEC in term infants compared with premature infants, and the treatment of NEC and discusses strategies in the prevention of NEC. Finally, we review the long-term consequences of NEC and the importance of primary care practitioners in the long-term care of infants after hospitalization for NEC.


Assuntos
Enterocolite Necrosante/diagnóstico , Enterocolite Necrosante/terapia , Cuidado do Lactente/métodos , Doenças do Prematuro/diagnóstico , Doenças do Prematuro/terapia , Recém-Nascido Prematuro , Diagnóstico Diferencial , Enterocolite Necrosante/etiologia , Enterocolite Necrosante/fisiopatologia , Humanos , Recém-Nascido , Doenças do Prematuro/etiologia , Doenças do Prematuro/fisiopatologia , Fatores de Risco , Resultado do Tratamento
3.
Nutrients ; 11(8)2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31416157

RESUMO

Human milk contains non-nutritional factors that promote intestinal maturation and protect against infectious and inflammatory conditions. In the Neonatal Intensive Care Unit (NICU) setting, donor milk (DM) is recommended when availability of own mother's milk (OMM) is not enough. Our aim was to compare the incidence of necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) in very preterm infants (VPI) after the introduction of DM. Growth and breastfeeding rates were examined as secondary outcomes. Single center, observational and retrospective cohort study comparing 227 VPI admitted to our neonatal unit before (Group 1, n = 99) and after (Group 2, n = 128) DM introduction. Enteral nutrition was started earlier after DM availability (2.6 ± 1.1 vs. 2.1 ± 1 days, p = 0.001). Incidence of NEC decreased in group 2 (9.1% vs. 3.4%, p = 0.055), especially in those born between 28 and 32 weeks (5.4 vs. 0.0%, p = 0.044). Surgical NEC was also less frequent. Suffering NEC was 4 times more likely in group 1 (multivariate analysis). Availability of DM did not impact breastfeeding rates or preterm growth. Our findings support the protective role of DM against NEC, particularly in non-extreme VPI, a group less frequently included in clinical guidelines and research studies on the use of DM.


Assuntos
Peso ao Nascer , Alimentação Artificial , Extração de Leite , Desenvolvimento Infantil , Enterocolite Necrosante/prevenção & controle , Recém-Nascido Prematuro/crescimento & desenvolvimento , Leite Humano , Fatores Etários , Enterocolite Necrosante/epidemiologia , Enterocolite Necrosante/fisiopatologia , Idade Gestacional , Humanos , Incidência , Recém-Nascido , Sepse Neonatal/epidemiologia , Sepse Neonatal/fisiopatologia , Sepse Neonatal/prevenção & controle , Valor Nutritivo , Fatores de Proteção , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Espanha/epidemiologia
4.
Am J Physiol Gastrointest Liver Physiol ; 317(1): G57-G66, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31125264

RESUMO

Prenatal inflammation is a risk factor for necrotizing enterocolitis (NEC), and it increases intestinal injury in a rat NEC model. We previously showed that maldevelopment of the intestinal microvasculature and lack of vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) signaling play a role in experimental NEC. However, whether prenatal inflammation affects the intestinal microvasculature remains unknown. In this study, mouse dams were injected intraperitoneally with lipopolysaccharide (LPS) or saline at embryonic day 17. Neonatal intestinal microvasculature density, endothelial cell proliferation, and intestinal VEGF-A and VEGFR2 proteins were assessed in vivo. Maternal and fetal serum TNF concentrations were measured by ELISA. The impact of TNF on the neonatal intestinal microvasculature was examined in vitro and in vivo, and we determined whether prenatal LPS injection exacerbates experimental NEC via TNF. Here we found that prenatal LPS injection significantly decreased intestinal microvascular density, endothelial cell proliferation, and VEGF and VEGFR2 protein expression in neonatal mice. Prenatal LPS injection increased maternal and fetal serum levels of TNF. TNF decreased VEGFR2 protein in vitro in neonatal endothelial cells. Postnatal TNF administration in vivo decreased intestinal microvasculature density, endothelial cell proliferation, and VEGF and VEGFR2 protein expression and increased the incidence of severe NEC. These effects were ameliorated by stabilizing hypoxia-inducible factor-1α, the master regulator of VEGF. Furthermore, prenatal LPS injection significantly increased the incidence of severe NEC in our model, and the effect was dependent on endogenous TNF. Our study suggests that prenatal inflammation increases the susceptibility to NEC, downregulates intestinal VEGFR2 signaling, and affects perinatal intestinal microvascular development via a TNF mechanism. NEW & NOTEWORTHY This report provides new evidence that maternal inflammation decreases neonatal intestinal VEGF receptor 2 signaling and endothelial cell proliferation, impairs intestinal microvascular development, and predisposes neonatal mouse pups to necrotizing enterocolitis (NEC) through inflammatory cytokines such as TNF. Our data suggest that alteration of intestinal microvascular development may be a key mechanism by which premature infants exposed to prenatal inflammation are at risk for NEC and preserving the VEGF/VEGF receptor 2 signaling pathway may help prevent NEC development.


