Oral lactoferrin for the treatment of sepsis and necrotizing enterocolitis in neonates

USDA-ARS?s Scientific Manuscript database

Neonatal sepsis and necrotizing enterocolitis (NEC) cause significant neonatal mortality and morbidity in spite of appropriate antibiotic therapy. Enhancing host defense and modulating inflammation by using lactoferrin as an adjunct to antibiotics in the treatment of sepsis and/or NEC may improve cl...

Oral lactoferrin for the treatment of sepsis and necrotizing enterocolitis in neonates

USDA-ARS?s Scientific Manuscript database

Neonatal sepsis and necrotizing enterocolitis (NEC) cause significant neonatal mortality and morbidity in spite of appropriate antibiotic therapy. Enhancing host defence and modulating inflammation by using lactoferrin as an adjunct to antibiotics in the treatment of sepsis and/or NEC may improve cl...

Pasteurization of breastmilk decreases the rate of postnatally acquired cytomegalovirus infections, but shows a nonsignificant trend to an increased rate of necrotizing enterocolitis in very preterm infants--a preliminary study.

PubMed

Stock, Katharina; Griesmaier, Elke; Brunner, Barbara; Neubauer, Vera; Kiechl-Kohlendorfer, Ursula; Trawöger, Rudolf

2015-03-01

This study assessed whether feeding preterm infants unpasteurized breastmilk (1) decreases the rate of late-onset sepsis and necrotizing enterocolitis and (2) increases the rate of postnatally acquired cytomegalovirus infections. Between January 2008 and July 2013, preterm infants below 32 completed weeks of gestational age admitted to the neonatal intensive care unit of Innsbruck Medical University (Innsbruck, Austria) (n=344) were eligible for the study. Of those, 323 fed breastmilk were retrospectively enrolled in the study. Two groups were formed, with 164 infants being fed unpasteurized and 159 infants being fed pasteurized breastmilk. There was no significant difference in the rate of late-onset sepsis or necrotizing enterocolitis between the unpasteurized and pasteurized breastmilk groups (late-onset sepsis, 15.9% versus 15.1% [p=0.486]; necrotizing enterocolitis, 2.4% versus 4.4% [p=0.254]). The number of infants diagnosed with postnatally acquired cytomegalovirus infection was significantly higher in the unpasteurized group (39.3%) compared with the pasteurized group (4.2%) (p=0.008). Feeding preterm infants unpasteurized breastmilk increases the rate of postnatally acquired cytomegalovirus infections. However, we also demonstrate a nonsignificant trend to a decreased rate of necrotizing enterocolitis in the unpasteurized group, which needs to be confirmed in larger studies.

[Prognostic factors related to mortality in newborns with necrotising enterocolitis].

PubMed

Bracho-Blanchet, Eduardo; Torrecilla-Navarrete, María Esther; Zalles-Vidal, Cristian; Ibarra-Ríos, Daniel; Fernández-Portilla, Emilio; Dávila-Pérez, Roberto

2015-01-01

Necrotizing enterocolitis is the most frequent and severe acquired gastrointestinal disease in newborns and still has high mortality. There are few published papers about prognostic factors of death in our country. To know the factors associated with death in patients with necrotizing enterocolitis. Retrospective, descriptive, comparative study with a case-control design was conducted on patients with necrotizing enterocolitis during a 5-year period. Deceased patients had significantly lower platelet counts compared to survivors (P=0.022) and the prognostic factors associated with mortality were anaemia (P=0.006, OR = 15.62), stage III of necrotizing enterocolitis (P<0.001, OR = 47.5), to require surgical treatment (P<0.001, OR = 47.5), to have intestinal necrosis (P=0.001, OR = 48.5) or perforation (P=0.016, OR =24.25), to have medical complications, specifically intravascular disseminated coagulation (P<.001, RR = 98), and multi-organ failure (P<0.001, RR = 2). It was also found that patients with gastrointestinal symptoms and diagnosis of necrotising enterocolitis when they were hospitalized were more likely to have surgical treatment. We must be aware of the factors associated with mortality, as well as those associated with surgical treatment to reduce overall mortality for this condition. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

Diminished citrulline-arginine-nitric oxide production rates are associated with necrotizing enterocolitis incidence in premature pigs

USDA-ARS?s Scientific Manuscript database

Necrotizing enterocolitis (NEC) is a major gastrointestinal disease in premature infants that is associated with formula feeding and intestinal hypoxia. Low arginine availability in these infants has been linked to NEC since arginine is the sole precursor of nitric oxide (NO), a critical mediator of...

Oral lactoferrin for the prevention of sepsis and necrotizing enterocolitis in preterm infants

USDA-ARS?s Scientific Manuscript database

Lactoferrin, a normal component of human colostrum, milk, tears, and saliva can enhance host defence and may be effective in the prevention of sepsis and necrotizing enterocolitis (NEC) in preterm neonates. To assess the safety and effectiveness of oral lactoferrin in the prevention of sepsis and NE...

Abdominal near-infrared spectroscopy measurements are lower in preterm infants at risk for necrotizing enterocolitis

USDA-ARS?s Scientific Manuscript database

Near-infrared spectroscopy is a noninvasive method of measuring local tissue oxygenation (StO[2]). Abdominal StO[2] measurements in preterm piglets are directly correlated with changes in intestinal blood flow and markedly reduced by necrotizing enterocolitis. The objectives of this study were to us...

Improved gut barrier function via increased threonine utilization may explain enhanced resistance to necrotizing enterocolitis in preterm pigs fed colostrum

USDA-ARS?s Scientific Manuscript database

Threonine is an essential amino acid necessary for synthesis of gut mucins that form the protective intestinal mucous layer. In premature infants, this function might be compromised leading to necrotizing enterocolitis (NEC). We hypothesized that enteral feeding with colostrum, relative to infant fo...

Low abdominal NIRS values and elevated plasma intestinal fatty acid-binding protein in a premature piglet model of necrotizing enterocolitis

USDA-ARS?s Scientific Manuscript database

To identify early markers of necrotizing enterocolitis (NEC), we hypothesized that continuous abdominal near-infrared spectroscopy (A-NIRS) measurement of splanchnic tissue oxygen saturation and intermittent plasma intestinal fatty-acid binding protein (pI-FABP) measured every 6 hours can detect NEC...

Delayed initiation but not gradual advancement of enteral formula feeding reduces the incidence of necrotizing enterocolitis (NEC) in preterm pigs

USDA-ARS?s Scientific Manuscript database

Enteral formula feeding is a risk factor for necrotizing enterocolitis (NEC) in premature infants, yet studies are conflicting regarding the safest timing for introduction and advancement of feeds. Our aim was to test the effects of early vs. late initiation and abrupt vs. gradual advancement of ent...

Near-infrared spectroscopy measurement of abdominal tissue oxygenation is a useful indicator of intestinal blood flow and necrotizing enterocolitis in premature piglets

USDA-ARS?s Scientific Manuscript database

A major objective of necrotizing enterocolitis (NEC)research is to devise a noninvasive method of early detection. We hypothesized that abdominal near-infrared spectroscopy (A-NIRS) readings will identify impending NEC in a large animal model. Piglets were prematurely delivered and received parenter...

Enterocolic lymphocytic phlebitis: statistical analysis of histology features in viable and ischemic bowel.

PubMed

Medlicott, Shaun A C; Guggisberg, Kelly A; DesCôteaux, Jean-Gaston; Beck, Paul

2006-07-01

Enterocolic lymphocytic phlebitis is a rare cause of segmental ischemic enterocolitis. This artery-sparing transmural vasculitis is classically a circumferential phlebitis with perivenular lymphocyte cuffing and thrombi in the absence of systemic manifestations. Myointimal hyperplasia may represent a chronic phase of enterocolic lymphocytic phlebitis. Subclinical or early stage enterocolic lymphocytic phlebitis is not well delineated. We analyzed 600 submucosal and subserosal veins from both ischemic and intact bowel segments to discern if vascular morphology varied between sites. Crescentic and circumferential lymphocytic phlebitis is more common in viable bowel than in the ischemic segment. A nonsignificant trend was found for increased crescentic morphology between intact bowel remote from the ischemic focus compared with that adjacent to the ischemic focus. Hallmarks of ischemic bowel are necrotizing phlebitis and thrombi formation. Thrombophlebitis morphology is distinctly different in viable and ischemic bowel, changing from the classic lymphocytic to necrotizing lesions respectively.

Joseph's Story: A Case Study of Late-Onset Necrotizing Enterocolitis From Early Birth to Recovery.

PubMed

Gephart, Sheila M; Martin, Laura B; Kijewski, Amy; Johnson, Scott R

2015-01-01

Although necrotizing enterocolitis (NEC) is often catastrophic among premature infants, most cases occur in the first month after birth. This case study presents Joseph's story about a 24-week surviving twin who developed severe NEC at 5 months of age just days before he was to go home. The purpose of this case study report is to place Joseph and his parents' experience in the context of what is known about NEC risk factors, clinical presentation, and treatment, and then to offer recommendations to healthcare professionals to support families from NEC diagnosis to recovery. Now 5 years old, Joseph continues to manage consequences of NEC including deafness, developmental delay, multiple food allergies, and recurrent gastrointestinal challenges from short gut syndrome. Although NEC struck late and kept Joseph in the neonatal intensive care unit for 228 days, its consequences remain with this resilient child and his family.

Lactoferrin and necrotizing enterocolitis.

PubMed

Sherman, Michael P

2013-03-01

Lactoferrin (LF) is a multifunctional protein and a member of the transferrin family. LF and lysozyme in breast milk kill bacteria. In the stomach, pepsin digests and releases a potent peptide antibiotic called lactoferricin from native LF. The antimicrobial characteristics of LF may facilitate a healthy intestinal microbiome. LF is the major whey in human milk; its highest concentration is in colostrum. This fact highlights early feeding of colostrum and also fresh mature milk as a way to prevent necrotizing enterocolitis. Copyright © 2013 Elsevier Inc. All rights reserved.

Prevention of Necrotizing Enterocolitis Through Manipulation of the Intestinal Microbiota of the Premature Infant

PubMed Central

Vongbhavit, Kannikar; Underwood, Mark A.

2016-01-01

In spite of four decades of research, necrotizing enterocolitis (NEC) remains the most common gastrointestinal complication in premature infants with high mortality and long-term morbidity. The composition of the intestinal microbiota of the premature infant differs dramatically from that of the healthy term infant and appears to be an important risk factor for NEC. Promising NEC prevention strategies that alter the intestinal microbiota include probiotics, prebiotics, synbiotics, lacteroferrin, and human milk feeding. PMID:26872618

Necrotizing enterocolitis: Pathophysiology from a historical context.

PubMed

Hackam, David; Caplan, Michael

2018-02-01

Necrotizing enterocolitis (NEC) continues to afflict approximately 7% of preterm infants born weighing less than 1500g, though recent investigations have provided novel insights into the pathogenesis of this complex disease. The disease has been a major cause of morbidity and mortality in neonatal intensive care units worldwide for many years, and our current understanding reflects exceptional observations made decades ago. In this review, we will describe NEC from a historical context and summarize seminal findings that underscore the importance of enteral feeding, the gut microbiota, and intestinal inflammation in this complex pathophysiology. Copyright © 2018. Published by Elsevier Inc.

Prospective evaluation of radionuclide scanning in detection of intestinal necrosis in neonatal necrotizing enterocolitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haase, G.M.; Sfakianakis, G.N.; Lobe, T.E.

1981-06-01

The ability of external imaging to demonstrate intestinal infarction in neonatal necrotizing enterocolitis (NEC) was prospectively evaluated. The radiopharmaceutical technetium--99m diphosphonate was injected intravenously and the patients subsequently underwent abdominal scanning. Clinical patient care and interpretation of the images were entirely independent throughout the study. Of 33 studies, 7 were positive, 4 were suspicious, and 22 were negative. One false positive study detected ischemia without transmural infarction. The second false positive scan occurred postoperatively and was due to misinterpretation of the hyperactivity along the surgical incision. None of the suspicious cases had damaged bowel. The two false negative studies clearlymore » failed to demonstrate frank intestinal necrosis. The presence of very small areas of infarction, errors in technical settings, subjective interpretation of scans and delayed clearance of the radionuclide in a critically ill neonate may all limit the accuracy of external abdominal scanning. However, in spite of an error rate of 12%, it is likely that this technique will enhance the present clinical, laboratory, and radiologic parameters of patient management in NEC.« less

A study of pre-antibiotic bacteriology in 125 patients with necrotizing enterocolitis.

PubMed

Chan, K L; Saing, H; Yung, R W; Yeung, Y P; Tsoi, N S

1994-01-01

Over a five-year period, 125 newborns with necrotizing enterocolitis (NEC) were managed by us. Their mean birthweight was 1700 g and mean maturity was 32 weeks. Before commencement of antibiotics, routine septic work-up was done in order to define the bacterial spectrum and antibiotic sensitivity. The study includes aerobic and anaerobic cultures of gastric and pharyngeal aspirates, blood cultures, umbilical swabs and culture of umbilical catheter tips in relevant cases. Peritoneal swab results were also analyzed if laparatomy was performed. Positive cultures were present in 45 patients (36%) with 55 positive specimens. Fifteen types of organism were isolated: the commonest was Enterobacter (29%), followed by E. coli (14.5%) and Klebsiella (13%). They were resistant to ampicillin and first-generation cephalosporin. These organisms were usually opportunistic pathogens. Overgrowth of them may be the cause of NEC. Regular review of the antibiotic sensitivity of these organisms allows prompt and appropriate choice of antibiotics. At the same time, antibiotic sensitivity for these organisms was analyzed to guide us in the choice of antibiotic therapy.

Structural studies of O-polysaccharide isolated from Cronobacter sakazakii Sequence Type 12 from a case of neonatal necrotizing enterocolitis.

PubMed

Marszewska, Kinga; Czerwicka, Małgorzata; Forsythe, Stephen J; Ossowska, Karolina; Dziadziuszko, Halina; Kaczyński, Zbigniew

2015-04-30

The O-polysaccharide (OPS) of Cronobacter sakazakii NTU 696 (Sequence Type 12) from a case of neonatal necrotizing enterocolitis was isolated from the polysaccharide fraction obtained after lipopolysaccharide (LPS) hydrolysis. Purified OPS was analyzed by NMR spectroscopy ((1)H, COSY, TOCSY, NOESY, HSQC, HSQC-TOCSY and HMBC experiments) and chemical methods. Obtained monosaccharide derivatives analyzed by gas chromatography and gas chromatography-mass spectrometry allowed the identification of six sugar components. Performed experiments enabled to establish a structure of the OPS repeating unit of C. sakazakii NTU 696, as: [structure: see text]. Copyright © 2015 Elsevier Ltd. All rights reserved.

Necrotizing Enterocolitis and Human Milk Feeding: A Systematic Review.

PubMed

Cacho, Nicole Theresa; Parker, Leslie A; Neu, Josef

2017-03-01

This article summarizes evidence regarding whether a donor human milk (DHM) and/or an exclusively human milk (EHM) diet decreases the incidence of necrotizing enterocolitis (NEC) and the dose of human milk (HM) necessary to reduce the risk of NEC in premature infants. Additional research regarding protection afforded by DHM and EHM is necessary as well as research elucidating the exact dose of HM necessary for NEC risk reduction. Research is also needed to determine whether there is a dose-dependent effect of DHM, a combination of mother's own milk and DHM, and an EHM diet on NEC incidence. Copyright © 2016 Elsevier Inc. All rights reserved.

Probiotics and Necrotizing Enterocolitis: Finding the Missing Pieces of the Probiotic Puzzle

PubMed Central

Luedtke, Sherry A.; Yang, Jacob T.; Wild, Heather E.

2012-01-01

Necrotizing enterocolitis (NEC) is one of the leading causes of death in the neonatal intensive care unit. Morbidity and mortality rates significantly increase with decreases in gestational age and birth weight. Strong evidence suggests probiotic prophylaxis may significantly decrease the incidence of NEC and should therefore be incorporated into the standard of care for preterm infants. However, debate still remains because of limitations of completed studies. The purpose of this review was to provide an overview of the controversies regarding probiotic use in preterm infants and to shed light on the practical considerations for implementation of probiotic supplementation. PMID:23412969

Update in Pathogenesis and Prospective in Treatment of Necrotizing Enterocolitis

PubMed Central

Terrin, Gianluca; Scipione, Antonella; De Curtis, Mario

2014-01-01

Necrotizing enterocolitis (NEC) is among the most common and devastating diseases in neonates and, despite the significant advances in neonatal clinical and basic science investigations, its etiology is largely understood, specific treatment strategies are lacking, and morbidity and mortality remain high. Improvements in the understanding of pathogenesis of NEC may have therapeutic consequences. Pharmacologic inhibition of toll-like receptor signaling, the use of novel nutritional strategies, and microflora modulation may represent novel promising approaches to the prevention and treatment of NEC. This review, starting from the recent acquisitions in the pathogenic mechanisms of NEC, focuses on current and possible therapeutic perspectives. PMID:25147804

Evaluation of parenteral nutrition-associated liver disease in infants with necrotizing enterocolitis before and after the implementation of feeding guidelines.

PubMed

Tillman, Emma M; Norman, Johanna L; Huang, Eunice Y; Lazar, Linda F; Crill, Catherine M

2014-04-01

In 2009, an intestinal rehabilitation team implemented feeding guidelines for infants following gastrointestinal surgery at our institution. The purpose of this study was to determine the effect of enteral feeding guidelines on the incidence of parenteral nutrition (PN)-associated liver disease (PNALD) in infants with surgically managed necrotizing enterocolitis (NEC). This retrospective study included infants treated during 18-month time periods before and after the implementation of feeding guidelines. PNALD diagnosis was based on serum direct bilirubin >2 mg/dL after ≥14 days of PN exposure. Of the 140 infants identified, 64 were surgically managed and included in the analysis. The duration of PN and the time nil per os (NPO) were significantly reduced after guideline implementation from a median of 106 days to 65 days (P = .03) and from 29 days to 16 days (P = .02), respectively. The incidence of PNALD decreased from 73% before guideline implementation to 42% after guideline implementation (P = .01). Implementation of feeding guidelines resulted in decreased time NPO and duration of PN support. Significantly fewer infants developed PNALD after guideline implementation. These data suggest that feeding guidelines may expedite the transition from PN to enteral nutrition and may improve outcomes.

A novel pore-forming toxin in type A Clostridium perfringens is associated with both fatal canine hemorrhagic gastroenteritis and fatal foal necrotizing enterocolitis.

PubMed

Mehdizadeh Gohari, Iman; Parreira, Valeria R; Nowell, Victoria J; Nicholson, Vivian M; Oliphant, Kaitlyn; Prescott, John F

2015-01-01

A role for type A Clostridium perfringens in acute hemorrhagic and necrotizing gastroenteritis in dogs and in necrotizing enterocolitis of neonatal foals has long been suspected but incompletely characterized. The supernatants of an isolate made from a dog and from a foal that died from these diseases were both found to be highly cytotoxic for an equine ovarian (EO) cell line. Partial genome sequencing of the canine isolate revealed three novel putative toxin genes encoding proteins related to the pore-forming Leukocidin/Hemolysin Superfamily; these were designated netE, netF, and netG. netE and netF were located on one large conjugative plasmid, and netG was located with a cpe enterotoxin gene on a second large conjugative plasmid. Mutation and complementation showed that only netF was associated with the cytotoxicity. Although netE and netG were not associated with cytotoxicity, immunoblotting with specific antisera showed these proteins to be expressed in vitro. There was a highly significant association between the presence of netF with type A strains isolated from cases of canine acute hemorrhagic gastroenteritis and foal necrotizing enterocolitis. netE and netF were found in all cytotoxic isolates, as was cpe, but netG was less consistently present. Pulsed-field gel electrophoresis showed that netF-positive isolates belonged to a clonal population; some canine and equine netF-positive isolates were genetically indistinguishable. Equine antisera to recombinant Net proteins showed that only antiserum to rNetF had high supernatant cytotoxin neutralizing activity. The identifica-tion of this novel necrotizing toxin is an important advance in understanding the virulence of type A C. perfringens in specific enteric disease of animals.

A Novel Pore-Forming Toxin in Type A Clostridium perfringens Is Associated with Both Fatal Canine Hemorrhagic Gastroenteritis and Fatal Foal Necrotizing Enterocolitis

PubMed Central

Nowell, Victoria J.; Nicholson, Vivian M.; Oliphant, Kaitlyn; Prescott, John F.

2015-01-01

A role for type A Clostridium perfringens in acute hemorrhagic and necrotizing gastroenteritis in dogs and in necrotizing enterocolitis of neonatal foals has long been suspected but incompletely characterized. The supernatants of an isolate made from a dog and from a foal that died from these diseases were both found to be highly cytotoxic for an equine ovarian (EO) cell line. Partial genome sequencing of the canine isolate revealed three novel putative toxin genes encoding proteins related to the pore-forming Leukocidin/Hemolysin Superfamily; these were designated netE, netF, and netG. netE and netF were located on one large conjugative plasmid, and netG was located with a cpe enterotoxin gene on a second large conjugative plasmid. Mutation and complementation showed that only netF was associated with the cytotoxicity. Although netE and netG were not associated with cytotoxicity, immunoblotting with specific antisera showed these proteins to be expressed in vitro. There was a highly significant association between the presence of netF with type A strains isolated from cases of canine acute hemorrhagic gastroenteritis and foal necrotizing enterocolitis. netE and netF were found in all cytotoxic isolates, as was cpe, but netG was less consistently present. Pulsed-field gel electrophoresis showed that netF-positive isolates belonged to a clonal population; some canine and equine netF-positive isolates were genetically indistinguishable. Equine antisera to recombinant Net proteins showed that only antiserum to rNetF had high supernatant cytotoxin neutralizing activity. The identifica-tion of this novel necrotizing toxin is an important advance in understanding the virulence of type A C. perfringens in specific enteric disease of animals. PMID:25853427

Oral lactoferrin for the prevention of sepsis and necrotizing enterocolotis in preterm infants

USDA-ARS?s Scientific Manuscript database

Lactoferrin, a normal component of human colostrum, milk, tears and saliva can enhance host defence and may be effective in the prevention of sepsis and necrotizing enterocolitis (NEC) in preterm neonates. To assess the safety and effectiveness of oral lactoferrin in the prevention of sepsis and NEC...

16S rRNA Gene Sequencing, Multilocus Sequence Analysis, and Mass Spectrometry Identification of the Proposed New Species “Clostridium neonatale”

PubMed Central

Bouvet, Philippe; Ferraris, Laurent; Dauphin, Brunhilde; Popoff, Michel-Robert; Butel, Marie Jose

2014-01-01

In 2002, an outbreak of necrotizing enterocolitis in a Canadian neonatal intensive care unit was associated with a proposed novel species of Clostridium, “Clostridium neonatale.” To date, there are no data about the isolation, identification, or clinical significance of this species. Additionally, C. neonatale has not been formally classified as a new species, rendering its identification challenging. Indeed, the C. neonatale 16S rRNA gene sequence shows high similarity to another Clostridium species involved in neonatal necrotizing enterocolitis, Clostridium butyricum. By performing a polyphasic study combining phylogenetic analysis (16S rRNA gene sequencing and multilocus sequence analysis) and phenotypic characterization with mass spectrometry, we demonstrated that C. neonatale is a new species within the Clostridium genus sensu stricto, for which we propose the name Clostridium neonatale sp. nov. Now that the status of C. neonatale has been clarified, matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) can be used for better differential identification of C. neonatale and C. butyricum clinical isolates. This is necessary to precisely define the role and clinical significance of C. neonatale, a species that may have been misidentified and underrepresented during previous neonatal necrotizing enterocolitis studies. PMID:25232167

Very Low Birth Weight Preterm Infants With Surgical Short Bowel Syndrome: Incidence, Morbidity and Mortality, and Growth Outcomes at 18 to 22 Months

PubMed Central

Cole, Conrad R.; Hansen, Nellie I.; Higgins, Rosemary D.; Ziegler, Thomas R.; Stoll, Barbara J.

2009-01-01

OBJECTIVES The objective of this study was to determine the (1) incidence of short bowel syndrome in very low birth weight (<1500 g) infants, (2) associated morbidity and mortality during initial hospitalization, and (3) impact on short-term growth and nutrition in extremely low birth weight (<1000 g) infants. METHODS Infants who were born from January 1, 2002, through June 30, 2005, and enrolled in the National Institute of Child Health and Human Development Neonatal Research Network were studied. Risk factors for developing short bowel syndrome as a result of partial bowel resection (surgical short bowel syndrome) and outcomes were evaluated for all neonates until hospital discharge, death, or 120 days. Extremely low birth weight survivors were further evaluated at 18 to 22 months’ corrected age for feeding methods and growth. RESULTS The incidence of surgical short bowel syndrome in this cohort of 12 316 very low birth weight infants was 0.7%. Necrotizing enterocolitis was the most common diagnosis associated with surgical short bowel syndrome. More very low birth weight infants with short bowel syndrome (20%) died during initial hospitalization than those without necrotizing enterocolitis or short bowel syndrome (12%) but fewer than the infants with surgical necrotizing enterocolitis without short bowel syndrome (53%). Among 5657 extremely low birth weight infants, the incidence of surgical short bowel syndrome was 1.1%. At 18 to 22 months, extremely low birth weight infants with short bowel syndrome were more likely to still require tube feeding (33%) and to have been rehospitalized (79%). Moreover, these infants had growth delay with shorter lengths and smaller head circumferences than infants without necrotizing enterocolitis or short bowel syndrome. CONCLUSIONS Short bowel syndrome is rare in neonates but has a high mortality rate. At 18 to 22 months’ corrected age, extremely low birth weight infants with short bowel syndrome were more likely to have growth failure than infants without short bowel syndrome. PMID:18762491

Beneficial effects of mucous fistula refeeding in necrotizing enterocolitis neonates with enterostomies.

PubMed

Lau, Eugene C T; Fung, Adrian C H; Wong, Kenneth K Y; Tam, Paul K H

2016-12-01

Necrotizing enterocolitis in premature neonates often results in bowel resection and stoma formation. One way to promote bowel adaptation before stoma closure is to introduce proximal loop effluents into the mucous fistula. In this study, we reviewed our experience with distal loop refeeding with respect to control group. All patients with necrotizing enterocolitis between 2000 and 2014 necessitating initial diverting enterostomies and subsequent stoma closure in a tertiary referral center were included. Medical records were retrospectively reviewed. Demographic data, surgical procedures, and postoperative outcomes were analyzed. 92 patients were identified, with 77 patients receiving mucous fistula refeeding. The refeeding group showed less bowel ends size discrepancy (25 vs 53%, p=0.034) and less postoperative anastomotic leakage (3 vs 20%, p=0.029). Fewer refeeding group patients developed parenteral nutrition related cholestasis (42 vs 73%, p=0.045) and required shorter parenteral nutrition support (47 vs 135days, p=0.002). The mean peak bilirubin level was higher in the non-refeeding group (155 vs 275μmol/L, p<0.001). No major complication was associated with refeeding. Mucous fistula refeeding is safe and can decrease risk of anastomotic complication and parental nutrition related cholestasis. It provides both diagnostic and therapeutic value preoperatively and its use should be advocated. Level III Treatment Study in a Case Control Manner. Copyright © 2016 Elsevier Inc. All rights reserved.

Severe neurodevelopmental disability and healthcare needs among survivors of medical and surgical necrotizing enterocolitis: A prospective cohort study.

PubMed

Fullerton, Brenna S; Hong, Charles R; Velazco, Cristine S; Mercier, Charles E; Morrow, Kate A; Edwards, Erika M; Ferrelli, Karla R; Soll, Roger F; Modi, Biren P; Horbar, Jeffrey D; Jaksic, Tom

2017-10-12

This study characterizes neurodevelopmental outcomes and healthcare needs of extremely low birth weight (ELBW) survivors of necrotizing enterocolitis (NEC) compared to ELBW infants without NEC. Data were collected prospectively on neonates born 22-27weeks' gestation or 401-1000g at 47 Vermont Oxford Network member centers from 1999 to 2012. Detailed neurodevelopmental evaluations were conducted at 18-24months corrected age. Information regarding rehospitalizations, postdischarge surgeries, and feeding was also collected. "Severe neurodevelopmental disability" was defined as: bilateral blindness, hearing impairment requiring amplification, inability to walk 10 steps with support, cerebral palsy, and/or Bayley Mental or Psychomotor Developmental Index <70. Diagnosis of NEC required both clinical and radiographic findings. There were 9063 children without NEC, 417 with medical NEC, and 449 with surgical NEC evaluated. Significantly higher rates of morbidity were observed among infants with a history of NEC. Those with surgical NEC were more frequently affected across all outcome measures at 18-24months corrected age: 38% demonstrated severe neurodevelopmental disability, nearly half underwent postdischarge operations, and a quarter required tube feeding at home. At 18-24months, extremely low birth weight survivors of necrotizing enterocolitis were at markedly increased risk (p<0.001) for severe neurodevelopmental disability, postdischarge surgery, and tube feeding. II (prospective cohort study with <80% follow-up rate). Copyright © 2017 Elsevier Inc. All rights reserved.

Necrotizing enterocolitis

MedlinePlus

... the intestines or inflammation of the abdominal wall (peritonitis). In this surgery, the doctor will: Remove dead ... Complications may include: Peritonitis Sepsis Intestinal ... inability to tolerate enteral feeds and need for parenteral (IV) ...

Anemia, red blood cell transfusions, and necrotizing enterocolitis.

PubMed

Maheshwari, Akhil; Patel, Ravi M; Christensen, Robert D

2018-02-01

In the past 15 years, multiple clinical studies have identified a temporal association between red blood cell (RBC) transfusions and necrotizing enterocolitis (NEC). With some variability, most of these studies indicate that up to one-third of all cases of NEC involving very low-birth weight infants may occur within 24-48h after receiving a RBC transfusion. There is also evidence that the risk of such transfusion-associated NEC may be higher in infants transfused with the greatest severity of anemia. In this article, we summarize the clinical evidence pertaining to these issues; specifically, the contribution of RBC transfusions, and the contribution of severity of underlying anemia, to the pathogenesis of a type of NEC potentially termed, "transfusion/anemia-associated NEC." Copyright © 2018 Elsevier Inc. All rights reserved.

Necrotizing Enterocolitis

MedlinePlus

... large section of the intestine was removed, an ostomy is done. During an ostomy, surgeons bring an area of the intestine to ... to re-examine the intestines or close the ostomy. What Can I Expect? Most babies who develop ...

Therapeutic Use of Prebiotics, Probiotics, and Postbiotics to Prevent Necrotizing Enterocolitis: What is the Current Evidence?

PubMed Central

Patel, Ravi Mangal; Denning, Patricia Wei

2013-01-01

Synopsis Necrotizing enterocolitis (NEC) is a leading cause of neonatal morbidity and mortality and preventative therapies that are both effective and safe are urgently needed. Current evidence from therapeutic trials suggests that probiotics are effective in decreasing NEC in preterm infants and probiotics are currently the most promising therapy on the horizon for this devastating disease. However, concerns regarding safety and optimal dosing have limited the widespread adoption of routine clinical use of probiotics in preterm infants. In addition, prebiotics and postbiotics may be potential alternatives or adjunctive therapies to the administration of live microorganisms, although studies demonstrating their clinical efficacy in preventing NEC are lacking. This review summarizes the current evidence regarding the use of probiotics, prebiotics and postbiotics in the preterm infant, including its therapeutic role in preventing NEC. PMID:23415261

Human milk for the premature infant

PubMed Central

Underwood, Mark A.

2012-01-01

Synopsis Premature infants are a heterogeneous group with widely differing needs for nutrition and immune protection with risk of growth failure, developmental delays, necrotizing enterocolitis, and late-onset sepsis increasing with decreasing gestational age and birth weight. Human milk from women delivering prematurely has more protein and higher levels of many bioactive molecules compared to milk from women delivering at term. Human milk must be fortified for small premature infants to achieve adequate growth. Mother’s own milk improves growth and neurodevelopment and decreases the risk of necrotizing enterocolitis and late-onset sepsis and should therefore be the primary enteral diet of premature infants. Donor milk is a valuable resource for premature infants whose mothers are unable to provide an adequate supply of milk, but presents significant challenges including the need for pasteurization, nutritional and biochemical deficiencies and a limited supply. PMID:23178065

Impact of Probiotics on Necrotizing Enterocolitis

PubMed Central

Underwood, Mark A.

2016-01-01

A large number of randomized placebo-controlled clinical trials and cohort studies have demonstrated a decrease in the incidence of necrotizing enterocolitis with administration of probiotic microbes. These studies have prompted many neonatologists to adopt routine prophylactic administration of probiotics while others await more definitive studies and/or probiotic products with demonstrated purity and stable numbers of live organisms. Cross-contamination and inadequate sample size limit the value of further traditional placebo-controlled randomized controlled trials. Key areas for future research include mechanisms of protection, optimum probiotic species or strains (or combinations thereof) and duration of treatment, interactions between diet and the administered probiotic, and the influence of genetic polymorphisms in the mother and infant on probiotic response. Next generation probiotics selected based on bacterial genetics rather than ease of production and large cluster-randomized clinical trials hold great promise for NEC prevention. PMID:27836423

Intestinal Microbiota and Its Relationship with Necrotizing Enterocolitis

PubMed Central

Patel, Ravi Mangal; Denning, Patricia W.

2015-01-01

Necrotizing enterocolitis is a leading cause of morbidity and mortality in infants born prematurely. After birth, the neonatal gut must acquire a healthy complement of commensal bacteria. Disruption or delay of this critical process, leading to deficient or abnormal microbial colonization of the gut, has been implicated as key risk factor in the pathogenesis of NEC. Conversely, a beneficial complement of commensal intestinal microbiota may protect the immature gut from inflammation and injury. Interventions aimed at providing or restoring a healthy complement of commensal bacteria, such as probiotic therapy, are currently the most promising treatment to prevent NEC. Shifting the balance of intestinal microbiota from a pathogenic to protective complement of bacteria can protect the gut from inflammation and subsequent injury that leads to NEC. Herein, we review the relationship of intestinal microbiota and NEC in preterm infants. PMID:25992911

New Medical and Surgical Insights Into Neonatal Necrotizing Enterocolitis: A Review.

PubMed

Frost, Brandy L; Modi, Biren P; Jaksic, Tom; Caplan, Michael S

2017-01-01

Necrotizing enterocolitis (NEC) has long remained a significant cause of morbidity and mortality in neonatal intensive care units. While the mainstay of treatment for this devastating condition remains largely supportive, research efforts continue to be directed toward understanding pathophysiology as well as how best to approach surgical management when indicated. In this review, we first examine recent medical observations, including overviews on the microbiome and a brief review of the use of probiotics. Next, we discuss the use of biomarkers and how clinicians may be able to use them in the future to predict the course of disease and, perhaps, the need for surgical intervention. We then provide an overview on the use of exclusive human milk feeding and the utility of this approach in preventing NEC. Finally, we discuss recent developments in the surgical management of NEC, beginning with indications for surgery and following with a section on technical surgical considerations, including peritoneal drain vs laparotomy. The review concludes with outcomes from infants with surgically treated NEC. Although medical treatment options for NEC are largely unchanged, understanding of the disease continues to evolve. As new research methods are developed, NEC pathophysiology can be more completely understood. In time, it is hoped that data from ongoing and planned clinical trials will allow us to routinely add targeted preventive measures in addition to human milk, such as prebiotics and probiotics, to the management of high-risk infants. In addition, the discovery of novel biomarkers may not only prove useful in predicting severity of illness but also will hopefully allow for identification of the disease prior to onset of clinical signs. Finally, continued investigation into optimizing surgical outcomes is essential in this population of infants, many of whom require long-term parenteral therapy and intestinal rehabilitation.

Abdominal and hepatic uptake of /sup 99m/Tc-pyrophosphate in neonatal necrotizing enterocolitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Caride, V.J.; Touloukian, R.J.; Ablow, R.C.

1981-04-01

Abdominal /sup 99m/Tc-pyrophosphate (/sup 99m/Tc-PYP) scans were obtained in 15 neonates: 12 with neonatal necrotizing enterocolitis (NEC), two with osteomyelitis, and one with myocarditis. Ten of the babies with NEC had at least one positive scan; of these 10 studies, seven (Group A) showed both diffuse abdominal uptake and localized hepatic activity, two (Group B) showed abdominal uptake and questionable hepatic uptake, and one (Group C) demonstrated diffuse abdominal uptake only. The other two babies with NEC had normal scans (Group D). All NEC patients had normal scans. A patient with myocarditis had hepatic uptake of /sup 99m/Tc-PYP while themore » abdominal scan in the two infants with osteomyelitis was normal. These preliminary observations suggest that further study of a relationship between abdominal scan findings and the course of NEC is warranted.« less

Necrotizing Enterocolitis in the Premature Infant

PubMed Central

Gregory, Katherine E.; DeForge, Christine E.; Natale, Kristan M.; Phillips, Michele; Van Marter, Linda J.

2013-01-01

Necrotizing enterocolitis (NEC) remains one of the most catastrophic comorbidities associated with prematurity. In spite of extensive research, the disease remains unsolved. The aims of this paper are to present the current state of the science on the pathogenesis of NEC, summarize the clinical presentation and severity staging of the disease, and highlight the nursing assessments required for early identification of NEC and ongoing care for infants diagnosed with this gastrointestinal disease. The distributions of systemic and intestinal clinical signs that are most sensitive to nursing assessment and associated with Bell Staging Criteria are presented. This descriptive data is representative of 117 cases of NEC diagnosed in low gestational age infants (<29 weeks gestation). The data highlights the clinical signs most commonly observed in infants with NEC, and thus, provides NICU nurses an evidence-based guide for assessment and care of infants with NEC. PMID:21730907

Does abdominal sonography provide additional information over abdominal plain radiography for diagnosis of necrotizing enterocolitis in neonates?

PubMed

Dilli, Dilek; Suna Oğuz, S; Erol, Reyhan; Ozkan-Ulu, Hülya; Dumanlı, Hüseyin; Dilmen, Uğur

2011-03-01

To explore whether addition of abdominal sonography (AUS) to plain radiography is helpful in the management of premature newborns with necrotizing enterocolitis (NEC). This study is a prospective analysis of 93 premature neonates with NEC who were followed-up in our neonatal intensive care unit between October 2007 and April 2009. Patients were classified into two groups; group I with suspected NEC (stage I) (n = 54) and group II with definite NEC (stage ≥II) (n = 39). Pneumatosis intestinalis (PI) (n = 29), free air (n = 9), and portal venous gas (PVG) (n = 1) were observed in group II on plain radiography. In the same group, echoic free fluid (EFF) (n = 9), PVG (n = 6), PI (n = 5), and focal fluid collection (n = 3) were the most prominent sonographic findings. In patients with intestinal perforation, whereas EFF and bowel wall thinning were observed on AUS, free air was not detected on plain radiography as a sign of intestinal perforation. Our results suggest AUS to be superior to plain radiography on early detection of intestinal perforation by demonstrating PVG and EFF collection. Therefore, it may be life-saving by directing the surgeon to perform surgical intervention in the case of clinical deterioration in the course of NEC.

Efficacy of Saccharomyces boulardii on necrotizing enterocolitis or sepsis in very low birth weight infants: a randomised controlled trial.

PubMed

Serce, Ozge; Benzer, Derya; Gursoy, Tugba; Karatekin, Guner; Ovali, Fahri

2013-12-01

Probiotics have strain specific effects and the effects of fungi in preventing diseases in preterm infants have been investigated poorly. Saccharomyces boulardii is a yeast which acts both as a probiotic and a polyamine producer. The objective of this study was to investigate the efficacy of S. boulardii in preventing necrotizing enterocolitis (NEC) or sepsis in very low birth weight infants. A prospective, double blind, placebo controlled trial was conducted in preterm infants (≤ 32 GWs, ≤ 1500 g birth weight). They were randomized either to receive feeding supplementation with S. boulardii 50 mg/kg every 12 h or placebo, starting with the first feed until discharged. Necrotizing enterocolitis (NEC) or sepsis and NEC or death. Birth weight and gestational age of the study (n = 104) and the control (n = 104) groups were 1126 ± 232 vs 1162 ± 216 g and 28.8 ± 2.2 vs 28.7 ± 2.1 weeks, respectively. Neither the incidence of stage ≥ 2 NEC or death nor stage ≥ 2 NEC or late onset culture proven sepsis was significantly lower in the study group when compared with the control group (9.6% vs 7.7%, p = 0.62; 28.8% vs 23%, p = 0.34). Time to reach 100 mL/kg/day of enteral feeding (11.9 ± 7 vs 12.6 ± 7 days, p = 0.37) was not different between the groups. Saccharomyces boulardii did not decrease the incidence of NEC or sepsis. © 2013 Elsevier Ireland Ltd. All rights reserved.

[Study of the effects of the implementation of a human milk donor bank in preterm newborns in Aragon].

PubMed

Larena Fernández, Israel; Vara Callau, Marta; Royo Pérez, Delia; López Bernués, Ricardo; Cortés Sierra, Jesús; Samper Villagrasa, María Pilar

2015-01-01

Numerous obstacles may prevent a premature or sick neonate receiving their mother's milk. In these cases, pediatric scientific societies recommend feeding with donor human milk. In this article, it is explained what a milk bank is, how it works, the donors' selection method, and the benefits. We also describe the current situation in Aragon (Spain) is also described. A retrospective and descriptive study was conducted on the perinatal sample characteristics, as well as an analytical observational study, comparing two sample groups: pre- and post-human milk bank. Finally, differences in the post-bank stage between those patients fed with own-mother's or donor human milk were determined. The study included a total of 234 patients: 104 females and 130 males. Two groups: pre and post-bank, with 152 and 82 patients, respectively, which had similar characteristics at birth; length and head circumference were significantly higher in the post-bank group and a lower rate of necrotizing enterocolitis was also found. No statistically significant differences were found in other variables between subgroups fed with own-mother's milk and donor human milk. The establishment of the human milk donor bank has a beneficial effect, as it reduces neonatal morbidity in cases of necrotizing enterocolitis. Human milk feeding could be a protective factor against neonatal sepsis due to improve immunity. The incidence of necrotizing enterocolitis is lower after the establishment of the milk bank. Studies with more patients may demonstrate differences in other variables. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Characteristics and incidence of transfusion-associated necrotizing enterocolitis in the UKCharacteristics and incidence of transfusion-associated necrotizing enterocolitis in the UK.

PubMed

Faraday, Christopher; Hamad, Sheima; Jones, Kelsey; Sim, Kathleen; Cherian, Shobha; James, Anitha; Godambe, Sunit; New, Helen; Kroll; Clarke, Paul

2018-06-26

The etiology of necrotizing enterocolitis (NEC) is unclear and postulated as being multifactorial. It has been suggested that one causative factor is the transfusion of packed red bloods cells (PRBCs) leading to the disease entity commonly referred to as transfusion-associated NEC (TANEC). TANEC has been reported in North America but its incidence has not been formally investigated in the United Kingdom (UK). Our aims were to identify the incidence of NEC and TANEC in tertiary-level UK neonatal units and to describe characteristics of TANEC cases. Using strict case definitions for NEC and TANEC, we undertook a retrospective review to estimate the incidence of TANEC cases occurring in four UK tertiary-level centers during a 38-month period. Of 8007 consecutive neonatal admissions of all gestations to the four centers, 68 babies went on to develop NEC and all affected infants were of very low birth weight (VLBW); 34 of these had previously received a transfusion of PRBCs but did not fit the diagnostic criteria for TANEC, while 15 (22%) of the 68 babies with NEC qualified as TANEC cases. UK cases occurred at an earlier postnatal age than cases reported in multiple large North American series and were of a lower birth weight. We have confirmed the presence of TANEC in the UK VLBW neonatal population. Its incidence lies within the wide range described in previous reports of this phenomenon globally, though with some local variation in characteristics. Further work is needed to clarify causation, pathophysiology, and possible mechanisms of prevention of TANEC.

Can Monitoring Fetal Intestinal Inflammation Using Heart Rate Variability Analysis Signal Incipient Necrotizing Enterocolitis of the Neonate?

PubMed

Liu, Hai Lun; Garzoni, Luca; Herry, Christophe; Durosier, Lucien Daniel; Cao, Mingju; Burns, Patrick; Fecteau, Gilles; Desrochers, André; Patey, Natalie; Seely, Andrew J E; Faure, Christophe; Frasch, Martin G

2016-04-01

Necrotizing enterocolitis of the neonate is an acute inflammatory intestinal disease that can cause necrosis and sepsis. Chorioamnionitis is a risk factor of necrotizing enterocolitis. The gut represents the biggest vagus-innervated organ. Vagal activity can be measured via fetal heart rate variability. We hypothesized that fetal heart rate variability can detect fetuses with incipient gut inflammation. Prospective animal study. University research laboratory. Chronically instrumented near-term fetal sheep (n = 21). Animals were surgically instrumented with vascular catheters and electrocardiogram to allow manipulation and recording from nonanesthetized animals. In 14 fetal sheep, inflammation was induced with lipopolysaccharide (IV) to mimic chorioamnionitis. Fetal arterial blood samples were drawn at selected time points over 54 hours post lipopolysaccharide for blood gas and cytokines (interleukin-6 and tumor necrosis factor-α enzymelinked immunosorbent assay). Fetal heart rateV was quantified throughout the experiment. The time-matched fetal heart rate variability measures were correlated to the levels of interleukin-6 and tumor necrosis factor-α. Upon necropsy, ionized calcium binding adaptor molecule 1+ (Iba1+), CD11c+ (M1), CD206+ (M2 macrophages), and occludin (leakiness marker) immunofluorescence in the terminal ileum was quantified along with regional Iba1+ signal in the brain (microglia). Interleukin-6 peaked at 3 hours post lipopolysaccharide accompanied by mild cardiovascular signs of sepsis. At 54 hours, we identified an increase in Iba1+ and, specifically, M1 macrophages in the ileum accompanied by increased leakiness, with no change in Iba1 signal in the brain. Preceding this change on tissue level, at 24 hours, a subset of nine fetal heart rate variability measures correlated exclusively to the Iba+ markers of ileal, but not brain, inflammation. An additional fetal heart rate variability measure, mean of the differences of R-R intervals, correlated uniquely to M1 ileum macrophages increasing due to lipopolysaccharide. We identified a unique subset of fetal heart rate variability measures reflecting 1.5 days ahead of time the levels of macrophage activation and increased leakiness in terminal ileum. We propose that such subset of fetal heart rate variability measures reflects brain-gut communication via the vagus nerve. Detecting such noninvasively obtainable organ-specific fetal heart rate variability signature of inflammation would alarm neonatologists about neonates at risk of developing necrotizing enterocolitis and sepsis. Clinical validation studies are required.

Notes from the field: Fatal gastrointestinal mucormycosis in a premature infant associated with a contaminated dietary supplement--Connecticut, 2014.

PubMed

Vallabhaneni, Snigdha; Walker, Tiffany A; Lockhart, Shawn R; Ng, Dianna; Chiller, Tom; Melchreit, Richard; Brandt, Mary E; Smith, Rachel M

2015-02-20

In October 2014, a hospital in Connecticut notified CDC and the Connecticut Department of Public Health of a fatal case of gastrointestinal mucormycosis in a preterm infant. The infant, born at 29 weeks' gestation and weighing 1,400 grams (about 3 pounds), had developed signs and symptoms initially consistent with necrotizing enterocolitis approximately 1 week after birth. Exploratory laparotomy revealed complete ischemia of the gastrointestinal tract from the esophagus to the rectum; a portion of necrotic cecum was sent for microscopic examination. Following surgery, the infant developed multiple areas of vascular occlusion, including a large clot in the aorta, findings not usually associated with necrotizing enterocolitis. The infant died soon after. Histopathology results from the resected cecum revealed an angioinvasive fungal infection consistent with mucormycosis. Gastrointestinal mucormycosis is an extremely rare fungal infection caused by mold in the order Mucorales. It occurs predominantly in low birth weight infants, patients with diarrhea and malnutrition, and those receiving peritoneal dialysis; mortality is 85%. Local investigation revealed that the infant had received a dietary supplement, ABC Dophilus Powder, for 7 days, beginning on day 1 of life.

A Meta-Analysis of Probiotic Efficacy for Gastrointestinal Diseases

PubMed Central

Ritchie, Marina L.; Romanuk, Tamara N.

2012-01-01

Background Meta-analyses on the effects of probiotics on specific gastrointestinal diseases have generally shown positive effects on disease prevention and treatment; however, the relative efficacy of probiotic use for treatment and prevention across different gastrointestinal diseases, with differing etiology and mechanisms of action, has not been addressed. Methods/Principal Findings We included randomized controlled trials in humans that used a specified probiotic in the treatment or prevention of Pouchitis, Infectious diarrhea, Irritable Bowel Syndrome, Helicobacter pylori, Clostridium difficile Disease, Antibiotic Associated Diarrhea, Traveler's Diarrhea, or Necrotizing Enterocolitis. Random effects models were used to evaluate efficacy as pooled relative risks across the eight diseases as well as across probiotic species, single vs. multiple species, patient ages, dosages, and length of treatment. Probiotics had a positive significant effect across all eight gastrointestinal diseases with a relative risk of 0.58 (95% (CI) 0.51–0.65). Six of the eight diseases: Pouchitis, Infectious diarrhea, Irritable Bowel Syndrome, Helicobacter pylori, Clostridium difficile Disease, and Antibiotic Associated Diarrhea, showed positive significant effects. Traveler's Diarrhea and Necrotizing Enterocolitis did not show significant effects of probiotcs. Of the 11 species and species mixtures, all showed positive significant effects except for Lactobacillus acidophilus, Lactobacillus plantarum, and Bifidobacterium infantis. Across all diseases and probiotic species, positive significant effects of probiotics were observed for all age groups, single vs. multiple species, and treatment lengths. Conclusions/Significance Probiotics are generally beneficial in treatment and prevention of gastrointestinal diseases. Efficacy was not observed for Traveler's Diarrhea or Necrotizing Enterocolitis or for the probiotic species L. acidophilus, L. plantarum, and B. infantis. When choosing to use probiotics in the treatment or prevention of gastrointestinal disease, the type of disease and probiotic species (strain) are the most important factors to take into consideration. PMID:22529959

Using a count of neonatal morbidities to predict poor outcome in extremely low birth weight infants: added role of neonatal infection.

