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OBJECTIVE: Probiotic supplementation is associated with health benefits in preterm infants. The 2021 American Academy of Pediatrics (AAP) statement on probiotic use advised caution, citing heterogeneity and absence of federal regulation. We assessed the impact of the AAP statement and current institution-wide patterns of probiotic use across neonatal intensive care units (NICU) across the United States. STUDY DESIGN: A cross-sectional web-based institutional survey using REDCap was emailed to 430 Children's Hospital Neonatal Consortium (CHNC) and Pediatrix Medical Group institutions. The survey captured data on probiotic formulations, supplementation, initiation and cessation criteria, reasons for discontinuation, interest in initiating, and AAP statement's impact. RESULTS: Ninety-five (22.1%) hospitals, including 42/46 (91%) CHNC and 53/384 (14%) Pediatrix institutions, completed the survey. Thirty-seven (39%) currently use probiotics. Fourteen different probiotic formulations were reported. The common criteria for initiation were birth weight <1,500 g and gestational age <32 weeks. Parental consent or assent was obtained at only 30% of institutions. Five hospitals (11%) with prior probiotic use discontinued solely due to the AAP statement. Overall, 23 (24%) of hospitals indicated that the AAP statement significantly influenced their decision regarding probiotic use. Nineteen of 51 nonusers (37%) are considering initiation. CONCLUSION: Probiotic use in preterm infants is likely increasing in NICUs across the United States, but significant variability exists. The 2021 AAP statement had variable impact on NICUs' decision regarding probiotic use. The growing interest in adopting probiotics and the significant interhospital variability highlight the need for better regulation and consensus guidelines to ensure standardized use. KEY POINTS: · Probiotic use in preterm infants is likely increasing in U.S. NICUs, but clinical variability exists.. · The AAP statement on probiotic use in preterm infants had a modest impact on current practices.. · There's a need for better product regulation and consensus guidelines to ensure standardized use..
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OBJECTIVE: To compare extrahepatic adverse events during fish oil lipid emulsion (FOLE) or soybean oil lipid emulsion (SOLE) treatment in children with intestinal failure-associated liver disease (IFALD). STUDY DESIGN: In this multicenter integrated analysis, bleeding, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), infections, and signs of lipid emulsion intolerance were compared between FOLE recipients (1 g/kg/d) (n = 189) and historical controls who received SOLE (≤3 g/kg/d) (n = 73). RESULTS: When compared with SOLE recipients, FOLE recipients had a lower gestational age (30.5 vs 33.0 weeks; P = .0350) and higher baseline direct bilirubin (DB) (5.8 vs 3.0 mg/dL; P < .0001). FOLE recipients had a decreased incidence of bleeding (P < .0001), BPD (P < .001), ROP (P < .0156), bacterial and fungal infections (P < .0001), and lipid intolerance signs (P < .02 for all). Patients with bleeding vs patients without bleeding had higher baseline DB; the ORs for baseline DB (by mg/dL) and treatment (FOLE vs SOLE) were 1.20 (95% CI: 1.10, 1.31; P ≤ .0001) and 0.22 (95% CI: 0.11, 0.46; P ≤ .0001), respectively. In preterm infants, a higher BPD (P < .0001) and ROP incidence (P = .0071) was observed in SOLE recipients vs FOLE recipients. CONCLUSIONS: Children with IFALD who received FOLE had fewer extrahepatic adverse events, including a decreased incidence of bleeding, preterm comorbidities, and lipid intolerance signs compared with children with IFALD who received SOLE. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT00910104 and NCT00738101.