Assuntos
Enterocolite Necrosante/metabolismo , Inflamação/metabolismo , Intestino Delgado/irrigação sanguínea , Microvasos/metabolismo , Neovascularização Fisiológica , Efeitos Tardios da Exposição Pré-Natal , Fator de Necrose Tumoral alfa/metabolismo , Animais , Permeabilidade Capilar , Proliferação de Células , Células Cultivadas , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Enterocolite Necrosante/etiologia , Enterocolite Necrosante/patologia , Enterocolite Necrosante/fisiopatologia , Feminino , Idade Gestacional , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Inflamação/complicações , Inflamação/patologia , Inflamação/fisiopatologia , Lipopolissacarídeos , Camundongos Endogâmicos C57BL , Microvasos/patologia , Microvasos/fisiopatologia , Gravidez , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
5.
J Pediatr Surg ; 54(6): 1168-1173, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30879750

RESUMO

INTRODUCTION: Umbilical mesenchymal stem cells (USC) have been shown to reduce illness in animal models of necrotizing enterocolitis (NEC), possibly through the paracrine release of hydrogen sulfide (H2S). We hypothesized that animals treated with USCs with inhibited H2S synthesis would exhibit more severe disease. METHODS: NEC was induced in five-day-old mouse pups by formula feeding and hypoxic and hypothermic stress. Experimental groups received intraperitoneal injection of either saline vehicle or 80,000cells/gram of one of the following cell types: USC, USCs with negative-control siRNA, or USCs with targeted siRNA inhibition of the H2S-producing enzymes. Pups were monitored by clinical assessment and after euthanasia, intestine and lung histologic injury were scored. Tissue was homogenized, and concentrations of IL-6, IL-10, and VEGF were determined by ELISA. For statistical analysis, p<0.05 was considered significant. RESULTS: Animals treated with negative-control siRNA USCs were significantly improved compared to vehicle. Clinical sickness scores as well as intestinal and lung histologic injury scores in the targeted siRNA groups were significantly worse when compared to the negative-control siRNA group. IL-6, IL-10, and VEGF had varying patterns of expression in the different groups. CONCLUSION: Inhibition of H2S production in USCs reduces the beneficial effects of these cells during therapy in experimental NEC. LEVEL OF EVIDENCE: Animal studies are typically described as "foundational evidence" without a true level assigned. TYPE OF STUDY: Animal Study.


Assuntos
Enterocolite Necrosante , Sulfeto de Hidrogênio , Células-Tronco Mesenquimais , Substâncias Protetoras , Cordão Umbilical/citologia , Animais , Modelos Animais de Doenças , Enterocolite Necrosante/metabolismo , Enterocolite Necrosante/fisiopatologia , Sulfeto de Hidrogênio/metabolismo , Sulfeto de Hidrogênio/farmacologia , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/fisiologia , Camundongos , Substâncias Protetoras/metabolismo , Substâncias Protetoras/farmacologia
6.
Front Biosci (Schol Ed) ; 11: 9-28, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30844734

RESUMO

The etio-pathogenesis of necrotizing enterocolitis (NEC) is complex and multifactorial. Decades of research have not identified a definite etiology. Prematurity, enteral feeding, intestinal hypoxia/ischemia, inflammation and an abnormal microbiome are potential risk factors for developing this multisystem illness. Lack of specific diagnostic and prognostic markers adds to the challenges faced in managing NEC. Vascular mediators such as Nitric oxide (NO), catecholamines and endothelin (ET) regulate neonatal intestinal vascular resistance and may influence the pathophysiology of NEC. Neonatal morbidities, medications, transfusions, an altered microbiome and breast milk feeds may influence the vasculature in various ways. Better understanding of these mediators and their role in regulation of intestinal microcirculation and pathogenesis of NEC will assist in identifying strategies in prevention and management of this devastating illness.


