Hypertension induced by pregnancy and neonatal outcome: Results from a retrospective cohort study in preterm under 34 weeks.

OBJECTIVE: The present study seeks to assess the impact of gestational hypertensive disorders on premature newborns below 34 weeks and to establish the main morbidities and mortality in the neonatal period and at 18 months. MATERIALS AND METHODS: A retrospective observational study was carried out with 695 premature newborns of gestational age (GA) between 24 and 33 weeks and 6 days, born alive in the Neonatal ICU of Brasília's Mother and Child Hospital (HMIB), in the period from January 1, 2014, to July 31, 2019. In total, 308 infants were born to hypertensive mothers (G1) and 387 to normotensive mothers (G2). Twin pregnancies and diabetic patients with severe malformations were excluded. Outcomes during hospitalization and outcomes of interest were evaluated: respiratory distress syndrome (RDS), brain ultrasonography, diagnosis of bronchopulmonary dysplasia (BPD), diagnosis of necrotizing enterocolitis, retinopathy of prematurity, breastfeeding rate at discharge, survival at discharge and at 18 months of chronological age and relationship between weight and gestational age. RESULTS: Newborns with hypertensive mothers had significantly lower measurements of birth weight and head circumference. The G1 group had a higher risk small for gestational age (OR 2.4; CI 95% 1.6-3.6; p <0.00), as well as a greater risk of being born with a weight less than 850 g (OR 2.4; 95% CI 1.2-3.5; p <0.00). Newborns of mothers with hypertension presented more necrotizing enterocolitis (OR 2.0; CI 95% 1.1-3.7); however, resuscitation in the delivery room and the need to use surfactant did not differ between groups, nor did the length of stay on mechanical ventilation, or dependence on oxygen at 36 weeks of gestational age. Survival was better in newborns of normotensive mothers, and this was a protective factor against death (OR 0.7; 95% CI 0.5-0.9; p <0.01). In the follow-up clinic, survival at 18 months of chronological age was similar between groups, with rates of 95.3% and 92.1% among hypertensive and normotensive mothers, respectively. Exclusive breastfeeding at discharge was 73.4% in the group of hypertensive women and 77.3% in the group of normotensive mothers. There were no significant differences between groups. CONCLUSION: Among the analyzed outcomes, arterial hypertension during pregnancy can increase the risk of low weight, small babies for gestational age (SGA), deaths in the neonatal period and enterocolitis, with no differences in weight and survival at 18 months of chronological age. Arterial hypertension presents a high risk of prematurity in the neonatal period, with no difference at 18 months of age.

Acute kidney injury in newborns with necrotizing enterocolitis: risk factors and mortality / Daño renal agudo en recién nacidos con enterocolitis necrotizante: factores de riesgo y mortalidad

Abstract Background: Both necrotizing enterocolitis and acute kidney injury are tightly related conditions, which independently increase mortality in newborns. Necrotizing enterocolitis is an inflammatory disease with a systemic repercussion that leads to inflammatory kidney changes predisposing to renal damage. Methods: This study assessed risk factors for the development of acute kidney injury in patients diagnosed with necrotizing enterocolitis and compared mortality between patients with or without acute kidney injury. Thirty-nine patients with the diagnosis of necrotizing enterocolitis were included, regardless of the gestational age. Results: Of 39 patients, 38.5% developed acute kidney injury. Survival showed to be significantly lower in patients with acute kidney injury (54.4 days) when compared to newborns without acute kidney injury (76.22 days; p = 0.014). Mortality in patients with acute kidney injury was 46.7%, increasing up to 62.5% with severe kidney damage. The hazard ratio for mortality was 4.708 for acute kidney injury (p = 0.025). The severity of enterocolitis showed to be an independent risk factor in developing acute kidney injury and severe kidney injury (odds ratio [OR] = 1.841, p = 0.034 and OR = 1.917, p = 0.027, respectively). Conclusions: Newborns with necrotizing enterocolitis should be evaluated for early recognition of acute kidney injury. Prospective studies with a higher number of patients are needed to identify modifiable risk factors to impact in the prevention of these conditions.