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Emulsiones Grasas Intravenosas/efectos adversos , Aceites de Pescado/efectos adversos , Insuficiencia Intestinal/terapia , Hepatopatías/etiología , Nutrición Parenteral/efectos adversos , Aceite de Soja/efectos adversos , Emulsiones Grasas Intravenosas/uso terapéutico , Femenino , Aceites de Pescado/uso terapéutico , Humanos , Lactante , Recién Nacido , Insuficiencia Intestinal/complicaciones , Masculino , Nutrición Parenteral/métodos , Estudios Retrospectivos , Aceite de Soja/uso terapéutico , Resultado del TratamientoRESUMEN
Necrotizing enterocolitis (NEC) is a manifestation of maladaptive intestinal responses in preterm infants centrally medicated by unattenuated inflammation. Early in the postnatal period, preterm infants develop a deficit in arachidonic and docosahexaenoic acid, both potent regulators of inflammation. We hypothesized that the fatty acid composition of parenteral lipid emulsions uniquely induces blood and intestinal fatty acid profiles which, in turn, modifies the risk of NEC development. Forty-two preterm pigs were randomized to receive one of three lipid emulsions containing 100% soybean oil (SO), 15% fish oil (MO15), or 100% fish oil (FO100) with enteral feedings over an 8-day protocol. Blood and distal ileum tissue were collected for fatty acid analysis. The distal ileum underwent histologic, proteomic, and metabolomic analyses. Eight pigs [3/14 SO (21%), 3/14 MO15 (21%), and 2/14 FO100 (14%)] developed NEC. No differences in NEC risk were evident between groups despite differences in induced fatty acid profiles in blood and ileal tissue. Metabolomic analysis of NEC versus no NEC tissue revealed differences in tryptophan metabolism and arachidonic acid-containing glycerophospholipids. Proteomic analysis demonstrated no differences by lipid group; however, 15 proteins differentiated NEC versus no NEC in the domains of tissue injury, glucose uptake, and chemokine signaling. Exposure to parenteral lipid emulsions induces unique intestinal fatty acid and metabolomic profiles; however, these profiles are not linked to a difference in NEC development. Metabolomic and proteomic analyses of NEC versus no NEC intestinal tissue provide mechanistic insights into the pathogenesis of NEC in preterm infants.NEW & NOTEWORTHY Exposure to parenteral lipid emulsions induces unique intestinal fatty acid and metabolomic profiles; however, these profiles are not linked to a difference in NEC risk in preterm pigs. Metabolomic and proteomic analyses provide mechanistic insights into NEC pathogenesis. Compared with healthy ileal tissue, metabolites in tryptophan metabolism and arachidonic acid-containing glycerophospholipids are increased in NEC tissue. Proteomic analysis differentiates NEC versus no NEC in the domains of tissue injury, glucose uptake, and chemokine signaling.
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Enterocolitis Necrotizante/veterinaria , Emulsiones Grasas Intravenosas/farmacología , Ácidos Grasos/metabolismo , Íleon/efectos de los fármacos , Metaboloma , Animales , Enterocolitis Necrotizante/inducido químicamente , Humanos , Íleon/metabolismo , Nutrición Parenteral/efectos adversos , Nacimiento Prematuro , Factores de Riesgo , Porcinos , Enfermedades de los Porcinos/inducido químicamenteRESUMEN
OBJECTIVE: To compare the aspartate aminotransferase to platelet ratio index, liver transplantation, and mortality rates between children with intestinal failure-associated liver disease who received fish oil lipid emulsion (FOLE) or soybean oil intravenous lipid emulsion (SOLE). STUDY DESIGN: In this multicenter integrated analysis, FOLE recipients (1 g/kg/d) (n = 189) were compared with historical controls administered SOLE (≤3 g/kg/d) (n = 73). RESULTS: Compared with SOLE, FOLE recipients had a higher direct bilirubin level at baseline (5.8 mg/dL vs 3.0 mg/dL; P < .0001). Among FOLE recipients, 65% experienced cholestasis resolution vs 16% of SOLE recipients (P < .0001). The aspartate aminotransferase to platelet ratio index scores improved in FOLE recipients (1.235 vs 0.810 and 0.758, P < .02) but worsened in SOLE recipients (0.540 vs 2.564 and 2.098; P ≤ .0003) when baseline scores were compared with cholestasis resolution and end of study, respectively. Liver transplantation was reduced in FOLE vs SOLE (4% vs 12%; P = .0245). The probability of liver transplantation in relation to baseline direct or conjugated bilirubin (DB) was lower in FOLE vs SOLE recipients (1% vs 9% at DB of 2 mg/dL; 8% vs 35% at DB of 12.87 mg/dL; P = .0022 for both). Death rates were similar (FOLE vs SOLE: 10% vs 14% at DB of 2 mg/dL; 17% vs 23% at a DB of 12.87 mg/dL; P = .36 for both). CONCLUSIONS: FOLE recipients experienced a higher rate of cholestasis resolution, lower aspartate aminotransferase to platelet ratio index, and fewer liver transplants compared with SOLE. This study demonstrates that FOLE may be the preferred parenteral lipid emulsion in children with intestinal failure-associated liver disease when DB reaches 2 mg/dL. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00910104 and NCT00738101.