Assuntos
Enterocolite Necrosante/etiologia , Enterocolite Necrosante/metabolismo , Intestinos/patologia , Microcirculação , Óxido Nítrico/metabolismo , Idade de Início , Animais , Arginina/uso terapêutico , Catecolaminas/metabolismo , Modelos Animais de Doenças , Cães , Endotelinas/metabolismo , Enterocolite Necrosante/fisiopatologia , Humanos , Indometacina , Recém-Nascido , Inflamação , Leite Humano , Consumo de Oxigênio , Ratos , Ovinos , Vasodilatadores/metabolismo
7.
J Pediatr Surg ; 54(5): 949-954, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30782443

RESUMO

PURPOSE: Limited data exists for longitudinal growth outcomes in neonates with a history of necrotizing enterocolitis (NEC). We aimed to study 20-year growth outcomes in NEC survivors. METHODS: A retrospective matched cohort study included neonates diagnosed with NEC and control subjects matched for birth year, birth weight, and gestational age who had at least one post-discharge follow-up. The primary outcome was growth, measured by length and weight until 20 years. Logistic regression was used to test the change in growth from birth until most recent encounter. RESULTS: Five hundred twenty-seven neonates were included: 294 with NEC, and 233 controls. Sixty-eight percent of NEC cases were Bell's stage I, 25% were stage II, and 7% were stage III. Median gestational age was 29 weeks, and median birth weight was 1237 g. Infants with NEC had a longer NICU stay (p < 0.0001) and increased number of comorbidities (p < 0.0001). Compared to overall and sex-matched controls, infants with NEC had a significantly slower growth rate in terms of weight (p < 0.0068) but not length (p = 0.09). Neither group exhibited failure to thrive. CONCLUSIONS: These results suggest that non-surgical NEC may have a more profound impact on long-term growth than previously considered. TYPE OF STUDY: Retrospective Cohort-Matched Study. LEVEL OF EVIDENCE: Level III.


Assuntos
Estatura , Peso Corporal , Desenvolvimento Infantil , Enterocolite Necrosante/fisiopatologia , Doenças do Prematuro/fisiopatologia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Comorbidade , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Adulto Jovem
10.
J Neonatal Perinatal Med ; 12(1): 9-12, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30347623

RESUMO

BACKGROUND: Infants with duct-dependent congenital heart lesions are treated with a prostaglandin E1 infusion. We aimed to describe the feeding strategies used at our institution in such infants, and to describe the incidence of necrotising enterocolitis (NEC) in this patient group, investigating whether enteral feeding is associated with a higher risk. METHODS: Patients diagnosed with hypoplastic left heart syndrome, coarctation of the aorta, pulmonary atresia, or transposition of the great arteries born over a defined period were identified. Premature infants, those with pre-existing gastrointestinal disease, and those who never received prostaglandin were excluded. Data were compared using univariable and multivariable logistic regression models. RESULTS: A total of 177 patients were identified, of them 18 received a diagnosis of suspected or confirmed NEC. There was no association between the diagnosis of NEC and enteral feeding (P = 0.9). CONCLUSIONS: Based on these data, there does not appear to be an association between enteral feeding and NEC in infants receiving prostaglandin.


Assuntos
Nutrição Enteral , Cardiopatias Congênitas/terapia , Alprostadil/uso terapêutico , Nutrição Enteral/efeitos adversos , Nutrição Enteral/estatística & dados numéricos , Enterocolite Necrosante/etiologia , Enterocolite Necrosante/fisiopatologia , Feminino , Cardiopatias Congênitas/fisiopatologia , Humanos , Incidência , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Inibidores da Agregação de Plaquetas/uso terapêutico , Estudos Retrospectivos , Fatores de Risco
11.
Neurogastroenterol Motil ; 31(3): e13484, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30298607