PubMed

Bassler, Dirk; Stoll, Barbara J; Schmidt, Barbara; Asztalos, Elizabeth V; Roberts, Robin S; Robertson, Charlene M T; Sauve, Reg S

2009-01-01

A count of 3 neonatal morbidities (bronchopulmonary dysplasia, brain injury, and severe retinopathy of prematurity) strongly predict the risk of death or neurosensory impairment in extremely low birth weight infants who survive to 36 weeks' postmenstrual age. Neonatal infection has also been linked with later impairment. We examined whether the addition of infection to the count of 3 neonatal morbidities further improves the prediction of poor outcome. We studied 944 infants who participated in the Trial of Indomethacin Prophylaxis in Preterms and survived to 36 weeks' postmenstrual age. Culture-proven sepsis, meningitis, and stage II or III necrotizing enterocolitis were recorded prospectively. We investigated the incremental prognostic importance of neonatal infection by adding terms for the different types of infection to a logistic model that already contained terms for the count of bronchopulmonary dysplasia, brain injury, and severe retinopathy. Poor outcome at 18 months of age was death or survival with 1 or more of the following: cerebral palsy, cognitive delay, severe hearing loss, and bilateral blindness. There were 414 (44%) infants with at least 1 episode of infection or necrotizing enterocolitis. Meningitis and the presence of any type of infection added independent prognostic information to the morbidity-count model. The odds ratio associated with infection or necrotizing enterocolitis in this model was 50% smaller than the odds ratio associated with each count of the other 3 neonatal morbidities. Meningitis was rare and occurred in 22 (2.3%) of 944 infants. In this cohort of extremely low birth weight infants who survived to 36 weeks' postmenstrual age, neonatal infection increased the risk of a late death or survival with neurosensory impairment. However, infection was a weaker predictor of poor outcome than bronchopulmonary dysplasia, brain injury, and severe retinopathy.

Human milk feeding supports adequate growth in infants

USDA-ARS?s Scientific Manuscript database

Despite current nutritional strategies, premature infants remain at high risk for extrauterine growth restriction. The use of an exclusive human milk-based diet is associated with decreased incidence of necrotizing enterocolitis (NEC), but concerns exist about infants achieving adequate growth. The ...

A quality improvement initiative to reduce necrotizing enterocolitis across hospital systems.

PubMed

Nathan, Amy T; Ward, Laura; Schibler, Kurt; Moyer, Laurel; South, Andrew; Kaplan, Heather C

2018-04-20

Necrotizing enterocolitis (NEC) is a devastating intestinal disease in premature infants. Local rates of NEC were unacceptably high. We hypothesized that utilizing quality improvement methodology to standardize care and apply evidence-based practices would reduce our rate of NEC. A multidisciplinary team used the model for improvement to prioritize interventions. Three neonatal intensive care units (NICUs) developed a standardized feeding protocol for very low birth weight (VLBW) infants, and employed strategies to increase the use of human milk, maximize intestinal perfusion, and promote a healthy microbiome. The primary outcome measure, NEC in VLBW infants, decreased from 0.17 cases/100 VLBW patient days to 0.029, an 83% reduction, while the compliance with a standardized feeding protocol improved. Through reliable implementation of evidence-based practices, this project reduced the regional rate of NEC by 83%. A key outcome and primary driver of success was standardization across multiple NICUs, resulting in consistent application of best practices and reduction in variation.

The initial experience of antithrombin III in the management of neonates with necrotizing enterocolitis.

PubMed

St Peter, Shawn D; Little, Danny C; Calkins, Casey M; Holcomb, George W; Snyder, Charles L; Ostlie, Daniel J

2007-04-01

Necrotizing enterocolitis (NEC), the devastating enteric process of premature neonates, is marked by severe intravascular abnormalities and disseminated intravascular coagulation. Treatment to date remains historical and continues to be merely supportive without attempts to ameliorate progress within the inflammatory or coagulation cascades. Antithrombin III (ATIII) supplementation has been shown to favorably alter the process of disseminated intravascular coagulation and sepsis in adults. However, no reported use of this treatment exists in neonates. Therefore, we analyze the efficacy of our recent experience with ATIII replacement therapy in neonates with NEC. Age and diseased-matched controls with NEC were identified before the introduction of ATIII in our institution and compared against neonates with NEC undergoing ATIII replacement for diminished ATIII levels. Data collected included demographics, course of treatment parameters, and outcomes. Course of treatment parameters included hemoglobin, platelet count, prothrombin time, and partial thromboplastin time over the first 10 consecutive days of treatment. Outcome variables included packed red blood cell, platelet, fresh frozen plasma, and cryoprecipitate transfusions, as well as transfusion cost, length of stay, and survival. Over a 5-year period, 19 neonates with NEC received ATIII and were compared to 17 historical controls. Treatment hematologic profiles were not worsened in the ATIII-treated patients. The control patients received less overall transfusions and had a shorter length of stay. Antithrombin III appears to be safe in neonates with NEC, and its impact on reversing intravascular pathology in these patients warrants more thorough investigation.

Contrast-Enhanced Ultrasound and Near-Infrared Spectroscopy of the Neonatal Bowel: Novel, Bedside, Noninvasive, and Radiation-Free Imaging for Early Detection of Necrotizing Enterocolitis.

PubMed

Al-Hamad, Suzanne; Hackam, David J; Goldstein, Seth D; Huisman, Thierry A G M; Darge, Kassa; Hwang, Misun

2018-05-31

Despite extensive research and improvements in the field of neonatal care, the morbidity and mortality associated with necrotizing enterocolitis (NEC) have remained unchanged over the past three decades. Early detection of ischemia and necrotic bowel is vital in improving morbidity and mortality associated with NEC; however, strategies for predicting and preventing NEC are lacking. Contrast-enhanced ultrasound (CEUS) and near-infrared spectroscopy (NIRS) are novel techniques in pediatrics that have been proven as safe modalities. CEUS has benefits over conventional ultrasound (US) by its improved real-time evaluation of the micro- and macrovascularities of normally and abnormally perfused tissue. US has been implemented as a useful adjunct to X-ray for earlier evaluation of NEC. NIRS is another noninvasive technique that has shown promise in improving early detection of NEC. The purpose of this article is to review the current understanding of changes in bowel perfusion in NEC, discuss the accuracy of abdominal US in detecting NEC, and explain how the use of CEUS and NIRS will enhance the precise and early detection of altered/pathological bowel wall perfusion in the initial development and course of NEC. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Growth kinetics and model comparison of cronobacter sakazakii in reconstituted powdered infant formula

USDA-ARS?s Scientific Manuscript database

Cronobacter sakazakii is a life-threatening bacterium, primarily implicated in illnesses associated with the consumption of powdered infant formula (PIF). It can cause rare but invasive infections, leading to sepsis, meningitis, or necrotizing enterocolitis in infants fed with contaminated PIF. Th...

Necrotizing Enterocolitis (NEC)

MedlinePlus

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Bovine colostrum improves intestinal function following formula-induced gut inflammation in preterm pigs

USDA-ARS?s Scientific Manuscript database

Only few hours of formula feeding may induce proinflammatory responses and predispose to necrotizing enterocolitis (NEC) in preterm pigs. We hypothesized that bovine colostrum, rich in bioactive factors, would improve intestinal function in preterm pigs following an initial exposure to formula feedi...

The Microbiome and Metabolome of Preterm Infant Stool Are Personalized and Not Driven by Health Outcomes, Including Necrotizing Enterocolitis and Late-Onset Sepsis

PubMed Central

Wandro, Stephen; Osborne, Stephanie; Enriquez, Claudia; Bixby, Christine; Arrieta, Antonio

2018-01-01

ABSTRACT The assembly and development of the gut microbiome in infants have important consequences for immediate and long-term health. Preterm infants represent an abnormal case for bacterial colonization because of early exposure to bacteria and frequent use of antibiotics. To better understand the assembly of the gut microbiota in preterm infants, fecal samples were collected from 32 very low birth weight preterm infants over the first 6 weeks of life. Infant health outcomes included health, late-onset sepsis, and necrotizing enterocolitis (NEC). We characterized bacterial compositions by 16S rRNA gene sequencing and metabolomes by untargeted gas chromatography-mass spectrometry. Preterm infant fecal samples lacked beneficial Bifidobacterium spp. and were dominated by Enterobacteriaceae, Enterococcus, and Staphylococcus organisms due to nearly uniform antibiotic administration. Most of the variance between the microbial community compositions could be attributed to the baby from which the sample derived (permutational multivariate analysis of variance [PERMANOVA] R2 = 0.48, P < 0.001), while clinical status (health, NEC, or late-onset sepsis) and overlapping times in the neonatal intensive care unit (NICU) did not explain a significant amount of variation in bacterial composition. Fecal metabolomes were also found to be unique to the individual (PERMANOVA R2 = 0.43, P < 0.001) and weakly associated with bacterial composition (Mantel statistic r = 0.23 ± 0.05, P < 0.05). No measured metabolites were found to be associated with necrotizing enterocolitis, late-onset sepsis, or a healthy outcome. Overall, preterm infant gut microbial communities were personalized and reflected antibiotic usage. IMPORTANCE Preterm infants face health problems likely related to microbial exposures, including sepsis and necrotizing enterocolitis. However, the role of the gut microbiome in preterm infant health is poorly understood. Microbial colonization differs from that of healthy term babies because it occurs in the NICU and is often perturbed by antibiotics. We measured bacterial compositions and metabolomic profiles of 77 fecal samples from 32 preterm infants to investigate the differences between microbiomes in health and disease. Rather than finding microbial signatures of disease, we found that both the preterm infant microbiome and the metabolome were personalized and that the preterm infant gut microbiome is enriched in microbes that commonly dominate in the presence of antibiotics. These results contribute to the growing knowledge of the preterm infant microbiome and emphasize that a personalized view will be important to disentangle the health consequences of the preterm infant microbiome. PMID:29875143

The Microbiome and Metabolome of Preterm Infant Stool Are Personalized and Not Driven by Health Outcomes, Including Necrotizing Enterocolitis and Late-Onset Sepsis.

PubMed

Wandro, Stephen; Osborne, Stephanie; Enriquez, Claudia; Bixby, Christine; Arrieta, Antonio; Whiteson, Katrine

2018-06-27

The assembly and development of the gut microbiome in infants have important consequences for immediate and long-term health. Preterm infants represent an abnormal case for bacterial colonization because of early exposure to bacteria and frequent use of antibiotics. To better understand the assembly of the gut microbiota in preterm infants, fecal samples were collected from 32 very low birth weight preterm infants over the first 6 weeks of life. Infant health outcomes included health, late-onset sepsis, and necrotizing enterocolitis (NEC). We characterized bacterial compositions by 16S rRNA gene sequencing and metabolomes by untargeted gas chromatography-mass spectrometry. Preterm infant fecal samples lacked beneficial Bifidobacterium spp. and were dominated by Enterobacteriaceae , Enterococcus , and Staphylococcus organisms due to nearly uniform antibiotic administration. Most of the variance between the microbial community compositions could be attributed to the baby from which the sample derived (permutational multivariate analysis of variance [PERMANOVA] R 2 = 0.48, P < 0.001), while clinical status (health, NEC, or late-onset sepsis) and overlapping times in the neonatal intensive care unit (NICU) did not explain a significant amount of variation in bacterial composition. Fecal metabolomes were also found to be unique to the individual (PERMANOVA R 2 = 0.43, P < 0.001) and weakly associated with bacterial composition (Mantel statistic r = 0.23 ± 0.05, P < 0.05). No measured metabolites were found to be associated with necrotizing enterocolitis, late-onset sepsis, or a healthy outcome. Overall, preterm infant gut microbial communities were personalized and reflected antibiotic usage. IMPORTANCE Preterm infants face health problems likely related to microbial exposures, including sepsis and necrotizing enterocolitis. However, the role of the gut microbiome in preterm infant health is poorly understood. Microbial colonization differs from that of healthy term babies because it occurs in the NICU and is often perturbed by antibiotics. We measured bacterial compositions and metabolomic profiles of 77 fecal samples from 32 preterm infants to investigate the differences between microbiomes in health and disease. Rather than finding microbial signatures of disease, we found that both the preterm infant microbiome and the metabolome were personalized and that the preterm infant gut microbiome is enriched in microbes that commonly dominate in the presence of antibiotics. These results contribute to the growing knowledge of the preterm infant microbiome and emphasize that a personalized view will be important to disentangle the health consequences of the preterm infant microbiome. Copyright © 2018 Wandro et al.

Intestinal threonine utilization for protein and mucin synthesis is decreased in formula-fed preterm pigs

USDA-ARS?s Scientific Manuscript database

Threonine is an essential amino acid necessary for synthesis of intestinal (glyco)proteins such as mucin (MUC2) to maintain adequate gut barrier function. In premature infants, reduced barrier function may contribute to the development of necrotizing enterocolitis (NEC). Human milk protects against ...

Nutrient fortification of human donor milk affects intestinal function and protein metabolism in preterm pigs

USDA-ARS?s Scientific Manuscript database

Nutrient fortification of human milk is often required to secure adequate growth and organ development for very preterm infants. There is concern that formula-based fortifiers (FFs) induce intestinal dysfunction, feeding intolerance, and necrotizing enterocolitis (NEC). Bovine colostrum (BC) may be ...

Can non-invasive measurement of gut oxygenation predict necrotizing enterocolitis in preterm infants?

USDA-ARS?s Scientific Manuscript database

Factors that contribute to the development of NEC include hypoperfusion or decreased oxygenation of splanchnic tissue. Near-Infrared Spectroscopy (NIRS) will be used to assess gut oxygenation non-invasively. Typically NIRS is primarily used for cerebral hemodynamic monitoring; we intend to apply it ...

Intestinal trophic effect of enteral arginine is independent of blood flow in neonatal piglets

USDA-ARS?s Scientific Manuscript database

Arginine is an indispensable amino acid in neonates. Arginine is synthesized by gut epithelial cells and may have a protective role in preventing necrotizing enterocolitis. We hypothesized our method included that enteral arginine is a stimulus for intestinal blood flow and subsequent mucosal growth...

Selected pathogens of concern to industrial food processors: infectious, toxigenic, toxico-infectious, selected emerging pathogenic bacteria

USDA-ARS?s Scientific Manuscript database

Enterobacter sakazakii is a rod-shaped bacterium that has been implicated in rare cases of neonatal sepsis, meningitis and is associated with necrotizing enterocolitis in infants. Over 80 cases of E. sakazakii-related illness have been reported, although few of these have occurred in adults. There...

What Are the Common Treatments for Necrotizing Enterocolitis?

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The application of peritoneal drainage in the surgical treatment for neonates with necrotizing enterocolitis

NASA Astrophysics Data System (ADS)

Zhao, Jixue; Fu, Xin

2017-08-01

Object To explore the feasibility and effects of peritoneal drainage in the surgical treatment for the neonates with necrotizing enterocolitis. Methods: A retrospective analysis was conduct on 32 cases of newborns with extensive and multiple intestinal necrosis found intraoperatively, all of which could not accept first-stage resected, treated by traditional operation or by peritoneal drainage between January, 2013 to January 2017. Duration of operation, amount of bleeding, and the survival rate after operation were compared between the two groups, which were divided by surgical methods. Results: No significant difference was observed in age, and gender (P>0.05) between the two groups. However, duration of operation was significantly shorter, the amount of bleeding was significantly lessen, the survival rate was significantly higher in the patients by peritoneal drainage than the patients by traditional operation (P<0.05). Conclusion: To compare traditional operation or peritoneal drainage in neonates, a retrospective analysis conducted by us showed the feasibility and effects of peritoneal drainage in neonates, and a significant advantage in duration of operation and the survival rate after operation.

[Role of donor human milk feeding in preventing nosocomial infection in very low birth weight infants].

PubMed

Bi, Hong-Juan; Xu, Jing; Wei, Qiu-Fen

2018-02-01

To investigate the role of donor human milk in the prevention of nosocomial infection in very low birth weight infants. MeETHODS: A total of 105 hospitalized preterm infants with a very low birth weight were enrolled. They were classified into mother's own milk feeding group, donor human milk feeding group, and preterm formula feeding group, with 35 infants in each group. The three groups were compared in terms of incidence rates of nosocomial infection, necrotizing enterocolitis, and feeding intolerance, time to full enteral feeding, and early growth indices. Compared with the preterm formula feeding group, the donor human milk feeding group and the mother's own milk feeding group had significantly lower incidence rates of nosocomial infection and necrotizing enterocolitis and shorter time to full enteral feeding (P<0.05). There were no significant differences in head circumference, body length, and weight growth velocity among the three groups. Donor human milk can be used in case of a lack of mother's own milk and may help to reduce nosocomial infection.

PPAR-{gamma} agonist protects against intestinal injury during necrotizing enterocolitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baregamian, Naira; Mourot, Joshua M.; Ballard, Amie R.

2009-02-06

Necrotizing enterocolitis (NEC) remains a lethal condition for many premature infants. Peroxisome proliferator-activated receptor-{gamma} (PPAR-{gamma}), a member of the nuclear hormone receptor family, has been shown to play a protective role in cellular inflammatory responses; however, its role in NEC is not clearly defined. We sought to examine the expression of PPAR-{gamma} in the intestine using an ischemia-reperfusion (I/R) model of NEC, and to assess whether PPAR-{gamma} agonist treatment would ameliorate I/R-induced gut injury. Swiss-Webster mice were randomized to receive sham (control) or I/R injury to the gut induced by transient occlusion of superior mesenteric artery for 45 min withmore » variable periods of reperfusion. I/R injury resulted in early induction of PPAR-{gamma} expression and activation of NF-{kappa}B in small intestine. Pretreatment with PPAR-{gamma} agonist, 15d-PGJ{sub 2}, attenuated intestinal NF-{kappa}B response and I/R-induced gut injury. Activation of PPAR-{gamma} demonstrated a protective effect on small bowel during I/R-induced gut injury.« less

Human milk is the feeding strategy to prevent necrotizing enterocolitis!

PubMed

Maffei, Diana; Schanler, Richard J

2017-02-01

Human milk is the preferred diet for preterm infants as it protects against a multitude of NICU challenges, specifically necrotizing enterocolitis. Infants who receive greater than 50% of mother's own milk (MOM) in the 2 weeks after birth have a significantly decreased risk of NEC. An additional factor in the recent declining rates of NEC is the increased utilization of donor human milk (DHM). This creates a bridge until MOM is readily available, thus decreasing the exposure to cow milk protein. Preterm infants are susceptible to NEC due to the immaturity of their gastrointestinal and immune systems. An exclusive human milk diet compensates for these immature systems in many ways such as lowering gastric pH, enhancing intestinal motility, decreasing epithelial permeability, and altering the composition of bacterial flora. Ideally, preterm infants should be fed human milk and avoid bovine protein. A diet consisting of human milk-based human milk fortifier is one way to provide the additional nutritional supplements necessary for adequate growth while receiving the protective benefits of a human milk diet. Copyright © 2016 Elsevier Inc. All rights reserved.

Can a national dataset generate a nomogram for necrotizing enterocolitis onset?

PubMed

Gordon, P V; Clark, R; Swanson, J R; Spitzer, A

2014-10-01

Mother's own milk and donor human milk use is increasing as a means of necrotizing enterocolitis (NEC) prevention. Early onset of enteral feeding has been associated with improvement of many outcomes but has not been shown to reduce the incidence of NEC. Better definition of the window of risk for NEC by gestational strata should improve resource management with respect to donor human milk and enhance our understanding of NEC timing and pathogenesis. Our objective was to establish a NEC dataset of sufficient size and quality, then build a generalizable model of NEC onset from the dataset across gestational strata. We used de-identified data from the Pediatrix national dataset and filtered out all diagnostic confounders that could be identified by either specific diagnoses or logical exclusions (example dual diagnoses), with a specific focus on NEC and spontaneous intestinal perforation (SIP) as the outcomes of interest. The median day of onset was plotted against the gestational age for each of these diagnoses and analyzed for similarities and differences in the day of diagnosis. Onset time of medical NEC was inversely proportional to gestation in a linear relationship across all gestational ages. We found the medical NEC dataset displayed characteristics most consistent with a homogeneous disease entity, whereas there was a skew towards early presentation in the youngest gestation groups of surgical NEC (suggesting probable SIP contamination). Our national dataset demonstrates that NEC onset occurs in an inverse stereotypic, linear relationship with gestational age at birth. Medical NEC is the most reliable sub-cohort for the purpose of determining the temporal window of NEC risk.

Probiotics, Prebiotics, and Synbiotics for the Prevention of Necrotizing Enterocolitis.

PubMed

Johnson-Henry, Kathene C; Abrahamsson, Thomas R; Wu, Richard You; Sherman, Philip M

2016-09-01

Necrotizing enterocolitis (NEC) is a devastating intestinal disease in preterm infants characterized by barrier disruption, intestinal microbial dysbiosis, and persistent inflammation of the colon, which results in high mortality rates. Current strategies used to manage this disease are not sufficient, although the use of human breast milk reduces the risk of NEC. Mother's milk is regarded as a fundamental nutritional source for neonates, but pasteurization of donor breast milk affects the composition of bioactive compounds. Current research is evaluating the benefits and potential pitfalls of adding probiotics and prebiotics to pasteurized milk so as to improve the functionality of the milk and thereby reduce the burden of illness caused by NEC. Probiotics (live micro-organisms that confer health to the host) and prebiotics (nondigestible oligosaccharides that stimulate the growth of healthy bacteria) are functional foods known to mediate immune responses and modulate microbial populations in the gut. Clinical research shows strain- and compound-specific responses when probiotics or prebiotics are administered in conjunction with donor breast milk for the prevention of NEC. Despite ongoing controversy surrounding optimal treatment strategies, randomized controlled studies are now investigating the use of synbiotics to reduce the incidence and severity of NEC. Synbiotics, a combination of probiotics and prebiotics, have been proposed to enhance beneficial health effects in the intestinal tract more than either agent administered alone. This review considers the implications of using probiotic-, prebiotic-, and synbiotic-supplemented breast milk as a strategy to prevent NEC and issues that could be encountered with the preparations. © 2016 American Society for Nutrition.

Probiotics, Prebiotics, and Synbiotics for the Prevention of Necrotizing Enterocolitis12

PubMed Central

Wu, Richard You

2016-01-01

Necrotizing enterocolitis (NEC) is a devastating intestinal disease in preterm infants characterized by barrier disruption, intestinal microbial dysbiosis, and persistent inflammation of the colon, which results in high mortality rates. Current strategies used to manage this disease are not sufficient, although the use of human breast milk reduces the risk of NEC. Mother’s milk is regarded as a fundamental nutritional source for neonates, but pasteurization of donor breast milk affects the composition of bioactive compounds. Current research is evaluating the benefits and potential pitfalls of adding probiotics and prebiotics to pasteurized milk so as to improve the functionality of the milk and thereby reduce the burden of illness caused by NEC. Probiotics (live micro-organisms that confer health to the host) and prebiotics (nondigestible oligosaccharides that stimulate the growth of healthy bacteria) are functional foods known to mediate immune responses and modulate microbial populations in the gut. Clinical research shows strain- and compound-specific responses when probiotics or prebiotics are administered in conjunction with donor breast milk for the prevention of NEC. Despite ongoing controversy surrounding optimal treatment strategies, randomized controlled studies are now investigating the use of synbiotics to reduce the incidence and severity of NEC. Synbiotics, a combination of probiotics and prebiotics, have been proposed to enhance beneficial health effects in the intestinal tract more than either agent administered alone. This review considers the implications of using probiotic-, prebiotic-, and synbiotic-supplemented breast milk as a strategy to prevent NEC and issues that could be encountered with the preparations. PMID:27633108

Current Knowledge of Necrotizing Enterocolitis in Preterm Infants and the Impact of Different Types of Enteral Nutrition Products.

PubMed

Shulhan, Jocelyn; Dicken, Bryan; Hartling, Lisa; Larsen, Bodil Mk

2017-01-01

Preterm infants are extremely vulnerable to a range of morbidities and mortality. Underdeveloped cardiac, respiratory, gastrointestinal, and immune systems in the preterm period increase the risk of necrotizing enterocolitis (NEC), a serious disease of the gut. NEC affects 5-12% of very-low birth-weight infants, leads to surgery in 20-40% of cases, and is fatal in 25-50% of cases. There are multiple factors that may contribute to NEC, but the exact cause is not yet fully understood. Severe cases can result in intestinal resection or death, and the health care costs average >$300,000/infant when surgical management is required. Different types of nutrition may affect the onset or progression of NEC. Several studies have indicated that bovine milk-based infant formulas lead to a higher incidence of NEC in preterm infants than does human milk (HM). However, it is not clear why HM is linked to a lower incidence of NEC or why some infants fed an exclusively HM diet still develop NEC. An area that has not been thoroughly explored is the use of semielemental or elemental formulas. These specialty formulas are easy to digest and absorb in the gut and may be an effective nutritional intervention for reducing the risk of NEC. This review summarizes what is known about the factors that contribute to the onset and progression of NEC, discusses its health care cost implications, and explores the impact that different formulas and HM have on this disease. © 2017 American Society for Nutrition.

Current Knowledge of Necrotizing Enterocolitis in Preterm Infants and the Impact of Different Types of Enteral Nutrition Products12

PubMed Central

Dicken, Bryan; Hartling, Lisa

2017-01-01

Preterm infants are extremely vulnerable to a range of morbidities and mortality. Underdeveloped cardiac, respiratory, gastrointestinal, and immune systems in the preterm period increase the risk of necrotizing enterocolitis (NEC), a serious disease of the gut. NEC affects 5–12% of very–low birth-weight infants, leads to surgery in 20–40% of cases, and is fatal in 25–50% of cases. There are multiple factors that may contribute to NEC, but the exact cause is not yet fully understood. Severe cases can result in intestinal resection or death, and the health care costs average >$300,000/infant when surgical management is required. Different types of nutrition may affect the onset or progression of NEC. Several studies have indicated that bovine milk–based infant formulas lead to a higher incidence of NEC in preterm infants than does human milk (HM). However, it is not clear why HM is linked to a lower incidence of NEC or why some infants fed an exclusively HM diet still develop NEC. An area that has not been thoroughly explored is the use of semielemental or elemental formulas. These specialty formulas are easy to digest and absorb in the gut and may be an effective nutritional intervention for reducing the risk of NEC. This review summarizes what is known about the factors that contribute to the onset and progression of NEC, discusses its health care cost implications, and explores the impact that different formulas and HM have on this disease. PMID:28096129

Clostridial Strain-Specific Characteristics Associated with Necrotizing Enterocolitis.

PubMed

Schönherr-Hellec, Sophia; Klein, Geraldine L; Delannoy, Johanne; Ferraris, Laurent; Rozé, Jean Christophe; Butel, Marie José; Aires, Julio

2018-04-01

We aimed at identifying potential bacterial factors linking clostridia with necrotizing enterocolitis (NEC). We compared the phenotypic traits, stress responses, cellular cytotoxicity, and inflammatory capabilities of the largest collection of Clostridium butyricum and Clostridium neonatale strains isolated from fecal samples of NEC preterm neonates (PN) and control PNs. When strain characteristics were used as explanatory variables, a statistical discriminant analysis allowed the separation of NEC and control strains into separate groups. Strains isolated from NEC PN were characterized by a higher viability at 30°C ( P = 0.03) and higher aerotolerance ( P = 0.01), suggesting that NEC strains may have a competitive and/or survival advantage in the environmental gastrointestinal tract conditions of NEC PN. Heat-treated NEC bacteria induced higher production of interleukin-8 in Caco-2 cells ( P = 0.03), suggesting proinflammatory activity. In vitro , bacteria, bacterial components, and fecal filtrates showed variable cytotoxic effects affecting the cellular network and/or cell viability, without specific association with NEC or control samples. Altogether, our data support the existence of a specific clostridial strain signature associated with NEC. IMPORTANCE Clostridia are part of the commensal microbiota in preterm neonates (PN). However, microbiota analyses by culture and metagenomics have linked necrotizing enterocolitis (NEC) and intestinal colonization with clostridial species. Nevertheless, little is known about the specific characteristics that may be shared by clostridia associated with NEC compared to commensal clostridia. Therefore, our goal was to identify specific bacterial factors linking clostridial strains with NEC. We report the existence of a specific bacterial signature associated with NEC and propose that activation of the innate immune response may be a unifying causative mechanism for the development of NEC independent of a specific pathogenic organism. The present study provides new insights into NEC pathophysiology that are needed for better diagnostics and strategies for implementing prevention of the disease. Copyright © 2018 American Society for Microbiology.

Restricted versus liberal water intake for preventing morbidity and mortality in preterm infants.

PubMed

Bell, E F; Acarregui, M J

2008-01-23

Most premature infants are not sufficiently mature physiologically to ingest all of their required water and nutrients orally. Therefore, premature infants rely on their caregivers to regulate their volume of water intake. Thus, the caregiver must determine the amount of water to be given each day to such infants. The objective of this review is to examine the effects of water intake on postnatal weight loss and on the risks of dehydration, patent ductus arteriosus, necrotizing enterocolitis, bronchopulmonary dysplasia, intracranial hemorrhage, and death in premature infants. Randomized clinical trials identified in previous versions of this review were re-examined and, in each case, retained. Additional trials were sought that compared the outcomes of interest in groups of premature infants who were given different levels of water intake according to experimental protocol. Such trials were sought in a list of trials provided by the Cochrane Neonatal Review Group, with a PubMed search, and in the authors' personal files. Only randomized clinical trials of varying water intake in premature infants are included. The review was limited to trials that included infants whose water intake was provided mainly or entirely by intravascular infusion. Included studies reported at least one of the following outcomes: postnatal weight loss, dehydration, patent ductus arteriosus, necrotizing enterocolitis, bronchopulmonary dysplasia, intracranial hemorrhage, and death. Standard methods of the Cochrane Collaboration were used. The studies to be included were selected by two reviewers, each of whom also assessed the methodological quality of each trial. Data were independently extracted by the reviewers, who agreed on the key details. The data were then entered into tables using RevMan 4.3.1. The adverse event rates were calculated for the restricted and liberal water intake groups for each dichotomous outcome, and the relative risk and risk difference were computed. In addition, the maximal weight loss results were recorded, and the weighted mean difference was computed. The analyses - including calculation of relative risk, risk difference, and weighted mean difference - and tests of heterogeneity were accomplished using RevMan 4.3.1 software. The analysis of the five studies taken together indicates that restricted water intake significantly increases postnatal weight loss and significantly reduces the risks of patent ductus arteriosus and necrotizing enterocolitis. With restricted water intake, there are trends toward increased risk of dehydration and reduced risks of bronchopulmonary dysplasia, intracranial hemorrhage, and death, but these trends are not statistically significant. Based on this analysis, the most prudent prescription for water intake to premature infants would seem to be careful restriction of water intake so that physiological needs are met without allowing significant dehydration. This practice could be expected to decrease the risks of patent ductus arteriosus and necrotizing enterocolitis without significantly increasing the risk of adverse consequences.

Oxygen saturation target range for extremely preterm infants: a systematic review and meta-analysis.

PubMed

Manja, Veena; Lakshminrusimha, Satyan; Cook, Deborah J

2015-04-01

The optimal oxygen saturation (SpO2) target for extremely preterm infants is unknown. To systematically review evidence evaluating the effect of restricted vs liberal oxygen exposure on morbidity and mortality in extremely preterm infants. MEDLINE, PubMed, CENTRAL, and CINAHL databases from their inception to March 31, 2014, and abstracts submitted to Pediatric Academic Societies from 2000 to 2014. All published randomized trials evaluating the effect of restricted (SpO2, 85%-89%) vs liberal (SpO2, 91%-95%) oxygen exposure in preterm infants (<28 weeks' gestation at birth). All meta-analyses were performed using Review Manager 5.2. The Cochrane risk-of-bias tool was used to assess study quality. The summary of the findings and the level of confidence in the estimate of effect were assessed using GRADEpro. Treatment effect was analyzed using a random-effects model. Death before hospital discharge, death or severe disability before 24 months, death before 24 months, neurodevelopmental outcomes, hearing loss, bronchopulmonary dysplasia, necrotizing enterocolitis, and severe retinopathy of prematurity. Five trials were included in the final synthesis. These studies had a similar design with a prespecified composite outcome of death/disability at 18 to 24 months corrected for prematurity; however, this outcome has not been reported for 2 of the 5 trials. There was no difference in the outcome of death/disability before 24 months (risk ratio [RR], 1.02 [95% CI, 0.92-1.14]). Mortality before 24 months was not different (RR, 1.13 [95% CI, 0.97-1.33]); however, a significant increase in mortality before hospital discharge was found in the restricted oxygen group (RR, 1.18 [95% CI, 1.03-1.36]). The rates of bronchopulmonary dysplasia, neurodevelopmental outcomes, hearing loss, and retinopathy of prematurity were similar between the 2 groups. Necrotizing enterocolitis occurred more frequently in infants on restricted oxygen (RR, 1.24 [95% CI, 1.05-1.47]). Using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria, we found that the quality of evidence for these outcomes was moderate to low. Although infants cared for with a liberal oxygen target had significantly lower mortality before hospital discharge than infants cared for with a restricted oxygen target, the quality of evidence for this estimate of effect is low. Necrotizing enterocolitis occurred less frequently in the liberal oxygen group. We found no significant differences in death or disability at 24 months, bronchopulmonary dysplasia, retinopathy of prematurity, neurodevelopmental outcomes, or hearing loss at 24 months.

Association of Placebo, Indomethacin, Ibuprofen, and Acetaminophen With Closure of Hemodynamically Significant Patent Ductus Arteriosus in Preterm Infants: A Systematic Review and Meta-analysis.

PubMed

Mitra, Souvik; Florez, Ivan D; Tamayo, Maria E; Mbuagbaw, Lawrence; Vanniyasingam, Thuva; Veroniki, Areti Angeliki; Zea, Adriana M; Zhang, Yuan; Sadeghirad, Behnam; Thabane, Lehana

2018-03-27

Despite increasing emphasis on conservative management of patent ductus arteriosus (PDA) in preterm infants, different pharmacotherapeutic interventions are used to treat those developing a hemodynamically significant PDA. To estimate the relative likelihood of hemodynamically significant PDA closure with common pharmacotherapeutic interventions and to compare adverse event rates. The databases of MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception until August 15, 2015, and updated on December 31, 2017, along with conference proceedings up to December 2017. Randomized clinical trials that enrolled preterm infants with a gestational age younger than 37 weeks treated with intravenous or oral indomethacin, ibuprofen, or acetaminophen vs each other, placebo, or no treatment for a clinically or echocardiographically diagnosed hemodynamically significant PDA. Data were independently extracted in pairs by 6 reviewers and synthesized with Bayesian random-effects network meta-analyses. Primary outcome: hemodynamically significant PDA closure; secondary: included surgical closure, mortality, necrotizing enterocolitis, and intraventricular hemorrhage. In 68 randomized clinical trials of 4802 infants, 14 different variations of indomethacin, ibuprofen, or acetaminophen were used as treatment modalities. The overall PDA closure rate was 67.4% (2867 of 4256 infants). A high dose of oral ibuprofen was associated with a significantly higher odds of PDA closure vs a standard dose of intravenous ibuprofen (odds ratio [OR], 3.59; 95% credible interval [CrI], 1.64-8.17; absolute risk difference, 199 [95% CrI, 95-258] more per 1000 infants) and a standard dose of intravenous indomethacin (OR, 2.35 [95% CrI, 1.08-5.31]; absolute risk difference, 124 [95% CrI, 14-188] more per 1000 infants). Based on the ranking statistics, a high dose of oral ibuprofen ranked as the best pharmacotherapeutic option for PDA closure (mean surface under the cumulative ranking [SUCRA] curve, 0.89 [SD, 0.12]) and to prevent surgical PDA ligation (mean SUCRA, 0.98 [SD, 0.08]). There was no significant difference in the odds of mortality, necrotizing enterocolitis, or intraventricular hemorrhage with use of placebo or no treatment compared with any of the other treatment modalities. A high dose of oral ibuprofen was associated with a higher likelihood of hemodynamically significant PDA closure vs standard doses of intravenous ibuprofen or intravenous indomethacin; placebo or no treatment did not significantly change the likelihood of mortality, necrotizing enterocolitis, or intraventricular hemorrhage. PROSPERO Identifier: CRD42015015797.

Aerophagia induced by the nasal obstruction on experimental animals.

PubMed

Nakajima, K; Ohi, G

1977-04-01

The excessive accumulation of gas in the gastrointestinal tracts was invariably induced on experimental animals (mice, rats, guinea pigs, hamsters and rabbits) by simply obstructing nasal passages. The analysis of the gas showed the almost identical composition to the ambient air or flutus which was largely due to swallowed air. Also the numerous small foams were found on and underneath the epithelial lining of small intestine. The pathological evaluation was done both macroscopically and microscopically. Dying animals after nasal obstruction showed hemorrhagic and necrotic changes in the jejunum and ileum. This observation may cast some light to the pathogenesis of necrotizing enterocolitis in human neonatal.

A decrease in the number of cases of necrotizing enterocolitis associated with the enhancement of infection prevention and control measures during a Staphylococcus aureus outbreak in a neonatal intensive care unit.

PubMed

Lemyre, Brigitte; Xiu, Wenlong; Bouali, Nicole Rouvinez; Brintnell, Janet; Janigan, Jo-Anne; Suh, Kathryn N; Barrowman, Nicholas

2012-01-01

Most cases of necrotizing enterocolitis (NEC) are sporadic, but outbreaks in hospital settings suggest an infectious cause. Our neonatal intensive care unit (NICU) experienced an outbreak of methicillin-sensitive Staphylococcus aureus (MSSA). We aimed to assess whether the enhancement of infection prevention and control measures would be associated with a reduction in the number of cases of NEC. Retrospective chart review. A 24-bed, university-affiliated, inborn level 3 NICU. Infants of less than 30 weeks gestation or birth weight ≤ 1,500 g admitted to the NICU between January 2007 and December 2008 were considered at risk of NEC. All cases of NEC were reviewed. Infection prevention and control measures, including hand hygiene education, were enhanced during the outbreak. Avoidance of overcapacity in the NICU was reinforced, environmental services (ES) measures were enhanced, and ES hours were increased. Two hundred eighty-two at-risk infants were admitted during the study. Their gestational age and birth weight (mean ± SD) were 28.2 ± 2.7 weeks and 1,031 ± 290 g, respectively. The proportion of NEC was 18/110 (16.4%) before the outbreak, 1/54 (1.8%) during the outbreak, and 4/118 (3.4%) after the outbreak. After adjustment for gestational age, birth weight, gender, and singleton versus multiple births, the proportion was lower in the postoutbreak period than in the preoutbreak period (P < .002). Although this observational study cannot establish a causal relationship, there was a significant decrease in the incidence of NEC following implementation of enhanced infection prevention and control measures to manage an MSSA outbreak.

An exclusive human milk-based diet in extremely premature infants reduces the probability of remaining on total parenteral nutrition: A reanalysis of the data

USDA-ARS?s Scientific Manuscript database

We have previously shown that an exclusively human-milk-based diet is beneficial for extremely premature infants who are at risk for necrotizing enterocolitis (NEC). However, no significant difference in the other primary study endpoint, the length of time on total parenteral nutrition (TPN), was fo...

Probiotics and necrotizing enterocolitis.

PubMed

Fleming, Paul; Hall, Nigel J; Eaton, Simon

2015-12-01

Probiotics for the prevention of necrotizing enterocolitis have attracted a huge interest. Combined data from heterogeneous randomised controlled trials suggest that probiotics may decrease the incidence of NEC. However, the individual studies use a variety of probiotic products, and the group at greatest risk of NEC, i.e., those with a birth weight of less than 1000 g, is relatively under-represented in these trials so we do not have adequate evidence of either efficacy or safety to recommend universal prophylactic administration of probiotics to premature infants. These problems have polarized neonatologists, with some taking the view that it is unethical not to universally administer probiotics to premature infants, whereas others regard the meta-analyses as flawed and that there is insufficient evidence to recommend routine probiotic administration. Another problem is that the mechanism by which probiotics might act is not clear, although some experimental evidence is starting to accumulate. This may allow development of surrogate endpoints of effectiveness, refinement of probiotic regimes, or even development of pharmacological agents that may act through the same mechanism. Hence, although routine probiotic administration is controversial, studies of probiotic effects may ultimately lead us to effective means to prevent this devastating disease.

Changes in plasma and urinary nitrite after birth in premature infants at risk for necrotizing enterocolitis

PubMed Central

Pun, Priti; Jones, Jesica; Wolfe, Craig; Deming, Douglas D.; Power, Gordon G.; Blood, Arlin B.

2016-01-01

Background Plasma nitrite serves as a reservoir of nitric oxide (NO) bioactivity. Because nitrite ingestion is markedly lower in newborns than adults, we hypothesized plasma nitrite levels would be lower in newborns than in adults, and that infants diagnosed with necrotizing enterocolitis (NEC), a disease characterized by ischemia and bacterial invasion of intestinal walls, would have lower levels of circulating nitrite in the days prior to diagnosis. Methods Single blood and urine samples were collected from 9 term infants and 12 adults, 72 preterm infants every 5 d for 3 wk, and from 13 lambs before and after cord occlusion. Results Nitrite fell 50% relative to cord levels in the first day after birth; and within 15 min after cord occlusion in lambs. Urinary nitrite was higher in infants than adults. Plasma and urinary nitrite levels in infants who developed NEC were similar to those of preterm control infants on days 1 and 5, but significantly elevated at 15 and 20 d after birth. Conclusion Plasma nitrite falls dramatically at birth while newborn urinary nitrite levels are significantly greater than adults. Acute NEC is associated with elevated plasma and urinary nitrite levels. PMID:26539663

Fatal necrotising enterocolitis due to mydriatic eye drops.

PubMed

Ozgun, Uygur; Demet, Terek; Ozge, Koroglu A; Zafer, Dokumcu; Murat, Sezak; Mehmet, Yalaz; Nilgun, Kultursay

2014-05-01

Retinopathy of prematurity (ROP) is a serious problem of preterm infants which may lead to impairment of vision and even to blindness if untreated. Routine eye examination is necessary for early diagnosis and treatment of ROP in preterm infants. Mydriatic eye drops (cyclopentolate, tropicamide and phenylephrine) are applied before the ophthalmic examination. These agents are rarely absorbed to systemic circulation and in some cases result with serious side effects like skin rash, tachycardia, feeding intolerance, discomfort, apnea, gastric dilatation and ileus, despite different treatment models and dosage reducing strategies. We report here a preterm patient who died because of severe diffuse necrotizing enterocolitis (NEC) after topical application of 0.5% cyclopentolate and 1.25% phenylephrine during ROP screening to emphasise the serious side effects of these agents.

[FACTORS RELATED TO MORTALITY IN NECROTIZINGENTEROCOLITIS(NEC) IN NEONATES AND OLDER INFANTS

PubMed

Ríos D , Hugo; Rivera M , Juan

1997-01-01

In order to determine the factors related to mortality in Necrotizing enterocolitis (NEC), medical records of neonates and older infants diagnosed of NEC in the Instituto de Salud del Niño between 1984 and 1993 were retrospectively reviewed. Only the cases with a reliable roentgenologic, surgical or pathologic diagnosis were included. Sixty cases (46 infants and 14 neonates) were found, with a higher incidence in males (37 males vs 23 females). Twenty six cases required surgical treatment. Overall mortality was 77%, with no significant differences between neonates and infants, nor between those who were operated or not. Moderate or severe malnutrition, diarrhea as an early clinical manifestations, bronchopneumonia, shock and poor nutricional management were found as factors related to mortality.

Chemotherapy-induced neutropenic necrotizing enterocolitis: a review.

PubMed

Mehdi, Itrat; Al Bahrani, Bassim

2012-07-01

Neutropenia is a common toxicity of systemic cytotoxic therapy. Neutropenic enterocolitis (NE) is a rare occurrence but can be fatal, subsequent to neutropenia. The exact incidence and frequency is difficult to establish, but is usually underestimated. It is often missed but has recently been appreciated with increasing frequency in solid tumours. NE was initially reported with taxenes but now an increasing number of chemotherapeutic drugs are implicated. NE incidence is expected to increase with the use of dose dense regimens, myeloablative cytotoxic protocols, tissue transplants, and emerging newer molecules. The usual presentation is often non-specific and often over shadowed by the symptomatology of primary malignant disease and toxicity symptoms of chemotherapy. The basis of diagnosis is clinical, radiological (ultra sound/CT scan), per operative findings, and eventually post mortem. Treatment options of this highly fatal phenomenon varies from conservative to early surgical intervention. NE is expected to be diagnosed with increasing frequency. The factors leading to it are mucosal injury, caecal distension with resultant ischaemia, cytotoxic drugs, and microbiological agents. A high index of clinical suspicion and an early diagnosis is paramount for better outcome. Irrespective of management employed, conservative or upfront surgical intervention, it has a poor out come with high mortality. A clinical suspicion, early diagnosis, and prompt management are the key to a better result. There is need to identify people at high risk by prognostic factors, large scale studies, and formulating consensus management guidelines. At present individualized risk assessment based strategy is advocated.

Enteric serotonin and oxytocin: endogenous regulation of severity in a murine model of necrotizing enterocolitis.

PubMed

Gross Margolis, Kara; Vittorio, Jennifer; Talavera, Maria; Gluck, Karen; Li, Zhishan; Iuga, Alina; Stevanovic, Korey; Saurman, Virginia; Israelyan, Narek; Welch, Martha G; Gershon, Michael D

2017-11-01

Necrotizing enterocolitis (NEC), a gastrointestinal inflammatory disease of unknown etiology that may also affect the liver, causes a great deal of morbidity and mortality in premature infants. We tested the hypothesis that signaling molecules, which are endogenous to the bowel, regulate the severity of intestinal and hepatic damage in an established murine NEC model. Specifically, we postulated that mucosal serotonin (5-HT), which is proinflammatory, would exacerbate experimental NEC and that oxytocin (OT), which is present in enteric neurons and is anti-inflammatory, would oppose it. Genetic deletion of the 5-HT transporter (SERT), which increases and prolongs effects of 5-HT, was found to increase the severity of systemic manifestations, intestinal inflammation, and associated hepatotoxicity of experimental NEC. In contrast, genetic deletion of tryptophan hydroxylase 1 (TPH1), which is responsible for 5-HT biosynthesis in enterochromaffin (EC) cells of the intestinal mucosa, and TPH inhibition with LP-920540 both decrease the severity of experimental NEC in the small intestine and liver. These observations suggest that 5-HT from EC cells helps to drive the inflammatory damage to the gut and liver that occurs in the murine NEC model. Administration of OT decreased, while the OT receptor antagonist atosiban exacerbated, the intestinal inflammation of experimental NEC. Data from the current investigation are consistent with the tested hypotheses-that the enteric signaling molecules, 5-HT (positively) and OT (negatively) regulate severity of inflammation in a mouse model of NEC. Moreover, we suggest that mucosally restricted inhibition of 5-HT biosynthesis and/or administration of OT may be useful in the treatment of NEC. NEW & NOTEWORTHY Serotonin (5-HT) and oxytocin reciprocally regulate the severity of intestinal inflammation and hepatotoxicity in a murine model of necrotizing enterocolitis (NEC). Selective depletion of mucosal 5-HT through genetic deletion or inhibition of tryptophan hydroxylase-1 ameliorates, while deletion of the 5-HT uptake transporter, which increases 5-HT availability, exacerbates the severity of NEC. In contrast, oxytocin reduces, while the oxytocin receptor antagonist atosiban enhances, NEC severity. Peripheral tryptophan hydroxylase inhibition may be useful in treatment of NEC. Copyright © 2017 the American Physiological Society.

Enterocolic lymphocytic phlebitis: clinicopathologic features and review of the literature.

PubMed

Ngo, Nyethane; Chang, Fuju

2007-07-01

Enterocolic lymphocytic phlebitis (ELP) is a recently described entity and is of unknown etiology and pathogenesis. It is characterized by phlebitis of the bowel wall and mesentery, without arterial involvement or evidence of systemic vasculitis. The clinical presentation of ELP is varied, but it most commonly manifests with signs of an acute abdomen. Clinical, radiologic, and endoscopic findings are often conflicting and misdiagnosis is common as venous thrombosis is not suspected. The diagnosis of ELP is obtained histologically. There is a spectrum of histologic features associated with ELP, which includes lymphocytic phlebitis, necrotizing phlebitis, granulomatous phlebitis, and myointimal hyperplasia. Other features include venous thrombi and acute ischemic changes of the intestine. Surgical resection of the affected bowel is usually curative and recurrences are rare. The clinical and histopathologic features of ELP are reviewed.

Capsular profiling of the Cronobacter genus and the association of specific Cronobacter sakazakii and C. malonaticus capsule types with neonatal meningitis and necrotizing enterocolitis.

PubMed

Ogrodzki, P; Forsythe, S

2015-10-08

Cronobacter sakazakii and C. malonaticus can cause serious diseases especially in infants where they are associated with rare but fatal neonatal infections such as meningitis and necrotising enterocolitis. This study used 104 whole genome sequenced strains, covering all seven species in the genus, to analyse capsule associated clusters of genes involved in the biosynthesis of the O-antigen, colanic acid, bacterial cellulose, enterobacterial common antigen (ECA), and a previously uncharacterised K-antigen. Phylogeny of the gnd and galF genes flanking the O-antigen region enabled the defining of 38 subgroups which are potential serotypes. Two variants of the colanic acid synthesis gene cluster (CA1 and CA2) were found which differed with the absence of galE in CA2. Cellulose (bcs genes) were present in all species, but were absent in C. sakazakii sequence type (ST) 13 and clonal complex (CC) 100 strains. The ECA locus was found in all strains. The K-antigen capsular polysaccharide Region 1 (kpsEDCS) and Region 3 (kpsMT) genes were found in all Cronobacter strains. The highly variable Region 2 genes were assigned to 2 homology groups (K1 and K2). C. sakazakii and C. malonaticus isolates with capsular type [K2:CA2:Cell(+)] were associated with neonatal meningitis and necrotizing enterocolitis. Other capsular types were less associated with clinical infections. This study proposes a new capsular typing scheme which identifies a possible important virulence trait associated with severe neonatal infections. The various capsular polysaccharide structures warrant further investigation as they could be relevant to macrophage survival, desiccation resistance, environmental survival, and biofilm formation in the hospital environment, including neonatal enteral feeding tubes.

The potential of gut microbiota and fecal volatile organic compounds analysis as early diagnostic biomarker for necrotizing enterocolitis and sepsis in preterm infants.

PubMed

Berkhout, Daniel Johannes Cornelis; Niemarkt, Hendrik Johannes; de Boer, Nanne Klaas Hendrik; Benninga, Marc Alexander; de Meij, Timotheüs Gualtherus Jacob

2018-05-01

Although the exact pathophysiological mechanisms of both necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) in preterm infants are yet to be elucidated, evidence is emerging that the gut microbiota plays a key role in their pathophysiology. Areas covered: In this review, initial microbial colonization and factors influencing microbiota composition are discussed. For both NEC and LOS, an overview of studies investigating preclinical alterations in gut microbiota composition and fecal volatile organic compounds (VOCs) is provided. Fecal VOCs are considered to reflect not only gut microbiota composition, but also their metabolic activity and concurrent interaction with the host. Expert review: Heterogeneity in study protocols and applied analytical techniques hampers reliable comparison between outcomes of different microbiota studies, limiting the ability to draw firm conclusions. This dilemma is illustrated by the finding that study results often cannot be reproduced, or even contradict each other. A NEC- and sepsis specific microbial or metabolic signature has not yet been discovered. Identification of 'disease-specific' VOCs and microbiota composition may increase understanding on pathophysiological mechanisms and may allow for development of an accurate screening tool, opening avenues towards timely identification and initiation of targeted treatment for preterm infants at increased risk for NEC and sepsis.