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Colestasis/terapia , Emulsiones Grasas Intravenosas/administración & dosificación , Aceites de Pescado/administración & dosificación , Nutrición Parenteral Total/efectos adversos , Aspartato Aminotransferasas/sangre , Estudios de Casos y Controles , Colestasis/etiología , Colestasis/mortalidad , Femenino , Aceites de Pescado/farmacología , Humanos , Lactante , Recién Nacido , Enfermedades Intestinales/complicaciones , Trasplante de Hígado/estadística & datos numéricos , Masculino , Aceite de Soja/administración & dosificación , Aceite de Soja/efectos adversosRESUMEN
OBJECTIVE: To compare growth in children with intestinal failure-associated liver disease (IFALD) who received a fish oil intravenous lipid emulsion (FOLE) to those who received a soybean oil intravenous lipid emulsion (SOLE). STUDY DESIGN: This multisite, retrospective study pair-matched FOLE (n = 82) to SOLE recipients (n = 41) using baseline serum direct bilirubin levels and postmenstrual age. Study subjects received open-label FOLE (1 g/kg/day) until IFALD resolved or parenteral nutrition was stopped. Historical control subjects received SOLE (up to 3 g/kg/day). Growth measures (changes in body weight, height/length, and head circumference), prealbumin, triglycerides, and glucose were compared between groups over time using the Wilcoxon rank-sum test. RESULTS: Although changes in all of the growth measures were similar for both groups (P > .05), FOLE recipients demonstrated an overall improved growth trajectory. After 28 weeks, FOLE recipients had a mean body weight within a z score range of -1 to 1 indicating age-appropriate growth. FOLE recipients consistently had higher prealbumin, lower triglyceride, and more normal glucose concentrations over time compared with SOLE recipients. CONCLUSIONS: Children with IFALD who received FOLE had similar growth and fewer metabolic abnormalities compared with those who received SOLE. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00910104 and NCT00738101.
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Aceites de Pescado/administración & dosificación , Crecimiento/efectos de los fármacos , Enfermedades Intestinales/terapia , Hepatopatías/terapia , Nutrición Parenteral/métodos , Estudios de Casos y Controles , Preescolar , Ingestión de Energía , Emulsiones Grasas Intravenosas , Ácidos Grasos , Femenino , Humanos , Masculino , Estudios RetrospectivosAsunto(s)
Inteligencia Artificial , Recien Nacido Prematuro , Humanos , Recién Nacido , Intestinos/lesionesRESUMEN
BACKGROUND: Preterm infants who are fed breast milk in comparison to infant formula have decreased morbidity such as necrotizing enterocolitis. Multi-nutrient fortifiers used to increase the nutritional content of the breast milk are commonly derived from bovine milk. Human milk-derived multi-nutrient fortifier is now available, but it is not clear if it improves outcomes in preterm infants fed with breast milk. OBJECTIVES: To determine whether the fortification of breast milk feeds with human milk-derived fortifier in preterm infants reduces mortality, morbidity, and promotes growth and development compared to bovine milk-derived fortifier. SEARCH METHODS: We searched the following databases for relevant trials in September 2018. Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 9), electronic journal reference databases including MEDLINE (1980 to 20 September 2018), PREMEDLINE, Embase (1974 to 20 September 2018), CINAHL (1982 to 20 September 2018), biological abstracts in the database BIOSIS and conference abstracts from 'Proceedings First' (from 1992 to 2011). We also included the following clinical trials registries for ongoing or recently completed trials: ClinicalTrials.gov (ClinicalTrials.gov), the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP; www.whoint/ictrp/search/en/) and the ISRCTN Registry (www.isrctn.com/), and abstracts of conferences: proceedings of Pediatric Academic Societies (American Pediatric Society, Society for Pediatric Research and European Society for Paediatric Research) from 1990 in the 'Pediatric Research' journal and 'Abstracts online' (2000 to 2017). SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials that compared preterm infants fed breast milk fortified with human milk-derived fortifier versus those fed with breast milk fortified with bovine milk-derived fortifier. DATA COLLECTION AND ANALYSIS: The data were collected using the standard methods of Cochrane Neonatal. Two authors evaluated trial quality of the studies and extracted data. We reported dichotomous data using risk ratios (RRs), risk differences (RDs), number needed to treat (NNT) where applicable, and continuous data using mean differences (MDs). We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: One randomized trial with 127 infants met the eligibility criteria and had low risk of bias. Human milk-based fortifier did not decrease the risk of necrotizing enterocolitis in exclusively breast milk-fed preterm infants (RR 0.95, 95% CI 0.2 to 4.54; 1 study, 125 infants, low certainty of evidence). Human milk-derived fortifiers did not improve growth, decrease feeding intolerance, late-onset sepsis, or death. AUTHORS' CONCLUSIONS: There is insufficient evidence evaluating human milk-derived fortifier with bovine milk-derived fortifier in exclusively breast milk-fed preterm infants. Low-certainty evidence from one study suggests that in exclusively breast milk-fed preterm infants human milk-derived fortifiers in comparison with bovine milk-derived fortifier may not change the risk of necrotizing enterocolitis, mortality, feeding intolerance, infection, or improve growth. Well-designed randomized controlled trials are needed to evaluate short-term and long-term outcomes.