Resumen Introducción: La enterocolitis necrosante y el daño renal agudo son condiciones íntimamente relacionadas que incrementan independientemente la mortalidad en recién nacidos. La enterocolitis necrosante es una enfermedad inflamatoria sistémica que desencadena cambios renales inflamatorios, predisponiendo el desarrollo de daño renal. Métodos: Se analizaron los factores de riesgo para el desarrollo de daño renal agudo en pacientes con diagnóstico de enterocolitis necrosante y se comparó la mortalidad entre los pacientes sin daño renal y los pacientes con daño renal agudo. Se incluyeron 39 pacientes con diagnóstico de enterocolitis necrosante, independientemente de la edad gestacional. Resultados: De los 39 pacientes, el 38.5% desarrolló daño renal agudo. La sobrevida de los que desarrollaron daño renal agudo (54.4 días) mostró ser significativamente menor al compararse con los recién nacidos que no presentaron daño renal (76.22 días; p = 0.014). La mortalidad en los pacientes con daño renal agudo fue del 46.7%, que se incrementó hasta el 62.5% en aquellos con daño renal grave. El riesgo de mortalidad fue de 4.708 para daño renal agudo (p = 0.025). La gravedad de la enterocolitis necrosante demostró ser un factor de riesgo independiente para el desarrollo de daño renal agudo y de daño renal agudo severo (razón de momios [RM] = 1.841; p = 0.034 y RM = 1.917; p = 0.027, respectivamente). Conclusiones: Los recién nacidos con diagnóstico de enterocolitis necrosante deben ser evaluados para reconocer de forma temprana la presencia de daño renal agudo. Se requiere de estudios prospectivos con mayor número de pacientes para identificar factores de riesgo modificables que puedan impactar en la prevención de estas patologías.

Acute kidney injury in newborns with necrotizing enterocolitis: risk factors and mortality.

Background: Both necrotizing enterocolitis and acute kidney injury are tightly related conditions, which independently increase mortality in newborns. Necrotizing enterocolitis is an inflammatory disease with a systemic repercussion that leads to inflammatory kidney changes predisposing to renal damage. Methods: This study assessed risk factors for the development of acute kidney injury in patients diagnosed with necrotizing enterocolitis and compared mortality between patients with or without acute kidney injury. Thirty-nine patients with the diagnosis of necrotizing enterocolitis were included, regardless of the gestational age. Results: Of 39 patients, 38.5% developed acute kidney injury. Survival showed to be significantly lower in patients with acute kidney injury (54.4 days) when compared to newborns without acute kidney injury (76.22 days; p = 0.014). Mortality in patients with acute kidney injury was 46.7%, increasing up to 62.5% with severe kidney damage. The hazard ratio for mortality was 4.708 for acute kidney injury (p = 0.025). The severity of enterocolitis showed to be an independent risk factor in developing acute kidney injury and severe kidney injury (odds ratio [OR] = 1.841, p = 0.034 and OR = 1.917, p = 0.027, respectively). Conclusions: Newborns with necrotizing enterocolitis should be evaluated for early recognition of acute kidney injury. Prospective studies with a higher number of patients are needed to identify modifiable risk factors to impact in the prevention of these conditions.

Introducción: La enterocolitis necrosante y el daño renal agudo son condiciones íntimamente relacionadas que incrementan independientemente la mortalidad en recién nacidos. La enterocolitis necrosante es una enfermedad inflamatoria sistémica que desencadena cambios renales inflamatorios, predisponiendo el desarrollo de daño renal. Métodos: Se analizaron los factores de riesgo para el desarrollo de daño renal agudo en pacientes con diagnóstico de enterocolitis necrosante y se comparó la mortalidad entre los pacientes sin daño renal y los pacientes con daño renal agudo. Se incluyeron 39 pacientes con diagnóstico de enterocolitis necrosante, independientemente de la edad gestacional. Resultados: De los 39 pacientes, el 38.5% desarrolló daño renal agudo. La sobrevida de los que desarrollaron daño renal agudo (54.4 días) mostró ser significativamente menor al compararse con los recién nacidos que no presentaron daño renal (76.22 días; p = 0.014). La mortalidad en los pacientes con daño renal agudo fue del 46.7%, que se incrementó hasta el 62.5% en aquellos con daño renal grave. El riesgo de mortalidad fue de 4.708 para daño renal agudo (p = 0.025). La gravedad de la enterocolitis necrosante demostró ser un factor de riesgo independiente para el desarrollo de daño renal agudo y de daño renal agudo severo (razón de momios [RM] = 1.841; p = 0.034 y RM = 1.917; p = 0.027, respectivamente). Conclusiones: Los recién nacidos con diagnóstico de enterocolitis necrosante deben ser evaluados para reconocer de forma temprana la presencia de daño renal agudo. Se requiere de estudios prospectivos con mayor número de pacientes para identificar factores de riesgo modificables que puedan impactar en la prevención de estas patologías.