RESUMO

BACKGROUND: We have shown previously that a decreased high-frequency spectrum of heart rate variability (HF-HRV), indicative of reduced vagal tone, shows promise in predicting neonates likely to develop necrotizing enterocolitis (NEC) before its clinical onset. We hypothesized that NEC induction in rat pups decreases HF-HRV power; subdiaphragmatic vagotomy worsens the severity of the NEC phenotype, increases levels of pro-inflammatory cytokines, and alters the myenteric phenotype. METHODS: Newborn Sprague-Dawley rats, representative of preterm human neonates, were subjected to 7-8 days of brief periods of cold stress and hypoxia to induce NEC with or without unilateral subdiaphragmatic vagotomy. HRV was measured at postnatal days one and five, pups were sacrificed at day 8/9, and gastrointestinal tissues and blood were collected for immunohistochemical, corticosterone, and cytokine analysis. KEY RESULTS: Compared to control, NEC-induced rats showed the following: (a) typical histological signs of grade 2 NEC, which were more severe in rats that underwent vagotomy; (b) reduced developmental increases in time (RMSSD) and frequency (HF) HRV spectra when combined with the stress of laparotomy/vagotomy; (c) increases in nitric oxide synthase-immunoreactivity in the myenteric plexus of jejunum and ileum; furthermore, compared to mild NEC and controls, vagotomized NEC rats had increased plasma values of pro-inflammatory cytokines IL-1ß and IL-6. CONCLUSIONS AND INFERENCES: Our data suggest that in rodents, similar to neonatal observations, NEC induction attenuated developmental HF-HRV increases, furthermore, subdiaphragmatic vagotomy worsened the histological severity, increased pro-inflammatory cytokines, and altered the nitrergic myenteric phenotype, suggesting a role of the vagus in the development of NEC pathology.


Assuntos
Enterocolite Necrosante/fisiopatologia , Frequência Cardíaca , Animais , Animais Recém-Nascidos , Corticosterona/sangue , Citocinas/metabolismo , Feminino , Imuno-Histoquímica , Interleucina-1beta/sangue , Interleucina-6/sangue , Masculino , Plexo Mientérico/fisiopatologia , Óxido Nítrico Sintase/metabolismo , Gravidez , Ratos , Ratos Sprague-Dawley , Vagotomia
12.
BMC Pediatr ; 18(1): 372, 2018 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-30482190

RESUMO

BACKGROUND: Necrotizing enterocolitis (NEC) is a leading cause of death in preterm infants. Neonates weighing <1500 grams are at the highest risk for acquiring NEC, with a prevalence of nearly 7-10%, mortality up to 30%, and several long-term complications among survivors. Despite advancements in neonatal medicine, this disease remains a challenge to treat. The aim of this study is to investigate the effect of NEC on gut epithelial tight junctions and its barrier function using a NEC mouse model. METHODS: Three-day old C57BL/6 mouse pups were fed with Esbilac formula every 3 hours and then subjected to hypoxia twice daily followed by cold stress. Dam fed pups from the same litters served as controls. Pups were observed and sacrificed 96 hours after the treatments and intestines were removed for experiments. The successful induction of NEC was confirmed by histopathology. Changes in tight junction proteins in NEC intestines were studied by western blotting and immunofluorescent microscopy using specific protein markers. The gut leakage in NEC was visualized using biotin tracer molecules. RESULTS: Our study results demonstrate that we induced NEC in >50% of experimental pups, pups lost nearly 40% of weight and their intestines showed gross changes and microscopic changes associated with NEC. There were inflammatory changes with loss of tight junction barrier function and disruption of tight junction claudin proteins in the intestines of NEC mouse model. We have demonstrated for the first time that NEC intestines develop increased leakiness as visualized by biotin tracer leakage. CONCLUSIONS: NEC leads to breakdown of epithelial barrier due to changes in tight junction proteins with increased leakiness which may explain the transmigration of microbes and microbial products from the gut lumen into the blood stream leading to sepsis like signs clinically witnessed.