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Enterocolitis Necrotizante/prevención & control , Fenómenos Fisiológicos Nutricionales del Lactante , Recien Nacido Prematuro/crecimiento & desarrollo , Animales , Bovinos , Alimentos Fortificados , Humanos , Lactante , Fórmulas Infantiles , Recién Nacido , Leche , Leche Humana , Ensayos Clínicos Controlados Aleatorios como Asunto , Sepsis/prevención & controlRESUMEN
Necrotizing enterocolitis (NEC) is associated with low plasma arginine and vascular dysfunction. It is not clear whether low intestinal citrulline production, the precursor for arginine synthesis, occurs before and thus predisposes to NEC or if it results from tissue damage. This study was designed to test the hypothesis that whole body rates of citrulline, arginine, and nitric oxide synthesis are low in premature pigs and that they precede NEC. Piglets delivered by cesarean section at 103 days [preterm (PT)], 110 days [near-term (NT)], or 114 days [full-term (FT)] of gestation were given total parenteral nutrition and after 2 days orogastrically fed infant formula for 42 h to induce NEC. Citrulline and arginine fluxes were determined before and during the feeding protocol. Gross macroscopic and histological NEC scores and plasma fatty acid binding protein (iFABP) concentration were determined as indicators of NEC. Intestinal gene expression for enzymes of the arginine pathway were quantitated. A lower ( P < 0.05) survival rate was observed for PT (8/27) than for NT (9/9) and FT pigs (11/11). PT pigs had higher macroscopic gross ( P < 0.05) and histological NEC ( P < 0.05) scores and iFABP concentration ( P < 0.05) than pigs of more advanced gestational age. PT pigs had lower citrulline production and arginine fluxes ( P < 0.05) throughout and a reduced gene expression in genes of the citrulline-arginine pathway. In summary, intestinal enzyme expression and whole body citrulline and arginine fluxes were reduced in PT pigs compared with animals of more advance gestational age and preceded the development of NEC. NEW & NOTEWORTHY Arginine supplementation prevents necrotizing enterocolitis (NEC), the most common gastrointestinal emergency of prematurity. Citrulline (precursor for arginine) production is reduced during NEC, and this is believed to be a consequence of intestinal damage. In a swine model of NEC, we show that intestinal gene expression of the enzymes for citrulline production and whole body citrulline and arginine fluxes are reduced and precede the onset of NEC in premature pigs. Reduced citrulline production during prematurity may be a predisposition to NEC.
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Arginina/metabolismo , Citrulina/metabolismo , Enterocolitis Necrotizante/etiología , Desarrollo Fetal , Mucosa Intestinal/metabolismo , Óxido Nítrico/metabolismo , Animales , Enterocolitis Necrotizante/metabolismo , Enterocolitis Necrotizante/patología , Mucosa Intestinal/crecimiento & desarrollo , Mucosa Intestinal/patología , PorcinosRESUMEN
BACKGROUND: Necrotizing enterocolitis (NEC) is an inflammatory bowel necrosis of premature infants. Based on our recent findings of increased Smad7 expression in surgically resected bowel affected by NEC, we hypothesized that NEC macrophages undergo inflammatory activation because increased Smad7 expression renders these cells resistant to normal, gut-specific, transforming growth factor (TGF)-ß-mediated suppression of inflammatory pathways. METHODS: We used surgically resected human NEC tissue, murine models of NEC-like injury, bone marrow-derived and intestinal macrophages, and RAW264.7 cells. Smad7 and IκB kinase-beta (IKK-ß) were measured by quantitative PCR, western blots, and immunohistochemistry. Promoter activation was confirmed in luciferase reporter and chromatin immunoprecipitation assays. RESULTS: NEC macrophages showed increased Smad7 expression, particularly in areas with severe tissue damage and high bacterial load. Lipopolysaccharide-induced Smad7 expression suppressed TGF-ß signaling and augmented nuclear factor-kappa B (NF-κB) activation and cytokine production in macrophages. Smad7-mediated NF-κB activation was likely mediated via increased expression of IKK-ß, which, further increased Smad7 expression in a feed-forward loop. We show that Smad7 induced IKK-ß expression through direct binding to the IKK-ß promoter and its transcriptional activation. CONCLUSION: Smad7 expression in NEC macrophages interrupts TGF-ß signaling and promotes NF-κB-mediated inflammatory signaling in these cells through increased expression of IKK-ß.