Predicting Mortality or Intestinal Failure in Infants with Surgical Necrotizing Enterocolitis.

OBJECTIVE: To compare existing outcome prediction models and create a novel model to predict death or intestinal failure (IF) in infants with surgical necrotizing enterocolitis (NEC). STUDY DESIGN: A retrospective, observational cohort study conducted in a 2-campus health system in Atlanta, Georgia, from September 2009 to May 2015. Participants included all infants ≤37 weeks of gestation with surgical NEC. Logistic regression was used to model the probability of death or IF, as a composite outcome, using preoperative variables defined by specifications from 3 existing prediction models: American College of Surgeons National Surgical Quality Improvement Program Pediatric, Score for Neonatal Acute Physiology Perinatal Extension, and Vermont Oxford Risk Adjustment Tool. A novel preoperative hybrid prediction model was also derived and validated against a patient cohort from a separate campus. RESULTS: Among 147 patients with surgical NEC, discrimination in predicting death or IF was greatest with American College of Surgeons National Surgical Quality Improvement Program Pediatric (area under the receiver operating characteristic curve [AUC], 0.84; 95% CI, 0.77-0.91) when compared with the Score for Neonatal Acute Physiology Perinatal Extension II (AUC, 0.60; 95% CI, 0.48-0.72) and Vermont Oxford Risk Adjustment Tool (AUC, 0.74; 95% CI, 0.65-0.83). A hybrid model was developed using 4 preoperative variables: the 1-minute Apgar score, inotrope use, mean blood pressure, and sepsis. The hybrid model AUC was 0.85 (95% CI, 0.78-0.92) in the derivation cohort and 0.77 (95% CI, 0.66-0.86) in the validation cohort. CONCLUSIONS: Preoperative prediction of death or IF among infants with surgical NEC is possible using existing prediction tools and, to a greater extent, using a newly proposed 4-variable hybrid model.

Effect of Human Breast Milk on the Expression of Proinflammatory Cytokines in Caco-2 Cells after Hypoxia/Re-Oxygenation.

BACKGROUND: Neonatal necrotizing enterocolitis is a common and often fatal gastrointestinal disease, especially in premature infants. To study potential mechanisms underlying the protective effect of breast milk on neonatal necrotizing enterocolitis, we induced intestinal inflammation in a Caco-2 cell model of neonatal necrotizing enterocolitis by hypoxia/re-oxygenation to investigate whether breast milk supernatant fluid inhibited the expression of proinflammatory cytokines interleukin-1ß, interleukin-6, and tumor necrosis factor-α. METHODS: Caco-2 cells were divided into normal (control) and neonatal necrotizing enterocolitis groups. Neonatal necrotizing enterocolitis was mimicked by exposing Caco-2 cells to hypoxia/re-oxygenation. Cells were independently maintained in minimal essential medium alone, minimal essential medium containing 5% breast milk supernatant, or 5% boiled breast milk supernatant. Production of interleukin-1ß, interleukin-6, and tumor necrosis factor-α was investigated in cell culture supernatants by ELISA, reverse transcription polymerase chain reaction, and immunofluorescence. RESULTS: Hypoxia/re-oxygenation significantly increased the expression of interleukin-1ß, interleukin-6, and tumor necrosis factor-α. In the normal group, breast milk supernatant and boiled breast milk supernatant markedly downregulated the expression of interleukin-1ß, interleukin-6, and tumor necrosis factor-α when compared with the minimal essential medium group, with the reduction in inter-leukin-1ß expression being more pronounced in the breast milk group. In Caco-2 cells undergoing hypoxia/re-oxygenation, both breast milk supernatant and boiled breast milk supernatant significantly reduced the expression of interleukin-1ß, interleukin-6, and tumor necrosis factor-α, where the decrease in interleukin-1ß expression was greater in the breast milk group. CONCLUSIONS: Breast milk supernatant fluid inhibited the expression of proinflammatory cytokines interleukin-1ß, interleukin-6, and tumor necrosis factor-α in Caco-2 cells, especially after hypoxia/re-oxygenation. This may be one of the mechanisms underlying the protective effect of breast milk on neonatal necrotizing enterocolitis.