Assuntos
Permeabilidade Capilar/fisiologia , Enterocolite Necrosante/patologia , Enterocolite Necrosante/fisiopatologia , Mucosa Intestinal/irrigação sanguínea , Junções Íntimas/patologia , Animais , Claudinas/sangue , Modelos Animais de Doenças , Mediadores da Inflamação/sangue , Mucosa Intestinal/patologia , Camundongos , Camundongos Endogâmicos C57BL
13.
Sci Rep ; 8(1): 12612, 2018 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-30135601

RESUMO

Necrotizing enterocolitis (NEC) is one of the most devastating diseases affecting premature and mature infants. It is hypothesized that NEC is the result of neutrophils' active role in hyperinflammation after bacterial gut colonization, through their nuclear DNA release and formation of neutrophil extracellular traps (NETs) to combat pathogens. The aim of this study was to evaluate the importance of NETs in NEC pathogenesis, as well as to identify and validate markers of NETosis to predict NEC. NEC was induced in mice by gavage feeding of Neocate and lipopolysaccharide, followed by ten minutes of hypoxia (5% O2) q12h for five days, starting on day four postpartum (p.p.). The interrelation of NEC and neutrophils, including NETs, was assessed macroscopically (i.e. NEC score, SYTOX Orange), microscopically (i.e. Chiu score, citrullinated histone H3, neutrophil elastase), and in blood samples (i.e. cell-free DNA (cfDNA), DNase). In order to determine the exact role of NETs in NEC pathogenesis, a protein arginine deiminase (PAD) inhibition model was established (preventing NETs formation in mice) by injecting BB-Cl-amidine once daily, starting on day one p.p. Additionally, human intestinal samples of diagnostically verified NEC were analyzed. In total, 76 mice were analyzed in the experiment. Serum cfDNA correlated positively with NEC manifestation, as measured by macroscopic NEC score (r = 0.53, p = 0.001), and microscopic evaluation with Chiu score (r = 0.56, p < 0.001). Markers of neutrophil activation and NETosis were significantly increased in animals with NEC and in human samples as compared to controls. Further, prevention of NETosis by protein arginine deiminase (PAD) inhibition in mice significantly reduced mortality, tissue damage, and inflammation in mice induced with NEC. Our results suggest that the hyperinflammation observed in NEC is a NETs-dependent process, as NEC severity was significantly reduced in mice incapable of forming NETs (PAD inhibition) and markers for NEC and NETs correlated positively during the time course of NEC induction. Further, serum surrogate markers of NETosis (such as cfDNA and DNase) appear to predict NEC in neonatal mice. As findings of the mouse NEC model correlate positively with human NEC samples immunohistochemically, the hyperinflammation reaction observed in mice could potentially be applied to human NEC pathogenesis.


Assuntos
Enterocolite Necrosante/metabolismo , Armadilhas Extracelulares/metabolismo , Aminoácidos/farmacologia , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Carboidratos/farmacologia , Ácidos Nucleicos Livres , Células Cultivadas , Desoxirribonuclease I , Gorduras na Dieta/farmacologia , Modelos Animais de Doenças , Enterocolite Necrosante/fisiopatologia , Armadilhas Extracelulares/fisiologia , Feminino , Microbioma Gastrointestinal/fisiologia , Humanos , Hidrolases , Lactente , Recém-Nascido , Inflamação/metabolismo , Elastase de Leucócito/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ativação de Neutrófilo/fisiologia , Neutrófilos/metabolismo , Desiminases de Arginina em Proteínas/metabolismo
14.
Nutrients ; 10(6)2018 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-29857555

RESUMO

This systematic review and meta-analysis synthesised the post-1990 literature examining the effect of human milk on morbidity, specifically necrotising enterocolitis (NEC), late onset sepsis (LOS), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD) and neurodevelopment in infants born ≤28 weeks' gestation and/or publications with reported infant mean birth weight of ≤1500 g. Online databases including Medline, PubMed, CINAHL, Scopus, and the Cochrane Central Register of Controlled Trials were searched, and comparisons were grouped as follows: exclusive human milk (EHM) versus exclusive preterm formula (EPTF), any human milk (HM) versus EPTF, higher versus lower dose HM, and unpasteurised versus pasteurised HM. Experimental and observational studies were pooled separately in meta-analyses. Risk of bias was assessed for each individual study and the GRADE system used to judge the certainty of the findings. Forty-nine studies (with 56 reports) were included, of which 44 could be included in meta-analyses. HM provided a clear protective effect against NEC, with an approximate 4% reduction in incidence. HM also provided a possible reduction in LOS, severe ROP and severe NEC. Particularly for NEC, any volume of HM is better than EPTF, and the higher the dose the greater the protection. Evidence regarding pasteurisation is inconclusive, but it appears to have no effect on some outcomes. Improving the intake of mother's own milk (MOM) and/or donor HM results in small improvements in morbidity in this population.