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Enterocolitis Necrotizante/metabolismo , Mucosa Intestinal/metabolismo , Macrófagos/metabolismo , Proteína smad7/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Animales , Humanos , Quinasa I-kappa B/metabolismo , Inflamación , Lipopolisacáridos/metabolismo , Ratones , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Células RAW 264.7 , Transducción de SeñalRESUMEN
Argininosuccinate lyase (ASL) is required for the synthesis and channeling of L-arginine to nitric oxide synthase (NOS) for nitric oxide (NO) production. Congenital ASL deficiency causes argininosuccinic aciduria (ASA), the second most common urea-cycle disorder, and leads to deficiency of both ureagenesis and NO production. Subjects with ASA have been reported to develop long-term complications such as hypertension and neurocognitive deficits despite early initiation of therapy and the absence of documented hyperammonemia. In order to distinguish the relative contributions of the hepatic urea-cycle defect from those of the NO deficiency to the phenotype, we performed liver-directed gene therapy in a mouse model of ASA. Whereas the gene therapy corrected the ureagenesis defect, the systemic hypertension in mice could be corrected by treatment with an exogenous NO source. In an ASA subject with severe hypertension refractory to antihypertensive medications, monotherapy with NO supplements resulted in the long-term control of hypertension and a decrease in cardiac hypertrophy. In addition, the NO therapy was associated with an improvement in some neuropsychological parameters pertaining to verbal memory and nonverbal problem solving. Our data show that ASA, in addition to being a classical urea-cycle disorder, is also a model of congenital human NO deficiency and that ASA subjects could potentially benefit from NO supplementation. Hence, NO supplementation should be investigated for the long-term treatment of this condition.
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Aciduria Argininosuccínica/tratamiento farmacológico , Aciduria Argininosuccínica/fisiopatología , Terapia Genética , Óxido Nítrico/deficiencia , Óxido Nítrico/farmacología , Adolescente , Animales , Arginina/sangre , Argininosuccinatoliasa/genética , Aciduria Argininosuccínica/complicaciones , Aciduria Argininosuccínica/genética , Preescolar , Cromatografía Líquida de Alta Presión , Modelos Animales de Enfermedad , Humanos , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Hígado/enzimología , Masculino , Ratones , Óxido Nítrico/biosíntesisRESUMEN
UNLABELLED: We describe an infant with popliteal pterygia, syngnathia, cleft lip and palate, and retrognathia diagnosed with popliteal pterygium syndrome (PPS). The neonatal course was complicated by severe obstructive apnea necessitating tracheostomy. CONCLUSION: This report illustrates the potential for airway compromise in PPS patients and the need for thorough neonatal airway assessment.