Dual Roles of Endogenous Platelet-activating Factor Acetylhydrolase in a Murine Model of Necrotizing Enterocolitis

PubMed Central

Lu, Jing; Pierce, Marissa; Franklin, Andrew; Jilling, Tamas; Stafforini, Diana M.; Caplan, Michael

2010-01-01

Human preterm infants with necrotizing enterocolitis (NEC) have increased circulating and luminal levels of platelet-activating factor (PAF) and decreased serum PAF-acetylhydrolase (PAF-AH), the enzyme that inactivates PAF. Formula supplemented with recombinant PAF-AH decreases NEC in a neonatal rat model. We hypothesized that endogenous PAF-AH contributes to neonatal intestinal homeostasis, and therefore developed PAF-AH−/− mice using standard approaches to study the role of this enzyme in the neonatal NEC model. Following exposure to a well-established NEC model, intestinal tissues were evaluated for histology, pro-inflammatory cytokine mRNA synthesis, and death using standard techniques. We found that mortality rates were significantly lower in PAF-AH−/− pups compared to wild-type controls before 24 hours of life but surviving PAF-AH−/− animals were more susceptible to NEC development compared to wild-type controls. Increased NEC incidence was associated with prominent inflammation characterized by elevated intestinal mRNA expression of sPLA2, iNOS and CXCL1. In conclusion, the data support a protective role for endogenous PAF-AH in the development of NEC, and since preterm neonates have endogenous PAF-AH deficiency, this may place them at increased risk for disease. PMID:20531249

A comparison of Wisconsin Neonatal Intensive Care Units with National data on outcomes and practices

PubMed Central

Hagen, Erika W.; Sadek-Badawi, Mona; Albanese, Aggie; Palta, Mari

2009-01-01

Context: Improvements in neonatal care over the past three decades have resulted in increased survival of infants at lower birthweights and gestational ages. However, outcomes and practices vary considerably between hospitals. Objective: To describe maternal and infant characteristics, NICU practices, morbidity, and mortality in Wisconsin neonatal intensive care units (NICU) and to compare outcomes in Wisconsin to the National Institute of Child Health and Human Development network of large academic medical center NICUs. Design and Setting: The Newborn Lung Project Statewide Cohort is a prospective observational study of all very low birthweight (≤ 1500 grams) infants admitted during 2003 and 2004 to the 16 level III NICUs in Wisconsin. Anonymous data were collected for all admitted infants (N=1463). Main outcome measures: Major neonatal morbidities, including bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, and retinopathy of prematurity were evaluated. Results: The overall incidence of bronchopulmonary dysplasia was 24% (range 8-56% between NICUs); intraventricular hemorrhage incidence was 23% (9-41%); the incidence of necrotizing enterocolitis was 7% (0-21%); and the incidence of grade III or higher retinopathy of prematurity was 10% (0-35%). Conclusion: The incidence rates of major neonatal morbidities in Wisconsin were similar to those of a national network of academic NICUs. PMID:19180870

Maternal Risk Factors for Neonatal Necrotizing Enterocolitis

PubMed Central

March, Melissa I.; Gupta, Munish; Modest, Anna M.; Wu, Lily; Hacker, Michele R.; Martin, Camilia R.; Rana, Sarosh

2015-01-01

Objective This study aimed to investigate the relationship between maternal hypertensive disease and other risk factors and the neonatal development of necrotizing enterocolitis (NEC). Methods This was a retrospective case control study of infants with NEC from 2008 to 2012. The primary exposure of interest was maternal hypertensive disease, which has been hypothesized to put infants at risk for NEC. Other variables collected included demographics, pregnancy complications, medications, and neonatal hospital course. Data was abstracted from medical records. Results 28 cases of singleton neonates with NEC and 81 matched controls were identified and analyzed. There was no significant difference in the primary outcome. Fetuses with an antenatal diagnosis of growth restriction were more likely to develop NEC (p=0.008). Infants with NEC had lower median birth weight than infants without NEC (p=0.009). Infants with NEC had more late-onset sepsis (p=0.01) and mortality before discharge (p=0.001). Conclusions The factors identified by this case-control study that increased the risk of neonatal NEC included intrauterine growth restriction and lower neonatal birth weight. The primary exposure, hypertensive disease, did not show a significantly increased risk of neonatal NEC, however there was a nearly two-fold difference observed. Our study was underpowered to detect the observed difference. PMID:25162307

Intestinal alkaline phosphatase is protective to the preterm rat pup intestine.

PubMed

Heinzerling, Nathan P; Liedel, Jennifer L; Welak, Scott R; Fredrich, Katherine; Biesterveld, Ben E; Pritchard, Kirkwood A; Gourlay, David M

2014-06-01

Necrotizing enterocolitis (NEC) is the most common surgical emergency in neonates, with a mortality rate between 10 and 50%. The onset of necrotizing enterocolitis is highly variable and associated with numerous risk factors. Prior research has shown that enteral supplementation with intestinal alkaline phosphatase (IAP) decreases the severity of NEC. The aim of this study is to investigate whether IAP is protective to the preterm intestine in the presence of formula feeding and in the absence of NEC. Preterm rat pups were fed formula with or without supplementation with IAP, and intestine was obtained on day of life 3 for analysis of IAP activity, mRNA expression of TNFα, IL-6 and iNOS and permeability and cytokine expression after LPS exposure. There was no difference in the absolute and intestine specific alkaline phosphatase activity in both groups. Rat pups fed IAP had decreased mRNA expression of the inflammatory cytokines TNFα, IL-6 and iNOS. Pups supplemented with IAP had decreased permeability and inflammatory cytokine expression after exposure to LPS ex vivo when compared to formula fed controls. Our results support that IAP is beneficial to preterm intestine and decreases intestinal injury and inflammation caused by LPS. Copyright © 2014 Elsevier Inc. All rights reserved.

Intestinal Alkaline Phosphatase Is Protective to the Preterm Rat Pup Intestine

PubMed Central

Heinzerling, Nathan P.; Liedel, Jennifer L.; Welak, Scott R.; Fredrich, Katherine; Biesterveld, Ben E.; Pritchard, Kirkwood A.; Gourlay, David M.

2014-01-01

Background Necrotizing enterocolitis (NEC) is the most common surgical emergency in neonates, with a mortality rate between 10 and 50%. The onset of necrotizing enterocolitis is highly variable and associated with numerous risk factors. Prior research has shown enteral supplementation with intestinal alkaline phosphatase (IAP) decreases the severity of NEC. The aim of this study is to investigate whether IAP is protective to the preterm intestine in the presence of formula feeding and in the absence of NEC. Methods Preterm rat pups were fed formula with or without supplementation with IAP, and intestine was obtained on day of life 3 for analysis of IAP activity, mRNA expression of TNF-a, IL-6 and iNOS and permeability and cytokine expression after LPS. exposure. Results There was no difference in the absolute and intestine specific alkaline phosphatase activity in both groups. Rat pups fed IAP had decreased mRNA expression of the inflammatory cytokines TNFα, IL-6 and iNOS. Pups supplemented with IAP had decreased permeability and inflammatory cytokine expression after exposure to LPS ex vivo when compared to formula fed controls. Conclusions Our results support that IAP is beneficial to preterm intestine and decreases intestinal injury and inflammation caused by LPS. PMID:24888842

Bifidobacterium bifidum in a Rat Model of Necrotizing Enterocolitis: Antimicrobial Peptide and Protein Responses

PubMed Central

Underwood, Mark A.; Kananurak, Anchasa; Coursodon, Christine F.; Adkins-Reick, Camille K.; Chu, Hiutung; Bennett, Stephen H.; Wehkamp, Jan; Castillo, Patricia A.; Leonard, Brian C.; Tancredi, Daniel J.; Sherman, Michael P.; Dvorak, Bohuslav; Bevins, Charles L.

2013-01-01

Necrotizing enterocolitis (NEC) is a devastating disease of premature infants. Probiotics decrease the risk of NEC in clinical and experimental studies. Antimicrobial peptides protect the gut against noxious microbes and shape the commensal microbiota, but their role in NEC remains unclear. We report that like in human ontogeny, the rat pup has low expression of Paneth cell antimicrobials, which increases rapidly during normal development. To investigate the expression of antimicrobial peptides in experimental NEC and the impact of probiotics on their expression, premature rats were divided into three groups: dam fed (DF), hand fed with formula (FF), or hand fed with formula containing Bifidobacterium bifidum (FF+BIF). All groups were exposed to asphyxia and cold stress. The expression of lysozyme, secretory phospholipase A2, pancreatic-associated proteins 1 and 3 mRNA was elevated in the FF (NEC) group, compared to the DF and FF+BIF groups where disease was attenuated. We conclude that induction of antimicrobial peptides occurs in experimental NEC similar to that reported in human disease and is attenuated when disease is averted by probiotic B. bifidum. The induction of antimicrobial peptides is likely an adaptive mucosal response that is often not sufficient to prevent disease in the premature gut. PMID:22322385

The science and necessity of using animal models in the study of necrotizing enterocolitis.

PubMed

Ares, Guillermo J; McElroy, Steven J; Hunter, Catherine J

2018-02-01

Necrotizing enterocolitis (NEC) remains one of the highest causes of mortality and of acute and long-term morbidity in premature infants. Multiple factors are involved in the pathophysiology of NEC including the immaturity of the immune system and the complex changing composition of the intestinal microbiome. This is compounded by the fact that the premature infant should ideally still be a developing fetus and has an immature intestinal tract. Because these complexities are beyond the scope of studies in single-cell cultures, animal models are absolutely essential to understand the mechanisms involved in the pathophysiology of NEC and the effects of inflammation on the immature intestinal tract. To this end, investigators have utilized many different species (e.g., rats, mice, rabbits, quails, piglets, and non-human primates) and conditions to develop models of NEC. Each animal has distinct advantages and drawbacks related to its preterm viability, body size, genetic variability, and cost. The choice of animal model is strongly influenced by the scientific question being addressed. While no model perfectly mimics human NEC, each has greatly improved our understanding of disease. Examples of recent discoveries in NEC pathogenesis and prevention underscore the importance of continued animal research in NEC. Copyright © 2018 Elsevier Inc. All rights reserved.

Primary anastomosis or ostomy in necrotizing enterocolitis?

PubMed

Haricharan, Ramanathapura N; Gallimore, Jade Palazzola; Nasr, Ahmed

2017-11-01

In neonates requiring operation for necrotizing enterocolitis (NEC), the complications due to enterostomy (ES) and the need for another operation to restore continuity have prompted several surgeons to employ primary anastomosis (PA) after resection as the operative strategy of choice. Our objective was to compare primary anastomosis to stoma formation in this population using systematic review and meta-analysis. Publications describing both interventions were identified by searching multiple databases. Appropriate studies that reported outcomes after PA and ES for NEC were included for analysis that was performed using the MedCalc3000 software. Results are reported as odds ratios (OR, 95% CI). No randomized trials were identified. Twelve studies were included for the final analysis. Neonates who underwent PA were associated with significantly less risk of mortality when compared to those who underwent ES (OR 0.34, 95% CI 0.17-0.68, p 0.002), possibly due to differences in severity of NEC. Although the types of complications in these groups were different, there was no significant difference in risk of complication (OR 0.86, 0.55-1.33, p 0.50). In neonates undergoing an operation for severe NEC, there is no significant difference in the risk of complications between primary anastomosis and enterostomy. A definitive suggestion cannot be made regarding the choice of one operative strategy over another.

Probiotics for prevention of necrotizing enterocolitis in preterm infants.

PubMed

AlFaleh, Khalid; Anabrees, Jasim

2014-09-01

Necrotizing enterocolitis (NEC) and nosocomial sepsis are associated with increased morbidity and mortality in preterm infants. Through prevention of bacterial migration across the mucosa, competitive exclusion of pathogenic bacteria, and enhancing the immune responses of the host, prophylactic enteral probiotics (live microbial supplements) may play a role in reducing NEC and the associated morbidity. To compare the efficacy and safety of prophylactic enteral probiotics administration versus placebo or no treatment in the prevention of severe NEC or sepsis, or both, in preterm infants. For this update, searches were made of MEDLINE (1966 to October 2013), EMBASE (1980 to October 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2013, Issue 10), and abstracts of annual meetings of the Society for Pediatric Research (1995 to 2013). Only randomized or quasi-randomized controlled trials that enrolled preterm infants < 37 weeks gestational age or < 2500 g birth weight, or both, were considered. Trials were included if they involved enteral administration of any live microbial supplement (probiotics) and measured at least one prespecified clinical outcome. Standard methods of The Cochrane Collaboration and its Neonatal Group were used to assess the methodologic quality of the trials and for data collection and analysis. Twenty-four eligible trials were included. Included trials were highly variable with regard to enrolment criteria (that is birth weight and gestational age), baseline risk of NEC in the control groups, timing, dose, formulation of the probiotics, and feeding regimens. In a meta-analysis of trial data, enteral probiotics supplementation significantly reduced the incidence of severe NEC (stage II or more) (typical relative risk (RR) 0.43, 95% confidence interval (CI) 0.33 to 0.56; 20 studies, 5529 infants) and mortality (typical RR 0.65, 95% CI 0.52 to 0.81; 17 studies, 5112 infants). There was no evidence of significant reduction of nosocomial sepsis (typical RR 0.91, 95% CI 0.80 to 1.03; 19 studies, 5338 infants). The included trials reported no systemic infection with the supplemental probiotics organism. Probiotics preparations containing either lactobacillus alone or in combination with bifidobacterium were found to be effective. Enteral supplementation of probiotics prevents severe NEC and all cause mortality in preterm infants. Our updated review of available evidence strongly supports a change in practice. Head to head comparative studies are required to assess the most effective preparations, timing, and length of therapy to be utilized. Probiotics for prevention of necrotizing enterocolitis in preterm infants Necrotizing enterocolitis (NEC) is a serious disease that affects the bowel of premature infants in the first few weeks of life. Although the cause of NEC is not entirely known, milk feeding and bacterial growth play a role. Probiotics (dietary supplements containing potentially beneficial bacteria or yeast) have been used to prevent NEC. Our review of studies found that the use of probiotics reduces the occurrence of NEC and death in premature infants born weighing less than 1500 grams. There is insufficient data with regard to the benefits and potential adverse effects in the most at risk infants weighing less than 1000 grams at birth. Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Immature oxidative stress management as a unifying principle in the pathogenesis of necrotizing enterocolitis: insights from an agent-based model.

PubMed

Kim, Moses; Christley, Scott; Alverdy, John C; Liu, Donald; An, Gary

2012-02-01

Necrotizing enterocolitis (NEC) is a complex disease involving prematurity, enteral feeding, and bacterial effects. We propose that the underlying initial condition in its pathogenesis is reduced ability of the neonatal gut epithelial cells (NGECs) to clear oxidative stress (OS), and that when such a NGEC population is exposed to enteral feeding, the increased metabolic OS tips the population toward apoptosis, inflammation, bacterial activation, and eventual necrosis. The multi-factorial complexity of NEC requires characterization with computational modeling, and herein, we used an agent-based model (ABM) to instantiate and examine our unifying hypothesis of the pathogenesis of NEC. An ABM of the neonatal gut was created with NGEC computational agents incorporating rules for pathways for OS, p53, tight junctions, Toll-like receptor (TLR)-4, nitric oxide, and nuclear factor-kappa beta (NF-κB). The modeled bacteria activated TLR-4 on contact with NGECs. Simulations included parameter sweeps of OS response, response to feeding, addition of bacteria, and alterations in gut mucus production. The ABM reproduced baseline cellular respiration and clearance of OS. Reduction in OS clearance consistent with clinical NEC led to senescence, apoptosis, or inflammation, with disruption of tight junctions, but rarely to NGEC necrosis. An additional "hit" of bacteria activating TLR-4 potentiated a shift to NGEC necrosis across the entire population. The mucus layer was modeled to limit bacterial-NGEC interactions and reduce this effect, but concomitant apoptosis in the goblet cell population reduced the efficacy of the mucus layer and limited its protective effect in simulated experiments. This finding suggests a means by which increased apoptosis at the cellular population level can lead to a transition to the necrosis outcome. Our ABM incorporates known components of NEC and demonstrates that impaired OS management can lead to apoptosis and inflammation of NGECs, rendering the system susceptible to an additional insult involving regionalized mucus barrier failure and TLR-4 activation, which potentiates the necrosis outcome. This type of integrative dynamic knowledge representation can be a useful adjunct to help guide and contextualize research.

Necrotizing enterocolitis, a rare but severe condition with insidious postoperative complications.

PubMed

Bălălău, C; Motofei, I; Voiculescu, S; Popa, F; Scăunaşu, R V

2013-01-01

Necrotizing enterocolitis (NEC) is one of the most frequent causes of gastrointestinal perforation in premature neonates, only few case series and reports being described in adult patients. Early in the course of the disease, superficial mucosal ulceration, sub mucosal edema and hemorrhage occur. Further progression leads to transmural necrosis leading sometimes to bowel perforation. Six cases encountered in our clinic in recent years led us to resume discussions on necrotizing enteritis, not because it is a rare disease, but due to the severe postoperative complications. Our lot consisted of four stage 1 patients and two with Bell stage III NEC and severe intestinal injury, necrosis, and perforation. All of the patients were diagnosed preoperatory with other surgical conditions, like appendicitis with peritonitis, perforated duodenal ulcer or acute cholecystitis. We present to review two cases. For patients undergoing laparotomy, resection of the involved intestine mandates either enterostomy formation or primary anastomosis. An intermediate option is laparotomy with intestinal resection and delayed anastomosis 48 to 72 hours later. Because of the small number of patients in our lot, we cannot advise a certain surgical treatment, but a strategy involving bienterostomyper primam should be further analyzed. The choice of operative intervention reflects multiple variables, including age, physiologic status, institutional resources and surgeon preference based on experience. Primary peritoneal drainage for perforated NEC may help to resuscitate and treat a critically ill patient initially, and in some instances, may be definitive operative intervention. Relatively rare disease, of unknown etiology and elusive pathogenesis, NEC has initial non-specific symptoms and clinical features that mimic more common surgical diseases. There is considerable controversy regarding which procedure is preferable. Currently, in the absence of rigorous evidence supporting the superiority of one approach over the other, surgical intervention depends mostly on the treating institution or the individual surgeon.

Effect of routine probiotic, Lactobacillus reuteri DSM 17938, use on rates of necrotizing enterocolitis in neonates with birthweight < 1000 grams: a sequential analysis.

PubMed

Hunter, Chelsea; Dimaguila, Mary Ann V T; Gal, Peter; Wimmer, John E; Ransom, James Laurence; Carlos, Rita Q; Smith, McCrae; Davanzo, Christie C

2012-09-04

Necrotizing enterocolitis (NEC) is a disease in neonates, often resulting in death or serious medical or neurodevelopmental complications. The rate of NEC is highest in the smallest babies and many efforts have been tried to reduce the rate of NEC. In neonates born below 1500 grams, the rate of NEC has been significantly reduced with the use of various probiotics. This study examines the impact of routine use of a probiotic, Lactobacillus reuteri DSM 17938 (BioGaia®), on the rate of NEC in neonates at highest risk for developing NEC, those with birth weight ≤1000 grams. This is a retrospective cohort study comparing the rates of NEC in neonates with birth weight ≤ 1000 grams. The groups are separated into those neonates born from January 2004 to June 30, 2009, before introduction of L. reuteri , and neonates born July 2009 through April 2011 who received routine L. reuteri prophylaxis. The chart review study was approved by our institutional review board and exempted from informed consent.Neonates were excluded if they died or were transferred within the first week of life. The remainder were categorized as having no NEC, medical NEC, surgical NEC, or NEC associated death. Since no major changes occurred in our NICU practice in recent years, and the introduction of L. reuteri as routine prophylaxis was abrupt, we attributed the post-probiotic changes to the introduction of this new therapy. Rates of NEC were compared using Chi square analysis with Fisher exact t-test. Medical records for 311 neonates were reviewed, 232 before- and 79 after-introduction of L. reuteri prophylaxis. The incidence of NEC was significantly lower in the neonates who received L. reuteri (2 of 79 neonates [2.5%] versus 35 of 232 untreated neonates [15.1%]). Rates of late-onset gram-negative or fungal infections (22.8 versus 31%) were not statistically different between treated and untreated groups. No adverse events related to use of L reuteri were noted. Prophylactic initiation of L. reuteri as a probiotic for prevention of necrotizing enterocolitis resulted in a statistically significant benefit, with avoidance of 1 NEC case for every 8 patients given prophylaxis.

Restricted versus liberal water intake for preventing morbidity and mortality in preterm infants.

PubMed

Bell, Edward F; Acarregui, Michael J

2014-01-01

Most premature infants are physiologically not sufficiently mature to orally ingest all of their required water and nutrients. Therefore, premature infants rely on their caregivers to regulate their volume of water intake. Thus, the caregiver must determine the amount of water to be given each day to such infants. To determine the effect of water intake on postnatal weight loss and the risks of dehydration, patent ductus arteriosus, necrotizing enterocolitis, bronchopulmonary dysplasia, intracranial hemorrhage, and death in premature infants. Randomized clinical trials (RCTs) identified in previous versions of this review were re-examined and, in each case, retained. Additional trials were sought that compared the outcomes of interest in groups of premature infants who were given different levels of water intake according to an experimental protocol. Such trials were sought in a list of trials provided by the Cochrane Neonatal Review Group, with a PubMed search and in the authors' personal files.This search was updated in 2014. Only RCTs of varying water intake in premature infants were included. The review was limited to trials that included infants whose water intake was provided mainly or entirely by intravascular infusion. The standard methods of The Cochrane Collaboration were used. Study selection and data abstraction were performed independently by each review author. The adverse event rates were calculated for the restricted and liberal water intake groups for each dichotomous outcome, and the relative risk and risk difference were computed. In addition, the maximal weight loss results were recorded and the weighted mean difference was computed. The analysis of the five studies taken together indicated that restricted water intake significantly increased postnatal weight loss and significantly reduced the risks of patent ductus arteriosus and necrotizing enterocolitis. With restricted water intake, there were trends toward increased risk of dehydration and reduced risks of bronchopulmonary dysplasia, intracranial hemorrhage, and death but these trends were not statistically significant. Based on this analysis, the most prudent prescription for water intake to premature infants would seem to be careful restriction of water intake so that physiological needs are met without allowing significant dehydration. This practice could be expected to decrease the risks of patent ductus arteriosus and necrotizing enterocolitis without significantly increasing the risk of adverse consequences.

Effect of Donor Milk on Severe Infections and Mortality in Very Low-Birth-Weight Infants: The Early Nutrition Study Randomized Clinical Trial.

PubMed

Corpeleijn, Willemijn E; de Waard, Marita; Christmann, Viola; van Goudoever, Johannes B; Jansen-van der Weide, Marijke C; Kooi, Elisabeth M W; Koper, Jan F; Kouwenhoven, Stefanie M P; Lafeber, Hendrik N; Mank, Elise; van Toledo, Letty; Vermeulen, Marijn J; van Vliet, Ineke; van Zoeren-Grobben, Diny

2016-07-01

Infections and necrotizing enterocolitis, major causes of mortality and morbidity in preterm infants, are reduced in infants fed their own mother's milk when compared with formula. When own mother's milk is not available, human donor milk is considered a good alternative, albeit an expensive one. However, most infants at modern neonatal intensive care units are predominantly fed with own mother's milk. The benefits of add-on donor milk over formula are not clear. To determine whether providing donor milk instead of formula as supplemental feeding whenever own mother's milk is insufficiently available during the first 10 days of life reduces the incidence of serious infection, necrotizing enterocolitis, and mortality. The Early Nutrition Study was a multicenter, double-blind randomized clinical trial in very low-birth-weight infants (birth weight <1500 g) admitted to 1 of 6 neonatal intensive care units in the Netherlands from March 30, 2012, through August 17, 2014. Intent-to-treat analysis was performed. Infants received pasteurized donor milk or preterm formula during the first 10 days of life if own mother's milk was not (sufficiently) available. The primary end point was cumulative occurrence of serious infection (sepsis or meningitis), necrotizing enterocolitis, or mortality during the first 60 days of life. A total of 930 infants were screened for inclusion; 557 were excluded, resulting in 373 infants (183 receiving donor milk and 190 receiving formula) who were evaluated by intent-to-treat analysis (median birth weight, 1066 g; mean gestational age, 28.4 weeks). Own mother's milk comprised 89.1% and 84.5% of total mean intake during the intervention period for the donor milk and formula groups, respectively. The incidence of the combined outcome was not different (85 [44.7%] [formula] vs 77 [42.1%] [donor milk]; mean difference, 2.6%; 95% CI, -12.7% to 7.4%). The adjusted hazard ratio was 0.87 (95% CI, 0.63-1.19; P = .37). In the current study, pasteurized donor milk and preterm formula as supplemental feeding during the first 10 days of life yielded similar short-term outcomes in very low-birth-weight infants regarding safety and efficacy when own mother's milk availability was insufficient. Future studies investigating longer duration of use of human donor milk on short-term and long-term outcomes are necessary. trialregister.nl Identifier: NTR3225.

Human milk and necrotizing enterocolitis.

PubMed

Patel, Aloka L; Kim, Jae H

2018-02-01

NEC is a multifactorial disease that occurs when multiple risk factors and/or stressors overlap, leading to profound inflammation and intestinal injury. Human milk feedings, both from the infant's mother and donor human milk, have been associated with reductions in NEC in preterm infants. This article will review the protective factors in human milk, clinical studies of human milk and NEC, and practices to enhance human milk use in neonatal intensive care units. Copyright © 2018 Elsevier Inc. All rights reserved.

Probiotics Reduce Necrotizing Enterocolitis Severity in HIV-exposed Premature Infants.

PubMed

Van Niekerk, Evette; Nel, Daniel G; Blaauw, Reneé; Kirsten, Gert F

2015-06-01

To assess the effect of probiotics on the incidence of necrotizing enterocolitis (NEC) in premature infants born to human immunodeficiency virus (HIV)-positive and HIV-negative women. HIV-exposed and HIV-unexposed premature infants were randomized to either the probiotic or the placebo group. The probiotic consisted of 1 × 10(9) colony-forming units, Lactobacillus rhamnosus GG and Bifidobacterium infantis per day. In total, 74 HIV-exposed and 110 HIV-unexposed infants were enrolled and randomized. The incidence of death [4 (5.4%) vs. 7 (6%); p = 0.79] and NEC [4 (5%) vs. 5 (5%); p = 0.76] did not differ significantly between the HIV-exposed and HIV-unexposed groups. A significant difference was found for total NEC incidence between the study and control groups [3 (3%) vs. 6 (6%); p = 0.029]. The incidence of NEC in the HIV-exposed group differed significantly [Bells I 2 (5%) vs. Bells III 2 (5%); p = 0.045). Probiotic supplementation reduced the incidence of NEC in the premature very low birth weight infants; however, results failed to show a lower incidence of NEC in HIV-exposed premature infants. A reduction in the severity of disease was found in the HIV-exposed study group. © The Author [2015]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Risk factors of necrotizing enterocolitis].

PubMed

Tapia-Rombo, C A; Velasco-Lavín, M R; Nieto-Caldelas, A

1993-09-01

The purpose of the present study is to compare risk factors of necrotizing enterocolitis (NEC) between two group: group A, newborns with the disease and group B, newborns with other diseases different from NEC, in order to know if these risk factors are more frequent or not in the first group. We assessed the clinical records of all the patients hospitalized in the Neonatal Intensive Care Unit and Neonatology Service of the La Raza General Hospital between 1987 and 1991 with the diagnosis of NEC. They were compared with 65 clinical records chosen at random of patients hospitalized in the same Unit with other diagnosis at the same time, and who were discharged by improvement or deceased. In all of them were look for known risk factors for NEC generally accepted such as: prematurity, neonatal asphyxia, poliglobulia, cyanotic congenital heart disease, patent ductus arteriosus, respiratory distress syndrome, catheterization of umbilical vessels, early feeding of elevated formula increases, exchange exchange transfusion, hypoxic ischemic encephalopathy, infection, etc. Just 25 records of the possible 50 with the diagnosis of NEC full filled inclusion criteria. There were no statistically significant difference in weight, sex, mortality and known risk factors of NEC between both groups. Were concluded that NEC is a disease of unknown etiology that should be studied more thoroughly. The known risk factors must be avoided because the patient susceptibility probably play an important role.

Discovery and Validation of a New Class of Small Molecule Toll-Like Receptor 4 (TLR4) Inhibitors

PubMed Central

Neal, Matthew D.; Jia, Hongpeng; Eyer, Benjamin; Good, Misty; Guerriero, Christopher J.; Sodhi, Chhinder P.; Afrazi, Amin; Prindle, Thomas; Ma, Congrong; Branca, Maria; Ozolek, John; Brodsky, Jeffrey L.; Wipf, Peter; Hackam, David J.

2013-01-01

Many inflammatory diseases may be linked to pathologically elevated signaling via the receptor for lipopolysaccharide (LPS), toll-like receptor 4 (TLR4). There has thus been great interest in the discovery of TLR4 inhibitors as potential anti-inflammatory agents. Recently, the structure of TLR4 bound to the inhibitor E5564 was solved, raising the possibility that novel TLR4 inhibitors that target the E5564-binding domain could be designed. We utilized a similarity search algorithm in conjunction with a limited screening approach of small molecule libraries to identify compounds that bind to the E5564 site and inhibit TLR4. Our lead compound, C34, is a 2-acetamidopyranoside (MW 389) with the formula C17H27NO9, which inhibited TLR4 in enterocytes and macrophages in vitro, and reduced systemic inflammation in mouse models of endotoxemia and necrotizing enterocolitis. Molecular docking of C34 to the hydrophobic internal pocket of the TLR4 co-receptor MD-2 demonstrated a tight fit, embedding the pyran ring deep inside the pocket. Strikingly, C34 inhibited LPS signaling ex-vivo in human ileum that was resected from infants with necrotizing enterocolitis. These findings identify C34 and the β-anomeric cyclohexyl analog C35 as novel leads for small molecule TLR4 inhibitors that have potential therapeutic benefit for TLR4-mediated inflammatory diseases. PMID:23776545

Saccharomyces boulardii for prevention of necrotizing enterocolitis in preterm infants: a randomized, controlled study.

PubMed

Demirel, Gamze; Erdeve, Omer; Celik, Istemi Han; Dilmen, Ugur

2013-12-01

To evaluate the efficacy of orally administered Saccharomyces boulardii (S. boulardii) for reducing the incidence and severity of necrotizing enterocolitis (NEC) in very low-birth-weight (VLBW) infants. A prospective, randomised controlled trial was conducted in infants with gestational age ≤32 weeks and birth weight ≤1500 g. The study group received S. boulardii supplementation, and the control group did not. The primary outcomes were death or NEC (Bell's stage ≥2), and secondary outcomes were feeding intolerance and clinical or culture-proven sepsis. A total of 271 infants were enrolled in the study, 135 in the study group and 136 in the control group. There was no significant difference in the incidence of death (3.7% vs. 3.6%, 95% CI of the difference, -5.20-5.25; p = 1.0) or NEC (4.4% vs. 5.1%, 95% CI, -0.65-5.12; p = 1.0) between the groups. However, feeding intolerance and clinical sepsis were significantly lower in the probiotic group compared with control. Although Saccharomyces boulardii supplementation at a dose of 250 mg/day was not effective at reducing the incidence of death or NEC in VLBW infants, it improved feeding tolerance and reduced the risk of clinical sepsis. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Heparin-binding EGF-like growth factor and enteric neural stem cell transplantation in the prevention of experimental necrotizing enterocolitis in mice.

PubMed

Wei, Jia; Zhou, Yu; Besner, Gail E

2015-07-01

Necrotizing enterocolitis (NEC) is associated with loss of neurons and glial cells in the enteric nervous system (ENS). Our goal was to determine whether enteric neural stem cell (NSC) transplantation, in conjunction with heparin-binding epidermal growth factor-like growth factor (HB-EGF), could protect against experimental NEC. In vitro, HB-EGF on NSC proliferation and migration, and the effects of receptors utilized by HB-EGF to exert these effects, were determined. In vivo, mouse pups were exposed to experimental NEC and treated with NSC alone, HB-EGF alone, NSC+HB-EGF, or HB-EGF overexpressing NSC. NSC engraftment and differentiation into neurons in the ENS, intestinal injury, intestinal permeability, and intestinal motility were determined. HB-EGF promoted NSC proliferation via ErbB-1 receptors and enhanced NSC migration via ErbB-1, ErbB-4, and Nardilysin receptors. HB-EGF significantly enhanced the engraftment of transplanted NSC into the ENS during NEC. NSC transplantation significantly reduced NEC incidence and improved gut barrier function and intestinal motility, and these effects were augmented by simultaneous administration of HB-EGF or by transplantation of HB-EGF overexpressing NSC. HB-EGF promotes NSC proliferation and migration. HB-EGF and NSC reduce intestinal injury and improve gut barrier function and intestinal motility in experimental NEC. Combined HB-EGF and NSC transplantation may represent a potential future therapy to prevent NEC.

Characterization of outer membrane vesicles from a neonatal meningitic strain of Cronobacter sakazakii.

PubMed

Alzahrani, Hayat; Winter, Jody; Boocock, David; De Girolamo, Luigi; Forsythe, Stephen J

2015-06-01

Cronobacter sakazakii is associated with severe and often fatal cases of infant meningitis and necrotizing enterocolitis. The form of meningitis differs from that due to Neisseria meningitidis and Streptococcus spp., in that it is highly invasive and destructive towards human brain cells. However, there is relatively little understanding of the cytopathogenic interaction of C. sakazakii with host cells which results in stimulation of an inflammatory immune response. The production of Cronobacter outer membrane vesicles (OMV) and their potential pathogenic functions have not yet been elucidated. This study is the first to show that C. sakazakii produce OMV, which may play a role in the activation of cytopathogenic and host cell responses on human intestinal epithelial cells. Cronobacter sakazakii strain 767 was used which had been isolated from a fatal outbreak of neonatal meningitis and necrotizing enterocolitis. Cronobacter sakazakii OMV were internalized by Caco-2 cells, increased cell proliferation and stimulated the host's innate proinflammatory response without inducing overt toxicity. A total of 18 OMV-associated proteins were identified by mass spectrometry and their potential pathogenicity roles were evaluated. Collectively, these data indicate that C. sakazakii OMV could play a role in pathogenesis by delivering bacterial toxins into host epithelial cells, driving proliferative and proinflammatory responses. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The effect of an osmotic contrast agent on complete meconium evacuation in preterm infants.

PubMed

Haiden, Nadja; Norooz, Florentine; Klebermass-Schrehof, Kathrin; Horak, Anna Sophie; Jilma, Bernd; Berger, Angelika; Repa, Andreas

2012-12-01

To determine whether enteral application of the osmotic contrast agent Gastrografin accelerates complete meconium excretion and improves feeding tolerance in very low birth weight infants. This study was a stratified, randomized, placebo-controlled trial in premature infants with a birth weight <1500 g and a gestational age <32 weeks who received 3 mL/kg Gastrografin diluted 1:3 with water within their first 24 hours of life, or placebo. Passage of last meconium occurred after a median of 7 days (95% confidence interval: 6-9 days, n = 39) in the intervention group and after 8 days (95% confidence interval: 7-10 days, n = 39) in the control group (P = .61); however, Gastrografin application was associated with a 7.5-day shorter time to full enteral feedings, a 24-day shorter stay in the NICU, and a 17-day reduction in the overall hospital stay in the intervention group compared with the control group. A numerically higher incidence of necrotizing enterocolitis (21%) was observed in the intervention group, however. Gastrografin application did not accelerate meconium evacuation, but the higher stool frequency during the first week of life had a beneficial effect on the time to full enteral feedings and later hospital stay; however, it may increase the necrotizing enterocolitis risk. Further investigations are needed with modified protocols, and the prophylactic use of Gastrografin cannot currently be recommended without further clinical trials.

Packed red blood cell transfusion is not associated with increased risk of necrotizing enterocolitis in premature infants

PubMed Central

Sharma, R; Kraemer, DF; Torrazza, RM; Mai, V; Neu, J; Shuster, JJ; Hudak, ML

2015-01-01

OBJECTIVE Recent reports have posited a temporal association between blood transfusion with packed red blood cells (BT) and necrotizing enterocolitis (NEC). We evaluated the relationship between BT and NEC among infants at three hospitals who were consented at birth into a prospective observational study of NEC. STUDY DESIGN We used a case–control design to match each case of NEC in our study population of infants born at <33 weeks postmenstrual age (PMA) to one control infant using hospital of birth, PMA, birth weight and date of birth. RESULT The number of transfusions per infant did not differ between 42 NEC cases and their controls (4.0 ± 4.6 vs 5.4 ± 4.1, mean ± s.d., P = 0.063). A matched-pair analysis did not identify an association of transfusion with NEC in either the 48-h or 7-day time periods before the onset of NEC. Stratifying on matched-sets, the Cox proportional hazard model did not identify any difference in the total number of BTs between the two groups (hazard ratio 0.78, 95% confidence interval 0.57 to 1.07, P = 0.11). CONCLUSION In contrast to previous studies, our case–control study did not identify a significant temporal association between BT and NEC. Additional large prospective randomized studies are needed to clarify the relationship between BT and NEC. PMID:25144159

Liver damage, proliferation, and progenitor cell markers in experimental necrotizing enterocolitis.

PubMed

Miyake, Hiromu; Li, Bo; Lee, Carol; Koike, Yuhki; Chen, Yong; Seo, Shogo; Pierro, Agostino

2018-05-01

Necrotizing enterocolitis (NEC) is a disease known to cause injury to multiple organs including the liver. Liver regeneration is essential for the recovery after NEC-induced liver injury. Our aim was to investigate hepatic proliferation and progenitor cell marker expression in experimental NEC. Following ethical approval (#32238), NEC was induced in mice by hypoxia, gavage feeding of hyperosmolar formula, and lipopolysaccharide. Breastfed pups were used as control. We analyzed serum ALT level, liver inflammatory cytokines, liver proliferation markers, and progenitor cell marker expression. Comparison was made between NEC and controls. Serum ALT level was higher in NEC (p<0.05). The mRNA expression of inflammatory cytokines in the liver was also higher in NEC (IL6: p<0.05, TNF-α: p<0.01). Conversely, mRNA expression of proliferation markers in the liver was lower in NEC (Ki67; p<0.01, PCNA: p<0.01). LGR5 expression was also significantly decreased in NEC as demonstrated by mRNA (p<0.05) and protein (p<0.01) levels. Inflammatory injury was present in the liver during experimental NEC. Proliferation and LGR5 expression were impaired in the NEC liver. Modulation of progenitor cell expressing LGR5 may result in stimulation of liver regeneration in NEC-induced liver injury and improved clinical outcome. Level IV. Copyright © 2018. Published by Elsevier Inc.

Ranitidine is associated with infections, necrotizing enterocolitis, and fatal outcome in newborns.

PubMed

Terrin, Gianluca; Passariello, Annalisa; De Curtis, Mario; Manguso, Francesco; Salvia, Gennaro; Lega, Laura; Messina, Francesco; Paludetto, Roberto; Canani, Roberto Berni

2012-01-01

Gastric acidity is a major nonimmune defense mechanism against infections. The objective of this study was to investigate whether ranitidine treatment in very low birth weight (VLBW) infants is associated with an increased risk of infections, necrotizing enterocolitis (NEC), and fatal outcome. Newborns with birth weight between 401 and 1500 g or gestational age between 24 and 32 weeks, consecutively observed in neonatal intensive care units, were enrolled in a multicenter prospective observational study. The rates of infectious diseases, NEC, and death in enrolled subjects exposed or not to ranitidine were recorded. We evaluated 274 VLBW infants: 91 had taken ranitidine and 183 had not. The main clinical and demographic characteristics did not differ between the 2 groups. Thirty-four (37.4%) of the 91 children exposed to ranitidine and 18 (9.8%) of the 183 not exposed to ranitidine had contracted infections (odds ratio 5.5, 95% confidence interval 2.9-10.4, P < .001). The risk of NEC was 6.6-fold higher in ranitidine-treated VLBW infants (95% confidence interval 1.7-25.0, P = .003) than in control subjects. Mortality rate was significantly higher in newborns receiving ranitidine (9.9% vs 1.6%, P = .003). Ranitidine therapy is associated with an increased risk of infections, NEC, and fatal outcome in VLBW infants. Caution is advocated in the use of this drug in neonatal age.

The timing of ostomy closure in infants with necrotizing enterocolitis: a systematic review.

PubMed

Struijs, Marie-Chantal; Sloots, Cornelius E J; Hop, Wim C J; Tibboel, Dick; Wijnen, Rene M H

2012-07-01

The optimal timing of ostomy closure is a matter of debate. We performed a systematic review of outcomes of early ostomy closure (EC, within 8 weeks) and late ostomy closure (LC, after 8 weeks) in infants with necrotizing enterocolitis. PubMed, EMbase, Web-of-Science, and Cinahl were searched for studies that detailed time to ostomy closure, and time to full enteral nutrition (FEN) or complications after ostomy closure. Patients with Hirschsprung's disease or anorectal malformations were excluded. Analysis was performed using SPSS 17 and RevMan 5. Of 778 retrieved articles, 5 met the inclusion criteria. The median score for study quality was 9 [range 8-14 on a scale of 0 to 32 points (Downs and Black, J Epidemiol Community Health 52:377-384, 1998)]. One study described mean time to FEN: 19.1 days after EC (n = 13) versus 7.2 days after LC (n = 24; P = 0.027). Four studies reported complication rates after ostomy closure, complications occurred in 27% of the EC group versus 23% of the LC group. The combined odds ratio (LC vs. EC) was 1.1 [95% CI 0.5, 2.5]. Evidence that supports early or late closure is scarce and the published articles are of poor quality. There is no significant difference between EC versus LC in the complication rate. This systematic review supports neither early nor late ostomy closure.

A data-driven algorithm integrating clinical and laboratory features for the diagnosis and prognosis of necrotizing enterocolitis.

PubMed

Ji, Jun; Ling, Xuefeng B; Zhao, Yingzhen; Hu, Zhongkai; Zheng, Xiaolin; Xu, Zhening; Wen, Qiaojun; Kastenberg, Zachary J; Li, Ping; Abdullah, Fizan; Brandt, Mary L; Ehrenkranz, Richard A; Harris, Mary Catherine; Lee, Timothy C; Simpson, B Joyce; Bowers, Corinna; Moss, R Lawrence; Sylvester, Karl G

2014-01-01

Necrotizing enterocolitis (NEC) is a major source of neonatal morbidity and mortality. Since there is no specific diagnostic test or risk of progression model available for NEC, the diagnosis and outcome prediction of NEC is made on clinical grounds. The objective in this study was to develop and validate new NEC scoring systems for automated staging and prognostic forecasting. A six-center consortium of university based pediatric teaching hospitals prospectively collected data on infants under suspicion of having NEC over a 7-year period. A database comprised of 520 infants was utilized to develop the NEC diagnostic and prognostic models by dividing the entire dataset into training and testing cohorts of demographically matched subjects. Developed on the training cohort and validated on the blind testing cohort, our multivariate analyses led to NEC scoring metrics integrating clinical data. Machine learning using clinical and laboratory results at the time of clinical presentation led to two nec models: (1) an automated diagnostic classification scheme; (2) a dynamic prognostic method for risk-stratifying patients into low, intermediate and high NEC scores to determine the risk for disease progression. We submit that dynamic risk stratification of infants with NEC will assist clinicians in determining the need for additional diagnostic testing and guide potential therapies in a dynamic manner. http://translationalmedicine.stanford.edu/cgi-bin/NEC/index.pl and smartphone application upon request.

Poly(ADP-Ribose) Polymerase-1: A Novel Therapeutic Target in Necrotizing Enterocolitis

PubMed Central

Giannone, Peter J.; Alcamo, Alicia A.; Schanbacher, Brandon L.; Nankervis, Craig A.; Besner, Gail E.; Bauer, John A.

2011-01-01

Necrotizing enterocolitis (NEC) is the most common gastrointestinal disease of infancy, afflicting 11% of infants born 22–28 weeks gestational age. Both inflammation and oxidation may be involved in NEC pathogenesis through reactive nitrogen species production, protein oxidation and DNA damage. Poly(ADP-ribose) polymerase-1 (PARP-1) is a critical enzyme activated to facilitate DNA repair using nicotinamide adenine dinucleotide (NAD+) as a substrate. However, in the presence of severe oxidative stress and DNA damage, PARP-1 over-activation may ensue, depleting cells of NAD+ and ATP, killing them by metabolic catastrophe. Here we tested the hypothesis that NO dysregulation in intestinal epithelial cells during NEC leads to marked PARP-1 expression and that administration of a PARP-1 inhibitor (nicotinamide) attenuates intestinal injury in a newborn rat model of NEC. In this model, 56% of control pups developed NEC (any stage), versus 14% of pups receiving nicotinamide. Forty-four percent of control pups developed high-grade NEC (grades 3–4), whereas only 7% of pups receiving nicotinamide developed high-grade NEC. Nicotinamide treatment protects pups against intestinal injury incurred in the newborn rat NEC model. We speculate that PARP-1 over-activation in NEC may drive mucosal cell death in this disease and that PARP-1 may be a novel therapeutic target in NEC. PMID:21399558

The Cost of Morbidities in Very Low Birth Weight Infants

PubMed Central

Johnson, Tricia J.; Patel, Aloka L.; Jegier, Briana; Engstrom, Janet L.; Meier, Paula

2013-01-01

Objective The objective of this study was to determine the association between direct costs for the initial neonatal intensive care unit (NICU) hospitalization and four potentially preventable morbidities in a retrospective cohort of very low birth weight infants (VLBW; <1500g birth weight). Methods The sample included 425 VLBW infants born alive between July 2005 and June 2009 at Rush University Medical Center. Morbidities included brain injury, necrotizing enterocolitis, bronchopulmonary dysplasia, and late onset sepsis. Clinical and economic data were retrieved from the institution’s system-wide data warehouse and cost accounting system. A general linear regression model was fit to determine incremental direct costs associated with each morbidity. Results After controlling for birth weight, gestational age, and socio-demographic characteristics, the presence of brain injury was associated with a $12,048 (p=0.005) increase in direct costs; necrotizing enterocolitis with a $15,440 (p=0.005) increase; bronchopulmonary dysplasia with a $31,565 (p<0.001) increase; and late onset sepsis with a $10,055 (p<0.001) increase in direct costs. The absolute number of morbidities was also associated with significantly higher costs. Conclusions This study provides the first collective estimates of the direct costs during the NICU hospitalization for these four morbidities in VLBW infants. The incremental costs associated with these morbidities were high, and these data can inform future studies evaluating interventions to prevent or reduce these costly morbidities. PMID:22910099

From birth to ‘immuno-health’, allergies and enterocolitis

PubMed Central

Houghteling, Pearl D.; Walker, W. Allan

2015-01-01

Microbial signals stimulate development and maintenance of the neonatal immune system. The process begins in utero, with limited exposure to microbes in the intrauterine environment, as well as maternal immune signals priming the developing immune system. After birth and initial colonization, the immune system must be able to activate against pathogens, but also achieve oral tolerance of food and resident gut microbes. Through microbial signals and appropriate nutrition, the immune system is able to achieve homeostasis. Major challenges to successful colonization and immune system regulation include abnormal microbial inoculi (cesarean section, hygiene) and antibiotics. When normal colonization is interrupted, dysbiosis occurs. This imbalance of microbes and subsequently of the immune system can result in allergic diseases, asthma or necrotizing enterocolitis. Probiotics and probiotic-derived therapies represent an exciting avenue to replete the population of commensal microbes and to prevent the immune-mediated sequelae of dysbiosis. PMID:26447970

Management of necrotising appendicitis associated with widespread necrotising enterocolitis of the small and large bowel and perforated duodenal ulcer.

PubMed

Gupta, Vaibhav; Zani, Augusto; Jackson, Paul; Singh, Shailinder

2015-06-08

A 7-year-old boy presented in septic shock secondary to appendicitis with generalised peritonitis. Following crystalloid resuscitation, he underwent surgery. Faecopurulent contamination and free air were found. This was secondary to a perforated and gangrenous appendix, multiple large and small bowel segments with perforations, patches of necrosis, interspersed with healthy bowel and segments of questionable viability. There was also a perforated duodenal ulcer. Necrotic segments were resected using a 'clip-and-drop' technique to shorten operative duration and guide resection to preserve bowel length. After six laparotomies and multiple bowel resections, the child was discharged home with an ileostomy that was subsequently reversed. He is currently on a normal diet and pursuing all activities appropriate for his age. Perforated appendicitis can be associated with widespread bowel necrosis and multiple perforations. A conservative damage limitation approach using the 'clip-and-drop' technique and relook laparotomies is useful in the management of extensive bowel necrosis in children. 2015 BMJ Publishing Group Ltd.

Pathogenesis of NEC: Role of the Innate and Adaptive Immune Response

PubMed Central

Denning, Timothy L.; Bhatia, Amina M.; Kane, Andrea F.; Patel, Ravi M.; Denning, Patricia L.

2017-01-01

Necrotizing enterocolitis (NEC) is a devastating disease in premature infants with high case fatality and significant morbidity among survivors. Immaturity of intestinal host defenses predisposes the premature infant gut to injury. An abnormal bacterial colonization pattern with a deficiency of commensal bacteria may lead to a further breakdown of these host defense mechanisms, predisposing the infant to NEC. Here, we review the role of the innate and adaptive immune system in the pathophysiology of NEC. PMID:27940091

Typhlitis: selective surgical management.

PubMed

Moir, C R; Scudamore, C H; Benny, W B

1986-05-01

Typhlitis is a neutropenic enterocolitis of varying severity. Its incidence is increasing, particularly in patients with acute myelogenous leukemia undergoing high dose cytosine arabinoside chemotherapy. The onset is heralded by prodromal fever, watery or bloody diarrhea, abdominal distension, and nausea during the phase of severe neutropenia. The symptoms may then localize to the right lower quadrant with an associated increase in systemic toxicity. The diagnosis can be confirmed in these and other less specific cases by serial reexamination and abdominal radiographs, ultrasonography, computerized tomograms, or radionucleotide scans. The mainstay of management is complete bowel rest with nasogastric suction and total parenteral nutrition. Broad-spectrum combination antibiotics are essential, as is the avoidance of laxatives or antidiarrheal agents. Granulocyte support may be helpful. Patients with a history of nonspecific gastrointestinal complaints or of true typhlitis, successfully managed nonoperatively, should have prophylactic bowel rest and total parenteral nutrition instituted at the beginning of further chemotherapy. Patients with ongoing severe systemic sepsis who do not respond to chemotherapy and those with overt perforation, obstruction, massive hemorrhage, or abscess formation require surgical intervention. All necrotic material must be resected, usually by a right hemicolectomy, ileostomy, and mucous fistula. Divided ileostomy for less severe cases may be useful. Failure to remove the necrotic focus in these severely immunocompromised patients is fatal. With adequate recognition of typhlitis and its precipitating factors, the incidence of complications can be reduced through prevention and timely surgical intervention. Although typhlitis developed in a quarter of our acute myeloblastic leukemia patients, use of this combined approach was successful in all cases.