Effects of maternal ischemic preconditioning in the colon of newborn rats submitted to hypoxia-reoxygenation insult.

PURPOSE: To evaluate the effects of maternal remote ischemic preconditioning (IPCr) in the colonic mucosa of newborn rats subjected to hypoxia and reoxygenation. METHODS: Newborn Wistar rats were divided into three groups. Control Group (CG), Hypoxia and Reoxygenation Group (HRG) and Remote Ischemic Preconditioning Group (IPCrG). Hypoxia and reoxygenation was performed 2x per day, with an interval of 6 hours, on the 1st, 2nd and 3rd days of life, with 10 minutes of CO2 at 100%, followed by 10 minutes O2 at 100%(HRG/IPCrG). The maternal IPCr was performed 24 hours before delivery by applying a rubber band tourniquet to the left hind limb (IPCrG). Segments of the colon underwent histological (HE) and immunohistochemical analysis for caspase-3 and COX - 2. RESULTS: The histological findings showed no intestinal mucosal damage in the CG group and severe lesions in HRG that was attenuated in the IPCrG (p<0.05). The expression of the apoptotic cells was lower in the HRG group than in the CG and IPCrG. The COX-2 expression was intense in HRG and attenuated in the IPCrG (p<0.05). CONCLUSIONS: Maternal IPCr protected the colonic mucosa of newborn rats subjected to hypoxia and reoxygenation, reducing the morphological alterations and inflammatory response. It ameliorates the occurrence of apoptosis, keeping the physiological process of renewal and regeneration in the epithelial lining of the colonic mucosa.

Effects of maternal ischemic preconditioning in the colon of newborn rats submitted to hypoxia-reoxygenation insult

PURPOSE: To evaluate the effects of maternal remote ischemic preconditioning (IPCr) in the colonic mucosa of newborn rats subjected to hypoxia and reoxygenation. METHODS: Newborn Wistar rats were divided into three groups. Control Group (CG), Hypoxia and Reoxygenation Group (HRG) and Remote Ischemic Preconditioning Group (IPCrG). Hypoxia and reoxygenation was performed 2x per day, with an interval of 6 hours, on the 1st, 2nd and 3rd days of life, with 10 minutes of CO2 at 100%, followed by 10 minutes O2 at 100%(HRG/IPCrG). The maternal IPCr was performed 24 hours before delivery by applying a rubber band tourniquet to the left hind limb (IPCrG). Segments of the colon underwent histological (HE) and immunohistochemical analysis for caspase-3 and COX - 2. RESULTS: The histological findings showed no intestinal mucosal damage in the CG group and severe lesions in HRG that was attenuated in the IPCrG (p<0.05). The expression of the apoptotic cells was lower in the HRG group than in the CG and IPCrG. The COX-2 expression was intense in HRG and attenuated in the IPCrG (p<0.05). CONCLUSIONS: Maternal IPCr protected the colonic mucosa of newborn rats subjected to hypoxia and reoxygenation, reducing the morphological alterations and inflammatory response. It ameliorates the occurrence of apoptosis, keeping the physiological process of renewal and regeneration in the epithelial lining of the colonic mucosa. .

Urinary intestinal fatty acid binding protein predicts necrotizing enterocolitis.