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Anomalías Múltiples , Apnea/etiología , Labio Leporino/complicaciones , Fisura del Paladar/complicaciones , Anomalías del Ojo/complicaciones , Dedos/anomalías , Articulación de la Rodilla/anomalías , Deformidades Congénitas de las Extremidades Inferiores/complicaciones , Mandíbula/anomalías , Maxilar/anomalías , Anomalías de la Boca/complicaciones , Sindactilia/complicaciones , Anomalías Urogenitales/complicaciones , Apnea/diagnóstico , Labio Leporino/diagnóstico , Fisura del Paladar/diagnóstico , Anomalías del Ojo/diagnóstico , Femenino , Humanos , Recién Nacido , Deformidades Congénitas de las Extremidades Inferiores/diagnóstico , Imagen por Resonancia Magnética , Masculino , Anomalías de la Boca/diagnóstico , Embarazo , Diagnóstico Prenatal , Sindactilia/diagnóstico , Anomalías Urogenitales/diagnósticoRESUMEN
BACKGROUND: To determine variables associated with outcomes in infants with intestinal failure (IF) and ostomy following reanastomosis (RA). METHODS: A single-center, descriptive cohort study of 120 infants with IF and a stoma from January 2011 to December 2020 with subsequent RA during initial hospitalization. The primary outcome was achievement of enteral autonomy (EA) following RA. Other outcomes were duration of hospital stay, and mortality. Penalized logistic regression and linear regression were used for data analysis. RESULTS: The median gestational age was 26 weeks, and the median birth weight was 890 g. Three infants died. The median duration between ostomy creation and RA was 80 days (interquartile range; 62.5, 100.5). For each additional day of discontinuity, the odds of EA decreased by 2% (odds ratio [OR] = 0.980; 95% confidence interval [CI]: 0.962, 0.999; P = 0.038), and death increased by 4.2% (OR = 1.042; 95% CI: 1.010, 1.075; P = 0.009). For each additional mL/kg/day of enteral feeds at RA, the odds of EA increased by 7.5% (OR = 1.075; 95% CI: 1.027, 1.126, P = 0.002) and duration of hospital stay decreased by 0.35 days (slope coefficient = -0.351; 95% CI: -0.540, -0.163; P < 0.001). CONCLUSION: Shorter duration of intestinal discontinuity and enteral nutrition before RA could positively influence EA and duration of stay in infants with IF and ostomy following RA.
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Insuficiencia Intestinal , Estomía , Lactante , Humanos , Estudios de Cohortes , Intestinos/cirugía , Peso al NacerRESUMEN
OBJECTIVE: To evaluate the relationship between cholestasis and outcomes in medical and surgical necrotizing enterocolitis (NEC). STUDY DESIGN: A retrospective analysis of prospectively collected data from 1472 infants with NEC [455 medical (mNEC) and 1017 surgical (sNEC)] from the Children's Hospital Neonatal Database. RESULTS: The prevalence of cholestasis was lower in mNEC versus sNEC (38.2% vs 70.1%, p < 0.001). In both groups, cholestasis was associated with lower birth gestational age [mNEC: OR 0.79 (95% CI 0.68-0.92); sNEC: OR 0.86 (95% CI 0.79-0.95)] and increased days of parenteral nutrition [mNEC: OR 1.08 (95% CI 1.04-1.13); sNEC: OR 1.01 (95% CI 1.01-1.02)]. For both groups, the highest direct bilirubin was associated with the composite outcome mortality or length of stay >75th percentile [mNEC: OR 1.21 (95% CI 1.06-1.38); sNEC: OR 1.06 (95% CI 1.03-1.09)]. CONCLUSION: Cholestasis with both medical NEC and surgical NEC is associated with adverse patient outcomes including increased mortality or extreme length of stay.
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Colestasis , Enterocolitis Necrotizante , Enfermedades del Recién Nacido , Lactante , Niño , Recién Nacido , Humanos , Estudios Retrospectivos , Enterocolitis Necrotizante/epidemiología , Enterocolitis Necrotizante/cirugía , Enterocolitis Necrotizante/etiología , Edad Gestacional , Nutrición Parenteral/efectos adversos , Enfermedades del Recién Nacido/etiología , Colestasis/etiologíaRESUMEN
OBJECTIVE: Determine short-term outcomes following peritoneal drain (PD), laparotomy (LAP) after PD (PD-LAP), and LAP in extremely low birth weight (ELBW) infants with spontaneous intestinal perforation (SIP). STUDY DESIGN: ELBW infants with SIP were identified using the Children's Hospitals Neonatal Database. Mortality and length of stay (LOS) were compared among groups. RESULTS: Of 729 SIP infants from 6/2010-12/2016, 383(53%) received PD, 61(8%) PD-LAP, and 285(39%) LAP. PD infants had lower GA at birth, at SIP diagnosis and upon admission than PD-LAP or LAP; and higher sepsis rates than LAP. Bivariate analysis and Kaplan-Meier survival estimates suggested PD had increased mortality vs. PD-LAP and LAP (27%, 11.5%, and 15.8% respectively, p < 0.001). However, surgical approach was not significantly associated with mortality in multivariable analysis accounting for GA and illness severity. LOS did not differ by surgical approach. CONCLUSIONS: In ELBW infants with SIP, mortality, and LOS are independent of the initial surgical approach.