Necrotizing Enterocolitis and Growth in Preterm Infants Fed Predominantly Maternal Milk, Pasteurized Donor Milk, or Preterm Formula: A Retrospective Study.

PubMed

Sisk, Paula M; Lambeth, Tinisha M; Rojas, Mario A; Lightbourne, Teisha; Barahona, Maria; Anthony, Evelyn; Auringer, Sam T

2017-06-01

Objective  To evaluate the association between necrotizing enterocolitis (NEC), growth, and feeding. Methods  This is a retrospective study of 551 infants (birth weight ≤ 1,500 g, ≤32 weeks' gestation). NEC, Bell's stage ≥ 2, was confirmed by independent review of sentinel radiographs. Feeding type was defined as ≥ 50% maternal milk (MM), pasteurized donor human milk (PDHM), or preterm formula (PF). Demographic and clinical characteristics including growth were compared between the three groups. Multivariable regression analysis was performed to control variables that differed in bivariate analysis. Results  PDHM and PF mothers were more likely to be African-American, be enrolled in Medicaid, and have chorioamnionitis. PF mothers received antenatal steroids less frequently. NEC rates were different by feeding group (MM: 5.3%; PHDM: 4.3%; PF: 11.4%; p  = 0.04). Adjusting for group differences, lower gestational age (adjusted odds ratio [aOR]: 0.85; 95% confidence interval [CI]: 0.74-0.97; p  = 0.02], and PF (aOR: 2.53; 95% CI: 1.15-5.53; p  = 0.02] were associated with NEC. There were no differences in other health outcomes or growth at hospital discharge. Conclusion  MM and PDHM feedings, given until 34 weeks postmenstrual age, were associated with lower rates of NEC in very low birth weight infants without interfering with growth. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

A Multifaceted Approach to Improving Outcomes in the NICU: The Pediatrix 100 000 Babies Campaign.

PubMed

Ellsbury, Dan L; Clark, Reese H; Ursprung, Robert; Handler, Darren L; Dodd, Elizabeth D; Spitzer, Alan R

2016-04-01

Despite advances in neonatal medicine, infants requiring neonatal intensive care continue to experience substantial morbidity and mortality. The purpose of this initiative was to generate large-scale simultaneous improvements in multiple domains of care in a large neonatal network through a program called the "100,000 Babies Campaign." Key drivers of neonatal morbidity and mortality were identified. A system for retrospective morbidity and mortality review was used to identify problem areas for project prioritization. NICU system analysis and staff surveys were used to facilitate reengineering of NICU systems in 5 key driver areas. Electronic health record-based automated data collection and reporting were used. A quality improvement infrastructure using the Kotter organizational change model was developed to support the program. From 2007 to 2013, data on 422 877 infants, including a subset with birth weight of 501 to 1500 g (n = 58 555) were analyzed. Key driver processes (human milk feeding, medication use, ventilator days, admission temperature) all improved (P < .0001). Mortality, necrotizing enterocolitis, retinopathy of prematurity, bacteremia after 3 days of life, and catheter-associated infection decreased. Survival without significant morbidity (necrotizing enterocolitis, severe intraventricular hemorrhage, severe retinopathy of prematurity, oxygen use at 36 weeks' gestation) improved. Implementation of a multifaceted quality improvement program that incorporated organizational change theory and automated electronic health record-based data collection and reporting program resulted in major simultaneous improvements in key neonatal processes and outcomes. Copyright © 2016 by the American Academy of Pediatrics.

Incidence and timing of presentation of necrotizing enterocolitis in preterm infants.

PubMed

Yee, Wendy H; Soraisham, Amuchou Singh; Shah, Vibhuti S; Aziz, Khalid; Yoon, Woojin; Lee, Shoo K

2012-02-01

To examine the variation in the incidence and to identify the timing of the presentation of necrotizing enterocolitis (NEC) in a cohort of preterm infants within the Canadian Neonatal Network (CNN). This was a population-based cohort of 16 669 infants with gestational age (GA) <33 weeks, admitted to 25 NICUs participating in the CNN between January 1, 2003, and December 31(,) 2008. Variations in NEC incidence among the participating NICUs for the study period were examined. We categorized early-onset NEC as occurring at <14 days of age and late-onset NEC occurring at ≥14 days. Multivariate logistic regression analysis was performed to identify risk factors for early-onset NEC. The overall incidence of NEC was 5.1%, with significant variation in the risk adjusted incidence among the participating NICUs in the CNN. Early-onset NEC occurred at a mean of 7 days compared with 32 days for late-onset NEC. Early-onset NEC infants had lower incidence of respiratory distress syndrome, patent ductus treated with indomethacin, less use of postnatal steroids, and shorter duration of ventilation days. Multivariate logistic regression analysis identified that greater GA and vaginal delivery were associated with increased risk of early-onset NEC. Among infants <33 weeks' gestation, NEC appears to present at mean age of 7 days in more mature infants, whereas onset of NEC is delayed to 32 days of age in smaller, lower GA infants. Further studies are required to understand the etiology of this disease process.

Modeling the interactions of bacteria and Toll-like receptor-mediated inflammation in necrotizing enterocolitis

PubMed Central

Arciero, Julia; Ermentrout, G. Bard; Siggers, Richard; Afrazi, Amin; Hackam, David; Vodovotz, Yoram; Rubin, Jonathan

2016-01-01

Necrotizing enterocolitis (NEC) is a severe disease of the gastrointestinal tract in premature infants, characterized by a disrupted intestinal epithelium and an exaggerated pro-inflammatory response. Since the activation of Toll-like receptor-4 (TLR4) blocks cell migration and proliferation and contributes to an uncontrolled inflammatory response within the intestine, this receptor has been identified as a key contributor to the development of NEC. Toll-like receptor-9 (TLR9) has been shown to sense bacterial genome components (CpG DNA) and to play an anti-inflammatory role in NEC. We present in vitro results demonstrating direct inhibition of TLR4 activation by CpG DNA, and we develop a mathematical model of bacteria–immune interactions within the intestine to investigate how such inhibition of TLR4 signaling might alter inflammation, associated bacterial invasion of tissue, and resulting outcomes. The model predicts that TLR9 can inhibit both the beneficial and detrimental effects of TLR4, and thus a proper balance of action by these two receptors is needed to promote intestinal health. The model results are also used to explore three interventions that could potentially prevent the development of NEC: reducing bacteria in the mucus layer, administering probiotic treatment, and blocking TLR4 activation. While the model shows that these interventions would be successful in most cases, the model is also used to identify situations in which the proposed treatments might be harmful. PMID:23238281

Impact of Donor Milk Availability on Breast Milk Use and Necrotizing Enterocolitis Rates.

PubMed

Kantorowska, Agata; Wei, Julia C; Cohen, Ronald S; Lawrence, Ruth A; Gould, Jeffrey B; Lee, Henry C

2016-03-01

To examine the availability of donor human milk (DHM) in a population-based cohort and assess whether the availability of DHM was associated with rates of breast milk feeding at NICU discharge and rates of necrotizing enterocolitis (NEC). Individual patient clinical data for very low birth weight infants from the California Perinatal Quality Care Collaborative were linked to hospital-level data on DHM availability from the Mothers' Milk Bank of San José for 2007 to 2013. Trends of DHM availability were examined by level of NICU care. Hospitals that transitioned from not having DHM to having DHM availability during the study period were examined to assess changes in rates of breast milk feeding at NICU discharge and NEC. The availability of DHM increased from 27 to 55 hospitals during the study period. The availability increased for all levels of care including regional, community, and intermediate NICUs, with the highest increase occurring in regional NICUs. By 2013, 81.3% of premature infants cared for in regional NICUs had access to DHM. Of the 22 hospitals that had a clear transition to having availability of DHM, there was a 10% increase in breast milk feeding at NICU discharge and a concomitant 2.6% decrease in NEC rates. The availability of DHM has increased over time and has been associated with positive changes including increased breast milk feeding at NICU discharge and decrease in NEC rates. Copyright © 2016 by the American Academy of Pediatrics.

Probiotics in early life: a preventative and treatment approach.

PubMed

Hashemi, Ashkan; Villa, Christopher R; Comelli, Elena M

2016-04-01

Microbial colonization of the infant gut plays a key role in immunological and metabolic pathways impacting human health. Since the maturation of the gut microbiota coincides with early life development, failure to develop a health compatible microbiota composition may result in pathology and disease in later life. Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. Maternal transfer of microorganisms is possible during pregnancy and lactation, and the mother's diet and microbiota can influence that of her offspring. Furthermore, pre-term birth, Caesarean section birth, formula feeding, antibiotic use, and malnutrition have been linked to dysbiosis, which in turn is associated with several pathologies such as necrotizing enterocolitis, inflammatory bowel diseases, antibiotic associated diarrhea, colic, and allergies. Thus, early life should represent a preferred stage of life for probiotic interventions. In this context, they could be regarded as a means to 'program' the individual for health maintenance, in order to prevent pathologies associated with dysbiosis. In order to elucidate the mechanisms underlying the benefits of probiotic administration, pre-clinical studies have been conducted and found an array of positive results such as improved microbial composition, intestinal maturation, decreased pathogenic load and infections, and improved immune response. Moreover, specific probiotic strains administered during the perinatal period have shown promise in attenuating severity of necrotizing enterocolitis. The mechanisms elucidated suggest that probiotic interventions in early life can be envisaged for disease prevention in both healthy offspring and offspring at risk of chronic disease.

Necrotizing Enterocolitis is associated with Ureaplasma Colonization in Preterm Infants

PubMed Central

Okogbule-Wonodi, Adora C.; Gross, George W.; Sun, Chen-Chih J.; Agthe, Alexander G.; Xiao, Li; Waites, Ken B.; Viscardi, Rose Marie

2014-01-01

The study objective was to determine whether Ureaplasma respiratory tract colonization of preterm infants <33 weeks gestation is associated with an increased risk for necrotizing enterocolitis (NEC). One or more tracheal or nasopharyngeal aspirates for Ureaplasma culture and PCR were obtained during the first week of life from 368 infants <33 weeks gestation enrolled from 1999-2003 or from 2007-2009. NEC Bell stage ≥2 was confirmed by radiological criteria, and pathology, if available. Cord serum samples were analyzed for IL-6 and IL-1β concentrations and placentas were reviewed for histological chorioamnionitis in the first cohort. NEC was confirmed in 29/368 (7.9%) of the combined cohorts. The incidence of NEC was 2.2-fold higher in Ureaplasma-positive (12.3%) than Ureaplasma-negative infants (5.5%) <33 wk (OR 2.43, 95%CI 1.13-5.22, P=0.023) and 3.3-fold higher in Ureaplasma-positive (14.6%) than Ureaplasma-negative (4.4%) infants ≤28 wks (OR 3.67, 95%CI 1.36-9.93, P=0.01). Age of onset, hematologic parameters at onset, and NEC severity were similar between Ureaplasma-positive and negative infants. Cord serum IL-6 and IL-1β concentrations were significantly higher in Ureaplasma-positive than in Ureaplasma-negative NEC-affected infants. Ureaplasma may be a factor in NEC pathogenesis in preterm infants by contributing to intestinal mucosal injury and/or altering systemic or local immune responses. PMID:21258263

Roles and Experiences of Parents in Necrotizing Enterocolitis: An International Survey of Parental Perspectives of Communication in the NICU.

PubMed

Gadepalli, Samir K; Canvasser, Jennifer; Eskenazi, Yael; Quinn, Megan; Kim, Jae H; Gephart, Sheila M

2017-12-01

Although partnering with parents is important to improving neonatal outcomes, no studies have investigated what parents are taught, remember, or experience when their child is afflicted with necrotizing enterocolitis (NEC). To characterize parental perceptions of communication and support they were given about NEC. An online survey was developed, reviewed for face validity, and then administered to parents whose child had experienced NEC. Quantitative data were analyzed using descriptive statistics, and qualitative data were analyzed using a qualitative descriptive approach. Parents (N = 110) wanted to know the risk factors and warning signs for NEC and wanted to be told as soon as their child was admitted to the neonatal intensive care unit (NICU). Information provided before diagnosis was felt to be poor by the majority of families, with only 32% feeling satisfied or very satisfied. No parent wrote that they were "scared" by information provided to them about NEC; in fact, parents were dissatisfied when they received "sugar-coated" information. Engaged parents were significantly more satisfied than those who were not informed, had their concerns and suggestions dismissed, or who had to advocate for their baby against clinician opposition (eg, activating the chain of command). Areas for quality improvement include better communication and collaboration with parents through early engagement in NEC prevention using modalities beyond verbal instruction. More research is needed on how best to engage parents, especially to engage in prevention, and how doing so affects satisfaction and outcomes.

A Functional ATG16L1 (T300A) Variant is Associated with Necrotizing Enterocolitis in Premature Infants

PubMed Central

Sampath, Venkatesh; Bhandari, Vineet; Berger, Jessica; Merchant, Daniel; Zhang, Liyun; Ladd, Mihoko; Menden, Heather; Garland, Jeffery; Ambalavanan, Namasivayam; Mulrooney, Neil; Quasney, Michael; Dagle, John; Lavoie, Pascal M; Simpson, Pippa; Dahmer, Mary

2017-01-01

Background The genetic basis of dysfunctional immune responses in necrotizing enterocolitis (NEC) remains unknown. We hypothesized that variants in Nucleotide binding and Oligomerization Domain (NOD)-Like Receptors (NLRs) and Autophagy (ATG) genes modulate vulnerability to NEC. Methods We genotyped a multi-center cohort of premature infants with and without NEC for NOD1, NOD2, ATG16L1, CARD8 and NLRP3 variants. Chi-square tests and logistic regression were used for statistical analysis. Results In our primary cohort (n=1015), 86 (8.5%) infants developed NEC. The A allele of the ATG16L1 (Thr300Ala) variant was associated with increased NEC (AA vs. AG vs. GG; 11.3% vs. 8.4% vs. 4.8%, p=0.009). In regression models for NEC that adjusted for epidemiological confounders, GA (p=0.033) and the AA genotype (p=0.038) of ATG16L1 variant were associated with NEC. The association between the A allele of the ATG16L1 variant and NEC remained significant among Caucasian infants (p=0.02). In a replication cohort (n=259), NEC rates were highest among infants with the AA genotype but did not reach statistical significance. Conclusion We report a novel association between a hypomorphic variant in an autophagy gene (ATG16L1) and NEC in premature infants. Our data suggest that decreased autophagy arising from genetic variants may confer protection against NEC. PMID:27893720

An exclusively human milk diet reduces necrotizing enterocolitis.

PubMed

Herrmann, Kenneth; Carroll, Katherine

2014-05-01

This study tested the hypothesis that feeding an exclusively human milk (EHM) diet to premature infants reduces the incidence of necrotizing enterocolitis (NEC) associated with enteral feeding. An observational study for infants born at less than 33 weeks of gestational age was performed in a single neonatal intensive care unit. An EHM diet prospectively eliminated bovine-based artificial milk, including bovine-based fortifier, through 33 weeks postmenstrual age (PMA). The clinical data from a 2.5-year interval of the EHM diet were compared with data from the previous 6.5 years for similar infants who received bovine-based milk products before 33 weeks PMA. In the EHM diet cohort, 148 of 162 infants (91%) received EHM through 33 weeks PMA. In order to achieve an EHM diet, 140 of 162 infants (86%) received their own mother's milk, and 98 of 162 infants (60%) received donor human milk. The EHM cohort was also fed a human milk-based fortifier to truly eliminate bovine products. The distribution of NEC onset in the EHM cohort was significantly different from that in the control cohort for the day of onset (p=0.042) and the PMA at onset (p=0.011). In the control cohort, NEC onset after Day 7 of life occurred in 15 of 443 infants (3.4%), significantly more than in the EHM cohort where NEC occurred in two of 199 infants (1%) (p=0.009). Changing to an EHM milk diet through 33 weeks PMA reduced the incidence of NEC associated with enteral feeding.

Beyond Necrotizing Enterocolitis: Other Clinical Advantages of an Exclusive Human Milk Diet.

PubMed

Hair, Amy B; Rechtman, David J; Lee, Martin L; Niklas, Victoria

2018-06-07

Articles previously published by Sullivan et al. and Cristofalo et al. were reanalyzed using the proportion of cow milk-based nutrition received to determine whether that affected clinical outcomes during hospitalization for infants birth weight 500-1250 g. Abrams et al. showed in the same cohort incidences of necrotizing enterocolitis (NEC), NEC requiring surgery and sepsis increased proportionally to the amount of dietary cow milk. The data from the two studies conducted under essentially the same protocol were combined yielding a cohort of 260 infants receiving a diet ranging from 0% to 100% cow milk. Data analysis utilized negative binomial regression which mitigates differences between subjects in terms of their time on study by incorporating that number into the statistical model. The percent of cow milk-based nutrition was the only predictor investigated. For all outcomes the larger the amount of cow's milk in the diet the greater the number of days of that intervention required. A trend toward statistical significance was seen for ventilator days; however, only parenteral nutrition (PN) days and days to full feeds achieved statistical significance. Incorporation of any cow milk-based nutrition into the diet of extremely premature infants correlates with more days on PN and a longer time to achieve full feeds. There was a nonstatistically significant trend toward increased ventilator days. These represent additional clinical consequences of the use of any cow milk-based protein in feeding EP infants.

Association of Red Blood Cell Transfusion, Anemia, and Necrotizing Enterocolitis in Very Low-Birth-Weight Infants.

PubMed

Patel, Ravi M; Knezevic, Andrea; Shenvi, Neeta; Hinkes, Michael; Keene, Sarah; Roback, John D; Easley, Kirk A; Josephson, Cassandra D

2016-03-01

Data regarding the contribution of red blood cell (RBC) transfusion and anemia to necrotizing enterocolitis (NEC) are conflicting. These associations have not been prospectively evaluated, accounting for repeated, time-varying exposures. To determine the relationship between RBC transfusion, severe anemia, and NEC. In a secondary, prospective, multicenter observational cohort study from January 2010 to February 2014, very low-birth-weight (VLBW, ≤1500 g) infants, within 5 days of birth, were enrolled at 3 level III neonatal intensive care units in Atlanta, Georgia. Two hospitals were academically affiliated and 1 was a community hospital. Infants received follow-up until 90 days, hospital discharge, transfer to a non-study-affiliated hospital, or death (whichever came first). Multivariable competing-risks Cox regression was used, including adjustment for birth weight, center, breastfeeding, illness severity, and duration of initial antibiotic treatment, to evaluate the association between RBC transfusion, severe anemia, and NEC. The primary exposure was RBC transfusion. The secondary exposure was severe anemia, defined a priori as a hemoglobin level of 8 g/dL or less. Both exposures were evaluated as time-varying covariates at weekly intervals. Necrotizing enterocolitis, defined as Bell stage 2 or greater by preplanned adjudication. Mortality was evaluated as a competing risk. Of 600 VLBW infants enrolled, 598 were evaluated. Forty-four (7.4%) infants developed NEC. Thirty-two (5.4%) infants died (all cause). Fifty-three percent of infants (319) received a total of 1430 RBC transfusion exposures. The unadjusted cumulative incidence of NEC at week 8 among RBC transfusion-exposed infants was 9.9% (95% CI, 6.9%-14.2%) vs 4.6% (95% CI, 2.6%-8.0%) among those who were unexposed. In multivariable analysis, RBC transfusion in a given week was not significantly related to the rate of NEC (adjusted cause-specific hazard ratio, 0.44 [95% CI, 0.17-1.12]; P = .09). Based on evaluation of 4565 longitudinal measurements of hemoglobin (median, 7 per infant), the rate of NEC was significantly increased among VLBW infants with severe anemia in a given week compared with those who did not have severe anemia (adjusted cause-specific hazard ratio, 5.99 [95% CI, 2.00-18.0]; P = .001). Among VLBW infants, severe anemia, but not RBC transfusion, was associated with an increased risk of NEC. Further studies are needed to evaluate whether preventing severe anemia is more important than minimizing RBC transfusion.

[Advances in medical care for extremely low birth weight infants worldwide].

PubMed

Chen, Chun; Zhang, Qian-Shen

2013-08-01

Dramatic advances in neonatal medicine over recent decades have resulted in decreased mortality and morbidity rates for extremely low birth weight infants. However, the survival of these infants is associated with short- and long-term morbidity, including severe intraventricular hemorrhage, periventricular leukomalacia, nosocomial infection and necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity and adverse long-term neurodevelopmental sequelae. This article reviewed the latest advances in the medical care for extremely low birth weight infants including survival rate, ethical issues and short- and long-term morbidity, domestically and abroad.

Probiotics for the prevention of necrotizing enterocolitis in neonates: an 8-year retrospective cohort study.

PubMed

Li, D; Rosito, G; Slagle, T

2013-12-01

Probiotic therapy has been shown to reduce morbidity and mortality of necrotizing enterocolitis (NEC) in premature infants in several international studies using various probiotic agents. The purpose of this study(*) is to describe our experience of using probiotic therapy in preventing NEC in infants with very low birth weight (VLBW) in a neonatal intensive care unit (NICU) and to evaluate whether our records provide evidence of effectiveness for probiotic therapy. In a retrospective cohort study, the efficacy of probiotic therapy in preventing NEC in VLBW infants was investigated via chart review. A probiotic administration protocol using a three-strain (Streptococcus thermophilus, Bifidobacterium infantis and Bifidobacterium bifidum) supplement was implemented in August 2007. Patients admitted to the NICU from August 2003 through July 2011 were screened. Primary outcomes are the morbidity and mortality of NEC. The secondary outcomes were severity of NEC and incidence of where infant feeds were stopped but NEC was not diagnosed (NEC scare). There was a significant increased baseline risk of NEC development in the probiotics group, including younger gestational age, higher incidence of patent ductus arteriosus (PDA) and use of indomethacin. The incidence of NEC is similar between the control group (2·8%) and probiotics group (2·4%) (hazard ratio, 1·15; 95% confidence interval [CI], 0·42, 3·12). Mortality of NEC is also not statistically different. Incidence of NEC scare was decreased from 2·8% in control group to 1·4% in probiotics group, although the difference was not statistically significant (P = 0·38). Our findings suggest that probiotics are safe in NEC prevention in VLBW infants. We had no cases of infection related to the strains of bacteria used in our product. With the low incidence of NEC (2·8%) and NEC scare (2·8%) in our cohort, we do not have enough power to detect any change in outcome, particularly as our study was observational. However, it is hoped that our data give useful information for others on probiotic prophylactic therapy in the routine clinical management of VLBW infants. © 2013 John Wiley & Sons Ltd.

Protective effects of dexpanthenol in an experimental model of necrotizing enterocolitis.

PubMed

Karadag, Ahmet; Ozdemir, Ramazan; Kurt, Ahmet; Parlakpinar, Hakan; Polat, Alaadin; Vardi, Nigar; Taslidere, Elif; Karaman, Abdurrahman

2015-07-01

In pathogenesis of necrotizing enterocolitis (NEC), both oxidative stress and inflammation are considerable risk factors. The study was designed to evaluate whether administration of dexpanthenol (Dxp) is able to attenuate intestinal injury through the antioxidant and antiinflammatory mechanisms in a neonatal rat model of NEC. Forty newborn pups divided into four groups were included in the study: control, control+Dxp, NEC, and NEC+Dxp. NEC was induced by hyperosmolar formula and additionally the pups were exposed to hypoxia/hyperoxia and cold stress. They were sacrificed on postnatal day four, and their intestinal tissues were analyzed biochemically and histopathologically. Dxp caused a significant decrease in intestinal damage as determined by the histological score, villus height and number of goblet cells in NEC groups (p<0.0001). Tissue malondialdehyde, total oxidant status, and oxidative stress indexes levels were higher in the NEC group than in the control and control+Dxp groups (p<0.001). These values were reduced in the pups treated with Dxp (p≤0.004). Superoxide dismutase, glutathione peroxidase, and reduced glutathione activities were significantly reduced in the NEC group compared to the others (p<0.005). Treatment with Dxp significantly reduced elevations in tissue homogenate levels of tumor necrosis factor-α and interleukin-1β in the NEC+Dxp group (p=0.002 and p=0.01, respectively). Dexpanthenol seems to have antiinflammatory and antioxidant properties. Prophylaxis with Dxp has a potential to reduce the severity of intestinal damage in NEC in the animals. Copyright © 2015 Elsevier Inc. All rights reserved.

Severe hemolysis after plasma transfusion in a neonate with necrotizing enterocolitis, Clostridium perfringens infection, and red blood cell T-polyagglutination.

PubMed

Moh-Klaren, Julia; Bodivit, Gwellaouen; Jugie, Myriam; Chadebech, Philippe; Chevret, Laurent; Mokhtari, Mostafa; Chamillard, Xavier; Gallon, Philippe; Tissières, Pierre; Bierling, Philippe; Djoudi, Rachid; Pirenne, France; Burin-des-Roziers, Nicolas

2017-11-01

Red blood cell (RBC) Thomsen-Friedenreich antigen exposure (T activation) in infants with necrotizing enterocolitis (NEC) has occasionally been associated with posttransfusional intravascular hemolysis thought to be due to anti-T antibodies in the donor plasma. We describe an infant with NEC and Clostridium perfringens infection complicated by severe hemolysis after plasma transfusion. After this case, infants with confirmed NEC were prospectively evaluated for T activation. We checked for hemolysis in patients with T activation receiving plasma-containing blood products. The infant had received 80 mL of fresh-frozen plasma (FFP). His RBCs displayed strong T activation, and agglutination was observed with four of six ABO-compatible FFP units. A direct antiglobulin test was negative. IgM-class anti-T antibodies were present in small amounts (titer of 8) in the transfused FFP. Anti-T antibodies from the blood donor were not hemolytic in vitro. In the prospective study, T activation was observed in three of 28 infants with NEC (11%). One infant presented moderate T activation and two infants presented very strong T activation but only moderate decreases in sialic acid expression on the RBC membrane. These three infants presented no signs of hemolysis after transfusion with unwashed blood products or FFP. Anti-T antibodies are unlikely to be the etiologic factor for the hemolytic reactions observed in infants with NEC and T activation. Massive RBC desialylation and the direct action of bacterial toxins are more probable causes. Strict avoidance of plasma-containing blood products does not seem justified in these infants. © 2017 AABB.

The hepatic bile acid transporters Ntcp and Mrp2 are downregulated in experimental necrotizing enterocolitis.

PubMed

Cherrington, Nathan J; Estrada, Teresa E; Frisk, Harrison A; Canet, Mark J; Hardwick, Rhiannon N; Dvorak, Bohuslav; Lux, Katie; Halpern, Melissa D

2013-01-01

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency of premature infants and is characterized by an extensive hemorrhagic inflammatory necrosis of the distal ileum and proximal colon. We have previously shown that, during the development of experimental NEC, the liver plays an important role in regulating inflammation in the ileum, and accumulation of ileal bile acids (BA) along with dysregulation of ileal BA transporters contributes to ileal damage. Given these findings, we speculated that hepatic BA transporters would also be altered in experimental NEC. Using both rat and mouse models of NEC, levels of Cyp7a1, Cyp27a1, and the hepatic BA transporters Bsep, Ntcp, Oatp2, Oatp4, Mrp2, and Mrp3 were investigated. In addition, levels of hepatic BA transporters were also determined when the proinflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-18, which are both elevated in NEC, are neutralized during disease development. Ntcp and Mrp2 were decreased in NEC, but elevated ileal BA levels were not responsible for these reductions. However, neutralization of TNF-α normalized Ntcp, whereas removal of IL-18 normalized Mrp2 levels. These data show that the hepatic transporters Ntcp and Mrp2 are downregulated, whereas Cyp27a1 is increased in rodent models of NEC. Furthermore, increased levels of TNF-α and IL-18 in experimental NEC may play a role in the regulation of Ntcp and Mrp2, respectively. These data suggest the gut-liver axis should be considered when therapeutic modalities for NEC are developed.

Predictors of outcome at 2 years of age after early intrauterine growth restriction.

PubMed

Torrance, H L; Bloemen, M C T; Mulder, E J H; Nikkels, P G J; Derks, J B; de Vries, L S; Visser, G H A

2010-08-01

To examine the relative importance of antenatal and perinatal variables on short- and long-term outcome of preterm growth restricted fetuses with umbilical artery (UA) Doppler abnormalities. This was a cohort study of 180 neonates with birth weight < 10(th) percentile, gestational age at delivery < 34 weeks and abnormal Doppler ultrasound examination of the UA. Various antenatal and perinatal variables were studied in relation to short- and long-term outcome. Neonatal and overall mortality (up to 2 years of age) were predicted by low gestational age at delivery. Neonatal mortality was additionally predicted by absent or reversed UA end-diastolic flow, while the presence of severe neonatal complications and placental villitis were additional predictors of both infant (between 28 days and 1 year of postnatal life) and overall mortality. Placental villitis was found to be the only predictor of necrotizing enterocolitis. Low gestational age at delivery, male sex, abnormal cardiotocography, absent or reversed UA end-diastolic flow and the HELLP syndrome predicted respiratory distress syndrome. Abnormal neurodevelopmental outcome at 2 years was predicted by low birth weight (< 2.3(rd) percentile), fetal acidosis (UA pH < 7.00), and placental villitis. Less advanced gestation at delivery remains an important predictor of short-term outcome in growth-restricted fetuses. In addition, the presence of placental villitis may aid neonatologists in the early identification of infants at increased risk of necrotizing enterocolitis, death and abnormal neurodevelopment at 2 years of age. Abnormal neurodevelopment was related to low weight and acidosis at birth, indicating that the severity of malnutrition and fetal acidosis affect long-term outcome.

A double-blinded randomized trial on growth and feeding tolerance with Saccharomyces boulardii CNCM I-745 in formula-fed preterm infants.

PubMed

Xu, Lingfen; Wang, Yun; Wang, Yang; Fu, Jianhua; Sun, Mei; Mao, Zhiqin; Vandenplas, Yvan

2016-01-01

The use of probiotics is increasingly popular in preterm neonates, as they may prevent necrotizing enterocolitis sepsis and improve growth and feeding tolerance. There is only limited literature on Saccharomyces boulardii CNCM I-745 (S. boulardii) in preterm infants. A prospective, randomized, case-controlled trial with the probiotic S. boulardii (50mg/kg twice daily) was conducted in newborns with a gestational age of 30-37 weeks and a birth weight between 1500 and 2500g. 125 neonates were enrolled; 63 in the treatment and 62 in the control group. Weight gain (16.14±1.96 vs. 10.73±1.77g/kg/day, p<0.05) and formula intake at maximal enteral feeding (128.4±6.7 vs. 112.3±7.2mL/kg/day, p<0.05) were significantly higher in the intervention group. Once enteral feeding was started, the time needed to reach full enteral feeding was significantly shorter in the probiotic group (0.4±0.1 vs. 1.7±0.5 days, p<0.05). There was no significant difference in sepsis. Necrotizing enterocolitis did not occur. No adverse effects related to S. boulardii were observed. Prophylactic supplementation of S. boulardii at a dose of 50mg/kg twice a day improved weight gain, improved feeding tolerance, and had no adverse effects in preterm infants >30 weeks old. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Cost and Cost-Effectiveness of Donor Human Milk to Prevent Necrotizing Enterocolitis: Systematic Review.

PubMed

Buckle, Abigail; Taylor, Celia

2017-11-01

Necrotizing enterocolitis (NEC) is a costly gastrointestinal disorder that mainly affects preterm and low-birth-weight infants and can lead to considerable morbidity and mortality. Mother's own milk is protective against NEC but is not always available. In such cases, donor human milk has also been shown to be protective (although to a lesser extent) compared with formula milk, but it is more expensive. This systematic review aimed at evaluating the cost of donor milk, the cost of treating NEC, and the cost-effectiveness of exclusive donor milk versus formula milk feeding to reduce the short-term health and treatment costs of NEC. We systematically searched five relevant databases to find studies with verifiable costs or charges of donor milk and/or treatment of NEC and any economic evaluations comparing exclusive donor milk with exclusive formula milk feeding. All search results were double screened. Seven studies with verifiable donor milk costs and 17 with verifiable NEC treatment costs were included. The types of cost or charge included varied considerably across studies, so quantitative synthesis was not attempted. Estimates of the incremental length of stay associated with NEC were ∼18 days for medical NEC and 50 days for surgical NEC. Two studies claimed to report economic evaluations but did not do so in practice. It is likely that donor milk provides short-term cost savings by reducing the incidence of NEC. Future studies should provide more details on cost components included and a full economic evaluation, including long-term outcomes, should be undertaken.

Effects of boric acid and 2-aminoethoxydiphenyl borate on necrotizing enterocolitis.

PubMed

Yazıcı, Selçuk; Akşit, Hasan; Korkut, Oğuzhan; Sunay, Bahar; Çelik, Tanju

2014-01-01

The aim was to study the effects of boric acid (BA) and 2-aminoethoxydiphenyl borate (2-APB) on oxidative stress and inflammation in an experimental necrotizing enterocolitis (NEC) rat model. Experimental NEC was induced in 40 newborn Sprague-Dawley rats by asphyxia and hypothermia applied in 3 consecutive days. Rats were subdivided into 4 subgroups as NEC, NEC+BA, NEC+2-APB, and controls. BA and 2-APB were applied daily before the procedure. Serum total antioxidant status, superoxide dismutase (SOD), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and erythrocyte glutathione (GSH) levels were measured. Pathological changes for NEC in intestinal architecture were evaluated by a grading system. Pretreatment with BA and 2-APB resulted in a decrease in NEC incidence. In all of the NEC groups, decreased serum levels of GSH and SOD were measured. Boron limited GSH consumption but had no effect on SOD levels. Total antioxidant status levels were not statistically different among groups. In our experimental NEC model, BA, but not 2-APB, prevented the increase of TNF-α. Pretreatment with BA and 2-APB downregulated the activity levels of IL-6 in NEC. In the experimental NEC model, BA and 2-APB partly prevent NEC formation, modulate the oxidative stress parameters, bring a significant decrease in GSH consumption, and enhance the antioxidant defense mechanism, but have no effect on total antioxidant status. BA inhibits the hypoxia and hypothermia-induced increase in both IL-6 and TNF-a, but 2-APB only in IL-6. Boron may be beneficial in preventing NEC.

Heat susceptibility of interleukin-10 and other cytokines in donor human milk.

PubMed

Untalan, Peter B; Keeney, Susan E; Palkowetz, Kimberly H; Rivera, Audelio; Goldman, Armond S

2009-09-01

Holder pasteurization renders donor human milk safe for consumption. Because human milk reduces the risk of necrotizing enterocolitis in preterm infants, we tested whether Holder pasteurization affects certain factors in human milk that protect the intestines: epidermal growth factor (EGF), transforming growth factor (TGF)-beta1, erythropoietin (EPO), and interleukin (IL)-10. Donor human milk from a milk bank was examined. The aqueous phase of 17 samples of donor term human milk (mean duration of lactation, 8 +/- 3.5 months) was examined before and after Holder pasteurization. In the case of IL-10, lesser degrees of pasteurization were also evaluated. The agents were quantified using enzyme immunoassays. The function of IL-10 was also tested. Concentrations of EGF and IL-10 were markedly lower than previously reported values in human milk from earlier phases of lactation. Holder pasteurization significantly reduced the concentrations of EPO and IL-10, whereas lesser degrees of heating increased the detection of IL-10. The immunosuppression of T-cell proliferation by human milk, thought to be attributed to IL-10 alone, persisted after Holder pasteurization. Holder pasteurization greatly decreased concentrations of EPO and IL-10 in human milk. These decreases may impact the ability of human milk to protect against necrotizing enterocolitis. Evidence of possible binding of IL-10 to other proteins in human milk was also found. Experiments to test whether Holder pasteurization affects the function of IL-10 in human milk produced evidence for an agent in human milk other than IL-10 that inhibits T-cell proliferation and resists Holder pasteurization.

Antibiotics modulate intestinal immunity and prevent necrotizing enterocolitis in preterm neonatal piglets

PubMed Central

Jensen, Michael L.; Thymann, Thomas; Cilieborg, Malene S.; Lykke, Mikkel; Mølbak, Lars; Jensen, Bent B.; Schmidt, Mette; Kelly, Denise; Mulder, Imke; Burrin, Douglas G.

2013-01-01

Preterm birth, bacterial colonization, and formula feeding predispose to necrotizing enterocolitis (NEC). Antibiotics are commonly administered to prevent sepsis in preterm infants, but it is not known whether this affects intestinal immunity and NEC resistance. We hypothesized that broad-spectrum antibiotic treatment improves NEC resistance and intestinal structure, function, and immunity in neonates. Caesarean-delivered preterm pigs were fed 3 days of parenteral nutrition followed by 2 days of enteral formula. Immediately after birth, they were assigned to receive either antibiotics (oral and parenteral doses of gentamycin, ampicillin, and metronidazole, ANTI, n = 11) or saline in the control group (CON, n = 13), given twice daily. NEC lesions and intestinal structure, function, microbiology, and immunity markers were recorded. None of the ANTI but 85% of the CON pigs developed NEC lesions by day 5 (0/11 vs. 11/13, P < 0.05). ANTI pigs had higher intestinal villi (+60%), digestive enzyme activities (+53–73%), and goblet cell densities (+110%) and lower myeloperoxidase (−51%) and colonic microbial density (105 vs. 1010 colony-forming units, all P < 0.05). Microarray transcriptomics showed strong downregulation of genes related to inflammation and innate immune response to microbiota and marked upregulation of genes related to amino acid metabolism, in particular threonine, glucose transport systems, and cell cycle in 5-day-old ANTI pigs. In a follow-up experiment, 5 days of antibiotics prevented NEC at least until day 10. Neonatal prophylactic antibiotics effectively reduced gut bacterial load, prevented NEC, intestinal atrophy, dysfunction, and inflammation and enhanced expression of genes related to gut metabolism and immunity in preterm pigs. PMID:24157972

Use of probiotics in pediatric infectious diseases.

PubMed

Caffarelli, Carlo; Cardinale, Fabio; Povesi-Dascola, Carlotta; Dodi, Icilio; Mastrorilli, Violetta; Ricci, Giampaolo

2015-01-01

We summarize current evidence and recommendations for the use of probiotics in childhood infectious diseases. Probiotics may be of benefit in treating acute infectious diarrhea and reducing antibiotic-associated diarrhea. Potential benefits of probiotic on prevention of traveler's diarrhea,Clostridium difficile-associated diarrhea, side effects of triple therapy in Helicobacter pylori eradication, necrotizing enterocolitis, acute diarrhea, acute respiratory infections and recurrent urinary tract infections remain unclear. More studies are needed to investigate optimal strain, dosage, bioavailability of drops and tablets, duration of treatment and safety. Probiotics and recombinant probiotic strain represent a promising source of molecules for the development of novel anti-infectious therapy.

Sharing the science on human milk feedings with mothers of very-low-birth-weight infants.

PubMed

Rodriguez, Nancy A; Miracle, Donna J; Meier, Paula P

2005-01-01

Mother's milk provides protection from serious and costly morbidity for very-low-birth-weight infants (<1500 g), including enteral feeding intolerance, nosocomial infection, and necrotizing enterocolitis. However, NICU and maternity nurses may be hesitant to encourage mothers to initiate lactation because of a reluctance to make mothers feel guilty or coerced. This article reviews the evidence for the health outcomes of mothers' milk feeding in very-low-birth-weight infants and provides examples of ways to share this science with mothers so that they can make an informed feeding decision.

The Roles of Bacteria and TLR4 in Rat and Murine Models of Necrotizing Enterocolitis1

PubMed Central

Jilling, Tamas; Simon, Dyan; Lu, Jing; Meng, Fan Jing; Li, Dan; Schy, Robert; Thomson, Richard B.; Soliman, Antoine; Arditi, Moshe; Caplan, Michael S.

2009-01-01

Bacteria are thought to contribute to the pathogenesis of necrotizing enterocolitis (NEC), but it is unknown whether their interaction with the epithelium can participate in the initiation of mucosal injury or they can act only following translocation across a damaged intestinal barrier. Our aims were to determine whether bacteria and intestinal epithelial TLR4 play roles in a well-established neonatal rat model and a novel neonatal murine model of NEC. Neonatal rats, C57BL/6J, C3HeB/FeJ (TLR4 wild type), and C3H/HeJ (TLR4 mutant) mice were delivered by Cesarean section and were subjected to formula feeding and cold asphyxia stress or were delivered naturally and were mother-fed. NEC incidence was evaluated by histological scoring, and gene expression was quantified using quantitative real-time PCR from cDNA generated from intestinal total RNA or from RNA obtained by laser capture microdissection. Spontaneous feeding catheter colonization or supplementation of cultured bacterial isolates to formula increased the incidence of experimental NEC. During the first 72 h of life, i.e., the time frame of NEC development in this model, intestinal TLR4 mRNA gradually decreases in mother-fed but increases in formula feeding and cold asphyxia stress, correlating with induced inducible NO synthase. TLR4, inducible NO synthase, and inflammatory cytokine induction occurred in the intestinal epithelium but not in the submucosa. NEC incidence was diminished in C3H/HeJ mice, compared with C3HeB/FeJ mice. In summary, bacteria and TLR4 play significant roles in experimental NEC, likely via an interaction of intraluminal bacteria and aberrantly overexpressed TLR4 in enterocytes. PMID:16920968

Using a Mathematical Model to Analyze the Role of Probiotics and Inflammation in Necrotizing Enterocolitis

PubMed Central

Arciero, Julia C.; Ermentrout, G. Bard; Upperman, Jeffrey S.; Vodovotz, Yoram; Rubin, Jonathan E.

2010-01-01

Background Necrotizing enterocolitis (NEC) is a severe disease of the gastrointestinal tract of pre-term babies and is thought to be related to the physiological immaturity of the intestine and altered levels of normal flora in the gut. Understanding the factors that contribute to the pathology of NEC may lead to the development of treatment strategies aimed at re-establishing the integrity of the epithelial wall and preventing the propagation of inflammation in NEC. Several studies have shown a reduced incidence and severity of NEC in neonates treated with probiotics (beneficial bacteria species). Methodology/Principal Findings The objective of this study is to use a mathematical model to predict the conditions under which probiotics may be successful in promoting the health of infants suffering from NEC. An ordinary differential equation model is developed that tracks the populations of pathogenic and probiotic bacteria in the intestinal lumen and in the blood/tissue region. The permeability of the intestinal epithelial layer is treated as a variable, and the role of the inflammatory response is included. The model predicts that in the presence of probiotics health is restored in many cases that would have been otherwise pathogenic. The timing of probiotic administration is also shown to determine whether or not health is restored. Finally, the model predicts that probiotics may be harmful to the NEC patient under very specific conditions, perhaps explaining the detrimental effects of probiotics observed in some clinical studies. Conclusions/Significance The reduced, experimentally motivated mathematical model that we have developed suggests how a certain general set of characteristics of probiotics can lead to beneficial or detrimental outcomes for infants suffering from NEC, depending on the influences of probiotics on defined features of the inflammatory response. PMID:20419099

Probiotics feeding in prevention of urinary tract infection, bacterial sepsis and necrotizing enterocolitis in preterm infants. A prospective double-blind study.

PubMed

Dani, Carlo; Biadaioli, Roberto; Bertini, Giovanna; Martelli, Elena; Rubaltelli, Firmino F

2002-08-01

It has been suggested that probiotics can reduce the overgrowth of pathogens in the bowels of preterm infants and contribute to the reduction of the incidence of nosocomial infections in neonatal intensive care units (NICUs). The purpose of this study was to evaluate the effectiveness of Lactobacillus GG supplementation in reducing the incidence of urinary tract infections (UTIs), bacterial sepsis and necrotizing enterocolitis (NEC) in preterm infants. A double-blind study was conducted in 12 Italian NICUs. Newborn infants with a gestational age <33 weeks or birthweight <1,500 g were randomized to receive standard milk feed supplemented with Lactobacillus GG (Dicoflor), Dicofarm, Rome, Italy) in a dose of 6 x 10(9) colony-forming units (cfu) once a day until discharge, starting with the first feed or placebo. Five hundred eighty-five patients were studied. The probiotics group (n = 295) and the placebo group (n = 290) exhibited similar clinical characteristics. The duration of Lactobacillus GG and placebo supplementation was 47.3 +/- 26.0 and 48.2 +/- 24.3 days, respectively. Although UTIs (3.4 vs. 5.8%) and NEC (1.4 vs. 2.7%) were found less frequently in the probiotic group compared to the control group, these differences were not significant. Bacterial sepsis was more frequent in the probiotics group (4.4%, n = 11) than in the placebo group (3.8%, n = 9), but the difference was not significant. Seven days of Lactobacillus GG supplementation starting with the first feed is not effective in reducing the incidence of UTIs, NEC and sepsis in preterm infants. Further studies are required to confirm our results in lower birthweight populations. Copyright 2002 S. Karger AG, Basel

Beyond Necrotizing Enterocolitis Prevention: Improving Outcomes with an Exclusive Human Milk-Based Diet.

PubMed

Hair, Amy B; Peluso, Allison M; Hawthorne, Keli M; Perez, Jose; Smith, Denise P; Khan, Janine Y; O'Donnell, Andrea; Powers, Richard J; Lee, Martin L; Abrams, Steven A

2016-03-01

The aim of this study was to compare outcomes of infants pre and post initiation of a feeding protocol providing an exclusive human milk-based diet (HUM). In a multicenter retrospective cohort study, infants with a birth weight <1,250 g who received a bovine-based diet (BOV) of mother's own milk fortified with bovine fortifier and/or preterm formula were compared to infants who received a newly introduced HUM feeding protocol. Infants were excluded if they had major congenital anomalies or died in the first 12 hours of life. Data were collected 2-3 years prior to and after introduction of an exclusive HUM diet. Primary outcomes were necrotizing enterocolitis (NEC) and mortality. Secondary outcomes included late-onset sepsis, retinopathy of prematurity (ROP), and bronchopulmonary dysplasia (BPD). A total of 1,587 infants were included from four centers in Texas, Illinois, Florida, and California. There were no differences in baseline demographics or growth of infants. The HUM group had significantly lower incidence of proven NEC (16.7% versus 6.9%, p < 0.00001), mortality (17.2% versus 13.6%, p = 0.04), late-onset sepsis (30.3% versus 19.0%, p < 0.00001), ROP (9% versus 5.2%, p = 0.003), and BPD (56.3% versus 47.7%, p = 0.0015) compared with the BOV group. Extremely premature infants who received an exclusive HUM diet had a significantly lower incidence of NEC and mortality. The HUM group also had a reduction in late-onset sepsis, BPD, and ROP. This multicenter study further emphasizes the many benefits of an exclusive HUM diet, and demonstrates multiple improved outcomes after implementation of such a feeding protocol.

Outcomes of Extremely Preterm Infants Born to Insulin-Dependent Diabetic Mothers

PubMed Central

Boghossian, Nansi S.; Hansen, Nellie I.; Brumbaugh, Jane E.; Stoll, Barbara J.; Laptook, Abbot R.; Shankaran, Seetha; Wyckoff, Myra H.; Colaizy, Tarah T.; Das, Abhik; Higgins, Rosemary D.

2016-01-01

BACKGROUND AND OBJECTIVE: Little is known about in-hospital morbidities and neurodevelopmental outcomes among extremely preterm infants born to women with insulin-dependent diabetes mellitus (IDDM). We examined risks of mortality, in-hospital morbidities, and neurodevelopmental outcomes at 18 to 22 months’ corrected age between extremely preterm infants of women with insulin use before pregnancy (IBP), with insulin use started during pregnancy (IDP), and without IDDM. METHODS: Infants 22 to 28 weeks’ gestation born or cared for at a Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network center (2006–2011) were studied. Regression models compared the association between maternal IDDM and timing of insulin use and the outcomes of the 3 groups. RESULTS: Of 10 781 infants, 536 (5%) were born to women with IDDM; 58% had IBP, and 36% had IDP. Infants of mothers with IBP had higher risks of necrotizing enterocolitis (adjusted relative risk [RR] = 1.55 [95% confidence interval (CI) 1.17–2.05]) and late-onset sepsis (adjusted RR = 1.26 [95% CI 1.07–1.48]) than infants of mothers without IDDM. There was some indication of higher in-hospital mortality risk among infants of mothers with IBP compared with those with IDP (adjusted RR = 1.33 [95% CI 1.00–1.79]). Among survivors evaluated at 18 to 22 months’ corrected age, average head circumference z score was lower for infants of mothers with IBP compared with those without IDDM, but there were no differences in risk of neurodevelopmental impairment. CONCLUSIONS: In this cohort of extremely preterm infants, infants of mothers with IBP had higher risks of necrotizing enterocolitis, sepsis, and small head circumference. PMID:27244849

Hemodynamic and permeability characteristics of acute experimental necrotizing enterocolitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, M.J.; Adams, J.; Gu, X.A.

1990-10-01

We examined the local hemodynamic response of intestinal loops during acute necrotizing enterocolitis (NEC) in anesthetized rabbits. NEC was induced in ileal loops by transmural injection of a solution containing casein (10 mg/ml) and calcium gluconate (50 mg/ml) acidified to pH 4.0 with propionic or acetic acid. Control loops received casein only (pH 5.0). Mucosal damage was quantified by the blood-to-lumen movement of (51Cr)EDTA, fluid shifts into the lumen, and histology. Mean arterial pressure and loop blood flow were steady over the 3-hr period, loop fluid volume decreased, and there was no evidence of necrosis or epithelial damage. In loopsmore » receiving acidified casein and calcium gluconate, there was an immediate dramatic increase in loop blood flow that returned to baseline by 50 min. In addition, loop fluid volume was dramatically increased, necrosis was noted in the form of blunting and loss of villi, and sevenfold increase in (51Cr)EDTA permeability was evident. Administration of CV 1808 (30 mg/kg/hr), a selective adenosine2 agonist, which maintained and elevated loop blood flow throughout the 3 hr protocol, failed to alter the changes in loop fluid volume or prevent necrosis. Histamine levels in loop fluid levels were significantly elevated 20-30 min after NEC induction when compared to saline controls, indicating an early activation of mucosal defenses with this luminal insult. Thus, this model of NEC is characterized by a transient, acute hyperemia, increased intestinal permeability, and histamine release. As mucosal damage was independent of ischemia and could not be prevented by vasodilatory therapy, this model supports the clinical findings that NEC is correlated with luminal factors related to feeding and independent of cardiovascular stress.« less

Patent Ductus Arteriosus Therapy: Impact on Neonatal and 18-Month Outcome

PubMed Central

Madan, Juliette C.; Kendrick, Douglas; Hagadorn, James I.; Frantz, Ivan D.