Assuntos
Nutrição Enteral , Medicina Baseada em Evidências , Fenômenos Fisiológicos da Nutrição do Lactente , Doenças do Prematuro/prevenção & controle , Leite Humano , Nascimento Prematuro/dietoterapia , Enterocolite Necrosante/etiologia , Enterocolite Necrosante/fisiopatologia , Enterocolite Necrosante/prevenção & controle , Humanos , Lactente , Fórmulas Infantis , Lactente Extremamente Prematuro , Recém-Nascido , Doenças do Prematuro/etiologia , Doenças do Prematuro/fisiopatologia , Recém-Nascido de muito Baixo Peso , Sepse Neonatal/etiologia , Sepse Neonatal/fisiopatologia , Sepse Neonatal/prevenção & controle , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/fisiopatologia , Transtornos do Neurodesenvolvimento/prevenção & controle , Nascimento Prematuro/fisiopatologia , Índice de Gravidade de Doença
15.
Semin Perinatol ; 42(4): 253-261, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29954594

RESUMO

Optimal management of patent ductus arteriosus (PDA) is unclear. One treatment, surgical ligation, is associated with adverse outcomes. We reviewed data from the Kids' Inpatient Database (2000-2012) to determine if PDA ligation rates: (1) changed over time, (2) varied geographically, or (3) influenced surgical complication rates. In 2012, 47,900 infants <1500g birth weight were born in the United States, including 2,800 undergoing PDA ligation (5.9%). Ligation was more likely in infants <1000g (85.9% vs. 46.2%), and associated with necrotizing enterocolitis (59.2% vs. 37.5%), BPD (54.6% vs. 15.2%), severe intraventricular hemorrhage (16.4% vs. 5.3%), and hospital transfer (37.6% vs. 16.4%). Ligation rates peaked in 2006 at 87.4 per 1000 hospital births, dropping to 58.8 in 2012, and were consistently higher in Western states. Infants undergoing ligation were more likely to experience comorbidities. Rates of ligation-associated vocal cord paralysis increased over time (1.2-3.9%); however, mortality decreased (12.4-6.5%). Thus, PDA ligation has become less frequent, although infants being ligated are smaller and more medically complex. Despite increase in some complications, mortality rates improved perhaps reflecting advances in care.


Assuntos
Permeabilidade do Canal Arterial/epidemiologia , Permeabilidade do Canal Arterial/cirurgia , Recém-Nascido de muito Baixo Peso , Ligadura/efeitos adversos , Ligadura/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Hemorragia Cerebral Intraventricular/epidemiologia , Hemorragia Cerebral Intraventricular/etiologia , Hemorragia Cerebral Intraventricular/fisiopatologia , Estudos Transversais , Permeabilidade do Canal Arterial/fisiopatologia , Enterocolite Necrosante/epidemiologia , Enterocolite Necrosante/etiologia , Enterocolite Necrosante/fisiopatologia , Feminino , Humanos , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Recém-Nascido , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos/epidemiologia , Paralisia das Pregas Vocais/epidemiologia , Paralisia das Pregas Vocais/etiologia , Paralisia das Pregas Vocais/fisiopatologia
16.
J Neonatal Perinatal Med ; 11(3): 231-239, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29843272