Necrotizing enterocolitis, characterized by sudden onset and rapid progression, remains the most significant gastrointestinal disorder among premature infants. In seeking a predictive biomarker, we found intestinal fatty acid binding protein, an indicator of enterocyte damage, was substantially increased within three and seven days before the diagnosis of necrotizing enterocolitis.

Fisiopatología de la enterocolitis necrotizante (ECN) / Pathophysiology of necrotizing enterocolitis (NEC)

La enterocolitis necrotizante (ECN) es la emergencia gastrointestinal más frecuente en recién nacidos (RN)de pretérmino; pese a ello su patogenia es aún motivo de investigación; el tratamiento es difícil y frecuentementeha probado no ser el más adecuado y hasta el momento no se ha encontrado una estrategia de prevención realmenteeficaz.1 A pesar de que el uso de corticoides prenatales podría disminuir su incidencia,2 como observamos ennuestro laboratorio, no tendría la misma acción en los seres humanos. En este contexto de comprensión de las bases biológicas de la génesis de la entidad enmarcamos la presente revisión bibliográfica.

Milk epidermal growth factor and gut protection.

Maternal milk is a complex fluid, with multifunctional roles within the developing gastrointestinal tract. Epidermal growth factor (EGF) and heparin-binding EGF-like growth factor (HB-EGF) are members of the family of EGF-related peptides. Biological actions of these growth factors are mediated via interaction with the EGF-receptor (EGF-R). In the early postnatal period, breast milk is the major source of EGF for the developing intestinal mucosa. HB-EGF is also detected in breast milk, but in concentrations 2 to 3 times lower than EGF. With normal physiological conditions, the intestinal epithelium undergoes a continuing process of cell proliferation, differentiation, and maturation. EGF plays an important role in these processes. In pathophysiologic situations, EGF contributes to epithelial protection from injury and post-injury mucosal repair. Necrotizing enterocolitis (NEC) is a devastating disease affecting infants born prematurely. The pathogenesis of NEC is not known, and there is no effective treatment for this disease. In an experimental NEC model, oral administration of a physiological dose of EGF significantly reduces the incidence and severity of NEC. HB-EGF provides similar protection against NEC, but only when pharmacological doses are used. Further studies are necessary before EGF can be introduced as an efficient therapeutic approach of intestinal injury.

Estado actual de las imágenes en enterocolitis necrotizante: radiografía simple y ultrasonido / Current state of the images in necrotizing enterocolitis: ultrasound and radiography

La enterocolitis necrotizante (ECN) es la causa más común de abdomen agudo durante el período neonatal. La radiografía (Rx) de abdomen simple ha sido la modalidad de elección para la evaluación y seguimiento de los pacientes. Con alguna frecuencia, los hallazgos no son específicos o muestran signos discordantes, por lo que no contribuyen a realizar cambios precoces en el manejo médico o quirúrgico. Estudios recientes han reportado la utilidad del ultrasonido (US) en la evaluación complementaria del paciente con ECN, permitiendo evaluar engrosamiento parietal, estado de perfusión de las asas intestinales y presencia de líquido peritoneal. El objetivo de este artículo es actualizar las indicaciones de la Rx simple y del US en el diagnóstico y seguimiento de los recién nacidos con ECN.

Necrotizing enterocolitis is the most common cause of acute abdomen during the neonatal period. Plain film of abdomen has been the modality of choice for the evaluation and follow up of this patients. Sometimes, radiographic findings are not specific or do not help to make early changes of medical or surgical management. Recent papers have reported the utility of the ultrasound in the complementary evaluation of the patient with necrotizing enterocolitis, showing parietal thickening and perfusion of the intestinal wall and peritoneal fluid, as additional findings. In this article images of both techniques and applications are commented.

Endothelial nitric oxide synthase in human intestine resected for necrotizing enterocolitis.