2009-01-01

OBJECTIVE The purpose of this work was to evaluate therapy for patent ductus arteri-osus as a risk factor for death or neurodevelopmental impairment at 18 to 22 months, bronchopulmonary dysplasia, or necrotizing enterocolitis in extremely low birth weight infants. METHODS We studied infants in the National Institute of Child Health and Human Development Neonatal Research Network Generic Data Base born between 2000 and 2004 at 23 to 28 weeks’ gestation and at <1000-g birth weight with patent ductus arteriosus. Patent ductus arteriosus therapy was evaluated as a risk factor for outcomes in bivariable and multivariable analyses. RESULTS Treatment for subjects with patent ductus arteriosus (n = 2838) included 403 receiving supportive treatment only, 1525 treated with indomethacin only, 775 with indomethacin followed by secondary surgical closure, and 135 treated with primary surgery. Patients who received supportive therapy for patent ductus arteriosus did not differ from subjects treated with indomethacin only for any of the outcomes of interest. Compared with indomethacin treatment only, patients undergoing primary or secondary surgery were smaller and more premature. When compared with indomethacin alone, primary surgery was associated with increased adjusted odds for neurodevelopmental impairment and bronchopulmonary dysplasia in multivariable logistic regression. Secondary surgical closure was associated with increased odds for neurodevelopmental impairment and increased adjusted odds for bronchopulmonary dysplasia but decreased adjusted odds for death. Risk of necrotizing enterocolitis did not differ among treatments. Indomethacin prophylaxis did not significantly modify these results. CONCLUSIONS Our results suggest that infants treated with primary or secondary surgery for patent ductus arteriosus may be at increased risk for poor short- and long-term outcomes compared with those treated with indomethacin. Prophylaxis with indomethacin in the first 24 hours of life did not modify the subsequent outcomes of patent ductus arteriosus therapy. PMID:19171637

Lactobacillus rhamnosus HN001 decreases the severity of necrotizing enterocolitis in neonatal mice and preterm piglets: evidence in mice for a role of TLR9

PubMed Central

Good, Misty; Sodhi, Chhinder P.; Ozolek, John A.; Buck, Rachael H.; Goehring, Karen C.; Thomas, Debra L.; Vikram, Amit; Bibby, Kyle; Morowitz, Michael J.; Firek, Brian; Lu, Peng

2014-01-01

Necrotizing enterocolitis (NEC) is the leading cause of death from gastrointestinal disease in premature infants and develops partly from an exaggerated intestinal epithelial immune response to indigenous microbes. There has been interest in administering probiotic bacteria to reduce NEC severity, yet concerns exist regarding infection risk. Mechanisms of probiotic activity in NEC are unknown although activation of the microbial DNA receptor Toll-like receptor-9 (TLR9) has been postulated. We now hypothesize that the Gram-positive bacterium Lactobacillus rhamnosus HN001 can attenuate NEC in small and large animal models, that its microbial DNA is sufficient for its protective effects, and that protection requires activation of the Toll-like receptor 9 (TLR9). We now show that oral administration of live or UV-inactivated Lactobacillus rhamnosus HN001 attenuates NEC severity in newborn mice and premature piglets, as manifest by reduced histology score, attenuation of mucosal cytokine response, and improved gross morphology. TLR9 was required for Lactobacillus rhamnosus-mediated protection against NEC in mice, as the selective decrease of TLR9 from the intestinal epithelium reversed its protective effects. Strikingly, DNA of Lactobacillus rhamnosus HN001 reduced the extent of proinflammatory signaling in cultured enterocytes and in samples of resected human ileum ex vivo, suggesting the therapeutic potential of this probiotic in clinical NEC. Taken together, these findings illustrate that Lactobacillus rhamnosus HN001 is an effective probiotic for NEC via activation of the innate immune receptor TLR9 and that Lactobacillus rhamnosus DNA is sufficient for its protective effects, potentially reducing concerns regarding the infectious risk of this novel therapeutic approach. PMID:24742987

Impact of umbilical cord milking and pasteurized donor human milk on necrotizing enterocolitis: a retrospective review.

PubMed

Sekhon, Mehtab K; Yoder, Bradley A

2018-05-08

Necrotizing enterocolitis (NEC) is a serious complication of prematurity. Our objective was to evaluate the impact of an umbilical cord milking protocol (UCM) and pasteurized donor human milk (PDHM) on NEC rates in infants less than 30 weeks gestational age from January 1, 2010 to September 30, 2016. We hypothesized an incremental decrease in NEC after each intervention. We performed a retrospective review of 638 infants born less than 30 weeks gestational age. Infants were grouped into three epochs: pre-UCM/pre-PDHM (Epoch 1, n = 159), post-UCM/pre-PDHM (Epoch 2, n = 133), and post-UCM/post-PDHM (Epoch 3, n = 252). The incidence of NEC, surgical NEC, and NEC/death were compared. Logistic regression was used to determine independent significance of time epoch, gestational age, birth weight, and patent ductus arteriosus for NEC, surgical NEC, and death/NEC. At birth, infants in Epoch 1 were younger than Epoch 2 and 3 (26.8 weeks versus 27.3 and 27.2, respectively, P = 0.036) and smaller (910 g versus 1012 and 983, respectively, P = 0.012). Across epochs, there was a significant correlation between patent ductus arteriosus treatment and NEC rate (P < 0.001, Cochran-Mantel-Haenszel). There was a significant decrease in rates of NEC, surgical NEC, and NEC/death between groups. Logistic regression showed this as significant for rates of NEC and surgical NEC between Epoch 1 and 3. Patent ductus arteriosus was a significant variable affecting the incidence of NEC, but not surgical NEC or death/NEC. An umbilical cord milking protocol and pasteurized donor human milk availability was associated with decreased rates of NEC and surgical NEC. This suggests an additive effect of these interventions in preventing NEC.

Enteral but not parenteral antibiotics enhance gut function and prevent necrotizing enterocolitis in formula-fed newborn preterm pigs.

PubMed

Birck, Malene M; Nguyen, Duc Ninh; Cilieborg, Malene S; Kamal, Shamrulazhar S; Nielsen, Dennis S; Damborg, Peter; Olsen, John E; Lauridsen, Charlotte; Sangild, Per T; Thymann, Thomas

2016-03-01

Preterm infants are susceptible to infection and necrotizing enterocolitis (NEC) and are often treated with antibiotics. Simultaneous administration of enteral and parenteral antibiotics during the first days after preterm birth prevents formula-induced NEC lesions in pigs, but it is unknown which administration route is most effective. We hypothesized that only enteral antibiotics suppress gut bacterial colonization and NEC progression in formula-fed preterm pigs. Caesarean-delivered preterm pigs (90-92% of gestation) were fed increasing amounts of infant formula from birth to day 5 and given saline (CON) or antibiotics (ampicillin, gentamicin, and metronidazole) via the enteral (ENT) or parenteral (PAR) route (n = 16-17). NEC lesions, intestinal morphology, function, microbiology, and inflammatory mediators were evaluated. NEC lesions were completely prevented in ENT pigs, whereas there were high incidences of mild NEC lesions (59-63%) in CON and PAR pigs (P < 0.001). ENT pigs had elevated intestinal weight, villus height/crypt depth ratio, and goblet cell density and reduced gut permeability, mucosal adherence of bacteria, IL-8 levels, colonic lactic acid levels, and density of Gram-positive bacteria, relative to CON pigs (P < 0.05). Values in PAR pigs were intermediate with few affected parameters (reduced lactic acid levels and density and adherence of Gram-positive bacteria, relative to CON pigs, P < 0.05). There was no evidence of increased antimicrobial resistance following the treatments. We conclude that enteral, but not parenteral, administration of antibiotics reduces gut bacterial colonization, inflammation, and NEC lesions in newborn, formula-fed preterm pigs. Delayed colonization may support intestinal structure, function, and immunity in the immediate postnatal period of formula-fed preterm neonates. Copyright © 2016 the American Physiological Society.

Cost savings of human milk as a strategy to reduce the incidence of necrotizing enterocolitis in very low birth weight infants.

PubMed

Johnson, Tricia J; Patel, Aloka L; Bigger, Harold R; Engstrom, Janet L; Meier, Paula P

2015-01-01

Necrotizing enterocolitis (NEC) is a costly morbidity in very low birth weight (VLBW; <1,500 g birth weight) infants that increases hospital length of stay and requires expensive treatments. To evaluate the cost of NEC as a function of dose and exposure period of human milk (HM) feedings received by VLBW infants during the neonatal intensive care unit (NICU) hospitalization and determine the drivers of differences in NICU hospitalization costs for infants with and without NEC. This study included 291 VLBW infants enrolled in an NIH-funded prospective observational cohort study between February 2008 and July 2012. We examined the incidence of NEC, NICU hospitalization cost, and cost of individual resources used during the NICU hospitalization. Twenty-nine (10.0%) infants developed NEC. The average total NICU hospitalization cost (in 2012 USD) was USD 180,163 for infants with NEC and USD 134,494 for infants without NEC (p = 0.024). NEC was associated with a marginal increase in costs of USD 43,818, after controlling for demographic characteristics, risk of NEC, and average daily dose of HM during days 1-14 (p < 0.001). Each additional ml/kg/day of HM during days 1-14 decreased non-NEC-related NICU costs by USD 534 (p < 0.001). Avoidance of formula and use of exclusive HM feedings during the first 14 days of life is an effective strategy to reduce the risk of NEC and resulting NICU costs in VLBW infants. Hospitals investing in initiatives to feed exclusive HM during the first 14 days of life could substantially reduce NEC-related NICU hospitalization costs. © 2015 S. Karger AG, Basel.

Resuscitation With 100% Oxygen Causes Intestinal Glutathione Oxidation and Reoxygenation Injury in Asphyxiated Newborn Piglets

PubMed Central

Haase, Erika; Bigam, David L.; Nakonechny, Quentin B.; Jewell, Laurence D.; Korbutt, Gregory; Cheung, Po-Yin

2004-01-01

Objective: To compare mesenteric blood flow, oxidative stress, and mucosal injury in piglet small intestine during hypoxemia and reoxygenation with 21%, 50%, or 100% oxygen. Summary Background Data: Necrotizing enterocolitis is a disease whose pathogenesis likely involves hypoxia-reoxygenation and the generation of oxygen-free radicals, which are known to cause intestinal injury. Resuscitation of asphyxiated newborns with 100% oxygen has been shown to increase oxidative stress, as measured by the glutathione redox ratio, and thus may predispose to free radical-mediated tissue injury. Methods: Newborn piglets subjected to severe hypoxemia for 2 hours were resuscitated with 21%, 50%, or 100% oxygen while superior mesenteric artery (SMA) flow and hemodynamic parameters were continuously measured. Small intestinal tissue samples were analyzed for histologic injury and levels of oxidized and reduced glutathione. Results: SMA blood flow decreased to 34% and mesenteric oxygen delivery decreased to 9% in hypoxemic piglets compared with sham-operated controls. With reoxygenation, SMA blood flow increased to 177%, 157%, and 145% of baseline values in piglets resuscitated with 21%, 50%, and 100% oxygen, respectively. Mesenteric oxygen delivery increased to more than 150% of baseline values in piglets resuscitated with 50% or 100% oxygen, and this correlated significantly with the degree of oxidative stress, as measured by the oxidized-to-reduced glutathione ratio. Two of eight piglets resuscitated with 100% oxygen developed gross and microscopic evidence of pneumatosis intestinalis and severe mucosal injury, while all other piglets were grossly normal. Conclusions: Resuscitation of hypoxemic newborn piglets with 100% oxygen is associated with an increase in oxygen delivery and oxidative stress, and may be associated with the development of small intestinal hypoxia-reoxygenation injury. Resuscitation of asphyxiated newborns with lower oxygen concentrations may help to decrease the risk of necrotizing enterocolitis. PMID:15273563

Brain injury and altered brain growth in preterm infants: predictors and prognosis.

PubMed

Kidokoro, Hiroyuki; Anderson, Peter J; Doyle, Lex W; Woodward, Lianne J; Neil, Jeffrey J; Inder, Terrie E

2014-08-01

To define the nature and frequency of brain injury and brain growth impairment in very preterm (VPT) infants by using MRI at term-equivalent age and to relate these findings to perinatal risk factors and 2-year neurodevelopmental outcomes. MRI scans at term-equivalent age from 3 VPT cohorts (n = 325) were reviewed. The severity of brain injury, including periventricular leukomalacia and intraventricular and cerebellar hemorrhage, was graded. Brain growth was assessed by using measures of biparietal width (BPW) and interhemispheric distance. Neurodevelopmental outcome at age 2 years was assessed across all cohorts (n = 297) by using the Bayley Scales of Infant Development, Second Edition (BSID-II) or Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), and evaluation for cerebral palsy. Of 325 infants, 107 (33%) had some grade of brain injury and 33 (10%) had severe injury. Severe brain injury was more common in infants with lower Apgar scores, necrotizing enterocolitis, inotropic support, and patent ductus arteriosus. Severe brain injury was associated with delayed cognitive and motor development and cerebral palsy. Decreased BPW was related to lower gestational age, inotropic support, patent ductus arteriosus, necrotizing enterocolitis, prolonged parenteral nutrition, and oxygen at 36 weeks and was associated with delayed cognitive development. In contrast, increased interhemispheric distance was related to male gender, dexamethasone use, and severe brain injury. It was also associated with reduced cognitive development, independent of BPW. At term-equivalent age, VPT infants showed both brain injury and impaired brain growth on MRI. Severe brain injury and impaired brain growth patterns were independently associated with perinatal risk factors and delayed cognitive development. Copyright © 2014 by the American Academy of Pediatrics.

Intestinal alkaline phosphatase to treat necrotizing enterocolitis.

PubMed

Biesterveld, Ben E; Koehler, Shannon M; Heinzerling, Nathan P; Rentea, Rebecca M; Fredrich, Katherine; Welak, Scott R; Gourlay, David M

2015-06-15

Intestinal alkaline phosphatase (IAP) activity is decreased in necrotizing enterocolitis (NEC), and IAP supplementation prevents NEC development. It is not known if IAP given after NEC onset can reverse the course of the disease. We hypothesized that enteral IAP given after NEC induction would not reverse intestinal injury. NEC was induced in Sprague-Dawley pups by delivery preterm followed by formula feedings with lipopolysaccharide (LPS) and hypoxia exposure and continued up to 4 d. IAP was added to feeds on day 2 until being sacrificed on day 4. NEC severity was scored based on hematoxylin and eosin-stained terminal ileum sections, and AP activity was measured using a colorimetric assay. IAP and interleukin-6 expression were measured using real time polymerase chain reaction. NEC pups' alkaline phosphatase (AP) activity was decreased to 0.18 U/mg compared with controls of 0.57 U/mg (P < 0.01). Discontinuation of LPS and hypoxia after 2 d increased AP activity to 0.36 U/mg (P < 0.01). IAP supplementation in matched groups did not impact total AP activity or expression. Discontinuing LPS and hypoxia after NEC onset improved intestinal injury scores to 1.14 compared with continued stressors, score 2.25 (P < 0.01). IAP supplementation decreased interleukin-6 expression two-fold (P < 0.05), though did not reverse NEC intestinal damage (P = 0.5). This is the first work to demonstrate that removing the source of NEC improves intestinal damage and increases AP activity. When used as a rescue treatment, IAP decreased intestinal inflammation though did not impact injury making it likely that IAP is best used preventatively to those neonates at risk. Copyright © 2015 Elsevier Inc. All rights reserved.

The Mediterranean diet adherence by pregnant women delivering prematurely: association with size at birth and complications of prematurity.

PubMed

Parlapani, Elisavet; Agakidis, Charalampos; Karagiozoglou-Lampoudi, Thomais; Sarafidis, Kosmas; Agakidou, Eleni; Athanasiadis, Apostolos; Diamanti, Elisavet

2017-11-13

The Mediterranean diet (MD) is associated with decreased risk of metabolic syndrome and gestational diabetes due to the anti-inflammatory and antioxidative properties of its components. The aim was to investigate the potential association of MD adherence (MDA) during pregnancy by mothers delivering prematurely, with intrauterine growth as expressed by neonates' anthropometry at birth and complications of prematurity. This is a single-center, prospective, observational cohort study of 82 women who delivered preterm singletons at post conceptional age (PCA) ≤ 34 weeks and their live-born neonates. Maternal and neonatal demographic and clinical data were recorded. All mothers filled in a food frequency questionnaire, and the MDA score was calculated. Based on 50th centile of MD score, participants were classified into high-MDA and low-MDA groups. The low-MDA mothers had significantly higher pregestational BMI and rates of overweight/obesity (odd ratios (OR) 3.5) and gestational hypertension/preeclampsia (OR 3.8). Neonates in the low-MDA group had significantly higher incidence of intrauterine growth restriction (IUGR) (OR 3.3) and lower z-scores of birth weight and BMI. Regarding prematurity-related complications, the low MDA-group was more likely to develop necrotizing enterocolitis, bronchopulmonary dysplasia, and retinopathy of prematurity (OR 3.2, 1.3, and 1.6, respectively), while they were less likely to develop respiratory distress syndrome (OR 0.49), although the differences were not statistically significant. However, adjustment for confounders revealed MDA as a significant independent predictor of hypertension/preeclampsia, IUGR, birth weight z-score, necrotizing enterocolitis, and bronchopulmonary dysplasia. High MDA during pregnancy may favorably affect intrauterine growth and certain acute and chronic complications of prematurity as well as maternal hypertension/preeclampsia.

Antioxidant capacity and oxygen radical diseases in the preterm newborn.

PubMed

Rogers, S; Witz, G; Anwar, M; Hiatt, M; Hegyi, T

2000-06-01

Bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, and retinopathy of prematurity may be different manifestations of oxygen radical diseases of prematurity (ORDP). To test the hypothesis that the antioxidant capacity of cord blood serum will predict risk of ORDP. An inception cohort of premature neonates was followed up from birth until discharge or death to determine if outcome was related to cord blood serum antioxidant capacity, as determined by a manual assay measuring the relative inhibition of oxidation of 2,2'-azino-di-(3-ethylbenzthiazoline)-6 sulfonic acid (ABTS). Possible correlations between antioxidant capacity and various perinatal factors were also tested. Level 3 newborn intensive care unit. All inborn very low-birth-weight neonates from whom cord blood was available and for whom maternal consent was obtained were included. Newborns who died in the first week of life or who had major congenital malformations were excluded. A convenience sample of newborns weighing more than 1500 g was used to perfect assay and explore confounders. Significant ORDP was defined as the presence of intraventricular hemorrhage greater than grade 2, retinopathy of prematurity greater than stage 1, bronchopulmonary dysplasia at the postconceptional age of 36 weeks, or necrotizing enterocolitis with the hypothesis that neonates with ORDP will have lower antioxidant capacity in cord blood serum. Serum antioxidant capacity at birth correlated with gestational age for the entire sample of 41 neonates and for the 26 neonates born before 32 weeks' gestation. After correction for gestational age, cord serum antioxidant capacity did not correlate with maternal smoking, preeclampsia, chorioamnionitis, cord pH Apgar scores, or any of the ORDP studied. Cord serum antioxidant capacity correlates with gestational age but does not predict ORDP risk.

Cost Savings of Human Milk as a Strategy to Reduce the Incidence of Necrotizing Enterocolitis in Very Low Birth Weight Infants

PubMed Central

Johnson, Tricia J.; Patel, Aloka L.; Bigger, Harold R.; Engstrom, Janet L.; Meier, Paula P.

2015-01-01

Background Necrotizing enterocolitis (NEC) is a costly morbidity in very low birth weight (VLBW; <1500g birth weight) infants that increases hospital length of stay and requires expensive treatments. Objectives To evaluate the cost of NEC as a function of dose and exposure period of human milk (HM) feedings received by VLBW infants during the neonatal intensive care unit (NICU) hospitalization and determine the drivers of differences in NICU hospitalization costs for infants with and without NEC. Methods This study included 291 VLBW infants enrolled in an NIH-funded prospective observational cohort study between February 2008 and July 2012. We examined the incidence of NEC, NICU hospitalization cost, and cost of individual resources used during the NICU hospitalization. Results Twenty-nine (10.0%) infants developed NEC. The average total NICU hospitalization cost (in 2012 dollars) was $180,163 for infants with NEC and $134,494 for infants without NEC (p=0.024). NEC was associated with a marginal increase in costs of $43,818, after controlling for demographic characteristics, risk of NEC and average daily dose of HM during Days 1–14 (p<0.001). Each additional mL/kg/day of HM during Days 1–14 decreased non-NEC-related NICU costs by $534 (p<0.001). Conclusions Avoidance of formula and use of exclusive HM feedings during the first 14 days of life is an effective strategy to reduce the risk of NEC and resulting NICU costs in VLBW infants. Hospitals investing in initiatives to feed exclusive HM during the first 14 days of life could substantially reduce NEC-related NICU hospitalization costs. PMID:25765818

Risk Factors for Retinopathy of Prematurity: Insights from Outlier Infants

PubMed Central

Port, Alexander D.; Chan, R.V. Paul; Ostmo, Susan; Choi, Dongseok; Chiang, Michael F.

2014-01-01

Purpose To investigate the characteristics of outlier infants for insights into ROP risk. Methods Chart data were collected from 1354 infants screened for ROP at Weill Cornell Medical Center and Columbia University Medical Center. ROP exam results and clinical risk factors were recorded. The cohort was stratified by weight, highest ROP stage, and need for ROP treatment. Descriptive and correlational statistics were performed. Results For the overall cohort, regression analysis found that birth weight (OR: 0.741 per 100g; 95% CI: 0.606, 0.905), gestational age at birth (OR: 0.563 per week; 95% CI: 0.454, 0.697), multiple gestation (OR 2.02, 95% CI: 1.15, 3.56), bronchopulmonary dysplasia (OR: 4.68, 95% CI: 1.93, 11.35), and necrotizing enterocolitis (OR 2.80, 95% CI: 1.40, 5.16) were independent risk factors for treatment-requiring ROP. Black race was found to be a protective factor for treatment-requiring ROP (OR 0.244, 95% CI: 0.095, 0.626). Among 15 infants with BW <500g, there were no significant differences in any clinical risk factors between the 12 (80%) with ROP vs. the 3 (20%) without ROP. Similarly, among infants with BW >1500g, the 17 (9%) with ROP only differed from the 166 (91%) without ROP with respect to a higher incidence of necrotizing enterocolitis among those with ROP (11.8% vs 0%). Conclusions Although known clinical risk factors were predictive of ROP stage and need for laser treatment in this cohort, they were not significantly associated with ROP at extremes of birth weight. This suggests that other clinical, maternal, or genetic factors may protect from or predispose to ROP. PMID:25053346

Risk factors for retinopathy of prematurity: insights from outlier infants.

PubMed

Port, Alexander D; Chan, R V Paul; Ostmo, Susan; Choi, Dongseok; Chiang, Michael F

2014-10-01

To investigate the characteristics of outlier infants for insights into ROP risk. Chart data were collected from 1,354 infants screened for ROP at Weill Cornell Medical Center and Columbia University Medical Center. ROP exam results and clinical risk factors were recorded. The cohort was stratified by weight, highest ROP stage, and need for ROP treatment. Descriptive and correlational statistics were performed. For the overall cohort, regression analysis found that birth weight (OR: 0.741 per 100 g; 95 % CI: 0.606, 0.905), gestational age at birth (OR: 0.563 per week; 95 % CI: 0.454, 0.697), multiple gestation (OR 2.02, 95 % CI: 1.15, 3.56), bronchopulmonary dysplasia (OR: 4.68, 95 % CI: 1.93, 11.35), and necrotizing enterocolitis (OR 2.80, 95 % CI: 1.40, 5.16) were independent risk factors for treatment-requiring ROP. Black race was found to be a protective factor for treatment-requiring ROP (OR 0.244, 95 % CI: 0.095, 0.626). Among 15 infants with BW <500 g, there were no significant differences in any clinical risk factors between the 12 (80 %) with ROP vs the three (20 %) without ROP. Similarly, among infants with BW >1500 g, the 17 (9 %) with ROP only differed from the 166 (91 %) without ROP with respect to a higher incidence of necrotizing enterocolitis among those with ROP (11.8 % vs 0 %). Although known clinical risk factors were predictive of ROP stage and need for laser treatment in this cohort, they were not significantly associated with ROP at extremes of birth weight. This suggests that other clinical, maternal, or genetic factors may protect from or predispose to ROP.

Impact of Optimized Breastfeeding on the Costs of Necrotizing Enterocolitis in Extremely Low Birthweight Infants.

PubMed

Colaizy, Tarah T; Bartick, Melissa C; Jegier, Briana J; Green, Brittany D; Reinhold, Arnold G; Schaefer, Andrew J; Bogen, Debra L; Schwarz, Eleanor Bimla; Stuebe, Alison M

2016-08-01

To estimate risk of necrotizing enterocolitis (NEC) for extremely low birth weight (ELBW) infants as a function of preterm formula (PF) and maternal milk intake and calculate the impact of suboptimal feeding on the incidence and costs of NEC. We used aORs derived from the Glutamine Trial to perform Monte Carlo simulation of a cohort of ELBW infants under current suboptimal feeding practices, compared with a theoretical cohort in which 90% of infants received at least 98% human milk. NEC incidence among infants receiving ≥98% human milk was 1.3%; 11.1% among infants fed only PF; and 8.2% among infants fed a mixed diet (P = .002). In adjusted models, compared with infants fed predominantly human milk, we found an increased risk of NEC associated with exclusive PF (aOR = 12.1, 95% CI 1.5, 94.2), or a mixed diet (aOR 8.7, 95% CI 1.2-65.2). In Monte Carlo simulation, current feeding of ELBW infants was associated with 928 excess NEC cases and 121 excess deaths annually, compared with a model in which 90% of infants received ≥98% human milk. These models estimated an annual cost of suboptimal feeding of ELBW infants of $27.1 million (CI $24 million, $30.4 million) in direct medical costs, $563 655 (CI $476 191, $599 069) in indirect nonmedical costs, and $1.5 billion (CI $1.3 billion, $1.6 billion) in cost attributable to premature death. Among ELBW infants, not being fed predominantly human milk is associated with an increased risk of NEC. Efforts to support milk production by mothers of ELBW infants may prevent infant deaths and reduce costs. Copyright © 2016 Elsevier Inc. All rights reserved.

Preventing necrotizing enterocolitis by food additives in neonates: A network meta-analysis revealing the efficacy and safety.

PubMed

Yu, Wentao; Sui, Wu; Mu, Linsong; Yi, Wenying; Li, Haijuan; Wei, Liqin; Yin, Weihong

2017-05-01

Necrotizing enterocolitis (NEC) is a serious multifactorial gastrointestinal disease which is often discovered in premature infants. Various additives have been used to prevent NEC; yet, their relative efficacy and safety remain disputed. This study aims to compare the efficacy and safety of 5 food additives, namely, probiotics, probiotics + fructo-oligosaccharides, pentoxifylline, arginine, and lactoferrin in preventing NEC in neonates. Embase, PubMed, and Cochrane Library had been searched for all eligible randomized control trials. Odds ratios (ORs) were estimated for dichotomous data and mean differences with 95% credible intervals (CrIs) were estimated for continuous data. Surface under the cumulative ranking curve was used to rank efficacy and safety of the prevention methods on each endpoint. A total of 27 eligible studies with 4649 preterm infants were included in this network meta-analysis (NMA), and the efficacy and safety of 5 food additives were evaluated. Probiotic and arginine exhibited better preventive efficacy compared with placebo (OR = 0.50, 95% CrIs: 0.32-0.73; OR = 0.30, 95% CrIs: 0.12-0.73, respectively). Only probiotic achieved a considerable decrease in the risk of mortality compared to placebo (OR = 0.68, 95% CrIs: 0.46-0.98). NEC patients with lactoferrin appeared to have lower incidence of sepsis than those of placebo (OR = 0.13, 95% CrIs: 0.03-0.61) or probiotic (OR = 0.18, 95% CrIs: 0.03-0.83). Based on this NMA, probiotics had the potential to be the most preferable additive, since it exhibited a significant superiority for NEC and mortality as well as a relatively balanced performance in safety.

Outcomes of Preterm Infants following Discussions about Withdrawal or Withholding of Life Support.

PubMed

James, Jennifer; Munson, David; DeMauro, Sara B; Langer, John C; Dworetz, April R; Natarajan, Girija; Bidegain, Margarita; Fortney, Christine A; Seabrook, Ruth; Vohr, Betty R; Tyson, Jon E; Bell, Edward F; Poindexter, Brenda B; Shankaran, Seetha; Higgins, Rosemary D; Das, Abhik; Stoll, Barbara J; Kirpalani, Haresh

2017-11-01

To describe the frequency of postnatal discussions about withdrawal or withholding of life-sustaining therapy (WWLST), ensuing WWLST, and outcomes of infants surviving such discussions. We hypothesized that such survivors have poor outcomes. This retrospective review included registry data from 18 centers of the National Institute of Child Health and Human Development Neonatal Research Network. Infants born at 22-28 weeks of gestation who survived >12 hours during 2011-2013 were included. Regression analysis identified maternal and infant factors associated with WWLST discussions and factors predicting ensuing WWLST. In-hospital and 18- to 26-month outcomes were evaluated. WWLST discussions occurred in 529 (15.4%) of 3434 infants. These were more frequent at 22-24 weeks (27.0%) compared with 27-28 weeks of gestation (5.6%). Factors associated with WWLST discussion were male sex, gestational age (GA) of ≤24 weeks, birth weight small for GA, congenital malformations or syndromes, early onset sepsis, severe brain injury, and necrotizing enterocolitis. Rates of WWLST discussion varied by center (6.4%-29.9%) as did WWLST (5.2%-20.7%). Ensuing WWLST occurred in 406 patients; of these, 5 survived to discharge. Of the 123 infants for whom intensive care was continued, 58 (47%) survived to discharge. Survival after WWLST discussion was associated with higher rates of neonatal morbidities and neurodevelopmental impairment compared with babies for whom WWLST discussions did not occur. Significant predictors of ensuing WWLST were maternal age >25 years, necrotizing enterocolitis, and days on a ventilator. Wide center variations in WWLST discussions occur, especially at ≤24 weeks GA. Outcomes of infants surviving after WWLST discussions are poor. ClinicalTrials.gov: NCT00063063. Copyright © 2017 Elsevier Inc. All rights reserved.

Toll-like Receptor 4-mediated Endoplasmic Reticulum Stress in Intestinal Crypts Induces Necrotizing Enterocolitis*

PubMed Central

Afrazi, Amin; Branca, Maria F.; Sodhi, Chhinder P.; Good, Misty; Yamaguchi, Yukihiro; Egan, Charlotte E.; Lu, Peng; Jia, Hongpeng; Shaffiey, Shahab; Lin, Joyce; Ma, Congrong; Vincent, Garrett; Prindle, Thomas; Weyandt, Samantha; Neal, Matthew D.; Ozolek, John A.; Wiersch, John; Tschurtschenthaler, Markus; Shiota, Chiyo; Gittes, George K.; Billiar, Timothy R.; Mollen, Kevin; Kaser, Arthur; Blumberg, Richard; Hackam, David J.

2014-01-01

The cellular cues that regulate the apoptosis of intestinal stem cells (ISCs) remain incompletely understood, yet may play a role in diseases characterized by ISC loss including necrotizing enterocolitis (NEC). Toll-like receptor-4 (TLR4) was recently found to be expressed on ISCs, where its activation leads to ISC apoptosis through mechanisms that remain incompletely explained. We now hypothesize that TLR4 induces endoplasmic reticulum (ER) stress within ISCs, leading to their apoptosis in NEC pathogenesis, and that high ER stress within the premature intestine predisposes to NEC development. Using transgenic mice and cultured enteroids, we now demonstrate that TLR4 induces ER stress within Lgr5 (leucine-rich repeat-containing G-protein-coupled receptor 5)-positive ISCs, resulting in crypt apoptosis. TLR4 signaling within crypts was required, because crypt ER stress and apoptosis occurred in TLR4ΔIEC-OVER mice expressing TLR4 only within intestinal crypts and epithelium, but not TLR4ΔIEC mice lacking intestinal TLR4. TLR4-mediated ER stress and apoptosis of ISCs required PERK (protein kinase-related PKR-like ER kinase), CHOP (C/EBP homologous protein), and MyD88 (myeloid differentiation primary response gene 88), but not ATF6 (activating transcription factor 6) or XBP1 (X-box-binding protein 1). Human and mouse NEC showed high crypt ER stress and apoptosis, whereas genetic inhibition of PERK or CHOP attenuated ER stress, crypt apoptosis, and NEC severity. Strikingly, using intragastric delivery into fetal mouse intestine, prevention of ER stress reduced TLR4-mediated ISC apoptosis and mucosal disruption. These findings identify a novel link between TLR4-induced ER stress and ISC apoptosis in NEC pathogenesis and suggest that increased ER stress within the premature bowel predisposes to NEC development. PMID:24519940

Toll-like receptor 4-mediated endoplasmic reticulum stress in intestinal crypts induces necrotizing enterocolitis.

PubMed

Afrazi, Amin; Branca, Maria F; Sodhi, Chhinder P; Good, Misty; Yamaguchi, Yukihiro; Egan, Charlotte E; Lu, Peng; Jia, Hongpeng; Shaffiey, Shahab; Lin, Joyce; Ma, Congrong; Vincent, Garrett; Prindle, Thomas; Weyandt, Samantha; Neal, Matthew D; Ozolek, John A; Wiersch, John; Tschurtschenthaler, Markus; Shiota, Chiyo; Gittes, George K; Billiar, Timothy R; Mollen, Kevin; Kaser, Arthur; Blumberg, Richard; Hackam, David J

2014-04-04

The cellular cues that regulate the apoptosis of intestinal stem cells (ISCs) remain incompletely understood, yet may play a role in diseases characterized by ISC loss including necrotizing enterocolitis (NEC). Toll-like receptor-4 (TLR4) was recently found to be expressed on ISCs, where its activation leads to ISC apoptosis through mechanisms that remain incompletely explained. We now hypothesize that TLR4 induces endoplasmic reticulum (ER) stress within ISCs, leading to their apoptosis in NEC pathogenesis, and that high ER stress within the premature intestine predisposes to NEC development. Using transgenic mice and cultured enteroids, we now demonstrate that TLR4 induces ER stress within Lgr5 (leucine-rich repeat-containing G-protein-coupled receptor 5)-positive ISCs, resulting in crypt apoptosis. TLR4 signaling within crypts was required, because crypt ER stress and apoptosis occurred in TLR4(ΔIEC-OVER) mice expressing TLR4 only within intestinal crypts and epithelium, but not TLR4(ΔIEC) mice lacking intestinal TLR4. TLR4-mediated ER stress and apoptosis of ISCs required PERK (protein kinase-related PKR-like ER kinase), CHOP (C/EBP homologous protein), and MyD88 (myeloid differentiation primary response gene 88), but not ATF6 (activating transcription factor 6) or XBP1 (X-box-binding protein 1). Human and mouse NEC showed high crypt ER stress and apoptosis, whereas genetic inhibition of PERK or CHOP attenuated ER stress, crypt apoptosis, and NEC severity. Strikingly, using intragastric delivery into fetal mouse intestine, prevention of ER stress reduced TLR4-mediated ISC apoptosis and mucosal disruption. These findings identify a novel link between TLR4-induced ER stress and ISC apoptosis in NEC pathogenesis and suggest that increased ER stress within the premature bowel predisposes to NEC development.

Ileostomy Complications in Infants less than 1500 grams - Frequent but Manageable.

PubMed

Kargl, Simon; Wagner, Oliver; Pumberger, Wolfgang

2017-01-01

In very low birth weight infants abdominal emergency surgery may result in ileostomy formation. We observed a frequent stoma complications in these patients. This retrospective analysis put light on ileostomy-related problems and complications in very low birth weight (VLBW) infants. In a seven-year retrospective chart review (2008 - 2014) infants with ileostomy formation weighing less than 1500 grams at time of operation were identified and reviewed. Data analysis included demographic data, complications and short term outcomes. Thirty patients were included. Ileostomy was formed for spontaneous intestinal perforation (SIP) (n=17), meconium obstruction of prematurity (MOP) (n=6), midgut volvulus (MV) (n=5), necrotizing enterocolitis (NEC) (n=1) and Hirschsprung's disease (HD) (n=1). Three patients died before ileostomy reversal was considered. In seven patients planned ileostomy reversal was done. Twenty infants had stoma related complications (stoma prolapse, prestomal obstruction, stoma retraction, high output stoma, peristomal skin excoriation, and stomal ischemia). Complications did not correlate with underlying diseases. Stomal complications necessitated earlier stoma reversal (mean 62 days). Postoperative complications after stoma reversal occurred in three children (wound dehiscence, adhesion ileus, anastomotic stricture). Although ileostomy related complications are frequent in very low birth weight infants, mortality is low. Morbidity is manageable.

Practical approaches to probiotics use.

PubMed

Taibi, Amel; Comelli, Elena M

2014-08-01

Probiotics are microorganisms exerting beneficial effects on the host. They can be ingested through foods or supplements and their inclusion in these products is regulated in Canada by the Health Canada Health Products and Food Branch. The aim of this article is to summarize current evidence from randomized controlled trials and guidelines from Health Canada, the World Health Organization, and internationally recognized expert committees in the hope that it will help practitioners and professionals recommending probiotics to healthy and diseased patients, with a focus on the Canadian setting. From a general perspective, probiotics can be recommended for prevention of diseases that are associated to altered intestinal ecology. Specifically, they can be recommended for prevention of upper respiratory tract infections and pouchitis, for prevention and management of necrotizing enterocolitis, bacterial vaginosis and antibiotic associated diarrhea, including Clostridium difficile infection, and for treatment of atopic eczema in cow's milk allergy and of infectious diarrhea. Additional substantiated probiotic benefits include prevention of hypercholesterolemia, management of constipation, reduction of recurrent urinary tract infections, improvement of irritable bowel syndrome symptoms, and reduction of antibiotics side effects in Helicobacter pylori eradication. Because probiotics are generally recognized as safe and can be removed with antimicrobial agents, their use should be considered in patients of all ages.

How I manage children with neutropenia.

PubMed

Dale, David C

2017-08-01

Neutropenia, usually defined as a blood neutrophil count <1·5 × 10 9 /l, is a common medical problem for children and adults. There are many causes for neutropenia, and at each stage in life the clinical pattern of causes and consequences differs significantly. I recommend utilizing the age of the child and clinical observations for the preliminary diagnosis and primary management. In premature infants, neutropenia is quite common and contributes to the risk of sepsis with necrotizing enterocolitis. At birth and for the first few months of life, neutropenia is often attributable to isoimmune or alloimmune mechanisms and predisposes to the risk of severe bacterial infections. Thereafter when a child is discovered to have neutropenia, often associated with relatively minor symptoms, it is usually attributed to autoimmune disorder or viral infection. The congenital neutropenia syndromes are usually recognized when there are recurrent infections, the neutropenia is severe and there are congenital anomalies suggesting a genetic disorder. This review focuses on the key clinical finding and laboratory tests for diagnosis with commentaries on treatment, particularly the use of granulocyte colony-stimulating factor to treat childhood neutropenia. © 2017 John Wiley & Sons Ltd.

Lactoferrin and prematurity: a promising milk protein?

PubMed

Ochoa, Theresa J; Sizonenko, Stéphane V

2017-02-01

Lactoferrin (Lf) is the major whey protein in milk, with multiple beneficial health effects including direct antimicrobial activities, anti-inflammatory effects, and iron homeostasis. Oral Lf supplementation in human preterm infants has been shown to reduce the incidence of sepsis and necrotizing enterocolitis. In preclinical models of antenatal stress and perinatal brain injury, bovine Lf protected the developing brain from neuronal loss, improved connectivity, increased neurotrophic factors, and decreased inflammation. It also supported brain development and cognition. Further, Lf can prevent preterm delivery by reducing proinflammatory factors and inhibiting premature cervix maturation. We review here the latest research on Lf in the field of neonatology.

Ureaplasma species: Role in Neonatal Morbidities and Outcomes

PubMed Central

Viscardi, Rose Marie

2014-01-01

The genital mycoplasma species, Ureaplasma parvum and U. urealyticum are the most common organisms isolated from infected amniotic fluid and placentas and they contribute to adverse pregnancy outcomes including preterm birth and neonatal morbidities. In our institution, almost half of preterm infants less than 32 weeks gestation are Ureaplasma-positive in one or more compartment (respiratory, blood, and/or cerebrospinal fluid), indicating that these organisms are the most common pathogens affecting this population. This review will focus on the compelling epidemiologic and experimental evidence linking perinatal Ureaplasma species exposure to important morbidities of prematurity such as bronchopulmonary dysplasia, intraventricular hemorrhage, and necrotizing enterocolitis. PMID:23960141

A quality of life quandary: a framework for navigating parental refusal of treatment for co-morbidities in infants with underlying medical conditions.

PubMed

Kunz, Sarah N; McAdams, Ryan M; Diekema, Douglas S; Opel, Douglas J

2015-01-01

Parental refusal of a recommended treatment is not an uncommon scenario in the neonatal intensive care unit. These refusals may be based upon the parents' perceptions of their child's projected quality of life. The inherent subjectivity of quality of life assessments, however, can exacerbate disagreement between parents and healthcare providers. We present a case of parental refusal of surgical intervention for necrotizing enterocolitis in an infant with Bartter syndrome and develop an ethical framework in which to consider the appropriateness of parental refusal based upon an infant's projected quality of life. Copyright 2015 The Journal of Clinical Ethics. All rights reserved.

Heart transplantation on the first day of life from an anencephalic donor.

PubMed

Parisi, F; Squitieri, C; Carotti, A; Di Carlo, D; Gagliardi, M G

1999-05-01

Heart transplantation on the first day of life, and graft harvesting from anencephalic donors, have been very rare events in the history of transplantation. At Bambino Gesù Hospital (Rome), heart transplantation was performed on a newborn 9 h after birth, using a graft harvested from an anencephalic donor. This graft achieved a good cardiocirculatory function, but the recipient died of necrotizing enterocolitis (NEC) on post-operative day (POD) 10. Despite failure, this case and other reports support the concept that hearts from anencephalic donors can work normally, and indicate that heart transplantation on the first day of life may have a favorable outcome if postoperative maintenance of multi-organ balance and function is successful.

Human Milk Oligosaccharides and the Preterm Infant: A Journey in Sickness and in Health.

PubMed

Moukarzel, Sara; Bode, Lars

2017-03-01

Human milk oligosaccharides (HMOs) are a group of approximately 200 different unconjugated sugar structures in human milk proposed to support infant growth and development. Data from several preclinical animal studies and human cohort studies suggest HMOs reduce preterm infant mortality and morbidity by shaping the gut microbiome and protecting against necrotizing enterocolitis, candidiasis, and several other immune-related diseases. Current feeding practices and clinical algorithms do not consider infant HMO intake when assessing dietary adequacy or disease risk. Advancements in HMO analytical methodologies and HMO synthesis facilitate cohort and intervention studies to investigate which particular HMOs are most relevant in supporting preterm infants. Copyright © 2016 Elsevier Inc. All rights reserved.

Neonatal polycythaemia: critical review and a consensus statement of the Israeli Neonatology Association.

PubMed

Mimouni, Francis B; Merlob, Paul; Dollberg, Shaul; Mandel, Dror

2011-10-01

The aim of this paper is to critically review neonatal polycythaemia (NP) literature, in terms of definition, diagnosis and management. We reviewed all Medline articles on NP up to December 2009. (i) The textbook definition of NP [venous haematocrit (HCT) > 65%] is empirical and not based on statistical definition, symptoms or complications. (ii) Measurement of viscosity is not better than HCT in predicting complications. (iii) Normovolaemic NP because of increased erythropoiesis may be different from hypervolaemic polycythaemia because of excessive foetal transfusion. (iv) Coexisting hypoglycaemia may worsen long-term outcome. (v) Four clinical trials (CTs) studied partial exchange transfusion (PET) on outcomes. In all trials, PET was performed after 6 h of life. There is no evidence that PET improves neurodevelopmental outcome of asymptomatic NP, and it might increase the risk of necrotizing enterocolitis. These CTs have inherent design flaws: (a) CNS 'damage' may occur before PET. (b) Confounding variables that may affect outcome have not been studied. (vi) If PET is performed, normal saline is the best alternative. (vii) The long-term effect of PET on symptomatic infants has not been studied. Current definition and management of NP are little evidence based, thus the need for a consensus based on expert opinion. © 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.

Longitudinal Analysis of the Premature Infant Intestinal Microbiome Prior to Necrotizing Enterocolitis: A Case-Control Study

PubMed Central

Zhou, Yanjiao; Shan, Gururaj; Sodergren, Erica; Weinstock, George; Walker, W. Allan; Gregory, Katherine E.

2015-01-01

Necrotizing enterocolitis (NEC) is an inflammatory disease of the newborn bowel, primarily affecting premature infants. Early intestinal colonization has been implicated in the pathogenesis of NEC. The objective of this prospective case-control study was to evaluate differences in the intestinal microbiota between infants who developed NEC and unaffected controls prior to disease onset. We conducted longitudinal analysis of the 16S rRNA genes of 312 samples obtained from 12 NEC cases and 26 age-matched controls with a median frequency of 7 samples per subject and median sampling interval of 3 days. We found that the microbiome undergoes dynamic development during the first two months of life with day of life being the major factor contributing to the colonization process. Depending on when the infant was diagnosed with NEC (i.e. early vs. late onset), the pattern of microbial progression was different for cases and controls. The difference in the microbiota was most overt in early onset NEC cases and controls. In proximity to NEC onset, the abundances of Clostridium sensu stricto from Clostridia class were significantly higher in early onset NEC subjects comparing to controls. In late onset NEC, Escherichia/Shigella among Gammaproteobacteria, showed an increasing pattern prior to disease onset, and was significantly higher in cases than controls six days before NEC onset. Cronobacter from Gammaproteobacteria was also significantly higher in late onset NEC cases than controls 1-3 days prior to NEC onset. Thus, the specific infectious agent associated with NEC may vary by the age of infant at disease onset. We found that intravenously administered antibiotics may have an impact on the microbial diversity present in fecal material. Longitudinal analysis at multiple time points was an important strategy utilized in this study, allowing us to appreciate the dynamics of the premature infant intestinal microbiome while approaching NEC at various points. PMID:25741698

An animal model of necrotizing enterocolitis (NEC) in preterm rabbits.

PubMed

Bozeman, Andrew P; Dassinger, Melvin S; Birusingh, Rhea J; Burford, Jeffrey M; Smith, Samuel D

2013-04-01

Creation of an animal model of necrotizing enterocolitis (NEC) allowing adjustment of severity and potential recoverability is needed to study effectiveness of prevention and treatment strategies. This study describes a novel model in preterm rabbits capable of adjusting severity of NEC-like histologic changes. Rabbit pups (n = 151) were delivered by cesarean section 2 days preterm. In the treatment groups, tissue adhesive was applied to anal openings to simulate the poor intestinal function and dysmotility of preterm neonates. Pups were placed into five groups: 3INT (3 day intermittent block), 4INT (4 day intermittent block), 3COM (3 day complete block), 4COM (4 day complete block), based on differences in type of anal blockage and day of life sacrificed. The fifth group, 4CON, was comprised of a control arm (n = 28) without anal block, with sacrifice of subjects on day 4. All pups were gavage fed with formula contaminated with Enterobacter cloacae, ranitidine, and indomethacin. Following sacrifice, the intestines were harvested for pathologic evidence of NEC. A blinded pathologist graded histologic changes consistent with NEC using a grading scale 0-4 with 4 being most severe. Fifty-seven pups (57/123) (46%) in the research arm survived to sacrifice, compared to 26/28 (93%) in the control arm of the investigation, p < 0.0001. The incidence and severity of NEC-like damage increased with the duration and completeness of the anal blockage. 44/57 (77%) of survivors revealed various degrees of NEC-like damage to large and small bowel, and 3/26 (12%) exhibited early NEC-like mucosal injury in the research and control arms, respectively. This animal model produces NEC-like pathologic changes in both small and large intestine in preterm rabbits. Because incidence and severity of damage increases with duration and completeness of intestinal dysmotility, this allows future effectiveness studies for nonsurgical treatment and prevention of NEC.

Multiple strains probiotics appear to be the most effective probiotics in the prevention of necrotizing enterocolitis and mortality: An updated meta-analysis.

PubMed

Chang, Hung-Yang; Chen, Jin-Hua; Chang, Jui-Hsing; Lin, Hung-Chih; Lin, Chien-Yu; Peng, Chun-Chih

2017-01-01

Some oral probiotics have been shown to prevent necrotizing enterocolitis (NEC) and decrease mortality effectively in preterm very low birth weight (PVLBW) infants. However, it is unclear whether a single probiotic or a mixture of probiotics is most effective for the prevention of NEC. A meta-analysis was conducted by reviewing the most up to date literature to investigate whether multiple strains probiotics are more effective than a single strain in reducing NEC and death in PVLBW infants. Relevant studies were identified by searches of the MEDLINE, EMBASE, and Cochrane CENTRAL databases, from 2001 to 2016. The inclusion criteria were randomized controlled trials of any enteral probiotic supplementation that was initiated within the first 7 days and continued for at least 14 days in preterm infants (≤ 34 weeks' gestation) and/or those of a birth weight ≤1500 g. A total of 25 trials (n = 7345 infants) were eligible for inclusion in the meta-analysis using a fixed-effects model. Multiple strains probiotics were associated with a marked reduction in the incidence of NEC, with a pooled OR of 0.36 (95% CI, 0.24-0.53; P < .00001). Single strain probiotic using Lactobacillus species had a borderline effect in reducing NEC (OR of 0.60; 95% CI 0.36-1.0; P = .05), but not mortality. Multiple strains probiotics had a greater effectiveness in reducing mortality and were associated with a pooled OR of 0.58 (95% CI, 0.43-0.79; P = .0006). Trials using single strain of Bifidobacterium species and Saccharomyces boulardii did not reveal any beneficial effects in terms of reducing NEC or mortality. This updated report found that multiple strains probiotics appear to be the most feasible and effective strategy for the prevention of NEC and reduction of mortality in PVLBW neonates. Further clinical trials should focus on which probiotic combinations are most effective.

Association of neonatal necrotizing enterocolitis with myeloid differentiation-2 and GM2 activator protein genetic polymorphisms.

PubMed

Zhou, Wei; Yuan, Weiming; Huang, Longguang; Wang, Ping; Rong, Xiao; Tang, Juan

2015-07-01

The aim of the present study was to investigate the association of neonatal necrotizing enterocolitis (NEC) with myeloid differentiation-(MD-2) and GM2 activator protein (GM2A) genetic polymorphisms. Gene resequencing of the MD-2 and GM2A gene exons was performed on 42 neonates, diagnosed with NEC (NEC group), as well as in the rs11465996 locus, located in the MD-2 gene promoter region. The aim was to detect the genetic polymorphisms present in the neonates with NEC and compare the functional polymorphic loci with 83 neonates without NEC (control group), who had been born during the same period. A polymorphic locus with abnormal frequency was detected in the exon region of the MD-2 gene. In the NEC group, the frequency of genotypes carrying the low frequency allele (G) in the rs11465996 locus (MD-2 promoter region) was significantly higher compared with the control group (χ(2)=4.388, P=0.036). Furthermore, the frequencies of genotypes carrying the low frequency A and C alleles in the rs1048719 (GM2A gene exon 1) and rs2075783 loci (GM2A intron), respectively, were significantly higher in the NEC group compared with the control group (χ(2)=4.316, P=0.038; and χ(2)=13.717, P=0.000, respectively). In addition, the rs11465996 polymorphism in the MD-2 gene promoter region was found to be associated with the severity of NEC. Furthermore, the rs2075783 polymorphism in the GM2A gene exon 1 and the rs1048719 polymorphism in the intron region of this gene, were associated with the occurrence of NEC. The present study demonstrated that gene polymorphisms of MD-2 and GM2A were associated with the occurrence or severity of NEC; however, further in-depth exploration is required to clarify the associations between genetic predispositions to polymorphisms, and NEC.