RESUMO

BACKGROUND: Necrotizing Enterocolitis (NEC) is a multifactorial condition where PRBC transfusion is associated with necrotizing enterocolitis (TANEC) in about a third of all cases of NEC. We have investigated the role of feeding practices in incidence of TANEC. We sought to compare infants diagnosed with TANEC versus infants diagnosed with classic NEC and investigated the effects of a standardized slow enteral feeding (SSEF) protocol on TANEC incidence as well as the effects of SSEF on growth of infants with NEC. METHODS: We conducted a retrospective cohort study, where medical records of infants born in a tertiary care neonatal intensive care unit (level IIIb) from January 1997 to May 2014 with birth weight < 1500 grams and gestational age≤34 weeks with NEC stage IIa or greater according to the modified Bell's staging were reviewed. RESULTS: During the study period, 111 infants developed NEC, and 41/111 (37%) were diagnosed with TANEC. Infants with TANEC were smaller, more premature, had higher SNAPPE scores and were more anemic prior to transfusion compared with infants with 'classic NEC'. The severity of NEC did not differ between the two groups, however, infants with TANEC had worse outcomes and longer NICU stays. Introduction of SSEF protocol, led to a significant decrease in TANEC. There was no difference in weight and head circumference of infants in the two groups at 2 years corrected age. CONCLUSION: SSEF led to a significant reduction in the incidence of TANEC without impairing growth at 2 years corrected age.


Assuntos
Transfusão de Sangue/métodos , Nutrição Enteral/métodos , Enterocolite Necrosante/terapia , Doenças do Prematuro/terapia , Reação Transfusional , Enterocolite Necrosante/etiologia , Enterocolite Necrosante/fisiopatologia , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/fisiopatologia , Recém-Nascido de muito Baixo Peso , Masculino , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
17.
Mediators Inflamm ; 2018: 7456857, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29686534

RESUMO

This state-of-the-art review article aims to highlight the most recent evidence about the therapeutic options of surgical necrotizing enterocolitis, focusing on the molecular basis of the gut-brain axis in relevance to the neurodevelopmental outcomes of primary peritoneal drainage and primary laparotomy. Current evidence favors primary laparotomy over primary peritoneal drainage as regards neurodevelopment in the surgical treatment of necrotizing enterocolitis. The added exposure to inhalational anesthesia in infants undergoing primary laparotomy is an additional confounding variable but requires further study. The concept of the gut-brain axis suggests that bowel injury initiates systemic inflammation potentially affecting the developing central nervous system. Signals about microbes in the gut are transduced to the brain and the limbic system via the enteric nervous system, autonomic nervous system, and hypothalamic-pituitary axis. Preterm infants with necrotizing enterocolitis have significant differences in the diversity of the microbiome compared with preterm controls. The gut bacterial flora changes remarkably prior to the onset of necrotizing enterocolitis with a predominance of pathogenic organisms. The type of initial surgical approach correlates with the length of functional gut and microbiome equilibrium influencing brain development and function through the gut-brain axis. Existing data favor patients who were treated with primary laparotomy over those who underwent primary peritoneal drainage in terms of neurodevelopmental outcomes. We propose that this is due to the sustained injurious effect of the remaining diseased and necrotic bowel on the developing newborn brain, in patients treated with primary peritoneal drainage, through the gut-brain axis and probably not due to the procedure itself.


Assuntos
Encéfalo/fisiologia , Enterocolite Necrosante/fisiopatologia , Animais , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Microbiota/fisiologia
18.
J Pediatr Surg ; 53(6): 1197-1202, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29627178

RESUMO

PURPOSE: The purpose of this study was to examine postnatal growth outcomes and predictors of growth failure at 18-24months corrected age among extremely low birth weight (ELBW) survivors of necrotizing enterocolitis (NEC) compared to survivors without NEC. METHODS: Data were collected prospectively on ELBW (22-27weeks gestation or 401-1000g birth weight) infants born 2000-2013 at 46 centers participating in the Vermont Oxford Network follow-up project. Severe growth failure was defined as <3rd percentile weight-for-age. RESULTS: There were 9171 evaluated infants without NEC, 416 with medical NEC, and 462 with surgical NEC. Rates of severe growth failure at discharge were higher among infants with medical NEC (56%) and surgical NEC (61%), compared to those without NEC (36%). At 18-24months follow-up, rates of severe growth failure decreased and were similar between without NEC (24%), medical NEC (24%), and surgical NEC (28%). On multivariable analysis, small for gestational age, chronic lung disease, severe intraventricular hemorrhage or cystic periventricular leukomalacia, severe growth failure at discharge, and postdischarge tube feeding predicted <3rd percentile weight-for-age at follow-up. CONCLUSIONS: ELBW survivors of NEC have higher rates of severe growth failure at discharge. While NEC is not associated with severe growth failure at follow-up, one quarter of ELBW infants have severe growth failure at 18-24months. TYPE OF STUDY: Prognosis study. LEVEL OF EVIDENCE: II.