OBJECTIVE: To determine the expression and function of endothelial nitric oxide synthase (eNOS) in submucosal arterioles harvested from human intestine resected for necrotizing enterocolitis (NEC) or congenital bowel disease. STUDY DESIGN: eNOS expression was determined by using immunohistochemistry. The arteriolar diameter was measured in vitro at pressures of 10 to 40 mm Hg and also in response to the eNOS agonist acetylcholine (ACh), the exogenous nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine, and the smooth muscle relaxant papaverine. Arteriolar release of NO in response to ACh was determined with a Sievers NOAnalyzer. Hemodynamics were also determined at flow rates of 50 and 100 microL/min. RESULTS: eNOS was present in microvessels from both groups, but NEC arterioles failed to demonstrate physiological evidence of eNOS function: they constricted in response to pressure, failed to dilate or generate NO in response to ACh, and failed to dilate in response to flow. However, they dilated in response to exogenous NO and papaverine, indicating functional vascular smooth muscle and vasodilator reserve. CONCLUSION: eNOS-derived NO, a vasodilator in the newborn intestine, did not contribute to vasoregulation in arterioles harvested from intestine resected for NEC. These vessels were constricted; lack of eNOS-derived NO may contribute to this vasoconstriction.

Endothelin-1 in human intestine resected for necrotizing enterocolitis.

OBJECTIVES: We asked if the tissue concentration of the potent vasoconstrictor endothelin-1 (ET-1) is greater in areas of human preterm intestine that demonstrate histologic evidence of necrotizing enterocolitis (NEC) when compared with relatively healthy areas within the same resection specimen. We then evaluated if ET-1 participates in hemodynamic regulation within intestinal subserosal arterioles harvested from portions of human preterm intestine that demonstrate NEC. STUDY DESIGN: Human preterm intestine resected for NEC was divided into three zones based on proximity to the perforation (zone 1 most proximal, zone 3 most distal). Histologic evidence of NEC was determined in each zone (normal = 0, advanced necrosis = 6). The tissue concentration of ET-1 was determined by enzyme-linked immunosorbent assay within intestinal homogenates prepared from each zone. Arteriolar hemodynamics were determined in vitro on subserosal arterioles harvested from different zones. Arteriolar flow rate, diameter, and resistance were determined at pressure gradients (DeltaP) of 20 and 40 mmHg under control conditions and again after blockade of endothelin ET A receptors with BQ610 (10 -9 mol/L). RESULTS: The tissue concentration of ET-1 (pg/mg protein) and histologic score in the three zones were: zone 1: 84 +/- 14, 5.5 +/- 0.3; zone 2: 99 +/- 12, 4.7 +/- 0.4, and zone 3: 33 +/- 9, 0.8 +/- 0.6, respectively (M +/- SD, n = 10 resection specimens, P < .05, zone 3 vs zones 1 and 2). Zone 2 arterioles demonstrated significantly lower flow rate and diameter and increased resistance under control conditions than zone 3 arterioles when DeltaP was either 20 or 40 mmHg (n = 7, P < .05). Treatment with BQ610 had no effect on zone 3 arterioles but significantly vasodilated zone 2 arterioles, increasing flow rate and vessel diameter, and decreasing vascular resistance (n = 7, P < .05). CONCLUSIONS: The tissue concentration of ET-1 is greater in human preterm intestine that demonstrates histologic evidence of NEC. Arterioles harvested from intestine exhibiting histologic evidence of NEC demonstrate vasoconstriction when compared with arterioles from relatively healthy intestine in the same resection specimen. This vasoconstriction was reversed by blockade of endothelin ET A receptors.

[Advances in necrotizing enterocolitis]. / Avanços em enterocolite necrosante.

OBJECTIVE: To evaluate recently reported findings on necrotizing enterocolitis, Paying particular attention to pathogenesis, management and preventative strategies. DATA SOURCES: The articles covered in this report consist of randomized and quasi-randomized trials, case control studies, meta-analyses and reviews published recently. Certain other articles were also included because of their utmost importance to the subject. RESULTS: Necrotizing enterocolitis remains a major cause of morbidity and mortality in preterm infants. Those who are born with intra-uterine-growth retardation are at a several-fold increased risk. Possible pathophysiologic processes beginning in utero and continuing after birth are discussed in this review. Other factors involved in the process are related to the role of arginine and the production of intestinal nitric oxide and the action of epidermal growth factor in the regulation of cell regeneration. Perforated necrotizing enterocolitis is a complex surgical problem; definitive evidence-based guidelines for the best approach are yet to be determined. After surgery, although residual small bowel length and the presence of the ileo-cecal valve remain important predictors of duration of parenteral nutrition in infants, other factors, such as the early use of breast milk or amino acid-based formula, may also play a role in intestinal re-adaptation. Prevention strategies have centered on feeding practices and emerging experiments such as amino acid supplementation, are also discussed. CONCLUSION: Significant results in terms of mortality and morbidity will be achieved through better understanding of necrotizing enterocolitis pathogenesis and clinical and surgical management in addition to the employment of preventative strategies.