Necrotizing enterocolitis as a prognostic factor for the neurodevelopmental outcome of preterm infants - match control study after 2years.

PubMed

Allendorf, Antje; Dewitz, Ruth; Weber, Joy; Bakthiar, Shahrzad; Schloesser, Rolf; Rolle, Udo

2018-01-31

Necrotizing enterocolitis (NEC) in very low birth weight infants is a risk factor for developmental delay. To our knowledge, there are no studies published investigating the neurodevelopmental outcome of patients with NEC comparing surgically treated and conservatively treated patients versus match paired controls. The aim of this retrospective case control study was to measure the neurodevelopmental outcome of patients with NEC who were treated surgically or conservatively METHODS: All patients were identified, who have been diagnosed with NEC (ICD-10 code, P77) born between 2006 and 2013. Patients with NEC received antibiotic therapy, nasogastric decompression and fasting. Surgical treatment was indicated for patients with Bell stages IIIb. We excluded patients suffering from other relevant diseases with a possible impact on their neurodevelopmental outcome (e.g., intraventricular hemorrhage, associated malformations, asphyxia, focal intestinal perforation, short bowel syndrome). Patients were tested at the corrected gestational age of 24months according to the Bayley Scales of Infant Development II. Each participant was compared to a child of the same sex, gestational age at birth (+/-two days), birth weight (+/-10%), and age at neurodevelopmental testing (IRB approval, No. 14/2014). The outcome measures were the psychomotor index (PDI) and the mental developmental index (MDI). We included 13 conservatively and 24 surgically treated patients. The patients in group A (without surgery) achieved a mean PDI of 106, and those in group B (with surgery) a mean PDI of 90. These values were significantly higher in the conservative group A. The mean MDIs were 99 in the patient group A and 85 in patient group B. This difference was also significant. We found significantly lower MDIs and PDIs in children with surgical treatment of NEC. Further systematic prospective research on the prevention of NEC and systematic follow-ups at later stages in the patients' development are necessary in order to implement early intervention. case control study. III. Copyright © 2018. Published by Elsevier Inc.

Carbohydrate maldigestion induces necrotizing enterocolitis in preterm pigs

PubMed Central

Thymann, Thomas; Møller, Hanne K.; Stoll, Barbara; Støy, Ann Cathrine F.; Buddington, Randal K.; Bering, Stine B.; Jensen, Bent B.; Olutoye, Oluyinka O.; Siggers, Richard H.; Mølbak, Lars; Sangild, Per T.

2009-01-01

Necrotizing enterocolitis (NEC) remains the most severe gastrointestinal disorder in preterm infants. It is associated with the initiation of enteral nutrition and may be related to immature carbohydrate digestive capacity. We tested the hypothesis that a formula containing maltodextrin vs. a formula containing lactose as the principal source of carbohydrate would predispose preterm pigs to a higher NEC incidence. Cesarean-derived preterm pigs were given total parenteral nutrition for 48 h followed by total enteral nutrition with a lactose-based (n = 11) or maltodextrin-based (n = 11) formula for 36 h. A higher incidence (91% vs. 27%) and severity (score of 3.3 vs. 1.8) of NEC were observed in the maltodextrin than in the lactose group. This higher incidence of NEC in the maltodextrin group was associated with significantly lower activities of lactase, maltase, and aminopeptidase; reduced villus height; transiently reduced in vivo aldohexose uptake; and reduced ex vivo aldohexose uptake capacity in the middle region of the small intestine. Bacterial diversity was low for both diets, but alterations in bacterial composition and luminal concentrations of short-chain fatty acids were observed in the maltodextrin group. In a second study, we quantified net portal absorption of aldohexoses (glucose and galactose) during acute jejunal infusion of a maltodextrin- or a lactose-based formula (n = 8) into preterm pigs. We found lower net portal aldohexose absorption (4% vs. 42%) and greater intestinal recovery of undigested carbohydrate (68% vs. 27%) in pigs acutely perfused with the maltodextrin-based formula than those perfused with the lactose-based formula. The higher digestibility of the lactose than the maltodextrin in the formulas can be attributed to a 5- to 20-fold higher hydrolytic activity of tissue-specific lactase than maltases. We conclude that carbohydrate maldigestion is sufficient to increase the incidence and severity of NEC in preterm pigs. PMID:19808655

Causes and timing of death in extremely premature infants from 2000 through 2011.

PubMed

Patel, Ravi M; Kandefer, Sarah; Walsh, Michele C; Bell, Edward F; Carlo, Waldemar A; Laptook, Abbot R; Sánchez, Pablo J; Shankaran, Seetha; Van Meurs, Krisa P; Ball, M Bethany; Hale, Ellen C; Newman, Nancy S; Das, Abhik; Higgins, Rosemary D; Stoll, Barbara J

2015-01-22

Understanding the causes and timing of death in extremely premature infants may guide research efforts and inform the counseling of families. We analyzed prospectively collected data on 6075 deaths among 22,248 live births, with gestational ages of 22 0/7 to 28 6/7 weeks, among infants born in study hospitals within the National Institute of Child Health and Human Development Neonatal Research Network. We compared overall and cause-specific in-hospital mortality across three periods from 2000 through 2011, with adjustment for baseline differences. The number of deaths per 1000 live births was 275 (95% confidence interval [CI], 264 to 285) from 2000 through 2003 and 285 (95% CI, 275 to 295) from 2004 through 2007; the number decreased to 258 (95% CI, 248 to 268) in the 2008-2011 period (P=0.003 for the comparison across three periods). There were fewer pulmonary-related deaths attributed to the respiratory distress syndrome and bronchopulmonary dysplasia in 2008-2011 than in 2000-2003 and 2004-2007 (68 [95% CI, 63 to 74] vs. 83 [95% CI, 77 to 90] and 84 [95% CI, 78 to 90] per 1000 live births, respectively; P=0.002). Similarly, in 2008-2011, as compared with 2000-2003, there were decreases in deaths attributed to immaturity (P=0.05) and deaths complicated by infection (P=0.04) or central nervous system injury (P<0.001); however, there were increases in deaths attributed to necrotizing enterocolitis (30 [95% CI, 27 to 34] vs. 23 [95% CI, 20 to 27], P=0.03). Overall, 40.4% of deaths occurred within 12 hours after birth, and 17.3% occurred after 28 days. We found that from 2000 through 2011, overall mortality declined among extremely premature infants. Deaths related to pulmonary causes, immaturity, infection, and central nervous system injury decreased, while necrotizing enterocolitis-related deaths increased. (Funded by the National Institutes of Health.).

Bacterial community structure and functional contributions to emergence of health or necrotizing enterocolitis in preterm infants

PubMed Central

2013-01-01

Background Preterm infants represent a unique patient population that is born functionally immature and must accomplish development under the influence of a hospital environment. Neonatal necrotizing enterocolitis (NEC) is an inflammatory intestinal disorder affecting preterm infants. The purpose of this study was to evaluate the progression of intestinal microbiota community development between preterm infants who remained healthy compared to preterm infants who developed NEC. Results Weekly fecal samples from ten preterm infants, five with NEC and five matched healthy controls were obtained. Bacterial DNA from individual fecal samples was subjected to sequencing of 16S rRNA-based inventories using the 454 GS-FLX platform. Fecal samples from control infants demonstrated a temporal pattern in their microbiota, which converged toward that of a healthy full term breast-fed infant. Microbiota development in NEC patients diverged from controls beginning three weeks prior to diagnosis. Shotgun metagenomic sequencing was performed to identify functional differences in the respective microbiota of fecal samples from a set of twins in which one twin developed NEC and one did not. The majority of the differentially abundant genes in the NEC patient were associated with carbohydrate metabolism and mapped to members of the family Enterobacteriaceae. This may indicate an adaptation of the community to an altered profile of substrate availability for specific members as a first step towards the development of NEC. We propose that the microbial communities as a whole may metabolize milk differently, resulting in differential substrate availability for specific microbial groups. Additional differentially represented gene sets of interest were related to antibiotic resistance and vitamin biosynthesis. Conclusions Our results suggest that there is a temporal component to microbiome development in healthy preterm infants. Thus, bacteriotherapy for the treatment or prevention of NEC must consider this temporal component of the microbial community in addition to its taxonomic composition and functional content. PMID:24450928

Brain Barrier Disruption and Region-Specific Neuronal Degeneration during Necrotizing Enterocolitis in Preterm Pigs.

PubMed

Brunse, Anders; Abbaspour, Afrouz; Sangild, Per Torp

2018-06-06

Necrotizing enterocolitis (NEC) increases the risk of brain injury and impaired neurodevelopment. Rapid brain maturation prior to birth may explain why preterm brains are particularly vulnerable to serious infections. Using pigs as models, we hypothesized that preterm birth was associated with altered blood-cerebrospinal fluid (CSF) barrier (BCSFB) function and cerebral structural deficits, and that NEC was associated with systemic inflammation, BCSFB disruption, and neuroinflammation. First, cesarean-delivered preterm and term pigs (n = 43-44) were euthanized at birth to investigate BCSFB function and markers of brain structural maturation, or on day 5 to measure markers of blood-brain barrier maturation in the hippocampus and striatum (experiment 1). Next, preterm pigs (n = 162) were fed increasing volumes of infant formula to assess NEC lesions, systemic inflammation, BCSFB permeability, cerebral histopathology, hippocampal micro-glial density, and cytokine levels on day 5 (experiments 2 and 3). In experiment 1, preterm newborns had increased CSF-plasma ratios of albumin and raffinose, reduced CSF glucose levels, as well as increased cerebral hydration and reduced white matter myelination compared with term animals. We observed lower hippocampal (but not striatal) perivascular astrocyte coverage for the first 5 days after preterm birth, accompanied by altered cell junction protein levels. In experiments 2 and- 3, piglets with severe NEC lesions showed reduced blood thrombocytes and increased plasma C-reactive protein and interleukin-6 levels. NEC was associated with increased CSF-plasma albumin and raffinose ratios, reduced CSF leukocyte numbers, and increased cerebral hydration. In the hippocampus, NEC was associated with pyramidal neuron loss and increased interleukin-6 levels. In the short term, NEC did not affect cerebral myelination or microglia density. In conclusion, altered BCSFB properties and brain structural deficits were observed in pigs after preterm birth. Acute gastrointestinal NEC lesions were associated with systemic inflammation, increased BCSFB permeability and region-specific neuronal damage. The results demonstrate the importance of early interventions against NEC to prevent brain injury in preterm infants. © 2018 S. Karger AG, Basel.

Clostridium neonatale sp. nov. linked to necrotizing enterocolitis in neonates and a clarification of species assignable to the genus Clostridium (Prazmowski 1880) emend. Lawson and Rainey 2016.

PubMed

Bernard, Kathryn; Burdz, Tamara; Wiebe, Deborah; Alfa, Michelle; Bernier, Anne-Marie

2018-06-11

A description of an outbreak of necrotizing enterocolitis among neonates, linked to the putative novel species Clostridium neonatale and assignable to the genus Clostridium, was previously reported in brief but that name had never been validly published (Alfa et al. Clin Inf Dis 2002;35:S101-S105). Features of this taxon group and its phylogenetic position with respect to contemporary species in the genus Clostridium were recently reviewed and still found to be unique. Therefore, we provide here a description based on biochemical, chemotaxonomic and antimicrobial susceptibility testing (AST), matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS, 16S rRNA gene sequencing as well as information obtained by whole genome sequencing (WGS) for strains 99A005 T and 99A006. Those two C. neonatale strains were essentially identical to each other, with genome sizes of 4 658 596-4 705 520 bp and G+C content of 28.4-28.5 mol% (WGS). AST inferred susceptibility to 14 antibiotics. MALDI-TOF spectra were unique and could potentially be used for identification. The type strain is (NML) LCDC 99A005 T [=ATCC BAA-265 T =CCUG 46077 T =St. Boniface Hospital 30686 T ]. While performing this review, we found that the names of 24 validly published species assignable to the genus Clostridium had been omitted from the emended description of the genus (Lawson and Rainey Int J Syst Evol Microbiol 2016;66 :1009-1016). Those species are listed in brief here. Lastly, based on this review, we also propose that Eubacterium budayi, Eubacterium nitritogenes and Eubacterium combesii be transferred to the emended genus Clostridium, as Clostridium budayi comb. nov., Clostridium nitritogenes comb. nov. and Clostridium combesii comb. nov., respectively.

Food protein-induced enterocolitis syndrome: a review of the new guidelines.

PubMed

Leonard, Stephanie A; Pecora, Valentina; Fiocchi, Alessandro Giovanni; Nowak-Wegrzyn, Anna

2018-01-01

Food protein-induced enterocolitis syndrome (FPIES) is a non IgE-mediated gastrointestinal food allergy that presents with delayed vomiting after ingestion primarily in infants. While the pathophysiology of FPIES is poorly understood, the clinical presentation of acute FPEIS reactions has been well characterized. The first International Consensus Guidelines for the Diagnosis and Management of Food Protein-induced Enterocolitis Syndrome were published in 2017 and reviewed epidemiology, clinical presentation, and prognosis of acute and chronic FPIES. The workgroup outlined clinical phenotypes, proposed diagnostic criteria, and made recommendations on management. This article summarizes the guidelines and adds recent updates. FPIES is gaining recognition, however there continues to be delays in diagnosis and misdiagnosis due to overlap of symptoms with over conditions, lack of a diagnostic test, and because some of the common trigger foods are not thought of as allergenic. More research into disease mechanisms and factors influencing differences between populations is needed.

[Prevention and treatment of necrotizing enterocolitis in the newborn infant from the pediatric point of view].

PubMed

Pohlandt, F

1990-10-01

1. Enteral feeding and factors promoting hypoxia and ischaemia of the gut are thought to cause necrotising enterocolitis of the newborn but have not been proven as factors in the pathogenesis of NEC. Enteral feeding may be started in principle on the first day of life at a rate of 10-20 ml/kg/day. Controlled results to the contrary have not been published. 2. Drugs which have a high osmolarity should be diluted with milk as far as possible to avoid mucosal damage. 3. In cases of epidemic NEC, infants with proven disease should be isolated. The use of a bactericidal and virucidal disinfectant is imperative for hand disinfection. 4. Early diagnosis and early treatment are necessary to prevent progression to advanced stages. 5. Antibiotic treatment should be selected to cover the entire bacterial spectrum of the ward. 6. Frequent physical, radiological and ultrasound examinations should be done to monitor the course of the disease. Laboratory analyses should include: acid-basis status, leukocytes, differential blood picture, thrombocytes, C-reactive protein, haematocrit, serum electrolytes. 7. Large amounts of fluid may be necessary to prevent and treat hypovolaemic shock. 8. Abdominal paracentesis helps to recognise peritonitis and intestinal gangrene and allows surgical treatment as early as possible.

Lethal pneumatosis coli in a 12-month-old child caused by acute intestinal gas gangrene after prolonged artificial nutrition: a case report

PubMed Central

Kircher, Stefan; Wössner, Rupert; Müller-Hermelink, Hans-Konrad; Völker, Hans-Ullrich

2008-01-01

Introduction Pneumatosis coli is a rare disease with heterogeneous symptoms which can be detected in the course of various acute and chronic intestinal diseases in children, such as necrotizing enterocolitis, intestinal obstruction and intestinal bacteriological infections. Case presentation We report the case of a 12-month-old boy who died of pneumatosis coli caused by an acute intestinal gas gangrene after prolonged artificial alimentation. Conclusion While intestinal gas gangrene is a highly uncommon cause of pneumatosis coli, it is important to consider it as a differential diagnosis, especially in patients receiving a prolonged artificial food supply. These patients may develop intestinal gas gangrene due to a dysfunctional intestinal barrier. PMID:18652650

Inhibition of Cronobacter sakazakii Virulence Factors by Citral.

PubMed

Shi, Chao; Sun, Yi; Liu, Zhiyuan; Guo, Du; Sun, Huihui; Sun, Zheng; Chen, Shan; Zhang, Wenting; Wen, Qiwu; Peng, Xiaoli; Xia, Xiaodong

2017-02-24

Cronobacter sakazakii is a foodborne pathogen associated with fatal forms of necrotizing enterocolitis, meningitis and sepsis in neonates and infants. The aim of this study was to determine whether citral, a major component of lemongrass oil, could suppress putative virulence factors of C. sakazakii that contribute to infection. Sub-inhibitory concentrations of citral significantly decreased motility, quorum sensing, biofilm formation and endotoxin production. Citral substantially reduced the adhesion and invasion of C. sakazakii to Caco-2 cells and decreased bacterial survival and replication within the RAW 264.7 macrophage cells. Citral also repressed the expression of eighteen genes involved in the virulence. These findings suggest that citral has potential to be developed as an alternative or supplemental agent to mitigate the infections caused by C. sakazakii.

The importance of pro-inflammatory signaling in neonatal NEC

PubMed Central

Frost, Brandy L.; Jilling, Tamas; Caplan, Michael S.

2008-01-01

Despite modern medical advances, necrotizing enterocolitis (NEC) remains a significant cause of morbidity and mortality in neonatal intensive care units, affecting 10 percent of premature neonates born weighing less than 1500 grams. Although many advances have been made in the understanding of this disease, the etiology and pathophysiology remain incompletely understood, and treatment is limited to supportive care. In recent years, studies have focused on the role of the inflammatory cascade and its’ impact on the disease process, and investigators are evaluating strategies to attenuate inflammatory signaling that might prevent and/or ameliorate neonatal NEC. In this review, we examine the key points in the signaling pathways involved in NEC, and potential strategies for prevention and treatment of this dreaded disease. PMID:18346533

Development of Bioluminescent Cronobacter sakazakii ATCC 29544 in a Mouse Model.

PubMed

Wang, Xiwen; Li, Zhiping; Dong, Xiaolin; Chi, Hang; Wang, Guannan; Li, Jiakuan; Sun, Rui; Chen, Man; Zhang, Xinying; Wang, Yuanyuan; Qu, Han; Sun, Yu; Xia, Zhiping; Li, Qianxue

2015-05-01

Cronobacter sakazakii is an emerging pathogen that causes severe and life-threatening conditions including meningitis, bacteremia, and necrotizing enterocolitis. An animal model study for extrapolation of C. sakazakii infection can provide a better understanding of pathogenesis. However, methods for real-time monitoring of the course of C. sakazakii infection in living animals have been lacking. We developed a bioluminescent C. sakazakii strain (ATCC 29544) that can be used for real-time monitoring of C. sakazakii infection in BALB/c mice. C. sakazakii ATCC 29544 mainly colonized brain, liver, spleen, kidney, and gastrointestinal tract, as indicated by bioluminescence imaging. This work provides a novel approach for studying the progression of C. sakazakii infection and evaluating therapeutics in a living mouse model.

Functional Screening of the Cronobacter sakazakii BAA-894 Genome reveals a role for ProP (ESA_02131) in carnitine uptake.

PubMed

Feeney, Audrey; Sleator, Roy D

2015-01-01

Cronobacter sakazakii is a neonatal pathogen responsible for up to 80% of fatalities in infected infants. Low birth weight infants and neonates infected with C. sakazakii suffer necrotizing enterocolitis, bacteraemia and meningitis. The mode of transmission most often associated with infection is powdered infant formula (PIF) which, with an aw of ∼0.2, is too low to allow most microorganisms to persist. Survival of C. sakazakii in environments subject to extreme hyperosmotic stress has previously been attributed to the uptake of compatible solutes including proline and betaine. Herein, we report the construction and screening of a C. sakazakii genome bank and the identification of ProP (ESA_02131) as a carnitine uptake system.

[Nutritional epigenetics and epigenetic effects of human breast milk].

PubMed

Lukoyanova, O L; Borovik, T E

The article provides an overview of the current literature on nutritional epigenetics. There are currently actively studied hypothesis that nutrition especially in early life or in critical periods of the development, may have a role in modulating gene expression, and, therefore, have later effects on health in adults. Nutritional epigenetics concerns knowledge about the possible effects of nutrients on gene expression. Human breast milk is well-known for its ability in preventing necrotizing enterocolitis, infectious diseases, and also non-communicable diseases, such as obesity and related disorders. This paper discusses about presumed epigenetic effects of human breast milk and some its components. While evidence suggests that a direct relationship may exist of some components of human breast milk with epigenetic changes, the mechanisms involved are stillunclear.

Probiotics and Innate and Adaptive Immune Responses in Premature Infants

PubMed Central

Underwood, Mark A.

2017-01-01

Premature infants are at increased risk for morbidity and mortality due to necrotizing enterocolitis (NEC) and sepsis. Probiotics decrease the risk of NEC and death in premature infants; however, mechanisms of action are unclear. A wide variety of probiotic species have been evaluated for potential beneficial properties in vitro, in animal models, and in clinical trials of premature infants. Although there is variation by species and even strain, common mechanisms of protection include attenuation of intestinal inflammation, apoptosis, dysmotility, permeability, supplanting other gut microbes through production of bacteriocins, and more effective use of available nutrients. Here, we review the most promising probiotics and what is known about their impact on the innate and adaptive immune response. PMID:28966796

CRISPR-cas loci profiling of Cronobacter sakazakii pathovars.

PubMed

Ogrodzki, Pauline; Forsythe, Stephen James

2016-12-01

Cronobacter sakazakii sequence types 1, 4, 8 and 12 are associated with outbreaks of neonatal meningitis and necrotizing enterocolitis infections. However clonality results in strains which are indistinguishable using conventional methods. This study investigated the use of clustered regularly interspaced short palindromic repeats (CRISPR)-cas loci profiling for epidemiological investigations. Seventy whole genomes of C. sakazakii strains from four clonal complexes which were widely distributed temporally, geographically and origin of source were profiled. All strains encoded the same type I-E subtype CRISPR-cas system with a total of 12 different CRISPR spacer arrays. This study demonstrated the greater discriminatory power of CRISPR spacer array profiling compared with multilocus sequence typing, which will be of use in source attribution during Cronobacter outbreak investigations.

Probiotics for gastrointestinal disorders: Proposed recommendations for children of the Asia-Pacific region.

PubMed

Cameron, Donald; Hock, Quak Seng; Kadim, Musal; Mohan, Neelam; Ryoo, Eell; Sandhu, Bhupinder; Yamashiro, Yuichiro; Jie, Chen; Hoekstra, Hans; Guarino, Alfredo

2017-12-07

Recommendations for probiotics are available in several regions. This paper proposes recommendations for probiotics in pediatric gastrointestinal diseases in the Asia-Pacific region. Epidemiology and clinical patterns of intestinal diseases in Asia-Pacific countries were discussed. Evidence-based recommendations and randomized controlled trials in the region were revised. Cultural aspects, health management issues and economic factors were also considered. Final recommendations were approved by applying the Likert scale and rated using the GRADE system. Saccharomyces boulardii CNCM I-745 (Sb) and Lactobacillus rhamnosus GG ( LGG ) were strongly recommended as adjunct treatment to oral rehydration therapy for gastroenteritis. Lactobacillus reuteri could also be considered. Probiotics may be considered for prevention of (with the indicated strains): antibiotic-associated diarrhea (LGG or Sb); Clostridium difficile -induced diarrhea (Sb); nosocomial diarrhea (LGG); infantile colic ( L reuteri ) and as adjunct treatment of Helicobacter pylori (Sb and others). Specific probiotics with a history of safe use in preterm and term infants may be considered in infants for prevention of necrotizing enterocolitis. There is insufficient evidence for recommendations in other conditions. Despite a diversity of epidemiological, socioeconomical and health system conditions, similar recommendations apply well to Asia pacific countries. These need to be validated with local randomized-controlled trials.

The knowns and unknowns of human milk banking.

PubMed

Simmer, Karen

2011-01-01

The provision of donor human milk instead of formula is an important contribution to the nutrition and protection from infections for preterm infants. Systematic reviews suggest a lower risk of necrotizing enterocolitis with pasteurized donor human milk (PDHM) as opposed to artificial formula, although evidence supporting PDHM use from randomized control trials is limited. Human milk banks (HMBs) must have a risk management system to maintain a safe product especially as many operate in an unregulated environment. To ensure safety, the HMB in Australia has committed to meet the appropriate standards recommended in the Code of Good Manufacturing Practices (Blood and Tissues) and models risk management during processing on Codex HACCP (Hazard Analysis Critical Control Point) requirements. There is scope to continually reevaluate the screening of donors and quality standards recommended during HMB. This will be most effective if strong networks of HMBs are developed with regional reference laboratories to encourage compliance with safety guidelines. Further research and development is needed to refine technology for treating donor milk such as thermal ultrasound and ultraviolet light, aimed at the retention of full bioactivity. HMB networks will facilitate collection of evidence for refining HMB practice which should translate to improved outcomes for preterm and sick infants. Cost effectiveness is most likely when HMBs are associated with large neonatal intensive care units. Copyright © 2011 S. Karger AG, Basel.

Treatment of patent ductus arteriosus and neonatal mortality/morbidities: adjustment for treatment selection bias.

PubMed

Mirea, Lucia; Sankaran, Koravangattu; Seshia, Mary; Ohlsson, Arne; Allen, Alexander C; Aziz, Khalid; Lee, Shoo K; Shah, Prakesh S

2012-10-01

To examine the association between treatment for patent ductus arteriosus (PDA) and neonatal outcomes in preterm infants, after adjustment for treatment selection bias. Secondary analyses were conducted using data collected by the Canadian Neonatal Network for neonates born at a gestational age ≤ 32 weeks and admitted to neonatal intensive care units in Canada between 2004 and 2008. Infants who had PDA and survived beyond 72 hours were included in multivariable logistic regression analyses that compared mortality or any severe neonatal morbidity (intraventricular hemorrhage grades ≥ 3, retinopathy of prematurity stages ≥ 3, bronchopulmonary dysplasia, or necrotizing enterocolitis stages ≥ 2) between treatment groups (conservative management, indomethacin only, surgical ligation only, or both indomethacin and ligation). Propensity scores (PS) were estimated for each pair of treatment comparisons, and used in PS-adjusted and PS-matched analyses. Among 3556 eligible infants with a diagnosis of PDA, 577 (16%) were conservatively managed, 2026 (57%) received indomethacin only, 327 (9%) underwent ligation only, and 626 (18%) were treated with both indomethacin and ligation. All multivariable and PS-based analyses detected significantly higher mortality/morbidities for surgically ligated infants, irrespective of prior indomethacin treatment (OR ranged from 1.25-2.35) compared with infants managed conservatively or those who received only indomethacin. No significant differences were detected between infants treated with only indomethacin and those managed conservatively. Surgical ligation of PDA in preterm neonates was associated with increased neonatal mortality/morbidity in all analyses adjusted for measured confounders that attempt to account for treatment selection bias. Copyright © 2012 Mosby, Inc. All rights reserved.

Inhibition of Cronobacter sakazakii Virulence Factors by Citral

PubMed Central

Shi, Chao; Sun, Yi; Liu, Zhiyuan; Guo, Du; Sun, Huihui; Sun, Zheng; Chen, Shan; Zhang, Wenting; Wen, Qiwu; Peng, Xiaoli; Xia, Xiaodong

2017-01-01

Cronobacter sakazakii is a foodborne pathogen associated with fatal forms of necrotizing enterocolitis, meningitis and sepsis in neonates and infants. The aim of this study was to determine whether citral, a major component of lemongrass oil, could suppress putative virulence factors of C. sakazakii that contribute to infection. Sub-inhibitory concentrations of citral significantly decreased motility, quorum sensing, biofilm formation and endotoxin production. Citral substantially reduced the adhesion and invasion of C. sakazakii to Caco-2 cells and decreased bacterial survival and replication within the RAW 264.7 macrophage cells. Citral also repressed the expression of eighteen genes involved in the virulence. These findings suggest that citral has potential to be developed as an alternative or supplemental agent to mitigate the infections caused by C. sakazakii. PMID:28233814

Defensin-barbed innate immunity: clinical associations in the pediatric population.

PubMed

Underwood, Mark A; Bevins, Charles L

2010-06-01

Defensins and related antimicrobial peptides serve a central role in innate immunity in all species of plants and animals. In humans, defensins are widely expressed, including in neutrophils, skin, and mucosal epithelia. Most defensins are potent antibiotics, and some have chemotactic and toxin-neutralizing activities. Results of recent studies on the homeostatic and disease-fighting activities of human defensins point to a key relevance in several pediatric disorders. Inherited variation in defensin gene expression may contribute to susceptibility to several diseases, including psoriasis and Crohn disease. We review here the recent discoveries in innate immunity that shed light on the potential roles of defensins, and other antimicrobial molecules, in the pathophysiology of common pediatric diseases such as atopic dermatitis, necrotizing enterocolitis, cystic fibrosis, and otitis media.

Oxidative Stress Related Diseases in Newborns

PubMed Central

Aykac, Kubra

2016-01-01

We review oxidative stress-related newborn disease and the mechanism of oxidative damage. In addition, we outline diagnostic and therapeutic strategies and future directions. Many reports have defined oxidative stress as an imbalance between an enhanced reactive oxygen/nitrogen species and the lack of protective ability of antioxidants. From that point of view, free radical-induced damage caused by oxidative stress seems to be a probable contributing factor to the pathogenesis of many newborn diseases, such as respiratory distress syndrome, bronchopulmonary dysplasia, periventricular leukomalacia, necrotizing enterocolitis, patent ductus arteriosus, and retinopathy of prematurity. We share the hope that the new understanding of the concept of oxidative stress and its relation to newborn diseases that has been made possible by new diagnostic techniques will throw light on the treatment of those diseases. PMID:27403229

Virulent and pathogenic features on the Cronobacter sakazakii polymyxin resistant pmr mutant strain s-3.

PubMed

Bao, Xuerui; Yang, Ling; Chen, Lequn; Li, Bing; Li, Lin; Li, Yanyan; Xu, Zhenbo

2017-09-01

Cronobacter sakazakii is a well-known opportunistic pathogen responsible for necrotizing enterocolitis, meningitis and septicaemia in the premature, immunocompromised infants and neonates. This pathogen possesses various virulence factors and regulatory systems, and pmrA/pmrB regulatory system has been identified in a variety of bacterial species. The current study aims to investigate role of pmrA gene in the pathogenicity and virulence characteristics of Cronobacter sakazakii using whole genome sequencing and RNA-seq. Results demonstrated that the absence of pmrA has the potential to affect Cronobacter sakazakii on its pathogenicity, virulence and resistance abilities by regulating expression of numerous related genes, including CusB, CusC, CusR and ESA_pESA3p05434. Copyright © 2017 Elsevier Ltd. All rights reserved.

Intestinal microbiota and blue baby syndrome

PubMed Central

Ellis, Collin L; Rutledge, John C

2010-01-01

Necrotizing enterocolitis (NEC) is the most common intestinal emergency among premature infants. Risk factors in premature infants include immature intestinal immunity and an intestinal microbiota dominated by hospital-acquired bacteria. Some probiotics have been shown to decrease the incidence of NEC in premature infants. Among term infants, NEC is rare. However, among term infants with cyanotic congenital heart disease (CCHD), the incidence of NEC is similar to that of premature infants but with even greater mortality rates. Mechanisms by which NEC occurs in term infants with CCHD are unknown. Of central interest is the potential role of changes in the intestinal microbiota and whether these can be modified with probiotic bacteria; accordingly, we review the literature, propose hypotheses and present the rationale for future studies involving preliminary probiotic clinical trials. PMID:21468216

[About two cases of primitive necrotizing fasciitis of the chest wall].

PubMed

Rabiou, S; Lakranbi, M; Issoufou, I; Ammor, F Z; Belliraj, L; Ouadnouni, Y; Smahi, M

2016-05-01

Necrotizing fasciitis is a severe bacterial necrotic infection that affects the skin and soft tissues. We report a rare observation of necrotizing fasciitis located at the thoracic wall. The management requires an appropriate antibiotherapy preceding a large necrosectomy taking all the affected areas, thus preparing the underlying tissues for a possible skin graft. Through these two observations and a literature review, we describe the medical and surgical management of necrotizing fasciitis. Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Intestinal lesions in dogs with acute hemorrhagic diarrhea syndrome associated with netF-positive Clostridium perfringens type A.

PubMed

Leipig-Rudolph, Miriam; Busch, Kathrin; Prescott, John F; Mehdizadeh Gohari, Iman; Leutenegger, Christian M; Hermanns, Walter; Wolf, Georg; Hartmann, Katrin; Verspohl, Jutta; Unterer, Stefan

2018-04-01

Acute hemorrhagic diarrhea syndrome (AHDS), formerly named canine hemorrhagic gastroenteritis, is one of the most common causes of acute hemorrhagic diarrhea in dogs, and is characterized by acute onset of diarrhea, vomiting, and hemoconcentration. To date, histologic examinations have been limited to postmortem specimens of only a few dogs with AHDS. Thus, the aim of our study was to describe in detail the distribution, character, and grade of microscopic lesions, and to investigate the etiology of AHDS. Our study comprised 10 dogs with AHDS and 9 control dogs of various breeds, age, and sex. Endoscopic biopsies of the gastrointestinal tract were taken and examined histologically (H&E, Giemsa), immunohistochemically ( Clostridium spp., parvovirus), and bacteriologically. The main findings were acute necrotizing and neutrophilic enterocolitis (9 of 10) with histologic detection of clostridia-like, gram-positive bacteria on the necrotic mucosal surface (9 of 10). Clostridium perfringens isolated from the duodenum was identified as type A (5 of 5) by multiplex PCR (5 of 5). In addition, each of the 5 genotyped isolates encoded the pore-forming toxin netF. Clostridium spp. (not C. perfringens) were cultured from duodenal biopsies in 2 of 9 control dogs. These findings suggest that the pore-forming netF toxin is responsible for the necrotizing lesions in the intestines of a significant proportion of dogs with AHDS. Given that the stomach was not involved in the process, the term "acute hemorrhagic diarrhea syndrome" seems more appropriate than the frequently used term "hemorrhagic gastroenteritis."

Outcomes of expectantly managed pregnancies with multiple gestations and preterm premature rupture of membranes prior to 26 weeks.

PubMed

Wong, Luchin F; Holmgren, Calla M; Silver, Robert M; Varner, Michael W; Manuck, Tracy A

2015-02-01

The objective of the study was to determine the obstetric and neonatal outcomes of expectantly managed multifetal pregnancies complicated by early preterm premature rupture of membranes (PPROM) prior to 26 weeks. This was a retrospective cohort of all multifetal pregnancies complicated by documented PPROM occurring before 26 0/7 weeks and managed expectantly by a single maternal-fetal medicine practice between July 4, 2002, and Sept. 1, 2013. Neonatal and maternal outcomes were assessed and comparisons made between the fetus with ruptured membranes and the first fetus to deliver with intact membranes. Twenty-three pregnancies (46 fetuses) were analyzed with a median gestational age at PPROM of 22.9 weeks; 74% experienced PPROM at less than 24 weeks' gestation. A median latency of 11 days was achieved with expectant management. Of the 46 neonates, 20 (43%) survived to hospital discharge. Of these, 12 (60%) experienced severe neonatal morbidity defined as defined as grade III or IV intraventricular hemorrhage, bronchopulmonary dysplasia, pulmonary hypoplasia, necrotizing enterocolitis requiring surgical intervention, and/or grade 3 or 4 retinopathy of prematurity. Eight neonates survived to hospital discharge without severe neonatal morbidity. The multiple with ruptured membranes was more likely to experience intrauterine demise but otherwise had similar outcomes as the multiple with intact membranes. Maternal morbidity was considerable, with 7 of 23 pregnancies (30%) complicated by clinical chorioamnionitis, 12 of 23 (52%) delivering by cesarean, of which 3 of 12 (25%) were classical cesarean deliveries. Overall, neonatal survival to hospital discharge was 43%, but only 17% survived without significant neonatal morbidity. These data provide a basis for counseling and management of women with multifetal gestation complicated by very early PPROM. Copyright © 2015 Elsevier Inc. All rights reserved.

Costs of necrotizing enterocolitis and cost-effectiveness of exclusively human milk-based products in feeding extremely premature infants.

PubMed

Ganapathy, Vaidyanathan; Hay, Joel W; Kim, Jae H

2012-02-01

This study evaluated the cost-effectiveness of a 100% human milk-based diet composed of mother's milk fortified with a donor human milk-based human milk fortifier (HMF) versus mother's milk fortified with bovine milk-based HMF to initiate enteral nutrition among extremely premature infants in the neonatal intensive care unit (NICU). A net expected costs calculator was developed to compare the total NICU costs among extremely premature infants who were fed either a bovine milk-based HMF-fortified diet or a 100% human milk-based diet, based on the previously observed risks of overall necrotizing enterocolitis (NEC) and surgical NEC in a randomized controlled study that compared outcomes of these two feeding strategies among 207 very low birth weight infants. The average NICU costs for an extremely premature infant without NEC and the incremental costs due to medical and surgical NEC were derived from a separate analysis of hospital discharges in the state of California in 2007. The sensitivity of cost-effectiveness results to the risks and costs of NEC and to prices of milk supplements was studied. The adjusted incremental costs of medical NEC and surgical NEC over and above the average costs incurred for extremely premature infants without NEC, in 2011 US$, were $74,004 (95% confidence interval, $47,051-$100,957) and $198,040 (95% confidence interval, $159,261-$236,819) per infant, respectively. Extremely premature infants fed with 100% human-milk based products had lower expected NICU length of stay and total expected costs of hospitalization, resulting in net direct savings of 3.9 NICU days and $8,167.17 (95% confidence interval, $4,405-$11,930) per extremely premature infant (p < 0.0001). Costs savings from the donor HMF strategy were sensitive to price and quantity of donor HMF, percentage reduction in risk of overall NEC and surgical NEC achieved, and incremental costs of surgical NEC. Compared with feeding extremely premature infants with mother's milk fortified with bovine milk-based supplements, a 100% human milk-based diet that includes mother's milk fortified with donor human milk-based HMF may result in potential net savings on medical care resources by preventing NEC.

Necrotizing enterocolitis is associated with earlier achievement of enteral autonomy in children with short bowel syndrome.

PubMed

Sparks, Eric A; Khan, Faraz A; Fisher, Jeremy G; Fullerton, Brenna S; Hall, Amber; Raphael, Bram P; Duggan, Christopher; Modi, Biren P; Jaksic, Tom

2016-01-01

Necrotizing enterocolitis (NEC) remains one of the most common underlying diagnoses of short bowel syndrome (SBS) in children. The relationship between the etiology of SBS and ultimate enteral autonomy has not been well studied. This investigation sought to evaluate the rate of achievement of enteral autonomy in SBS patients with and without NEC. Following IRB approval, 109 patients (2002-2014) at a multidisciplinary intestinal rehabilitation program were reviewed. The primary outcome evaluated was achievement of enteral autonomy (i.e. fully weaning from parenteral nutrition). Patient demographics, primary diagnosis, residual small bowel length, percent expected small bowel length, median serum citrulline level, number of abdominal operations, status of the ileocecal valve (ICV), presence of ileostomy, liver function tests, and treatment for bacterial overgrowth were recorded for each patient. Median age at PN onset was 0 weeks [IQR 0-0]. Median residual small bowel length was 33.5 cm [IQR 20-70]. NEC was present in 37 of 109 (33.9%) of patients. 45 patients (41%) achieved enteral autonomy after a median PN duration of 15.3 [IQR 7.2-38.4]months. Overall, 64.9% of patients with NEC achieved enteral autonomy compared to 29.2% of patients with a different primary diagnosis (p=0.001, Fig. 1). Patients with NEC remained more likely than those without NEC to achieve enteral autonomy after two (45.5% vs. 12.0%) and four (35.7% vs. 6.3%) years on PN (Fig. 1). Logistic regression analysis demonstrated the following parameters as independent predictors of enteral autonomy: diagnosis of NEC (p<0.002), median serum citrulline level (p<0.02), absence of a jejunostomy or ileostomy (p=0.013), and percent expected small bowel length (p=0.005). Children with SBS because of NEC have a significantly higher likelihood of fully weaning from parenteral nutrition compared to children with other causes of SBS. Additionally, patients with NEC may attain enteral autonomy even after long durations of parenteral support. Copyright © 2016 Elsevier Inc. All rights reserved.

Variability in Antibiotic Regimens for Surgical Necrotizing Enterocolitis Highlights the Need for New Guidelines.

PubMed

Blackwood, Brian P; Hunter, Catherine J; Grabowski, Julia

Necrotizing enterocolitis or NEC is the most common gastrointestinal emergency in the newborn. The etiology of NEC remains unknown, and treatment consists of antibiotic therapy and supportive care with the addition of surgical intervention as necessary. Unlike most surgical diseases, clear guidelines for the type and duration of peri-operative antibiotic therapy have not been established. Our aim was to review the antibiotic regimen(s) applied to surgical patients with NEC within a single neonatal intensive care unit (NICU) and to evaluate outcomes and help develop guidelines for antibiotic administration in this patient population. A single-center retrospective review was performed of all patients who underwent surgical intervention for NEC from August 1, 2005 through August 1, 2015. Relevant data were extracted including gestational age, age at diagnosis, gender, pre-operative antibiotic treatment, post-operative antibiotic treatment, development of stricture, and mortality. Patients were excluded if there was incomplete data documentation. A total of 90 patients were identified who met inclusion criteria. There were 56 male patients and 34 female patients. The average gestational age was 30 5/7 wks and average age of diagnosis 16.7 d. A total of 22 different pre-operative antibiotic regimens were identified with an average duration of 10.6 d. The most common pre-operative regimen was ampicillin, gentamicin, and metronidazole for 14 d. A total of 15 different post-operative antibiotic regimens were identified with an average duration of 6.6 d. The most common post-operative regimen was ampicillin, gentamicin, and metronidazole for two days. There were 26 strictures and 15 deaths. No regimen or duration proved superior. We found that there is a high degree of variability in the antibiotic regimen for the treatment of NEC, even within a single NICU, with no regimen appearing superior over another. As data emerge that demonstrate the adverse effects of antibiotic overuse, our findings highlight the need for guidelines in the antibiotic treatment of NEC and suggest that an abbreviated course of post-operative antibiotics may be safe.

Immunoregulatory Protein Profiles of Necrotizing Enterocolitis versus Spontaneous Intestinal Perforation in Preterm Infants

PubMed Central

Leung, Fiona Wan Lun; Lam, Hugh Simon; Tam, Yuk Him; To, Ka Fai; Cheung, Hon Ming; Leung, Kam Tong; Poon, Terence Chuen Wai; Lee, Kim Hung; Li, Karen; Fok, Tai Fai

2012-01-01

Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are the most common acute surgical emergencies associated with high morbidity and mortality in preterm infants. We aimed to compare the profiles of immunoregulatory proteins and identify novel mediators in plasma of NEC and SIP infants. We also investigated the expression of target genes in resected intestinal tissues and an enterocyte cell line. Using Cytokine Antibody Array assay, we reported the first comparative profiles of immunoregulatory proteins in plasma of NEC and SIP infants, and showed that dysregulated proteins belonged to functionally diversified categories, including pro- and anti-inflammation, angiogenesis, cell growth, wound healing, anti-apoptosis, cell adhesion and extracellular matrix reorganization. Validation by ELISA confirmed significantly higher concentrations of interleukin (IL)-6, angiopoietin (Ang)-2, soluble type II interleukin-1 receptor (sIL-1RII), and soluble urokinase-type plasminogen activator receptor (suPAR) in NEC infants compared with gestational age-matched control, and a lower level of an epidermal growth factor receptor, secreted form of receptor tyrosine-protein kinase ErbB3 (sErbB3), compared with SIP infants. mRNA expressions of IL1-RII and uPAR were up-regulated in resected bowel tissues from NEC infants, indicating that immunoregulation also occurred at the cellular level. In FHs-74 Int cells, Ang-2, IL1-RII and uPAR mRNA expressions were significantly induced by the combined treatment with lipopolysaccharide (LPS) and platelet activating factor (PAF). Our study provided plasmatic signatures of immunoregulatory proteins in NEC and SIP infants, and demonstrated involvement of multiple functional pathways. The magnitude of changes in these proteins was significantly more extensive in NEC infants, reflecting the different nature of injury and/or severity of inflammation. We speculate that dysregulation of IL-6, Ang-2, IL-1RII and uPAR occurred at both systemic and cellular levels, and probably mediated via LPS and endogeneous PAF signals. Such exaggerated immunologic responses may account for the high morbidity and mortality in NEC compared with SIP patients. PMID:22606320

Effects of Probiotics on Necrotizing Enterocolitis, Sepsis, Intraventricular Hemorrhage, Mortality, Length of Hospital Stay, and Weight Gain in Very Preterm Infants: A Meta-Analysis.

PubMed

Sun, Jing; Marwah, Gayatri; Westgarth, Matthew; Buys, Nicholas; Ellwood, David; Gray, Peter H

2017-09-01

Probiotics are increasingly used as a supplement to prevent adverse health outcomes in preterm infants. We conducted a systematic review, meta-analysis, and subgroup analysis of findings from randomized controlled trials (RCTs) to assess the magnitude of the effect of the probiotics on health outcomes among very-low-birth-weight (VLBW) infants. Relevant articles from January 2003 to June 2017 were selected from a broad range of databases, including Medline, PubMed, Scopus, and Embase. Studies were included if they used an RCT design, involved a VLBW infant (birthweight <1500 g or gestational age <32 wk) population, included a probiotic intervention group, measured necrotizing enterocolitis (NEC) as a primary outcome, and measured sepsis, mortality, length of hospital stay, weight gain, and intraventricular hemorrhage (IVH) as additional outcomes. The initial database search yielded 132 potentially relevant articles and 32 ( n = 8998 infants) RCTs were included in the final meta-analysis. Subgroup analysis was used to evaluate the effects of the moderators on the outcome variables. In the probiotics group, it was found that NEC was reduced by 37% (95% CI: 0.51%, 0.78%), sepsis by 37% (95% CI: 0.72%, 0.97%), mortality by 20% (95% CI: 0.67%, 0.95%), and length of hospital stay by 3.77 d (95% CI: -5.94, -1.60 d). These findings were all significant when compared with the control group. There was inconsistent use of strain types among some of the studies. The results indicate that probiotic consumption can significantly reduce the risk of developing medical complications associated with NEC and sepsis, reduce mortality and length of hospital stay, and promote weight gain in VLBW infants. Probiotics are more effective when taken in breast milk and formula form, consumed for <6 wk, administered with a dosage of <10 9 CFU/d, and include multiple strains. Probiotics are not effective in reducing the incidence of IVH in VLBW infants. © 2017 American Society for Nutrition.

Multiple strains probiotics appear to be the most effective probiotics in the prevention of necrotizing enterocolitis and mortality: An updated meta-analysis

PubMed Central

Chang, Hung-Yang; Chen, Jin-Hua; Chang, Jui-Hsing; Lin, Hung-Chih; Lin, Chien-Yu; Peng, Chun-Chih

2017-01-01

Background Some oral probiotics have been shown to prevent necrotizing enterocolitis (NEC) and decrease mortality effectively in preterm very low birth weight (PVLBW) infants. However, it is unclear whether a single probiotic or a mixture of probiotics is most effective for the prevention of NEC. Objective A meta-analysis was conducted by reviewing the most up to date literature to investigate whether multiple strains probiotics are more effective than a single strain in reducing NEC and death in PVLBW infants. Data sources Relevant studies were identified by searches of the MEDLINE, EMBASE, and Cochrane CENTRAL databases, from 2001 to 2016. Data extraction and synthesis The inclusion criteria were randomized controlled trials of any enteral probiotic supplementation that was initiated within the first 7 days and continued for at least 14 days in preterm infants (≤ 34 weeks’ gestation) and/or those of a birth weight ≤1500 g. Results A total of 25 trials (n = 7345 infants) were eligible for inclusion in the meta-analysis using a fixed-effects model. Multiple strains probiotics were associated with a marked reduction in the incidence of NEC, with a pooled OR of 0.36 (95% CI, 0.24–0.53; P < .00001). Single strain probiotic using Lactobacillus species had a borderline effect in reducing NEC (OR of 0.60; 95% CI 0.36–1.0; P = .05), but not mortality. Multiple strains probiotics had a greater effectiveness in reducing mortality and were associated with a pooled OR of 0.58 (95% CI, 0.43–0.79; P = .0006). Trials using single strain of Bifidobacterium species and Saccharomyces boulardii did not reveal any beneficial effects in terms of reducing NEC or mortality. Conclusion This updated report found that multiple strains probiotics appear to be the most feasible and effective strategy for the prevention of NEC and reduction of mortality in PVLBW neonates. Further clinical trials should focus on which probiotic combinations are most effective. PMID:28182644

Role of amino acid supplementation in the prevention of necrotizing enterocolitis in preterm neonates - a review of current evidences.

PubMed

Garg, Bhawan Deep; Kabra, Nandkishor S

2018-09-01

Necrotizing enterocolitis (NEC) is one of the most common acute and fatal gastrointestinal emergency in very low birth weight (VLBW) preterm neonates with mortality range from 15 to 30%. NEC is likely due to multifactorial process such as oxidative injury, ischemic necrosis, and over-reactive inflammatory response to intestinal microbes. To evaluate the role of amino acid supplementation for reduction of neonatal NEC in preterm neonates. The literature search was done for various randomized control trial (RCT) by searching the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of Science, Scopus, Index Copernicus, African Index Medicus (AIM), Thomson Reuters (ESCI), Chemical Abstracts Service (CAS) and other database. This review included 15 RCTs that fulfilled inclusion criteria. The total neonates enrolled in these different RCT are 3424 (amino acid group 1711 and control 1713). Almost all participating neonates were of VLBW or extremely low birth weight (ELBW). In two trials, birth weight was between 1500-2000 grams. The intervention was started within first few days after birth and continued up to 30th day of postnatal age in most of the trials. In two trials, intervention was continued up to 120th day of postnatal age. Arginine, glutamine and N-acetyl cysteine (NAC) were used at the dose of 1.5 mol/kg/day (261 mg/kg/day), 0.3 grams/kg/day and 16-32 mg/kg/day, respectively. Role of amino acid in the prevention of neonatal NEC is not exclusively supported by the current evidence. Only three studies were able to show reduction in the incidence of NEC with amino acid supplementation (arginine, glutamine), and the remaining studies did not report any positive effect. Amino acid supplementation was not associated with significant reduction in mortality due to any causes. However, arginine supplementation was associated with significant reduction in mortality due to NEC. Two studies on glutamine were reported significant reduction in the incidence of invasive infection. Only one study reported significant positive effects on growth parameters and less time to reach full enteral feeds. None of the studies showed any effect on the duration of hospital stay.

Perinatal outcome and later implications of intrauterine growth restriction.