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OBJECTIVE: To determine factors leading to resolution of cholestasis in patients with parenteral nutrition-associated liver disease treated with fish oil-based lipid emulsion (FOLE). STUDY DESIGN: Prospective observational study of 57 infants <6 months of age with parenteral nutrition-associated liver disease who received parenteral FOLE as monotherapy. RESULTS: Median gestational age of subjects at birth was 28 weeks (range 22.7-39.5). Median conjugated bilirubin level at initiation of therapy with FOLE was 7.5 mg/dL (range 2.1-25). Resolution of hyperbilirubinemia (conjugated bilirubin <2.0 mg/dL) and survival to hospital discharge occurred in 47 (82.5%) infants. Median number of days to resolution of cholestasis was 35 (range 7-129). Ten infants (17.5%) died. Non-survivors showed a trend towards being more premature than survivors at birth (25.9 vs 29.1 weeks, P = .056). Infants with higher conjugated bilirubin at initiation of therapy (>10.0 compared with <5.0 mg/dL) had longer times to resolution (98 vs 56 days, P < .005). Time to resolution correlated inversely with gestational age at birth (r(2) = 0.14, P = .02) and directly with time to receive 100% calories enterally (r(2) = 0.12, P = .03). CONCLUSIONS: Younger gestational age infants demonstrated higher degree of cholestasis, longer time to resolution of cholestasis, and increased mortality. Higher levels of cholestasis were associated with longer time to resolution. FOLE monotherapy led to resolution of cholestasis in all surviving infants.
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Colestasis/etiología , Colestasis/terapia , Hepatopatías/etiología , Hepatopatías/terapia , Nutrición Parenteral/efectos adversos , Emulsiones Grasas Intravenosas/administración & dosificación , Femenino , Aceites de Pescado , Humanos , Hiperbilirrubinemia/complicaciones , Hiperbilirrubinemia/terapia , Lactante , Recién Nacido , Lípidos/química , Masculino , Estudios Prospectivos , Riesgo , Resultado del TratamientoRESUMEN
Necrotizing enterocolitis (NEC) is a neonatal disease with high mortality and morbidity. There is a lack of evidence-based recommendations on nutritional rehabilitation following NEC, and much of the current practice is guided by institutional policies and expert opinions. After a diagnosis of NEC, infants are exposed to an extended period of bowel rest and a prolonged course of antibiotics. Recognizing the patient characteristics that predict nutritional tolerance, early initiation of enteral nutrition, minimizing periods of bowel rest and antibiotic exposure, and standardization of dietary practices are the mainstay of post-NEC nutrition.
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Enterocolitis Necrotizante , Enfermedades Fetales , Enfermedades del Recién Nacido , Lactante , Femenino , Recién Nacido , Humanos , Enterocolitis Necrotizante/terapia , Enterocolitis Necrotizante/diagnóstico , Nutrición Enteral , IntestinosRESUMEN
BACKGROUND: Lipid-injectable emulsions (ILEs) are a necessity for neonates dependent on parenteral nutrition (PN). In this manuscript, we describe the patterns of ILE use in neonatal intensive care units (NICUs) in the United States (US). METHODS: An electronic survey was sent to 488 NICUs across the US between December 2020 and March 2021. Survey fields included availability and utilization of various ILE in neonates. RESULTS: The response rate was 22% (107 out of 488). Soybean oil ILE (SO-ILE) and soybean oil, medium-chain triglycerides, olive oil, fish oil ILE (SO, MCT, OO, FO-ILE) had similar availability (87% vs 86%, respectively), and SO, MCT, OO, FO-ILE was more commonly used (SO-ILE, 71% vs SO, MCT, OO, FO-ILE, 86%). Fish oil-ILE (FO-ILE) was used by 55% of centers. SO-ILE was most frequently used with PN and needs <4 weeks without cholestasis (79%). The most common reason for SO, MCT, OO, FO-ILE use was cholestasis (71%). ILE minimization was used by 28% of SO-ILE and 22% of SO, MCT, OO, FO-ILE users; 95% of these centers restrict SO, MCT, OO, FO-ILE to doses ≤2 g/kg/day. Twenty-two percent of centers started FO-ILE at direct bilirubin of >5 mg/dl. CONCLUSION: The results of this survey reveal significant variability in ILE usage across the US. Lipid minimization with SO, MCT, OO, FO-ILE and initiation of FO-ILE for cholestasis at higher bilirubin thresholds are prevalent. Such reports are crucial for a better understanding of ILE use in the NICU and in future ILE development.