Avanços em enterocolite necrosante / Advances in necrotizing enterocolitis

OBJETIVO: Avaliar relatos recentes sobre a enterocolite necrosante, com especial interesse na etiopatogenia, manejo e prevenção. FONTE DOS DADOS: Os artigos utilizados nessa revisão consistem em ensaios randomizados ou semi-randomizados, estudos de caso-controle, metanálises e artigos de revisão recentemente publicados. Alguns outros artigos foram selecionados devido à sua importância para o tema. RESULTADOS: A enterocolite necrosante é uma importante causa de morbimortalidade neonatal em prematuros. Entre esses, os nascidos com retardo de crescimento intra-uterino apresentam um risco mais elevado. O processo fisiopatológico inicia-se intra-útero e continua após o nascimento. Entre outros fatores envolvidos na fisiopatologia, estão a ação da arginina na produção do óxido nítrico intestinal e a ação do fator de crescimento epidérmico na regeneração celular. A perfuração intestinal ainda é um problema cirúrgico, e evidências melhores quanto à sua abordagem precisam ser avaliadas. Após a cirurgia, a extensão da alça intestinal remanescente, a preservação da válvula ileocecal, assim como a utilização precoce de leite materno ou solução de aminoácidos, são determinantes na duração da nutrição parenteral e no sucesso da readaptação intestinal. Estratégias preventivas estão centradas nas práticas alimentares e, recentemente, na suplementação de aminoácidos. CONCLUSAO: Com um melhor entendimento do processo fisiopatológico, do manejo clínico e cirúrgico, assim como das medidas de prevenção, importantes resultados serão alcançados em termos de redução da morbimortalidade conseqüente à enterocolite necrosante.

Tolerance of a sterile isotonic electrolyte solution containing select recombinant growth factors in neonates recovering from necrotizing enterocolitis.

OBJECTIVE: To assess the tolerance of a sterile isotonic electrolyte solution containing select recombinant growth factors enterally administered in neonates who were NPO because of necrotizing enterocolitis (NEC). STUDY DESIGN: A phase I trial was accomplished among 30 neonates. Patients received 5, 10, or 20 mL enterally of the study solution/kg/day divided into every 3-hour dosing, for 3 days prior to when feedings of milk were to resume. The occurrence of emesis, gastric residuals, diarrhea, bloody stools, abdominal distention, skin rashes and death were sought. RESULTS: Gestational ages ranged from 25.2 to 41.1 weeks. A total of 16 neonates had Stage IA NEC, six Stage IB, and eight Stage IIA. The solution was well tolerated in all 30; none developed diarrhea, guaiac positive or bloody stools, or abdominal distention. Administration of the solution was not prematurely discontinued in any infant. Two neonates died secondary to late-onset sepsis remote from the study period. CONCLUSIONS: Enteral administration of a sterile isotonic electrolyte solution containing select recombinant growth factors was well tolerated by neonates with NEC.

Necrotizing enterocolitis, pathogenesis and the protector effect of prenatal corticosteroids.

Necrotizing enterocolitis is the most frequently occurring gastrointestinal disorder in premature neonates. Animal models of necrotizing enterocolitis and prenatal administration of cortisone have demonstrated that cortisone may accelerate maturation of the mucosal barrier, therefore reducing the incidence of this gastrointestinal disorder. The authors present a review of the literature of the most important risk factors associated with necrotizing enterocolitis, such as inflammatory gastrointestinal mediators, enteral feeding and bacterial colonization, and immaturity of the gastrointestinal barrier, and we emphasize the necessity for additional studies to explore the prenatal administration of cortisone as a preventive strategy for necrotizing enterocolitis.