PubMed

Pallotto, Eugenia K; Kilbride, Howard W

2006-06-01

This chapter reviews outcomes for children who have intrauterine growth retardation (IUGR) or small-for-gestation-age (SGA) status at birth. Such infants are at risk for increased perinatal mortality, birth adaptation complications, including perinatal acidosis, hypoglycemia, hypothermia, coagulation abnormalities, and selected immunologic deficiencies. IUGR infants also appear to be at great risk for complications of prematurity, including chronic lung disease and necrotizing enterocolitis. Childhood implications for IUGR include an increased risk for short stature, cognitive delays with decreased academic achievement, and a small but significant increased risk of neurologic disorders, including cerebral palsy. Low socioeconomic status is correlated with the occurrence of IUGR and is significantly related to long-term disabilities. Morbidities associated with preterm delivery appear to be additive to those associated with fetal growth restriction so IUGR, preterm infants may be at great risk for poor neurodevelopmental outcome.

Probiotics in Pediatric Liver Disease.

PubMed

Miloh, Tamir

2015-01-01

The gut-liver axis involves complex interaction between the intestinal microbiome and the liver parenchyma. Probiotics are live microorganisms that are used in a variety of diseases. With currently only 2 randomized-controlled studies (one with Lactobacillus GG and the other with VSL #3), data are scarce to support the clinical effect of probiotic use in children with nonalcoholic fatty liver disease. There is evidence that probiotics decrease the risk of necrotizing enterocolitis and thereby reduce the prevalence of total parenteral nutrition-induced chronic liver disease. Probiotics are used with a few reported positive outcomes in patients with cystic fibrosis and familial hypercholesterolemia and may be promising in other liver conditions. Probiotics are generally safe and well tolerated in children, premature infants, and in patients after liver transplantation. Large, prospective, randomized clinical trials are needed to evaluate the benefit of probiotics in children with liver diseases.

Probiotics for gastrointestinal disorders: Proposed recommendations for children of the Asia-Pacific region

PubMed Central

Cameron, Donald; Hock, Quak Seng; Kadim, Musal; Mohan, Neelam; Ryoo, Eell; Sandhu, Bhupinder; Yamashiro, Yuichiro; Jie, Chen; Hoekstra, Hans; Guarino, Alfredo

2017-01-01

Recommendations for probiotics are available in several regions. This paper proposes recommendations for probiotics in pediatric gastrointestinal diseases in the Asia-Pacific region. Epidemiology and clinical patterns of intestinal diseases in Asia-Pacific countries were discussed. Evidence-based recommendations and randomized controlled trials in the region were revised. Cultural aspects, health management issues and economic factors were also considered. Final recommendations were approved by applying the Likert scale and rated using the GRADE system. Saccharomyces boulardii CNCM I-745 (Sb) and Lactobacillus rhamnosus GG (LGG) were strongly recommended as adjunct treatment to oral rehydration therapy for gastroenteritis. Lactobacillus reuteri could also be considered. Probiotics may be considered for prevention of (with the indicated strains): antibiotic-associated diarrhea (LGG or Sb); Clostridium difficile-induced diarrhea (Sb); nosocomial diarrhea (LGG); infantile colic (L reuteri) and as adjunct treatment of Helicobacter pylori (Sb and others). Specific probiotics with a history of safe use in preterm and term infants may be considered in infants for prevention of necrotizing enterocolitis. There is insufficient evidence for recommendations in other conditions. Despite a diversity of epidemiological, socioeconomical and health system conditions, similar recommendations apply well to Asia pacific countries. These need to be validated with local randomized-controlled trials. PMID:29259371

Vedolizumab treatment for immune checkpoint inhibitor-induced enterocolitis.

PubMed

Bergqvist, Viktoria; Hertervig, Erik; Gedeon, Peter; Kopljar, Marija; Griph, Håkan; Kinhult, Sara; Carneiro, Ana; Marsal, Jan

2017-05-01

Immune checkpoint inhibitors (ICPI), such as ipilimumab [anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody] and nivolumab or pembrolizumab [anti-programmed cell death protein-1 (PD-1) antibodies], improve survival in several cancer types. Since inhibition of CTLA-4 or PD-1 leads to non-selective activation of the immune system, immune-related adverse events (irAEs) are frequent. Enterocolitis is a common irAE, currently managed with corticosteroids and, if necessary, anti-tumor necrosis factor-α therapy. Such a regimen carries a risk of serious side-effects including infections, and may potentially imply impaired antitumor effects. Vedolizumab is an anti-integrin α4β7 antibody with gut-specific immunosuppressive effects, approved for Crohn's disease and ulcerative colitis. We report a case series of seven patients with metastatic melanoma or lung cancer, treated with vedolizumab off-label for ipilimumab- or nivolumab-induced enterocolitis, from June 2014 through October 2016. Clinical, laboratory, endoscopic, and histologic data were analyzed. Patients initially received corticosteroids but were steroid-dependent and/or partially refractory. One patient was administered infliximab but was refractory. The median time from onset of enterocolitis to start of vedolizumab therapy was 79 days. Following vedolizumab therapy, all patients but one experienced steroid-free enterocolitis remission, with normalized fecal calprotectin. This was achieved after a median of 56 days from vedolizumab start, without any vedolizumab-related side-effects noted. The patient in whom vedolizumab was not successful, due to active ulcerative colitis, received vedolizumab prophylactically. This is the first case series to suggest that vedolizumab is an effective and well-tolerated therapeutic for steroid-dependent or partially refractory ICPI-induced enterocolitis. A larger prospective study to evaluate vedolizumab in this indication is warranted.

Necrotizing Fasciitis

PubMed Central

Sadasivan, Jagdish; Maroju, Nanda Kishore; Balasubramaniam, Anandh

2013-01-01

Necrotizing fasciitis (NF) is among the most challenging surgical infections faced by a surgeon. The difficulty in managing this entity is due to a combination of difficulty in diagnosis, and also of early as well as late management. For the patient, such a diagnosis means prolonged hospital stay, painful dressings, an extended recovery, and in some unfortunate cases even loss of limb or life. Necrotizing fasciitis is a fairly common condition in surgical practice in the Indian context resulting in a fairly large body of clinical experience. This article reviews literature on MEDLINE with the key words “necrotizing,” “fasciitis,” and “necrotizing infections” from 1970, as well as from articles cross referenced therein. The authors attempt to draw comparisons to their own experience in managing this condition to give an Indian perspective to the condition. PMID:24459334

Radiation Enterocolitis Requiring Surgery in Patients With Gynecological Malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Iraha, Shiro; Ogawa, Kazuhiko; Moromizato, Hidehiko

Purpose: To identify the characteristics, risk factors, and clinical outcomes of radiation enterocolitis requiring surgery in patients with gynecologic malignancies. Methods and Materials: The records of 1,349 patients treated with pelvic radiotherapy were retrospectively reviewed. The majority of the patients (88%) were treated with 50 Gy or 50.4 Gy pelvic irradiation in conventional fractionations with anteroposterior fields. Results: Forty-eight patients (3.6%) developed radiation enterocolitis requiring surgery. Terminal ileum was the most frequent site (50%) and most of the lesions had stenosis or perforation. On univariate analysis, previous abdominopelvic surgery, diabetes mellitus (DM), smoking and primary site had an impact onmore » the complications, and on multivariate analysis, abdominopelvic surgery, DM, and smoking were independent predictors of the complications requiring surgery. After the surgical intervention, the frequency of Grade 2 or more bleeding was significantly lower in patients treated with intestinal resection in addition to decompression than those treated with intestinal decompression alone. Conclusions: Severe radiation enterocolitis requiring surgery usually occurred at the terminal ileum and was strongly correlated with previous abdominopelvic surgery, DM, and smoking. Concerning the management, liberal resection of the affected bowel appears to be the preferable therapy.« less

Role of Lactoferrin in Neonates and Infants: An Update.

PubMed

Manzoni, Paolo; Dall'Agnola, Alberto; Tomé, Daniel; Kaufman, David A; Tavella, Elena; Pieretto, Marta; Messina, Alessandro; De Luca, Daniele; Bellaiche, Marc; Mosca, Alexis; Piloquet, Hugues; Simeoni, Umberto; Picaud, Jean-Charles; Del Vecchio, Antonio

2018-05-01

Lactoferrin is one of the most represented and important bioactive proteins in human and mammal milk. In humans, lactoferrin is responsible for several actions targeting anti-infective, immunological, and gastrointestinal domains in neonates, infants, and young children. Evidence-based data vouch for the ability of supplemented lactoferrin to prevent sepsis and necrotizing enterocolitis in preterm infants and to reduce the burden of morbidity related to gastrointestinal and respiratory pathogens in young children. However, several issues remain pending regarding answers and clarification related to quality control, correct intakes, optimal schedules and schemes of supplementations, interactions with probiotics, and different types of milk and formulas. This review summarizes the current evidence regarding lactoferrin and discusses the areas in need of further guidance prior to the adoption of strategies that include a routine use of lactoferrin in neonates and young children. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Estimating the Probability of Rare Events Occurring Using a Local Model Averaging.

PubMed

Chen, Jin-Hua; Chen, Chun-Shu; Huang, Meng-Fan; Lin, Hung-Chih

2016-10-01

In statistical applications, logistic regression is a popular method for analyzing binary data accompanied by explanatory variables. But when one of the two outcomes is rare, the estimation of model parameters has been shown to be severely biased and hence estimating the probability of rare events occurring based on a logistic regression model would be inaccurate. In this article, we focus on estimating the probability of rare events occurring based on logistic regression models. Instead of selecting a best model, we propose a local model averaging procedure based on a data perturbation technique applied to different information criteria to obtain different probability estimates of rare events occurring. Then an approximately unbiased estimator of Kullback-Leibler loss is used to choose the best one among them. We design complete simulations to show the effectiveness of our approach. For illustration, a necrotizing enterocolitis (NEC) data set is analyzed. © 2016 Society for Risk Analysis.

[Human coronavirus infections: importance and diagnosis].

PubMed

Vabret, A; Brouard, J; Petitjean, J; Eugene-Ruellan, G; Freymuth, F

1998-11-14

POORLY-KNOWN VIRUS: Coronaviruses, so named because of their sun-ray-like aspect, were discovered in the sixties. The biology of these RNA viruses is complex and poorly understood. KNOWN PATHOGENS: Coronaviruses are known pathogens in veterinary medicine, causing disease states in several domestic species. In human medicine, they can cause benign respiratory infections, but few laboratories include coronaviruses in their routine diagnostic tests. SUSPECTED PATHOGENS: There is some data in the literature suggesting coronaviruses might be implicated in more severe diseases including multiple sclerosis, necrotizing enterocolitis, and lower respiratory tract infections, particularly in infants. IMPROVING DIAGNOSTIC METHODS: Due to the lack of reliable and sensitive diagnostic techniques, it is impossible to date to correctly assess the medical impact of these ubiquitous and endemic viruses. Molecular biology techniques enabling detection of human coronavirus infections should be applied to verifying the suspected implication of these viruses in diverse disease states.

The introduction of breast milk donation in a Muslim country.

PubMed

al-Naqeeb, N A; Azab, A; Eliwa, M S; Mohammed, B Y

2000-11-01

Breast milk donation (wet-nursing) for full-term babies is a well-known practice in Kuwait, but it has never been organized formally in a neonatal intensive care unit (NICU) for preterm babies. Donor milk banking as conducted in Western society is not considered to be ethical in Muslim society, where the milk donor and the recipient are required to know each other. Human milk is known to decrease the incidence of necrotizing enterocolitis; improve host defenses, digestion, absorption of nutrients, gastrointestinal function, and neurodevelopment of the child; and contribute to maternal physical and psychological well-being. A culturally accepted approach to donor milk banking is proposed as a means of overcoming the ethical issues surrounding milk donation in Muslim society. This report addresses the first step in raising awareness of the valuable contribution of donor milk to preterm babies and the organization of human milk donation for use in an NICU.

Human Milk Banking.

PubMed

Haiden, Nadja; Ziegler, Ekhard E

2016-01-01

Human milk banks play an essential role by providing human milk to infants who would otherwise not be able to receive human milk. The largest group of recipients are premature infants who derive very substantial benefits from it. Human milk protects premature infants from necrotizing enterocolitis and from sepsis, two devastating medical conditions. Milk banks collect, screen, store, process, and distribute human milk. Donating women usually nurse their own infants and have a milk supply that exceeds their own infants' needs. Donor women are carefully selected and are screened for HIV-1, HIV-2, human T-cell leukemia virus 1 and 2, hepatitis B, hepatitis C, and syphilis. In the milk bank, handling, storing, processing, pooling, and bacterial screening follow standardized algorithms. Heat treatment of human milk diminishes anti-infective properties, cellular components, growth factors, and nutrients. However, the beneficial effects of donor milk remain significant and donor milk is still highly preferable in comparison to formula. © 2017 S. Karger AG, Basel.

Deciphering the complexity of acute inflammation using mathematical models.

PubMed

Vodovotz, Yoram

2006-01-01

Various stresses elicit an acute, complex inflammatory response, leading to healing but sometimes also to organ dysfunction and death. We constructed both equation-based models (EBM) and agent-based models (ABM) of various degrees of granularity--which encompass the dynamics of relevant cells, cytokines, and the resulting global tissue dysfunction--in order to begin to unravel these inflammatory interactions. The EBMs describe and predict various features of septic shock and trauma/hemorrhage (including the response to anthrax, preconditioning phenomena, and irreversible hemorrhage) and were used to simulate anti-inflammatory strategies in clinical trials. The ABMs that describe the interrelationship between inflammation and wound healing yielded insights into intestinal healing in necrotizing enterocolitis, vocal fold healing during phonotrauma, and skin healing in the setting of diabetic foot ulcers. Modeling may help in understanding the complex interactions among the components of inflammation and response to stress, and therefore aid in the development of novel therapies and diagnostics.

The Impact of Neonatal Illness on Nutritional Requirements—One Size Does Not Fit All

PubMed Central

Ramel, Sara E.; Brown, Laura D.

2015-01-01

Sick neonates are at high risk for growth failure and poorer neurodevelopment than their healthy counterparts. The etiology of postnatal growth failure in sick infants is likely multi-factorial and includes undernutrition due to the difficulty of feeding them during their illness and instability. Illness also itself induces fundamental changes in cellular metabolism that appear to significantly alter nutritional demand and nutrient handling. Inflammation and physiologic stress play a large role in inducing the catabolic state characteristic of the critically ill newborn infant. Inflammatory and stress responses are critical short-term adaptations to promote survival, but are not conducive to promoting long-term growth and development. Conditions such as sepsis, surgery, necrotizing enterocolitis, chronic lung disease and intrauterine growth restriction and their treatments are characterized by altered energy, protein and micronutrient metabolism that result in nutritional requirements that are different from those of the healthy, growing term or preterm infant. PMID:25722954

Metabolomics in Newborns.

PubMed

Noto, Antonio; Fanos, Vassilios; Dessì, Angelica

2016-01-01

Metabolomics is the quantitative analysis of a large number of low molecular weight metabolites that are intermediate or final products of all the metabolic pathways in a living organism. Any metabolic profiles detectable in a human biological fluid are caused by the interaction between gene expression and the environment. The metabolomics approach offers the possibility to identify variations in metabolite profile that can be used to discriminate disease. This is particularly important for neonatal and pediatric studies especially for severe ill patient diagnosis and early identification. This property is of a great clinical importance in view of the newer definitions of health and disease. This review emphasizes the workflow of a typical metabolomics study and summarizes the latest results obtained in neonatal studies with particular interest in prematurity, intrauterine growth retardation, inborn errors of metabolism, perinatal asphyxia, sepsis, necrotizing enterocolitis, kidney disease, bronchopulmonary dysplasia, and cardiac malformation and dysfunction. © 2016 Elsevier Inc. All rights reserved.

Profiling of Virulence Determinants in Cronobacter sakazakii Isolates from Different Plant and Environmental Commodities.

PubMed

Singh, Niharika; Raghav, Mamta; Narula, Shifa; Tandon, Simran; Goel, Gunjan

2017-05-01

Cronobacter sakazakii is an emerging pathogen causing meningitis, sepsis and necrotizing enterocolitis in neonates and immune-compromised adults. The present study describes the profiling of different virulence factors associated with C. sakazakii isolates derived from plant-based materials and environmental samples (soil, water, and vacuum dust). All the isolates exhibited β-hemolysis and chitinase activity, and were able to utilize inositol. Among the nine virulence-associated genes, hly gene coding for hemolysin was detected in all the isolates followed by ompA (outer membrane protein); however, plasmid-borne genes were detected at a level of 60% for both cpa (cronobacter plasminogen activator) and eitA (Ferric ion transporter protein) gene, respectively. Furthermore, the isolate C. sakazakii N81 showed cytotoxicity for Caco-2 cells. The presence of the virulence determinants investigated in this study indicates the pathogenic potential of C. sakazakii with their plausible connection with clinical manifestations.

THE INTESTINAL MICROBIOME OF INFANTS AND THE USE OF PROBIOTICS

PubMed Central

Indrio, Flavia; Neu, Josef

2011-01-01

Purpose of the review The increasing use of probiotics in neonates deserves scrutiny of the therapeutic as well as potentially harmful effects of these bacteria. In this review we describe the possible application of probiotics in the more common disease in the neonatal period. Recent finding Recent advances our capability to identify microbes and their function in the gastrointestinal tract offer exciting opportunities to discover the pathophysiology of enigmatic diseases such as necrotizing enterocolitis (NEC) and late onset sepsis (LOS) in the neonate. The relationship of the resident intestinal microbes to neural and muscular processes such as intestinal motility and neurodevelopment are also being evaluated. Summary We focus the possibility of the application of probiotics for disorders of motility in the infant, NEC and LOS Here we will summarize some of the recent advances in these areas as they relate to clinical practice and discuss areas where additional research is needed. PMID:21415831

The Impact of the Milk Glycobiome on the Neonate Gut Microbiota

PubMed Central

Pacheco, Alline R.; Barile, Daniela; Underwood, Mark A.; Mills, David A.

2015-01-01

Human milk is a complete source of nourishment for the infant. Exclusive breastfeeding not only sustains the infant’s development but also guides the proliferation of a protective intestinal microbiota. Among the many components of milk that modulate the infant gut microbiota, the milk glycans, which comprise free oligosaccharides, glycoproteins, and glycolipids, are increasingly recognized as drivers of microbiota development and overall gut health. These glycans may display pleiotropic functions, conferring protection against infectious diseases and also acting as prebiotics, selecting for the growth of beneficial intestinal bacteria. The prebiotic effect of milk glycans has direct application to prevention of diseases such as necrotizing enterocolitis, a common and devastating disease of preterm infants. In this article, we review the impact of the human (and bovine) milk glycome on gut health through establishment of a milk-oriented microbiota in the neonate. PMID:25387230

Fortification of human milk for preterm infants.

PubMed

Radmacher, Paula G; Adamkin, David H

2017-02-01

Human milk is the preferred feeding for all infants, including those of very low birth weight (<1500 g). It has both nutritional and anti-infective properties which are especially important for infants at risk for sepsis and necrotizing enterocolitis. When maternal milk is not available or the amount produced is not sufficient to meet daily needs, donor human milk may (should) be used in its place. However, donor human milk is generally term in quality and likely has insufficient protein to promote appropriate growth. Whether donor or mother's own milk, fortification of human milk is required to meet nutrient requirements for growth and development for these preterm infants who are at high risk for growth faltering during the hospital stay. There are multiple strategies and products that may be employed to support desired growth rates. The advent of human milk analyzers may be helpful in a more customized approach to fortification. Copyright © 2016 Elsevier Ltd. All rights reserved.

Feed-related Splanchnic Oxygenation in Preterm Infants With Abnormal Antenatal Doppler Developing Gut Complications.

PubMed

Martini, Silvia; Aceti, Arianna; Beghetti, Isadora; Faldella, Giacomo; Corvaglia, Luigi

2018-05-01

Preterm infants with antenatal absent or reversed end diastolic flow (AREDF) in umbilical arteries are at major risk for gastrointestinal (GI) complications, such as necrotizing enterocolitis, intestinal perforation and feeding intolerance. Near-infrared spectroscopy provides continuous monitoring of splanchnic oxygenation (SrSO2) and may represent a useful tool to predict GI outcomes in this high-risk population. This observational, pilot study assessed feed-related SrSO2 patterns at enteral feeding introduction and full enteral feeding (FEF) achievement in twenty AREDF infants with gestational age ≤34 weeks. Enrolled infants were divided into 2 groups according to the development versus lack of GI complications. Infants developing GI complications showed significantly lower SrSO2 and increased splanchnic oxygen extraction in response to enteral feeds at both enteral feeding introduction and FEF. The potential role of these findings in predicting GI complications in AREDF preterm infants seems promising and deserves further evaluation.

Influence of aggressive nutritional support on growth and development of very low birth weight infants.

PubMed

Xu, Y M; Zhu, X P; Xiao, Z; Yu, L; Zhao, X

2014-01-01

To investigate the influence of the early postnatal aggressive nutritional support on the very low birth weight infants (VLBWI) during hospitalization. Surviving premature infants without obvious deformity, with gestational age more than 28 weeks and less than 32 weeks, birth weight 1,000 g to 1,500 g, admitted in NICU in Affiliated Children's Hospital of Suzhou University during 12 hours after birth and stay for two weeks or more from January 2008 to December 2011 were selected, including 44 cases (admitted from September 2010 to December 2011) in the observation group and 36 cases in the control group (admitted from January 2008 and September 2010). The infants in the observation group were treated by aggressive nutritional management, while traditional nutritional management for infants in the control group. The variations of nutritional intake, weight gain, jaundice index, blood biochemistry, serum electrolytes indexes, and complications were compared between the two groups. Compared to the control group, the average growth rate and the albumin (ALB) and prealbumin (PA) levels two week after birth and before leaving hospital of the infants in the observation group was significantly higher (p < 0.05), and the incidence of the extrauterine growth retardation was significantly decreasing (p < 0.05). However, the days of hyperbilirubinemia, highest value of the serum bilirubin, duration ofjaundice, platelets after intravenous nutrition, liver function, blood lipid levels, blood glucose, blood PH, serum creatinine, urea nitrogen, and electrolytes of the first day and the seventh day after birth and the in- cidence of parenteral nutrition-associated cholestasis (PNAC) and necrotizing enterocolitis (NEC) between the two group had no difference (p > 0.05). The implementation of aggressive nutritional management on the with VLBWI was safe and effective.

Indomethacin prophylaxis or expectant treatment of patent ductus arteriosus in extremely low birth weight infants?

PubMed

Cordero, L; Nankervis, C A; Delooze, D; Giannone, P J

2007-03-01

Indomethacin prophylaxis or expectant treatment are common strategies for the prevention or management of symptomatic patent ductus arteriosus (sPDA). To compare the clinical responses of extremely low birth weight (ELBW) infants to indomethacin prophylaxis with that of other infants who were managed expectantly by being treated with indomethacin or surgically only after an sPDA was detected. Retrospective cohort investigation of 167 ELBW infants who received indomethacin prophylaxis (study) and 167 ELBW infants (control) treated expectantly who were matched by year of birth (1999 to 2006), birth weight, gestational age (GA) and gender. Mothers of the two groups of infants were comparable demographically and on the history of preterm labor, pre-eclampsia, antepartum steroids and cesarean delivery. Study and control infants were similar in birth weight, GA, low 5 min Apgar scores, surfactant administration, the need for arterial blood pressure control, bronchopulmonary dysplasia and neonatal mortality. Necrotizing enterocolitis, spontaneous intestinal perforations, intraventricular hemorrhage grade III to IV, periventricular leukomalacia and stage 3 to 5 retinopathy of prematurity occurred also with similar frequency in both groups of infants. In the indomethacin prophylaxis group, 29% of the infants developed sPDA, and of them 38% responded to indomethacin treatment. In the expectantly treated group, 37% developed sPDA, and of them 59% responded to indomethacin treatment. Overall, surgical ligation rate for sPDA was similar between both groups of patients. In our experience, indomethacin prophylaxis does not show any advantages over expectant early treatment on the management of sPDA in ELBW infants. Although no deleterious effects were observed, prophylaxis exposed a significant number of infants who may have never developed sPDA, to potential indomethacin-related complications.

Postoperative Outcomes of Extremely Low Birth-Weight Infants With Necrotizing Enterocolitis or Isolated Intestinal Perforation

PubMed Central

Blakely, Martin L.; Lally, Kevin P.; McDonald, Scott; Brown, Rebeccah L.; Barnhart, Douglas C.; Ricketts, Richard R.; Thompson, W Raleigh; Scherer, L R.; Klein, Michael D.; Letton, Robert W.; Chwals, Walter J.; Touloukian, Robert J.; Kurkchubasche, Arlett G.; Skinner, Michael A.; Moss, R Lawrence; Hilfiker, Mary L.

2005-01-01

Objective: Purposes of this study were: 1) to compare mortality and postoperative morbidities (intra-abdominal abscess, wound dehiscence, and intestinal stricture) in extremely low birth weight (ELBW) infants who underwent initial laparotomy or drainage for necrotizing enterocolitis (NEC) or isolated intestinal perforation (IP); 2) to determine the ability to distinguish NEC from IP preoperatively and the importance of this distinction on outcome measures; and 3) to evaluate the association between extent of intestinal disease determined at operation and outcome measures. Background: ELBW infants who undergo operation for NEC or IP have a postoperative, in-hospital mortality rate of approximately 50%. Whether to perform laparotomy or drainage initially is controversial. Also unknown is the importance of distinguishing NEC from IP and the current ability to make this distinction based on objective data available prior to operation. Methods: A prospective, multicenter cohort study of 156 ELBW infants at 16 neonatal intensive care units (NICU) within the NICHD Neonatal Research Network. Results: Among the 156 enrolled infants, 80 underwent initial peritoneal drainage and 76 initial laparotomy. Mortality rate was 49% (76 of 156). Ninety-six patients had a preoperative diagnosis of NEC and 60 had presumed IP. There was a high level of agreement between the presumed preoperative diagnosis and intraoperative diagnosis in patients undergoing initial laparotomy (kappa = 0.85). The relative risk for death with a preoperative diagnosis of NEC (versus IP) was 1.4 (95% confidence interval, 0.99–2.1, P = 0.052). The overall incidence of postoperative intestinal stricture was 10.3%, wound dehiscence 4.4%, and intra-abdominal abscess 5.8%, and did not significantly differ between groups undergoing initial laparotomy versus initial drainage. Conclusions: Survival to hospital discharge after operation for NEC or IP in ELBW neonates remains poor (51%). Patients with a preoperative diagnosis of NEC have a relative risk for death of 1.4 compared with those with a preoperative diagnosis of IP. A distinction can be made preoperatively between NEC and IP based on abdominal radiographic findings and the patient's age at operation. Future randomized trials that compare laparotomy versus drainage would likely benefit from stratification of treatment assignment based on preoperative diagnosis. PMID:15912048

[Necrotizing fasciitis: study of 17 cases presenting a low mortality rate].

PubMed

Kibadi, K; Forli, A; Martin Des Pallieres, T; Debus, G; Moutet, F; Corcella, D

2013-04-01

Necrotizing fasciitis is a hypodermis, muscular fascia then dermis necrotizing infection. The originality of this study is to present a series of necrotizing fasciitis treated and followed these last five years, and to compare the therapeutic results with those of the literature. We led a retrospective study on the patients treated for necrotizing fasciitis between 2005 and 2009 by bringing together the demographic and clinical data, the bacteriological examinations and the results of management. Follow-up data from these patients during period of study (five years) were notified. Seventeen patients were treated (11 men and six women). The average age of the patients was 52 years (ranging from 28 to 82 years). Risk factors of necrotizing fasciitis for our patients were: nonsteroidal anti-inflammatory drugs (82.2%), cutaneous wound (76.4%), obesity (29.4%), oto-rhino-laryngologic diseases (23.5%), alcoholic and drug addicts (23.5%), and diabetis (11.7%). The most isolated and responsible germ was Streptococcus pyogenes in 75.5% of cases. Culture of specimens collected before antibiotic treatment showed that the bacterium was sensible to the antibiotics being administered (clindamycin in 70.5% of cases). The surgical management was early done with an average delay of 2.7 days (ranging from 1 to 15 days). We observed a low mortality rate (11.7%). One patient died during the period of follow-up after one year (average follow-up of 2.0 years; 1-3 years). Contrary to the data from the literature, this study presents a decrease of the mortality in necrotizing fasciitis with an early treatment and an adequate management. The precocity and the quality of surgical procedures as well as the presence of an underlying disease are determining factors for successful management of necrotizing fasciitis. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Midtrimester preterm prelabour rupture of membranes (PPROM): expectant management or amnioinfusion for improving perinatal outcomes (PPROMEXIL - III trial).

PubMed

van Teeffelen, Augustinus S P; van der Ham, David P; Willekes, Christine; Al Nasiry, Salwan; Nijhuis, Jan G; van Kuijk, Sander; Schuyt, Ewoud; Mulder, Twan L M; Franssen, Maureen T M; Oepkes, Dick; Jansen, Fenna A R; Woiski, Mallory D; Bekker, Mireille N; Bax, Caroline J; Porath, Martina M; de Laat, Monique W M; Mol, Ben W; Pajkrt, Eva

2014-04-04

Babies born after midtrimester preterm prelabour rupture of membranes (PPROM) are at risk to develop neonatal pulmonary hypoplasia. Perinatal mortality and morbidity after this complication is high. Oligohydramnios in the midtrimester following PPROM is considered to cause a delay in lung development. Repeated transabdominal amnioinfusion with the objective to alleviate oligohydramnios might prevent this complication and might improve neonatal outcome. Women with PPROM and persisting oligohydramnios between 16 and 24 weeks gestational age will be asked to participate in a multi-centre randomised controlled trial. random allocation to (repeated) abdominal amnioinfusion (intervention) or expectant management (control). The primary outcome is perinatal mortality. Secondary outcomes are lethal pulmonary hypoplasia, non-lethal pulmonary hypoplasia, survival till discharge from NICU, neonatal mortality, chronic lung disease (CLD), number of days ventilatory support, necrotizing enterocolitis (NEC), periventricular leucomalacia (PVL) more than grade I, severe intraventricular hemorrhage (IVH) more than grade II, proven neonatal sepsis, gestational age at delivery, time to delivery, indication for delivery, successful amnioinfusion, placental abruption, cord prolapse, chorioamnionitis, fetal trauma due to puncture. The study will be evaluated according to intention to treat. To show a decrease in perinatal mortality from 70% to 35%, we need to randomise two groups of 28 women (two sided test, β-error 0.2 and α-error 0.05). This study will answer the question if (repeated) abdominal amnioinfusion after midtrimester PPROM with associated oligohydramnios improves perinatal survival and prevents pulmonary hypoplasia and other neonatal morbidities. Moreover, it will assess the risks associated with this procedure. NTR3492 Dutch Trial Register (http://www.trialregister.nl).

Neonatal outcome of very preterm twins: policy of planned vaginal or cesarean delivery.

PubMed

Sentilhes, Loïc; Oppenheimer, Anne; Bouhours, Anne-Charlotte; Normand, Estelle; Haddad, Bassam; Descamps, Philippe; Marpeau, Loïc; Goffinet, François; Kayem, Gilles

2015-07-01

The objective of the study was to compare neonatal mortality and morbidity in very preterm twins with the first twin in cephalic presentation in hospitals with a policy of planned vaginal delivery (PVD) and those with a policy of planned cesarean delivery (PCD). Women with preterm cephalic first twins delivered after preterm labor and/or premature preterm rupture of membranes from 26(0/7) to 31(6/7) weeks of gestation were identified from the databases of 6 perinatal centers and classified as PVD or PCD according to the center's management policy from 1999 to 2010. Severe neonatal morbidity was defined as any of the following: intraventricular hemorrhage grades 3-4, periventricular leukomalacia, necrotizing enterocolitis, bronchopulmonary dysplasia, and hospital death. The independent effect of the planned mode of delivery, defined by the center's management policy, was tested and quantified with a 2-level multivariable logistic regression. The PVD group included 248 women, and the PCD group 63. Maternal characteristics did not differ between the 2 groups. The rate of vaginal delivery was 85.9% (213 of 248) vs 20.6% (13 of 63) (P < .001), and the rate of cesarean delivery for the second twin was 1.6% (4 of 248) vs 4.8% (3 of 63) (P = .13) for PVD and PCD. PVD had no independent effect on either newborn hospital mortality or severe neonatal composite morbidity. A policy of planned vaginal delivery of very preterm twins with the first twin in cephalic presentation does not increase either severe neonatal morbidity or mortality. Copyright © 2015 Elsevier Inc. All rights reserved.

Current obstetrical practice and umbilical cord prolapse.

PubMed

Usta, I M; Mercer, B M; Sibai, B M

1999-01-01

The aim of this study was to assess the contribution of current obstetrical practice to the occurrence and complications of umbilical cord prolapse. Maternal and neonatal charts of 87 pregnancies complicated by true umbilical cord prolapse during a 5-year period were reviewed. Twin gestation and noncephalic presentations were common features (14 and 41%, respectively). Eighty-nine percent (77) of infants were delivered by cesarean section of which 29% were classical and 88% were primary. The mean gestational age at delivery was 34.0 +/- 6.0 weeks, and the mean birth weight was 2318 +/- 1159 g. Obstetrical intervention preceded 41 (47%) cases (the obstetrical intervention group): amniotomy (9), scalp electrode application (4), intrauterine pressure catheter insertion (6), attempted external cephalic version (7), expectant management of preterm premature rupture of membranes (14), manual rotation of the fetal head (1), and amnioreduction (1). There were 11 perinatal deaths. Thirty-three percent of the infants (32) had a 5-min Apgar score < 7 and 34% had a cord pH < 7.20. Neonatal seizures, intracerebral hemorrhage, necrotizing enterocolitis, hyaline membrane disease, persistent fetal circulation, sepsis, assisted ventilation, and perinatal mortality were comparable in the "obstetrical intervention" and "no-intervention" groups. Most of the neonatal complications occurred in infants < 32 weeks' gestation. We conclude that obstetrical intervention contributes to 47% of umbilical cord prolapse cases; however, it does not increase the associated perinatal morbidity and mortality.

Single-specialty management and reconstruction of necrotizing fasciitis of the upper extremities: clinical and economic benefits from a case series.

PubMed

Mattison, Gennaya; Leis, Amber R; Gupta, Subhas C

2014-05-01

Patients with necrotizing fasciitis are managed with multiple prompt, radical surgical debridements and critical care support. Debridement and reconstruction are often provided by different surgical teams. Anecdotally, single-specialty management seemed to be a more efficient management strategy. This study aimed to investigate and compare the outcomes of management by plastic surgery versus multiple disciplines through a retrospective economic and clinical analysis of patients with necrotizing fasciitis treated over 8 years. We also present 3 index cases for which our service functioned as the primary management team. Necrotizing fasciitis cases evaluated and treated by our department, covering both Level I and Level II Trauma Centers, were reviewed for total charges, length of hospital stay, length of intensive care unit (ICU) stay, and number of procedures. The admission Acute Physiology and Chronic Health Evaluation II score was calculated for each patient. Three comparative index cases of upper extremity necrotizing fasciitis managed primarily by the plastic surgery team are presented in greater detail. Patients managed primarily by the plastic surgery service had equivalent Acute Physiology and Chronic Health Evaluation II scores to patients managed by multiple services for their necrotizing fasciitis, with the average score higher for patients managed by plastic surgery alone. In a case-matched series of upper extremity necrotizing fasciitis, the patients admitted directly to plastic surgery had shorter average lengths of hospital and ICU stays as well as decreased total number of procedures, resulting in decreased average total hospital charges. There were no amputations among the cases treated primarily by the plastic surgery. The patients also required smaller areas of reconstruction with skin grafting despite large initial areas of debridement compared to those whose reconstructive teams differed from the team performing the debridement. Improved economic and clinical outcomes-as indicated by the reduced lengths of overall and ICU stay, the reduced number of procedures, none of the cases requiring amputation, and the reduced need for skin grafting-may be attainable when the surgeon eventually performing the reconstruction is involved early in management. We propose that, in the interest of improving patient care, a closer collaboration should be established between the reconstructive and primary managing teams.

International consensus guidelines for the diagnosis and management of food protein-induced enterocolitis syndrome: Executive summary-Workgroup Report of the Adverse Reactions to Foods Committee, American Academy of Allergy, Asthma & Immunology.

PubMed

Nowak-Węgrzyn, Anna; Chehade, Mirna; Groetch, Marion E; Spergel, Jonathan M; Wood, Robert A; Allen, Katrina; Atkins, Dan; Bahna, Sami; Barad, Ashis V; Berin, Cecilia; Brown Whitehorn, Terri; Burks, A Wesley; Caubet, Jean-Christoph; Cianferoni, Antonella; Conte, Marisa; Davis, Carla; Fiocchi, Alessandro; Grimshaw, Kate; Gupta, Ruchi; Hofmeister, Brittany; Hwang, J B; Katz, Yitzhak; Konstantinou, George N; Leonard, Stephanie A; Lightdale, Jennifer; McGhee, Sean; Mehr, Sami; Sopo, Stefano Miceli; Monti, Giovanno; Muraro, Antonella; Noel, Stacey Katherine; Nomura, Ichiro; Noone, Sally; Sampson, Hugh A; Schultz, Fallon; Sicherer, Scott H; Thompson, Cecilia C; Turner, Paul J; Venter, Carina; Westcott-Chavez, A Amity; Greenhawt, Matthew

2017-04-01

Food protein-induced enterocolitis (FPIES) is a non-IgE cell- mediated food allergy that can be severe and lead to shock. Despite the potential seriousness of reactions, awareness of FPIES is low; high-quality studies providing insight into the pathophysiology, diagnosis, and management are lacking; and clinical outcomes are poorly established. This consensus document is the result of work done by an international workgroup convened through the Adverse Reactions to Foods Committee of the American Academy of Allergy, Asthma & Immunology and the International FPIES Association advocacy group. These are the first international evidence-based guidelines to improve the diagnosis and management of patients with FPIES. Research on prevalence, pathophysiology, diagnostic markers, and future treatments is necessary to improve the care of patients with FPIES. These guidelines will be updated periodically as more evidence becomes available. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Cervical necrotizing fasciitis as a complication of acute epiglottitis managed with minimally aggressive surgical intervention: Case report.

PubMed

Gollapalli, Rajesh Babu; Naiman, Ana Nusa; Merry, David

2015-07-01

Cervical necrotizing fasciitis secondary to epiglottitis is rare. The standard treatment of this severe condition has long been early and aggressive surgical debridement and adequate antimicrobial therapy. We report the case of an immunocompetent 59-year-old man who developed cervical necrotizing fasciitis as a complication of acute epiglottitis. We were able to successfully manage this patient with conservative surgical treatment (incision and drainage, in addition to antibiotic therapy) that did not involve aggressive debridement.

Surgical management of necrotizing cellulitis: Results of a survey conducted in French plastic surgery departments.

PubMed

Niddam, J; Bosc, R; Hersant, B; Bouhassira, J; Meningaud, J-P

2016-10-01

Necrotizing cellulitis (NC) is a severe infection of the skin and soft tissues, requiring an urgent multidisciplinary approach. We aimed to clarify the surgical management of NC in French plastic surgery departments. Thirty-two French plastic surgery departments were invited to complete a survey sent by email. Questions focused on diagnostic and therapeutic management of NC in France. Twenty-five plastic surgery departments completed the survey (78%) and each center had a lead plastic surgeon. Overall, 88% of surgeons declared to have managed at least five NC patients within the year. The plastic surgeon was the lead surgical specialist for NC in 80% of cases. Conversely, 76% of interviewed facilities reported not to have any lead medical specialist. Time between surgical indication and surgical management was less than six hours in 92% of cases. Overall, 24% of responding facilities declared that access to the operating room never delayed management. Finally, 80% of facilities declared to be in favor of dedicated care pathways to improve the management of necrotizing cellulitis patients. Our study results highlight the heterogeneity of necrotizing cellulitis management in France. The lack of a dedicated care pathway may lead to diagnostic and treatment delays. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

A critical question for NEC researchers: Can we create a consensus definition of NEC that facilitates research progress?

PubMed

Gordon, Phillip V; Swanson, Jonathan R; MacQueen, Brianna C; Christensen, Robert D

2017-02-01

In the last decades the reported incidence of preterm necrotizing enterocolitis (NEC) has been declining in large part due to implementing comprehensive NEC prevention initiatives, including breast milk feeding, standardized feeding protocols, transfusion guidelines, and antibiotic stewardship and improving the rigor with which non-NEC cases are excluded from NEC data. However, after more than 60 years of NEC research in animal models, the promise of a "magic bullet" to prevent NEC has yet to materialize. There are also serious issues involving clinical NEC research. There is a lack of a common, comprehensive definition of NEC. National datasets have their own unique definition and staging definitions. Even within academia, randomized trials and single center studies have widely disparate definitions. This makes NEC metadata of very limited value. The world of neonatology needs a comprehensive, universal, consensus definition of NEC. It also needs a de-identified, international data warehouse. Copyright © 2016 Elsevier Inc. All rights reserved.

Intrauterine growth restriction and prematurity influence regulatory T cell development in newborns.

PubMed

Mukhopadhyay, Dhriti; Weaver, Laura; Tobin, Richard; Henderson, Stephanie; Beeram, Madhava; Newell-Rogers, M Karen; Perger, Lena

2014-05-01

The aim of this study was to determine the relationship of birth weight and gestational age with regulatory T cells (Tregs) in cord blood of human newborns. Cord blood mononuclear cells (CBMCs) of 210 newborns were analyzed using flow cytometry to identify Tregs (CD3(+), CD4(+), CD25(high), FoxP3(high)) and measure FoxP3 mean fluorescence intensity (MFI). Suppressive index (SI) was calculated as FoxP3 MFI per Treg. Mode of delivery had no significant effect on Tregs at birth. Term babies with growth restriction had fewer Tregs than their appropriate weight counterparts but equivalent SI. Preterm babies had higher percentages of Tregs, but lower SI than term controls. SI steadily increased through gestation. Intrauterine growth restriction is correlated with fewer circulating Tregs and prematurity with decreased functionality of Tregs compared to term appropriate weight infants. This may have implications in diseases such as necrotizing enterocolitis that disproportionately affect premature and lower birth weight infants. Copyright © 2014 Elsevier Inc. All rights reserved.

Ultrasound predictors of neonatal outcome in intrauterine growth restriction.

PubMed

Craigo, S D; Beach, M L; Harvey-Wilkes, K B; D'Alton, M E

1996-11-01

Our purpose was to assess the value of commonly performed ultrasound parameters in predicting neonatal outcome of fetuses with intrauterine growth restriction (IUGR). One hundred twenty-seven patients were identified on ultrasound examination to have IUGR. Estimated weight percentile, amniotic fluid volume, umbilical artery Doppler velocimetry, and head circumference/abdominal circumference ratio were compared with neonatal outcome. Thirty infants had severely adverse courses. The degree of growth restriction was strongly associated with adverse outcome and neonatal death. Umbilical artery Doppler waveforms with absent or reverse end-diastolic flow were predicted of neonatal death, bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and adverse outcome in general. Oligohydramnios was predictive of adverse outcome and neonatal death. Logistic regression also showed that absent or reverse end-diastolic flow and oligohydramnios were independent predictors of adverse outcome. Ultrasound findings of low estimated weight percentile, absent or reverse end-diastolic umbilical blood flow, and oligohydramnios are independent predictors of adverse neonatal outcome of growth restricted fetuses.

The treatment of patent ductus arteriosus in preterm infants. A review and overview of randomized trials.

PubMed

Knight, D B

2001-02-01

Patent ductus arteriosus (PDA) is a common problem in very preterm infants. It results in a significant left-to-right shunt and an increase in left ventricular output. Pulmonary compliance can be reduced. Systemic effects result from the diastolic steal and retrograde diastolic blood flow. Randomized controlled trials of PDA closure fall into three groups: (i) prophylactic treatment in the first 24 h, (ii) pre-symptomatic treatment on ultrasound evidence of a PDA or the first clinical signs and (iii) treatment when it becomes haemodynamically significant. Prophylactic treatment with indomethacin reduces the incidence of intraventricular haemorrhage. All the trials have a decreased need to treat a subsequent PDA in the treatment group. There are no other improvements in outcome, without any change in mortality, bronchopulmonary dysplasia, necrotizing enterocolitis or retinopathy of prematurity. Clinical decisions on the treatment of the ductus should be individualized and based on the gestation of the baby, the respiratory condition and the size of the ductal shunt. Copyright 2001 Harcourt Publishers Ltd.

Association of necrotizing enterocolitis with anemia and packed red blood cell transfusions in preterm infants

PubMed Central

Singh, Rachana; Visintainer, Paul F.; Frantz, Ivan D.; Shah, Bhavesh L.; Meyer, Kathleen M.; Favila, Sarah A.; Thomas, Meredith S.; Kent, David M.

2011-01-01

Objective To determine association of anemia and RBC transfusions with NEC in preterm infants. Study Design 111 preterm infants with NEC ≥ Stage 2a were compared with 222 matched controls. 28 clinical variables, including hematocrit and RBC transfusions were recorded. Propensity scores and multivariate logistic regression models were created to examine effects on the risk of NEC. Results Controlling for other factors, lower hematocrit was associated with increased odds of NEC [OR 1.10, p =0.01]. RBC transfusion has a temporal relationship with NEC onset. Transfusion within 24h (OR=7.60, p=0.001) and 48h (OR=5.55, p=0.001) has a higher odds of developing NEC but this association is not significant by 96h (OR= 2.13, p =0.07), post transfusion Conclusions Anemia may increase the risk of developing NEC in preterm infants. RBC transfusions are temporally related to NEC. Prospective studies are needed to better evaluate the potential influence of transfusions on the development of NEC. PMID:21273983

Cronobacter species (formerly known as Enterobacter sakazakii) in powdered infant formula: a review of our current understanding of the biology of this bacterium.

PubMed

Yan, Q Q; Condell, O; Power, K; Butler, F; Tall, B D; Fanning, S

2012-07-01

Cronobacter species (formerly known as Enterobacter sakazakii) are opportunistic pathogens that can cause necrotizing enterocolitis, bacteraemia and meningitis, predominantly in neonates. Infection in these vulnerable infants has been linked to the consumption of contaminated powdered infant formula (PIF). Considerable research has been undertaken on this organism in the past number of years which has enhanced our understanding of this neonatal pathogen leading to improvements in its control within the PIF production environment. The taxonomy of the organism resulted in the recognition of a new genus, Cronobacter, which consists of seven species. This paper presents an up-to-date review of our current knowledge of Cronobacter species. Taxonomy, genome sequencing, current detection protocols and epidemiology are all discussed. In addition, consideration is given to the control of this organism in the manufacturing environment, as a first step towards reducing the occurrence of this pathogen in PIF. © 2012 The Authors. Journal of Applied Microbiology © 2012 The Society for Applied Microbiology.

The Glutaredoxin Gene, grxB, Affects Acid Tolerance, Surface Hydrophobicity, Auto-Aggregation, and Biofilm Formation in Cronobacter sakazakii.

PubMed

Ling, Na; Zhang, Jumei; Li, Chengsi; Zeng, Haiyan; He, Wenjing; Ye, Yingwang; Wu, Qingping

2018-01-01

Cronobacter species are foodborne pathogens that can cause neonatal meningitis, necrotizing enterocolitis, and sepsis; they have unusual abilities to survive in environmental stresses such as acid stress. However, the factors involved in acid stress responses and biofilm formation in Cronobacter species are poorly understood. In this study, we investigated the role of grxB on cellular morphology, acid tolerance, surface hydrophobicity, auto-aggregation (AAg), motility, and biofilm formation in Cronobacter sakazakii . The deletion of grxB decreased resistance to acid stresses, and notably led to weaker surface hydrophobicity, AAg, and biofilm formation under normal and acid stress conditions, compared with those of the wild type strain; however, motility was unaffected. Therefore, grxB appears to contribute to the survival of C. sakazakii in acid stresses and biofilm formation. This is the first report to provide valuable evidence for the role of grxB in acid stress responses and biofilm formation in C. sakazakii.

Insights into virulence factors determining the pathogenicity of Cronobacter sakazakii.

PubMed

Singh, Niharika; Goel, Gunjan; Raghav, Mamta

2015-01-01

Cronobacter sakazakii is an opportunistic pathogen associated with outbreaks of life-threatening necrotizing enterocolitis, meningitis and sepsis in neonates and infants. The pathogen possesses an array of virulence factors which aid in tissue adhesion, invasion and host cell injury. Although the identification and validation of C. sakazakii virulence factors has been hindered by availability of suitable neonatal animal model, various studies has reported outer membrane protein A (ompA) as a potential virulence marker. Various other plasmid associated genes such as filamentous hemagglutinin (fhaBC), Cronobacter plasminogen activator (cpa) and genes responsible for iron acquisition (eitCBAD and iucABD/iutA) have been reported in different strains of C. sakazakii. Besides these proposed virulence factors, several biophysical growth factors such as formation of biofilms and resistance to various environmental stresses also contributes to the pathogenic potential of this pathogen. This review provides an update on virulence determinants associated with the pathogenesis of C. sakazakii. The potential reservoirs of the pathogen, mode of transmission and epidemiology are also discussed.

Analysis on pathogenic and virulent characteristics of the Cronobacter sakazakii strain BAA-894 by whole genome sequencing and its demonstration in basic biology science.

PubMed

Bao, Xuerui; Yang, Ling; Chen, Lequn; Li, Bing; Li, Lin; Li, Yanyan; Xu, Zhenbo

2017-08-01

Cronobacter sakazakii is an opportunistic pathogen responsible for necrotizing enterocolitis, meningitis and septicaemia especially to infant and neonate, with high lethality ranging in 40%-80%. This strain is able to survive in infant milk formula and possesses capability of pathogenicity and virulence, biofilm formation, and high resistance to elevated osmotic, low pH, heat, oxidation, and desiccasion. This study is aims to investigate the molecular characteristics of Cronobacter sakazakii BAA 894, including mechanisms of its invasion and adherence, biofilm formation, unusual resistance to environmental stress employing whole genome sequencing and comparative genomics. Results in this study suggest that numerous genes and pathways, such as LysM, Cyx system, luxS, vancomycin resistance pathway, insulin resistance pathway, and sod encoding superoxide dismutase for the survival of C. sakazakii in macrophages, contribute to pathogenicity and resistance to stressful environment of C. sakazakii BAA 894. Copyright © 2017. Published by Elsevier Ltd.

Detection of Cronobacter spp. (formerly Enterobacter sakazakii) from medicinal plants and spices in Syria.

PubMed

Belal, Mouhammad; Al-Mariri, Ayman; Hallab, Lila; Hamad, Ibtesam

2013-02-15

Cronobacter spp. (formerly Enterobacter sakazakii) is an emerging food-borne pathogen that causes severe meningitis, sepsis, and necrotizing enterocolitis in neonates and infants. These infections have been reported from different parts of the world. The epidemiology and reservoir of Cronobacter spp. are still unknown, and most strains have been isolated from clinical specimens and from a variety of foods, including cheese, meat, milk, vegetables, grains, spices, and herbs. Our study aimed to detect and isolate Cronobacter spp. from different Syrian samples of spices, medicinal herbs and liquorices, depending on the pigment production and biochemical profile of isolates and PCR technique. This PCR method, which provides a powerful tool for rapid, specific, and sensitive detection of Cronobacter spp., is considered a reliable alternative to traditional bacteriological methods. This study revealed that the percentage of Cronobacter spp. was 94%, 52%, and 32% in liquorice, spices and medicinal herbs, respectively. In addition, it assured that the optimal enhancing growth temperature was 44°C, and optimal enhancing growth pH was 5.