Assuntos
Enterocolite Necrosante/fisiopatologia , Transtornos do Crescimento/etiologia , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Doenças do Prematuro/fisiopatologia , Nutrição Enteral , Enterocolite Necrosante/complicações , Enterocolite Necrosante/terapia , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/terapia , Masculino , Alta do Paciente , Sobreviventes
19.
Adv Neonatal Care ; 18(2): 121-127, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29300196

RESUMO

BACKGROUND: The multifactorial pathology and broad clinical presentation of necrotizing enterocolitis (NEC) development in premature infants make prediction of disease onset extremely challenging. Over the past decade, packed red blood cell (PRBC) transfusions have been temporally linked to the development of NEC in severely anemic preterm infants, although this issue is highly controversial. PURPOSE: In this case study, we describe events of an extremely low birth-weight infant who developed NEC complicated by pneumoperitoneum after receiving multiple PRBC transfusions. Specifically, we describe mesenteric tissue oxygenation trend changes as measured by continuous near-infrared spectroscopy (NIRS) technology. METHODS: As part of a larger prospective, observational investigation, this infant was monitored with NIRS (INVOS 5100C; Medtronic, Boulder, Colorado) before, during, and 48 hours following PRBC transfusions. RESULTS: The infant demonstrated severe, prolonged, and persistent reductions in mesenteric tissue oxygenation following blood transfusions, yet routine physiologic monitoring did not indicate intestinal hypoperfusion or impending NEC onset. IMPLICATIONS FOR PRACTICE: This report demonstrates the ability of NIRS to capture possible tissue ischemia during early stages of NEC that may help guide bedside therapeutic interventions. IMPLICATIONS FOR RESEARCH: Larger cohort studies to evaluate the ability of NIRS to capture early tissue ischemia are essential to validate the feasibility of adding this technology as a routine clinical bedside tool.Video Abstract available at https://journals.lww.com/advancesinneonatalcare/Pages/videogallery.aspx.


Assuntos
Enterocolite Necrosante/etiologia , Enterocolite Necrosante/fisiopatologia , Doenças do Prematuro/etiologia , Reação Transfusional/complicações , Bacteriemia/complicações , Transfusão de Sangue , Enterocolite Necrosante/terapia , Feminino , Humanos , Ileostomia , Recém-Nascido , Doenças do Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Leite Humano , Oxigênio/fisiologia , Pneumoperitônio/complicações , Estudos Prospectivos , Fatores de Risco , Resultado do Tratamento
20.
Am J Perinatol ; 35(8): 774-778, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29298457

RESUMO

INTRODUCTION: Necrotizing enterocolitis (NEC) is a devastating disease of infancy. Full-thickness bowel wall necrosis may lead to perforation, peritonitis, and death. Timeous clinical diagnosis of impending perforation is imperative. OBJECTIVE: The objective of this study was to determine whether a persistent tachycardia in an infant with proven NEC is indicative of full-thickness bowel wall necrosis and therefore impending perforation. STUDY DESIGN: This study was conducted at the University of Pretoria academic hospitals. Forty-five neonates with proven NEC were divided into a surgical group (32 progressed to full-thickness bowel necrosis) and a nonsurgical group (13 resolved on conservative treatment). Differences in the pulse rate between the groups were analyzed. RESULTS: The 24-hour leading average pulse rate data for the surgical group were analyzed over a period of 10 days leading up to surgery and compared with the nonsurgical group. A clear upward trend of the mean pulse rate was observed in the surgical group, 48 hours prior to surgery. This was statistically significant (p < 0.05). CONCLUSION: This study demonstrated that a persistent tachycardia in a neonate with NEC is a predictor of progression to full-thickness bowel wall necrosis. Pulse rate is therefore an important clinical tool when deciding on operative management in NEC.


Assuntos
Enterocolite Necrosante/fisiopatologia , Frequência Cardíaca , Perfuração Intestinal/fisiopatologia , Taquicardia/diagnóstico , Progressão da Doença , Enterocolite Necrosante/complicações , Enterocolite Necrosante/cirurgia , Feminino , Humanos , Recém-Nascido , Perfuração Intestinal/complicações , Perfuração Intestinal/cirurgia , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Taquicardia/etiologia
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