Asunto(s)
Colestasis , Emulsiones Grasas Intravenosas , Humanos , Recién Nacido , Estados Unidos , Aceite de Soja , Unidades de Cuidado Intensivo Neonatal , Aceites de Pescado , Aceite de Oliva , Bilirrubina , TriglicéridosRESUMEN
Due to recent advances, the mortality due to short bowel syndrome (SBS) has significantly decreased, but the morbidities are still high. Morbidities arising specifically due to dysmotility in SBS include feeding intolerance, prolonged dependence on parenteral nutrition, and associated complications such as intestinal failure associated liver disease, and bloodstream infections. The understanding of the pathogenesis of dysmotility in SBS has improved vastly. However, the tools to diagnose dysmotility in SBS in infants are restrictive, and the medical therapies to treat dysmotility are limited. Surgical techniques available for the treatment after failure of conservative management of dysmotility offer hope but carry their associated risks. The evidence to support either the medical therapies or the surgical techniques to treat dysmotility in SBS in children is scarce and weak. Development of newer therapies and efforts to build evidence to support currently available treatments in treating dysmotility in SBS is needed.
Asunto(s)
Enfermedades Intestinales , Hepatopatías , Síndrome del Intestino Corto , Niño , Humanos , Lactante , Recién Nacido , Enfermedades Intestinales/terapia , Nutrición Parenteral/efectos adversos , Síndrome del Intestino Corto/terapiaRESUMEN
Short bowel syndrome (SBS) of infancy is a cause of prolonged morbidity with intolerance to enteral feeding, specialized nutritional needs, and partial/total dependence on parenteral nutrition. These infants can benefit from individualized nutritional strategies to support and enhance the process of intestinal adaptation. Early introduction of enteral feeds during the period of intestinal adaptation is crucial, even though the enteral feedings may need to be supplemented with an effective, safe, and nutritionally adequate parenteral nutritional regimen. Newer generation intravenous lipid emulsions can be effective in preventing and treating intestinal failure-associated liver disease. Prevention of infection(s), pharmaceutical interventions to enhance bowel motility and prevent/mitigate bacteria overgrowth, and specialized multidisciplinary care to minimize the injury to other organs such as the liver, kidneys, and the brain can assist in nutritional rehabilitation and lower the morbidity in SBS.
Asunto(s)
Enfermedades Intestinales , Síndrome del Intestino Corto , Nutrición Enteral , Humanos , Lactante , Enfermedades Intestinales/terapia , Intestinos , Nutrición Parenteral , Síndrome del Intestino Corto/terapiaRESUMEN
BACKGROUND: In an era of improved management and treatment options, this study aims to describe the long-term outcomes and factors predictive of outcomes of neonatal-onset intestinal failure (IF) due to surgical short bowel syndrome (SBS). METHODS: Retrospective, single-center cohort study of infants born between January 2011 and December 2018 with inclusion criteria: <44 weeks postmenstrual age at SBS diagnosis, <28 days on admission, parenteral nutrition dependence >60 days, and documented intestinal resection. Primary outcomes included survival and achievement of enteral autonomy (EA). Data analysis utilized Fisher.s exact test, Kruskal-Wallis test, survival analysis methods, Cox proportional hazards regression, linear regression and logistic regression. RESULTS: Ninety-five patients (males 56%) were studied with median follow-up of 38 months (IQR 19, 59). Survival at last follow-up was 96%, and EA was achieved in 85%. Forty-eight patients had documented residual bowel length (RBL) with median length of 49 cm (IQR 36, 80). Survival in patients with RBL of <30cm (n = 8), 30-59cm (n = 19), and >60cm (n = 21) was 100%, 95%, and 95% respectively. Shorter RBL was associated with longer time to achieve EA (p = 0.007), but not with survival (p = 0.81). Delay in achieving EA was associated with absence of ileocecal valve (p = 0.002) and bloodstream infections (p < 0.001). Peak conjugated bilirubin correlated with increased mortality (p = 0.002). CONCLUSION: Overall high rate of survival and achievement of EA was found in neonatal onset IF due to SBS. EA but not survival was correlated with RBL. Ileocecal valve, bloodstream infections, and conjugated bilirubin levels were the other predictive factors of outcomes.