Insights into virulence factors determining the pathogenicity of Cronobacter sakazakii

PubMed Central

Singh, Niharika; Goel, Gunjan; Raghav, Mamta

2015-01-01

Cronobacter sakazakii is an opportunistic pathogen associated with outbreaks of life-threatening necrotizing enterocolitis, meningitis and sepsis in neonates and infants. The pathogen possesses an array of virulence factors which aid in tissue adhesion, invasion and host cell injury. Although the identification and validation of C. sakazakii virulence factors has been hindered by availability of suitable neonatal animal model, various studies has reported outer membrane protein A (ompA) as a potential virulence marker. Various other plasmid associated genes such as filamentous hemagglutinin (fhaBC), Cronobacter plasminogen activator (cpa) and genes responsible for iron acquisition (eitCBAD and iucABD/iutA) have been reported in different strains of C. sakazakii. Besides these proposed virulence factors, several biophysical growth factors such as formation of biofilms and resistance to various environmental stresses also contributes to the pathogenic potential of this pathogen. This review provides an update on virulence determinants associated with the pathogenesis of C. sakazakii. The potential reservoirs of the pathogen, mode of transmission and epidemiology are also discussed. PMID:25950947

CDC Grand Rounds: Public Health Strategies to Prevent Preterm Birth.

PubMed

Shapiro-Mendoza, Carrie K; Barfield, Wanda D; Henderson, Zsakeba; James, Arthur; Howse, Jennifer L; Iskander, John; Thorpe, Phoebe G

2016-08-19

Preterm birth (delivery before 37 weeks and 0/7 days of gestation) is a leading cause of infant morbidity and mortality in the United States. In 2013, 11.4% of the nearly 4 million U.S. live births were preterm; however, 36% of the 8,470 infant deaths were attributed to preterm birth (1). Infants born at earlier gestational ages, especially <32 0/7 weeks, have the highest mortality (Figure) and morbidity rates. Morbidity associated with preterm birth includes respiratory distress syndrome, necrotizing enterocolitis, and intraventricular hemorrhage; longer-term consequences include developmental delay and decreased school performance. Risk factors for preterm delivery include social, behavioral, clinical, and biologic characteristics (Box). Despite advances in medical care, racial and ethnic disparities associated with preterm birth persist. Reducing preterm birth, a national public health priority (2), can be accomplished by implementing and monitoring strategies that target modifiable risk factors and populations at highest risk, and by providing improved quality and access to preconception, prenatal, and interconception care through implementation of strategies with potentially high impact.

hPSC-derived lung and intestinal organoids as models of human fetal tissue

PubMed Central

Aurora, Megan; Spence, Jason R.

2016-01-01

In vitro human pluripotent stem cell (hPSC) derived tissues are excellent models to study certain aspects of normal human development. Current research in the field of hPSC derived tissues reveals these models to be inherently fetal-like on both a morphological and gene expression level. In this review we briefly discuss current methods for differentiating lung and intestinal tissue from hPSCs into individual 3-dimensional units called organoids. We discuss how these methods mirror what is known about in vivo signaling pathways of the developing embryo. Additionally, we will review how the inherent immaturity of these models lends them to be particularly valuable in the study of immature human tissues in the clinical setting of premature birth. Human lung organoids (HLOs) and human intestinal organoids (HIOs) not only model normal development, but can also be utilized to study several important diseases of prematurity such as respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), and necrotizing enterocolitis (NEC). PMID:27287882

Neurological consequences of systemic inflammation in the premature neonate.

PubMed

Patra, Aparna; Huang, Hong; Bauer, John A; Giannone, Peter J

2017-06-01

Despite substantial progress in neonatal care over the past two decades leading to improved survival of extremely premature infants, extreme prematurity continues to be associated with long term neurodevelopmental impairments. Cerebral white matter injury is the predominant form of insult in preterm brain leading to adverse neurological consequences. Such brain injury pattern and unfavorable neurologic sequelae is commonly encountered in premature infants exposed to systemic inflammatory states such as clinical or culture proven sepsis with or without evidence of meningitis, prolonged mechanical ventilation, bronchopulmonary dysplasia, necrotizing enterocolitis and chorioamnionitis. Underlying mechanisms may include cytokine mediated processes without direct entry of pathogens into the brain, developmental differences in immune response and complex neurovascular barrier system that play a critical role in regulating the cerebral response to various systemic inflammatory insults in premature infants. Understanding of these pathologic mechanisms and clinical correlates of such injury based on serum biomarkers or brain imaging findings on magnetic resonance imaging will pave way for future research and translational therapeutic opportunities for the developing brain.

Parenteral nutrition in patients with inborn errors of metabolism - a therapeutic problem.

PubMed

Kaluzny, L; Szczepanik, M; Siwinska-Mrozek, Z; Borkowska-Klos, M; Cichy, W; Walkowiak, J

2014-06-01

Parenteral nutrition is now a standard part of supportive treatment in pediatric departments. We describe four cases in which parenteral nutrition was extremely difficult due to coincidence with inborn errors of metabolism. The first two cases was fatty acid beta-oxidation disorders associated with necrotizing enterocolitis and congenital heart disease. Thus, limitations of intravenous lipid intake made it difficult to maintain a good nutritional status. The third case was phenylketonuria associated with a facial region tumour (rhabdomyosarcoma), in which parenteral nutrition was complicated because of a high phenylalanine content in the amino acid formulas for parenteral nutrition. The fourth patient was a child with late-diagnosed tyrosinemia type 1, complicated with encephalopathy - during intensive care treatment the patient needed nutritional support, including parenteral nutrition - we observed amino acid formula problems similar to those in the phenylketonuria patient. Parenteral nutrition in children with inborn errors of metabolism is a rare, but very important therapeutic problem. Total parenteral nutrition formulas are not prepared for this group of diseases.

Midtrimester preterm prelabour rupture of membranes (PPROM): expectant management or amnioinfusion for improving perinatal outcomes (PPROMEXIL – III trial)

PubMed Central

2014-01-01

Background Babies born after midtrimester preterm prelabour rupture of membranes (PPROM) are at risk to develop neonatal pulmonary hypoplasia. Perinatal mortality and morbidity after this complication is high. Oligohydramnios in the midtrimester following PPROM is considered to cause a delay in lung development. Repeated transabdominal amnioinfusion with the objective to alleviate oligohydramnios might prevent this complication and might improve neonatal outcome. Methods/Design Women with PPROM and persisting oligohydramnios between 16 and 24 weeks gestational age will be asked to participate in a multi-centre randomised controlled trial. Intervention: random allocation to (repeated) abdominal amnioinfusion (intervention) or expectant management (control). The primary outcome is perinatal mortality. Secondary outcomes are lethal pulmonary hypoplasia, non-lethal pulmonary hypoplasia, survival till discharge from NICU, neonatal mortality, chronic lung disease (CLD), number of days ventilatory support, necrotizing enterocolitis (NEC), periventricular leucomalacia (PVL) more than grade I, severe intraventricular hemorrhage (IVH) more than grade II, proven neonatal sepsis, gestational age at delivery, time to delivery, indication for delivery, successful amnioinfusion, placental abruption, cord prolapse, chorioamnionitis, fetal trauma due to puncture. The study will be evaluated according to intention to treat. To show a decrease in perinatal mortality from 70% to 35%, we need to randomise two groups of 28 women (two sided test, β-error 0.2 and α-error 0.05). Discussion This study will answer the question if (repeated) abdominal amnioinfusion after midtrimester PPROM with associated oligohydramnios improves perinatal survival and prevents pulmonary hypoplasia and other neonatal morbidities. Moreover, it will assess the risks associated with this procedure. Trial registration NTR3492 Dutch Trial Register (http://www.trialregister.nl). PMID:24708702

Management of a child with vomiting.

PubMed

Singhi, Sunit C; Shah, Ravi; Bansal, Arun; Jayashree, M

2013-04-01

Vomiting is a protective reflex that results in forceful ejection of stomach contents up to and out of the mouth. It is a common complaint and may be the presenting symptom of several life-threatening conditions. It can be caused by a variety of organic and nonorganic disorders; gastrointestinal (GI) or outside of GI. Acute gastritis and gastroenteritis (AGE) are the leading cause of acute vomiting in children. Important life threatening causes in infancy include congenital intestinal obstruction, atresia, malrotation with volvulus, necrotizing enterocolitis, pyloric stenosis, intussusception, shaken baby syndrome, hydrocephalus, inborn errors of metabolism, congenital adrenal hypoplasia, obstructive uropathy, sepsis, meningitis and encephalitis, and severe gastroenteritis, and in older children appendicitis, intracranial mass lesion, diabetic ketoacidosis, Reye's syndrome, toxic ingestions, uremia, and meningitis. Initial evaluation is directed at assessment of airway, breathing and circulation, assessment of hydration status and red flag signs (bilious or bloody vomiting, altered sensorium, toxic/septic/apprehensive look, inconsolable cry or excessive irritability, severe dehydration, concern for symptomatic hypoglycemia, severe wasting, Bent-over posture). The history and physical examination guides the approach in an individual patient. The diverse nature of causes of vomiting makes a "routine" laboratory or radiologic screen impossible. Investigations (Serum electrolytes and blood gases,renal and liver functions and radiological studies) are required in any child with dehydration or red flag signs, to diagnose surgical causes. Management priorities include treatment of dehydration, stoppage of oral fluids/feeds and decompression of the stomach with nasogastric tube in patients with bilious vomiting. Antiemetic ondansetron(0.2 mg/kg oral; parenteral 0.15 mg/kg; maximum 4 mg) is indicated in children unable to take orally due to persistent vomiting, post-operative vomiting, chemotherapy induced vomiting, cyclic vomiting syndrome and acute mountain sickness.

Feeding Intervals in Premature Infants ≤1750 g: An Integrative Review.

PubMed

Binchy, Áine; Moore, Zena; Patton, Declan

2018-06-01

The timely establishment of enteral feeds and a reduction in the number of feeding interruptions are key to achieving optimal nutrition in premature infants. Nutritional guidelines vary widely regarding feeding regimens and there is not a widely accepted consensus on the optimal feeding interval. To critically examine the evidence to determine whether there is a relationship to feeding intervals and feeding outcomes in premature infants. A systematic review of the literature in the following databases: PubMed, CINAHL, Embase and the Cochrane Library. The search strategy used the terms infant premature, low birth weight, enteral feeding, feed tolerance and feed intervals. Search results yielded 10 studies involving 1269 infants (birth weight ≤1750 g). No significant differences in feed intolerance, growth, or incidence of necrotizing enterocolitis were observed. Evidence suggests that infants fed at 2 hourly intervals reached full feeds faster than at 3 hourly intervals, had fewer days on parenteral nutrition, and fewer days in which feedings were withheld. Decrease in the volume of gastric residuals and feeding interruptions were observed in the infants fed at 3 hourly intervals than those who were continuously fed. Reducing the feed interval from 3 to 2 hourly increases nurse workload, yet may improve feeding outcomes by reducing the time to achieve full enteral feeding. Studies varied greatly in the definition and management of feeding intolerance and in how outcomes were measured, analyzed, and reported. The term "intermittent" is used widely but can refer to a 2 or 3 hourly interval.

A sutureless technique using cyanoacrylate adhesives when creating a stoma for extremely low birth weight infants.

PubMed

Nose, Satoko; Sasaki, Takashi; Saka, Ryuta; Minagawa, Kyoko; Okuyama, Hiroomi

2016-01-01

Intestinal perforation and necrotizing enterocolitis (NEC) are neonatal intestinal emergencies that are especially common in premature infants. While prompt surgical intervention, including stoma creation, is often required, the optimal surgical treatment has been controversial because of the substantial risks related to the stoma creation and management. The use of a tissue adhesive may have some advantages over the use of sutures when creating an intestinal stoma in extremely low birth weight (ELBW) infants. The purpose of this report was to present a novel approach for creating a stoma using a tissue adhesive in ELBW infants. A total of eight ELBW infants that underwent laparotomy with the creation of intestinal stomas using cyanoacrylate adhesive at our institution between 2009 and 2014 were enrolled. The clinical parameters, including the length of the operation, intra- and postoperative complications and the outcomes were evaluated. The median body weight and gestational age at birth were 630 g and 24.3 weeks, respectively. The median age at referral was 11.5 days. The median length of the procedure was 58.5 min, including the inspection and resection of the intestine. All procedures were completed without any intraoperative complications. There were no postoperative complications associated with the stoma. Two patients died of the associated septic status. Sutureless enterostomy using cyanoacrylate adhesive is a simple technique which has the potential to reduce the incidence of complications related to the intestinal stoma in ELBW infants.

Patent Ductus Arteriosus in the Preterm Infant: Diagnostic and Treatment Options.

PubMed

Prescott, Stephanie; Keim-Malpass, Jessica

2017-02-01

The incidence of hemodynamically significant patent ductus arteriosus (hsPDA) increases with decreasing gestational age and is associated with many common morbidities of extreme prematurity. Controversies remain surrounding the definition of hsPDA, the population of infants requiring treatment, the appropriate timing and method of treatment, and the outcomes associated with PDA and its therapies. This integrative literature review focuses on diagnostic and treatment recommendations derived from the highest levels of evidence. PubMed and CINAHL were searched using key words "neonatal" and "patent ductus arteriosus" to discover the highest levels of evidence surrounding diagnosis, treatment methods, and outcomes. The lack of consensus surrounding the diagnosis and clinical significance of PDA hinders meta-analysis across studies and confounds understanding of appropriate management strategies. Novel biomarkers, pharmaceutical choices, and transcatheter closure methods are expanding diagnostic and treatment options. Infants weighing less than 1000 g are at highest risk. Prophylactic closure is no longer recommended, although early asymptomatic therapy is still preferred by some to avoid prolonged pulmonary overcirculation or decreased renal and gut perfusion. Conservative treatment measures such as fluid restriction and diuretic administration have not consistently proven effective and are in some instances detrimental. Cyclooxygenase inhibitors are effective but have adverse renal and mesenteric effects. Oral ibuprofen is associated with lower instance of necrotizing enterocolitis. Well-defined staging criteria would aid in comparison and meta-analysis. Trials that include a control group that receives no therapy may help separate the outcomes associated with prematurity from those associated with PDA.

Necrotizing Lip Infection Causing Septic Thrombophlebitis of the Neck: A Rare Variant of Lemierre Syndrome.

PubMed

Cuddy, Karl; Saadat, Nariman; Khatib, Baber; Patel, Ashish

2018-01-01

Lemierre syndrome is an uncommon condition in which internal jugular vein thrombosis presents after recent oropharyngeal infection. Frequently, this is accompanied by septic emboli. This report outlines a variant of this disease process, with septic thrombophlebitis of the neck associated with a necrotizing skin infection of the lower lip and chin. A 25-year-old man with lower lip and chin swelling, initially managed with intravenous antibiotics, progressed to the development of a left facial vein thrombus, septic emboli to the lungs, and a necrotizing lower lip and chin infection that was managed with debridement, thrombectomy, and prolonged hemodynamic and pulmonary support. A necrotizing skin infection with thrombus of the jugular system and septic emboli is a very rare variant of Lemierre syndrome. Early recognition of an infection with septic emboli and/or necrotizing pathobiological findings allows for prompt antibiotic and surgical therapy, minimizing the mortality of these potentially lethal infections. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Long term healthcare costs of infants who survived neonatal necrotizing enterocolitis: a retrospective longitudinal study among infants enrolled in Texas Medicaid

PubMed Central

2013-01-01

Background Infants who survive advanced necrotizing enterocolitis (NEC) at the time of birth are at increased risk of having poor long term physiological and neurodevelopmental growth. The economic implications of the long term morbidity in these children have not been studied to date. This paper compares the long term healthcare costs beyond the initial hospitalization period incurred by medical and surgical NEC survivors with that of matched controls without a diagnosis of NEC during birth hospitalization. Methods The longitudinal healthcare utilization claim files of infants born between January 2002 and December 2003 and enrolled in the Texas Medicaid fee-for-service program were used for this research. Propensity scoring was used to match infants diagnosed with NEC during birth hospitalization to infants without a diagnosis of NEC on the basis of gender, race, prematurity, extremely low birth weight status and presence of any major birth defects. The Medicaid paid all-inclusive healthcare costs for the period from 6 months to 3 years of age among children in the medical NEC, surgical NEC and matched control groups were evaluated descriptively, and in a generalized linear regression framework in order to model the impact of NEC over time and by birth weight. Results Two hundred fifty NEC survivors (73 with surgical NEC) and 2,909 matched controls were available for follow-up. Medical NEC infants incurred significantly higher healthcare costs than matched controls between 6–12 months of age (mean incremental cost = US$ 5,112 per infant). No significant difference in healthcare costs between medical NEC infants and matched controls was seen after 12 months. Surgical NEC survivors incurred healthcare costs that were consistently higher than that of matched controls through 36 months of age. The mean incremental healthcare costs of surgical NEC infants compared to matched controls between 6–12, 12–24 and 24–36 months of age were US$ 18,274, 14,067 (p < 0.01) and 8,501 (p = 0.06) per infant per six month period, respectively. These incremental costs were found to vary between sub-groups of infants born with birth weight < 1,000g versus ≥ 1,000g (p < 0.05). Conclusions The all-inclusive healthcare costs of surgical NEC survivors continued to be substantially higher than that of matched controls through the early childhood development period. These results can have important treatment and policy implications. Further research in this topic is needed. PMID:23962093

Broad-spectrum Antibiotic Plus Metronidazole May Not Prevent the Deterioration of Necrotizing Enterocolitis From Stage II to III in Full-term and Near-term Infants

PubMed Central

Luo, Li-Juan; Li, Xin; Yang, Kai-Di; Lu, Jiang-Yi; Li, Lu-Quan

2015-01-01

Abstract Necrotizing enterocolitis (NEC) is the most common and frequently dangerous neonatal gastrointestinal disease. Studies have shown broad-spectrum antibiotics plus anaerobic antimicrobial therapy did not prevent the deterioration of NEC among very low birth preterm infants. However, few studies about this therapy which focused on full-term and near-term infant with NEC has been reported. The aim of this study was to evaluate the effect of broad-spectrum antibiotic plus metronidazole in preventing the deterioration of NEC from stage II to III in full-term and near-term infants. A retrospective cohort study based on the propensity score (PS) 1:1 matching was performed among the full-term and near-term infants with NEC (Bell stage ≥II). All infants who received broad-spectrum antibiotics were divided into 2 groups: group with metronidazole treatment (metronidazole was used ≥4 days continuously, 15 mg/kg/day) and group without metronidazole treatment. The depraved rates of stage II NEC between the 2 groups were compared. Meanwhile, the risk factors associated with the deterioration of stage II NEC were analyzed by case-control study in the PS-matched cases. A total of 229 infants met the inclusion criteria. Before PS-matching, we found the deterioration of NEC rate in the group with metronidazole treatment was higher than that in the group without metronidazole treatment (18.1% [28/155] vs 8.1% [6/74]; P = 0.048). After PS-matching, 73 pairs were matched, and the depraved rate of NEC in the group with metronidazole treatment was not lower than that in the group without metronidazole treatment (15.1% vs 8.2%; P = 0.2). Binary logistic regression analysis showed that sepsis after NEC (odds ratio [OR] 3.748, 95% confidence interval [CI] 1.171–11.998, P = 0.03), the need to use transfusion of blood products after diagnosis of NEC (OR 8.003, 95% CI 2.365–27.087, P = 0.00), and the need of longer time for nasogastric suction were risk factors for stage II NEC progressing to stage III (OR 1.102, 95% CI 1.004–1.21, P = 0.04). Broad-spectrum antibiotic plus metronidazole may not prevent the deterioration of NEC in full-term and near-term infants. Those infants who had sepsis required transfusion of blood products, and needed longer time for nasogastric suction after stage II NEC was more likely to progress to stage III. PMID:26496340

Association of antenatal corticosteroids with mortality and neurodevelopmental outcomes among infants born at 22–25 weeks gestation

PubMed Central

Carlo, Waldemar A.; McDonald, Scott A.; Fanaroff, Avroy A.; Vohr, Betty R.; Stoll, Barbara J.; Ehrenkranz, Richard A.; Andrews, William W.; Wallace, Dennis; Das, Abhik; Bell, Edward F.; Walsh, Michele C.; Laptook, Abbot R.; Shankaran, Seetha; Poindexter, Brenda B.; Hale, Ellen C.; Newman, Nancy S.; Davis, Alexis S.; Schibler, Kurt; Kennedy, Kathleen A.; Sanchez, Pablo J.; Van Meurs, Krisa P.; Goldberg, Ronald N.; Watterberg, Kristi L.; Faix, Roger G.; Frantz, Ivan D.; Higgins, Rosemary D.

2013-01-01

Context Current guidelines, initially published in 1995, recommend antenatal corticosteroids for mothers with preterm labor from 24–34 weeks gestational age, but not before 24 weeks because of lack of data. However, many infants born before 24 weeks are provided intensive care now. Objective To determine if antenatal corticosteroids are associated with improvement in major outcomes in infants born at 22 and 23 weeks. Design, Setting, Participants Data for this cohort study were collected prospectively on 401–1000 gram inborn infants (N=10,541) of 22–25 weeks gestation born between 1993–2009 at 23 academic perinatal centers in the United States. Certified examiners unaware of exposure to antenatal corticosteroids performed follow-up examinations on 4,924 (86.5%) of the infants born in 1993–2008 who survived to 18–22 months. Logistic regression models generated adjusted odds ratios, controlling for maternal and neonatal variables. Main Outcome Measures Mortality and neurodevelopmental impairment at 18–22 months corrected age RESULTS Death or neurodevelopmental impairment at 18–22 months was lower for infants whose mothers received antenatal corticosteroids born at 23 weeks (antenatal corticosteroids, 83.4% vs no antenatal corticosteroids, 90.5%; adjusted odds ratio 0.58; 95% CI, 0.42–0.80), at 24 weeks (antenatal corticosteroids, 68.4% vs no antenatal corticosteroids, 80.3%; adjusted odds ratio 0.62; 95% CI, 0.49–0.78), and at 25 weeks (antenatal corticosteroids, 52.7% vs no antenatal corticosteroids, 67.9%; adjusted odds ratio 0.61; 95% CI, 0.50–0.74) but not at 22 weeks (antenatal corticosteroids, 90.2% vs no antenatal corticosteroids, 93.1%; adjusted odds ratio 0.80; 95% CI, 0.29–12.21). Death by 18–22 months, hospital death, death/intraventricular hemorrhage/periventricular leukomalacia, and death/necrotizing enterocolitis were significantly lower for infants born at 23, 24, and 25 weeks gestational age if the mothers had received antenatal corticosteroids but the only outcome significantly lower at 22 weeks was death/necrotizing enterocolitis (antenatal corticosteroids, 73.5% vs no antenatal corticosteroids, 84.5%; adjusted odds ratio 0.54; 95% CI, 0.30–0.97). CONCLUSIONS Among infants born at 23–25 weeks gestation, use of antenatal corticosteroids compared to non-use was associated with a lower rate of death or neurodevelopmental impairment at 18–22 months. PMID:22147379

A meta-analysis of probiotics for preventing necrotizing enterocolitis in preterm neonates

PubMed Central

Yang, Y.; Guo, Y.; Kan, Q.; Zhou, X.G.; Zhou, X.Y.; Li, Y.

2014-01-01

Necrotizing enterocolitis (NEC) is one of the most common acquired diseases of the gastrointestinal tract in preterm infants. Some randomized, controlled trials (RCTs) have indicated that probiotics may potentially lower the incidence of NEC and mortality. However, debate still remains about the safety of probiotics and their influence on normal infant growth. We performed this meta-analysis to assess the safety and benefits of probiotic supplementation in preterm infants. We searched in PubMed, Embase, and Cochrane databases for English references, and in Wanfang, VIP, and CNKI databases for Chinese references. Ultimately, 27 RCTs (including 9 Chinese articles) were incorporated into this meta-analysis. Relative risk (RR) and weighted mean difference (WMD) were calculated using a random-effects or fixed-effects model, depending on the data type and heterogeneity. A total of 6655 preterm infants, including the probiotic group (n=3298) and the placebo group (n=3357), were eligible for inclusion in this meta-analysis. For Bell stage ≥I and gestational age <37 weeks, risk of NEC incidence was significantly lower in the probiotic group [RR=0.35, 95% confidence interval (CI)=0.27-0.44, P<0.00001]. For Bell stage ≥II or gestational age <34 weeks, there were likewise significant differences between the probiotic and placebo groups concerning NEC incidence (RR=0.34, 95%CI=0.25-0.48, P<0.00001; and RR=0.39, 95%CI=0.27-0.56, P<0.00001). Risk of death was significantly reduced in the probiotic group (RR=0.58, 95%CI=0.46-0.75, P<0.0001). In contrast, there was no significant difference concerning the risk of sepsis (RR=0.94, 95%CI=0.83-1.06, P=0.31). With respect to weight gain and the age at which infants reached full feeds, no significant differences were found between the probiotic and placebo groups (WMD=1.07, 95%CI=−0.21-2.34, P=0.10; and WMD=−1.66, 95%CI=−3.6-0.27, P=0.09). This meta-analysis has shown that, regardless of gestational age and NEC stage, probiotic supplementation could significantly reduce the risk of NEC in preterm infants. Analysis also indicated that such supplementation did not increase the incidence risk of sepsis or of mortality. Finally, the study showed that probiotic supplementation may have no adverse effect on normal feeding and growth. PMID:25098619

Hyperbaric Oxygen Therapy - An Adjunct to Optimal Combat Trauma Management

DTIC Science & Technology

2004-09-01

the morbidity and mortality of necrotizing fasciitis and gas gangrene, where treatment with HBO2 results in clinical improvement even when standard...04. Hirn, M. (1993). "Hyperbaric oxygen in the treatment of gas gangrene and perineal necrotizing fasciitis . A clinical and experimental study...34Hyperbaric oxygen therapy for necrotizing fasciitis reduces mortality and the need for debridements." Surgery 108(5): 847-50. Rosenthal, E., A. Benderly

Necrotizing fasciitis and its mimics: what radiologists need to know.

PubMed

Chaudhry, Ammar A; Baker, Kevin S; Gould, Elaine S; Gupta, Rajarsi

2015-01-01

The purpose of this article is to review the imaging features of necrotizing fasciitis and its potential mimics. Key imaging features are emphasized to enable accurate and efficient interpretation of variables that are essential in appropriate management. Necrotizing fasciitis is a medical emergency with potential lethal outcome. Dissecting gas along fascial planes in the absence of penetrating trauma (including iatrogenic) is essentially pathognomonic. However, the lack of soft-tissue emphysema does not exclude the diagnosis. Mimics of necrotizing fasciitis include nonnecrotizing fasciitis (eosinophilic, paraneoplastic, inflammatory (lupus myofasciitis, Churg-Strauss, nodular, or proliferative), myositis, neoplasm, myonecrosis, inflammatory myopathy, and compartment syndrome. Necrotizing fasciitis is a clinical diagnosis, and imaging can reveal nonspecific or negative findings (particularly during the early course of disease). One should be familiar with salient clinical and imaging findings of necrotizing fasciitis to facilitate a more rapid and accurate diagnosis and be aware that its diagnosis necessitates immediate discussion with the referring physician.

Surgically Induced Necrotizing Scleritis Following Strabismus Surgery Treated Successfully with Topical N-acetylcysteine in a Child with Congenital Fibrosis of Extraocular Muscles and Varadi Papp Syndrome.

PubMed

Rajamani, Muralidhar; Nagasubramanian, Vidhya; Ayyavoo, Ahila; Raghupathy, Palany; Dandapani, Ramamurthy

2017-03-01

Surgically induced necrotizing scleritis (SINS) is a rare but serious disorder that can develop many years after strabismus surgery. It is generally treated with high-dose steroids or immunosuppression. We describe a patient with Varadi Papp syndrome and congenital fibrosis of the extraocular muscles, who developed surgically induced necrotizing scleritis a month after strabismus surgery and was successfully managed by oral vitamin C and topical N-acetylcysteine 10%. While SINS is conventionally treated with steroids/immunosuppression, a conservative approach may be tried in milder cases. The role of topical N-acetylcysteine in managing this complication needs to be explored.

[Evaluation of central parenteral alimentation in critically ill newborn infants at a provincial pediatric hospital].

PubMed

Yunes-Zárraga, J L; de la Garza-Garza, G; Velázquez-Quintana, N

1989-04-01

A revision was made on files of newborns whom received total parenteral nutrition (TPN) in the neonatal intensive care unit of the Hospital Infantil de Tamaulipas during a two and a half years period. We try to correlate dosage and caloric intake with weight gain, survival and complications. We reviewed the principal indications that motivated the use of total parenteral nutrition. The average period of administration was 15 days and caloric intake average 75 cal. There was significance in weight gain in newborns older than 35 weeks (14.6 g/kg/day) compared with younger than 34 weeks (9.2 g/kg/day) (p less than 0.001). There was no relation between days and dosage in both groups. Only one case showed cholestatic jaundice. Hyperglycemia was present statistically more frequent in the group lesser gestational age. There were no important electrolytic disturbances. Necrotizing enterocolitis was present more frequent in the older group. Some comments are made in relation to sepsis and a discussion of possible causes that do no permit a better assimilation of nutrients in these babies.

Nonprofit Human Milk Banking in the United States.

PubMed

Updegrove, Kimberly

2013-01-01

Human milk, widely understood to be beneficial for infants, can be lifesaving for preterm neonates, especially in reducing the risk of necrotizing enterocolitis. Donor human milk (DHM) is an option when mothers are unable to provide milk or have an inadequate supply for their infants. Nonprofit donor human milk banks are established to provide safe, processed human milk from milk donated by healthy lactating mothers who have undergone a rigorous screening process. These milk banks, operating under the auspices of the Human Milk Banking Association of North America, obtain, process, and dispense human milk under strict guidelines set by the association. Increasing the supply of donor human milk to meet a dramatic increase in demand poses a significant challenge for nonprofit milk banks. Efforts to increase supply nationwide include education of providers, use of social media to engage potential donors, and outreach to news media. In parallel, milk banks are establishing regional depots to collect donations, and additional milk banks are being developed. This article describes the current nonprofit milk bank industry in the United States, its challenges, and its future prospects. © 2013 by the American College of Nurse‐Midwives.

Immunology of breast milk.

PubMed

Palmeira, Patricia; Carneiro-Sampaio, Magda

2016-09-01

In the critical phase of immunological immaturity of the newborn, particularly for the immune system of mucous membranes, infants receive large amounts of bioactive components through colostrum and breast milk. Colostrum is the most potent natural immune booster known to science. Breastfeeding protects infants against infections mainly via secretory IgA (SIgA) antibodies, but also via other various bioactive factors. It is striking that the defense factors of human milk function without causing inflammation; some components are even anti-inflammatory. Protection against infections has been well evidenced during lactation against, e.g., acute and prolonged diarrhea, respiratory tract infections, including otitis media, urinary tract infection, neonatal septicemia, and necrotizing enterocolitis. The milk's immunity content changes over time. In the early stages of lactation, IgA, anti-inflammatory factors and, more likely, immunologically active cells provide additional support for the immature immune system of the neonate. After this period, breast milk continues to adapt extraordinarily to the infant's ontogeny and needs regarding immune protection and nutrition. The need to encourage breastfeeding is therefore justifiable, at least during the first 6 months of life, when the infant's secretory IgA production is insignificant.

[Human milk, immune responses and health effects].

PubMed

Løland, Beate Fossum; Baerug, Anne B; Nylander, Gro

2007-09-20

Besides providing optimal nutrition to infants, human milk contains a multitude of immunological components. These components are important for protection against infections and also support the development and maturation of the infant's own immune system. This review focuses on the function of some classical immunocomponents of human milk. Relevant studies are presented that describe health benefits of human milk for the child and of lactation for the mother. Relevant articles were found mainly by searching PubMed. Humoral and cellular components of human milk confer protection against infections in the respiratory--, gastrointestinal--and urinary tract. Human milk also protects premature children from neonatal sepsis and necrotizing enterocolitis. There is evidence that human milk may confer long-term benefits such as lower risk of certain autoimmune diseases, inflammatory bowel disease and probably some malignancies. Human milk possibly affects components of the metabolic syndrome. Recent studies demonstrate long-term health benefits of lactation also for the mother. A reduced incidence of breast cancer is best documented. An increasing number of studies indicate protection against ovarian cancer, rheumatoid arthritis and type II diabetes.

Ureaplasma-associated prenatal, perinatal, and neonatal morbidities.

PubMed

Silwedel, Christine; Speer, Christian P; Glaser, Kirsten

2017-11-01

Ureaplasma species (spp.) have been acknowledged as major causative pathogens in chorioamnionitis and prematurity, but may also contribute to key morbidities in preterm infants. Several epidemiological and experimental data indicate an association of neonatal Ureaplasma colonization and/or infection with bronchopulmonary dysplasia. Furthermore, a potential causal relation with other inflammation-induced morbidities, such as intraventricular hemorrhage, white matter injury, necrotizing enterocolitis, and retinopathy of prematurity, has been debated. Areas covered: This review will summarize current knowledge on the role of Ureaplasma spp. in prenatal, perinatal, and neonatal morbidities, while furthermore examining mutual underlying mechanisms. We try to elaborate who is at particular risk of Ureaplasma-induced inflammation and subsequent secondary morbidities. Expert commentary: Most likely by complex interactions with immunological processes, Ureaplasma spp. can induce pro-inflammation, but may also downregulate the immune system. Tissue damage, possibly causing the above mentioned complications, is likely to result from both ways: either directly cytokine-associated, or due to a higher host vulnerability to secondary impact factors. These events are very likely to begin in prenatal stages, with the most immature preterm infants being most susceptible and at highest risk.

Impact of oral probiotics on neurodevelopmental outcomes in preterm infants.

PubMed

Akar, Melek; Eras, Zeynep; Oncel, Mehmet Yekta; Arayici, Sema; Guzoglu, Nilufer; Canpolat, Fuat Emre; Uras, Nurdan; Oguz, Serife Suna

2017-02-01

The aim of the study was to evaluate the neurodevelopment outcomes of very low birth weight (VLBW) preterm infants supplemented with oral probiotics for the prevention of necrotizing enterocolitis (NEC). A prospective follow-up study was performed in a cohort of VLBW preterm infants enrolled in a single center randomized controlled clinical trial to evaluate the efficacy of oral probiotics for the prevention of NEC. Cognitive and neuromotor developments were assessed by using the Bayley scales of infant development II. Sensory and neurological performance was evaluated by standard techniques. The primary outcome was neurodevelopmental impairment at 18-24 months' corrected age. A total of 400 infants completed the trial protocol. Of the 370 infants eligible for follow-up, 249 infants (124 in the probiotics group and 125 in the control group) were evaluated. There was no significant difference in any of the neurodevelopmental and sensory outcomes between the two groups. Oral probiotic given to VLBW infants to reduce the incidense and severity of NEC started with the first feed did not affect neuromotor, neurosensory and cognitive outcomes at 18-24 months' corrected age.

Human Milk Components Modulate Toll-Like Receptor-Mediated Inflammation.

PubMed

He, YingYing; Lawlor, Nathan T; Newburg, David S

2016-01-01

Toll-like receptor (TLR) signaling is central to innate immunity. Aberrant expression of TLRs is found in neonatal inflammatory diseases. Several bioactive components of human milk modulate TLR expression and signaling pathways, including soluble toll-like receptors (sTLRs), soluble cluster of differentiation (sCD) 14, glycoproteins, small peptides, and oligosaccharides. Some milk components, such as sialyl (α2,3) lactose and lacto-N-fucopentaose III, are reported to increase TLR signaling; under some circumstances this might contribute toward immunologic balance. Human milk on the whole is strongly anti-inflammatory, and contains abundant components that depress TLR signaling pathways: sTLR2 and sCD14 inhibit TLR2 signaling; sCD14, lactadherin, lactoferrin, and 2'-fucosyllactose attenuate TLR4 signaling; 3'-galactosyllactose inhibits TLR3 signaling, and β-defensin 2 inhibits TLR7 signaling. Feeding human milk to neonates decreases their risk of sepsis and necrotizing enterocolitis. Thus, the TLR regulatory components found in human milk hold promise as benign oral prophylactic and therapeutic treatments for the many gastrointestinal inflammatory disorders mediated by abnormal TLR signaling. © 2016 American Society for Nutrition.

Probiotics for Gastrointestinal Conditions: A Summary of the Evidence.

PubMed

Wilkins, Thad; Sequoia, Jacqueline

2017-08-01

Probiotics contain microorganisms, most of which are bacteria similar to the beneficial bacteria that occur naturally in the human gut. Probiotics have been widely studied in a variety of gastrointestinal diseases. The most-studied species include Lactobacillus, Bifidobacterium, and Saccharomyces. However, a lack of clear guidelines on when to use probiotics and the most effective probiotic for different gastrointestinal conditions may be confusing for family physicians and their patients. Probiotics have an important role in the maintenance of immunologic equilibrium in the gastrointestinal tract through the direct interaction with immune cells. Probiotic effectiveness can be species-, dose-, and disease-specific, and the duration of therapy depends on the clinical indication. There is high-quality evidence that probiotics are effective for acute infectious diarrhea, antibiotic-associated diarrhea, Clostridium difficile- associated diarrhea, hepatic encephalopathy, ulcerative colitis, irritable bowel syndrome, functional gastrointestinal disorders, and necrotizing enterocolitis. Conversely, there is evidence that probiotics are not effective for acute pancreatitis and Crohn disease. Probiotics are safe for infants, children, adults, and older patients, but caution is advised in immunologically vulnerable populations.

Beyond building better brains: bridging the docosahexaenoic acid (DHA) gap of prematurity.

PubMed

Harris, W S; Baack, M L

2015-01-01

Long-chain polyunsaturated fatty acids (LCPUFA) including docosahexaenoic acid (DHA) are essential for normal vision and neurodevelopment. DHA accretion in utero occurs primarily in the last trimester of pregnancy to support rapid growth and brain development. Premature infants, born before this process is complete, are relatively deficient in this essential fatty acid. Very low birth weight (VLBW) infants remain deficient for a long period of time due to ineffective conversion from precursor fatty acids, lower fat stores and a limited nutritional provision of DHA after birth. In addition to long-term visual and neurodevelopmental risks, VLBW infants have significant morbidity and mortality from diseases specific to premature birth, including bronchopulmonary dysplasia, necrotizing enterocolitis, and retinopathy of prematurity. There is increasing evidence that DHA has protective benefits against these disease states. The aim of this article is to identify the unique needs of premature infants, review the current recommendations for LCPUFA provision in infants and discuss the caveats and innovative new ways to overcome the DHA deficiency through postnatal supplementation, with the long-term goal of improving morbidity and mortality in this at-risk population.

Human Milk Components Modulate Toll-Like Receptor–Mediated Inflammation12

PubMed Central

He, YingYing; Lawlor, Nathan T

2016-01-01

Toll-like receptor (TLR) signaling is central to innate immunity. Aberrant expression of TLRs is found in neonatal inflammatory diseases. Several bioactive components of human milk modulate TLR expression and signaling pathways, including soluble toll-like receptors (sTLRs), soluble cluster of differentiation (sCD) 14, glycoproteins, small peptides, and oligosaccharides. Some milk components, such as sialyl (α2,3) lactose and lacto-N-fucopentaose III, are reported to increase TLR signaling; under some circumstances this might contribute toward immunologic balance. Human milk on the whole is strongly anti-inflammatory, and contains abundant components that depress TLR signaling pathways: sTLR2 and sCD14 inhibit TLR2 signaling; sCD14, lactadherin, lactoferrin, and 2′-fucosyllactose attenuate TLR4 signaling; 3′-galactosyllactose inhibits TLR3 signaling, and β-defensin 2 inhibits TLR7 signaling. Feeding human milk to neonates decreases their risk of sepsis and necrotizing enterocolitis. Thus, the TLR regulatory components found in human milk hold promise as benign oral prophylactic and therapeutic treatments for the many gastrointestinal inflammatory disorders mediated by abnormal TLR signaling. PMID:26773018

Neonatal Outcomes of Extremely Preterm Infants From the NICHD Neonatal Research Network

PubMed Central

Stoll, Barbara J.; Hansen, Nellie I.; Bell, Edward F.; Shankaran, Seetha; Laptook, Abbot R.; Walsh, Michele C.; Hale, Ellen C.; Newman, Nancy S.; Schibler, Kurt; Carlo, Waldemar A.; Kennedy, Kathleen A.; Poindexter, Brenda B.; Finer, Neil N.; Ehrenkranz, Richard A.; Duara, Shahnaz; Sánchez, Pablo J.; O’Shea, T. Michael; Goldberg, Ronald N.; Van Meurs, Krisa P.; Faix, Roger G.; Phelps, Dale L.; Frantz, Ivan D.; Watterberg, Kristi L.; Saha, Shampa; Das, Abhik; Higgins, Rosemary D.

2010-01-01

OBJECTIVE This report presents data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network on care of and morbidity and mortality rates for very low birth weight infants, according to gestational age (GA). METHODS Perinatal/neonatal data were collected for 9575 infants of extremely low GA (22–28 weeks) and very low birth weight (401–1500 g) who were born at network centers between January 1, 2003, and December 31, 2007. RESULTS Rates of survival to discharge increased with increasing GA (6% at 22 weeks and 92% at 28 weeks); 1060 infants died at ≤ 12 hours, with most early deaths occurring at 22 and 23 weeks (85% and 43%, respectively). Rates of prenatal steroid use (13% and 53%, respectively), cesarean section (7% and 24%, respectively), and delivery room intubation (19% and 68%, respectively) increased markedly between 22 and 23 weeks. Infants at the lowest GAs were at greatest risk for morbidities. Overall, 93% had respiratory distress syndrome, 46% patent ductus arteriosus, 16% severe intraventricular hemorrhage, 11% necrotizing enterocolitis, and 36% late-onset sepsis. The new severity-based definition of bronchopulmonary dysplasia classified more infants as having bronchopulmonary dysplasia than did the traditional definition of supplemental oxygen use at 36 weeks (68%, compared with 42%). More than one-half of infants with extremely low GAs had undetermined retinopathy status at the time of discharge. Center differences in management and outcomes were identified. CONCLUSION Although the majority of infants with GAs of ≥24 weeks survive, high rates of morbidity among survivors continue to be observed. PMID:20732945

The use of negative pressure in critical necrotizing fasciitis treatment: a case presentation.

PubMed

Ge, Kui; Xu, Bing; Wu, Jia-Jun; Wu, Minjie; Lu, Shuliang; Xie, Ting

2014-09-01

Surgery complemented by antibiotics forms the backbone of the successful management of necrotizing fasciitis. But it will be very difficult to clear away extensive necrotizing tissue thoroughly in critically ill patients when their vital signs are unstable. The authors report the case of a 33-year-old woman who had extensive necrotizing fasciitis of the right lower limb with septic shock. The patient was severely anemic and malnutrition and had been given conservative debridement at bedside, that is, only detached necrotizing tissues was taken away while some other necrotizing tissue still remained, so that the skin tissue within the same area could be saved as much as possible. After debridement, negative pressure was applied at 125 mm Hg. Broad-spectrum antibiotics and effective supplementation were also complemented, thus controlling the septic shock. All necrotizing tissues were detached, and the sparing vital skin on necrotizing fascia was preserved successfully after negative pressure treatment. The patient was finally saved. In conclusion, negative pressure treatment may help diminish toxin absorbance, detach gangrene tissue, and preserve sparing vital tissue. This case suggests the value of combined use of negative pressure therapy and conservative debridement in critically ill patients with extensive necrotizing fasciitis. © The Author(s) 2014.

Differentiation of histoplasma and cryptococcus in cytology smears: a diagnostic dilemma in severely necrotic cases.

PubMed

Ranjan, R; Jain, D; Singh, L; Iyer, V K; Sharma, M C; Mathur, S R

2015-08-01

The correct identification of fungal organisms is important for the appropriate clinical management of patients. It becomes difficult in necrotic smears when the tissue response is not clearly discernible. It is difficult to distinguish between histoplasma and cryptococcus in severely necrotic cases, where both appear as variably sized clear refractile haloes. Four cases of adrenal necrotic histoplasma infection were studied and the morphology was compared with that of non-necrotic histoplasmosis and cases of cryptococcal infection. Eleven cases were analysed in fine needle aspiration cytology (FNAC) smears. Ziehl-Neelsen (ZN) stain was performed to exclude tuberculosis in necrotic smears. A clinical and serology correlation was performed where available. Necrotic cases of histoplasma infection revealed negative refractile clear haloes similar to those of cryptococcus. Histoplasma showed methylene blue-stained organisms in ZN stains, whereas the cryptococcus cases were negative. Similar methylene blue-stained organisms were seen in non-necrotic histoplasma infection. As a result of morphological overlap between cryptococcus and histoplasma, the distinction between the two fungi can be difficult in many cases. ZN staining appears to have a role in the differentiation of these fungi in severely necrotic cases. This observation needs to be validated on a larger number of cases with complete correlation with clinical, serology and treatment records. © 2014 John Wiley & Sons Ltd.

Necrotizing fasciitis: treatment concepts and clinical results.

PubMed

Leiblein, M; Marzi, I; Sander, A L; Barker, J H; Ebert, F; Frank, J

2018-04-01

Necrotizing fasciitis is a life-threatening soft tissue infection characterized by a rapid spreading infection of the subcutaneous tissue and in particular the fascia. The management of infected tissues requires a rapid diagnosis, immediate aggressive surgical management and an extended debridement. In some cases early amputations of the affected tissues and maximum intensive care treatment, in case of sepsis, are required. Due to a rising number of cases we aimed to evaluate our patients in a retrospective review. All patients diagnosed with necrotizing fasciitis from 2014 to 2016 (21 months) in our level one trauma center were identified. Their charts were reviewed and data were analyzed in terms of demographic and social information, microbiological results, therapeutic course, socio-economic outcome and mortality. We found 15 patients with necrotizing fasciitis. None of these died in the observation period. The mean number of surgical interventions was seven. Two patients underwent limb amputation; diabetes mellitus was assigned with a significant higher risk for amputation. The mean hospitalization was 32 days, including 8 days on intensive care unit. Of the discovered bacteria 93% were sensitive to the initial antibiotic treatment with Ampicillin, Clindamycin and Clont. Surgical therapy is indicated if necrotizing fasciitis is suspected. Diabetes mellitus was a clinical predictor of limb amputation in patients with necrotizing fasciitis in our cohort. Aminopenicillin ± sulbactam in combination with clindamycin and/or metronidazole is recommended as initial calculated antibiotic treatment.

Skin-Sparing Débridement for Necrotizing Fasciitis in Children.

PubMed

Rüfenacht, Magali S; Montaruli, Ernesto; Chappuis, Eléonore; Posfay-Barbe, Klara M; La Scala, Giorgio C

2016-09-01

Necrotizing fasciitis is a serious soft-tissue infection associated with sepsis and tissue destruction. Surgical management usually requires extensive débridement of necrotic fascia and overlying skin, with significant aesthetic and functional consequences. The authors review the outcome of all recent cases of necrotizing fasciitis treated with skin-sparing débridement at their institution. The authors conducted a retrospective review of all of their cases of necrotizing fasciitis treated with skin-sparing débridement. Medical records were evaluated with a standard form gathering relevant demographic and clinical data. All cases were confirmed as necrotizing fasciitis histologically. Ten patients were admitted with a diagnosis of necrotizing fasciitis. The median age of the patients was 4.9 years (range, 1.7 to 15.1 years). The majority of initial lesions were caused by chickenpox, mostly on the trunk. Interval from admission to surgery was 6 hours (range, 1 to 27.5 hours), with a median hospital stay of 11 days (range, 5 to 43 days). Median fasciectomy was 2.5 percent (range, 1 to 15 percent) of total body surface area, with a median skin excision of 0.25 percent of total body surface area (range, 0.1 to 3 percent). All patients received intravenous amoxicillin/clavulanic acid plus clindamycin. Delayed direct closure was possible for all patients. Median follow-up was 17 months (range, 3 to 79 months). There was no death in this series. This surgical management restricts skin excision to the area of definite skin necrosis, limiting skin excision to one-tenth of excised fascia, with long-term favorable cosmetic and functional results. Therapeutic, IV.

Necrotizing Fasciitis Versus Pyoderma Gangrenosum: Securing the Correct Diagnosis! A Case Report and Literature Review

PubMed Central

Bisarya, Kamal; Azzopardi, Silvan; Lye, George; Drew, Peter James

2011-01-01

Objective: To highlight the key differences in history, examination, and management of pyoderma gangrenosum and necrotizing fasciitis and to outline the importance of distinguishing these 2 conditions. Method: We present a case report of a gentleman with a background of ulcerative colitis having a 1-week history of an erythematous wound and localized abscess to the right leg that failed to respond to antibiotic treatment and later on to surgical debridement of a presumed necrotizing fasciitis. Following referral to our plastic surgery unit, a diagnosis of pyoderma gangrenosum was made and this was confirmed following a response to steroid therapy within 48 hours. A literature review of pyoderma gangrenosum cases misdiagnosed for necrotizing fasciitis was carried out to compare and contrast pitfalls in misdiagnosing these 2 conditions. Results: Literature review of 10 cases confirmed the association of pyoderma gangrenosum with inflammatory bowel disease, hematological disease, and surgical trauma. The presence of necrotic tissue in a pyoderma gangrenosum lesion can be a diagnostic pitfall; although blood and tissue culture investigations are usually negative in pyoderma gangrenosum, this may not always be the case. Inflammatory markers can be significantly high in pyoderma gangrenosum and pyrexia is not a feature limited to necrotizing fasciitis. Conclusions: Inappropriate surgical debridement of pyoderma gangrenosum can cause rapid extension of the lesion by enhancing the posttraumatic response and lead to potential reconstructive challenges with psychological repercussions. On the contrary, treating necrotizing fasciitis with immunosuppressive therapy may worsen the condition. The importance of understanding the pathogenesis, clinical features, and management of both conditions cannot be overemphasized. PMID:21625613

Management of Necrotizing Fasciitis and Fecal Peritonitis following Ostomy Necrosis and Detachment by Using NPT and Flexi-Seal.

PubMed

Yetışır, Fahri; Şarer, Akgün Ebru; Acar, H Zafer

2015-01-01

Management of necrotizing fasciitis and severe faecal peritonitis following ostomy in elderly patient with comorbid disease is challenging. We would like to report management of frozen Open Abdomen (OA) with colonic fistula following ostomy necrosis and detachment in an elderly patient with comorbid disease and malignancy. 78-year-old woman with high stage rectum carcinoma was admitted to emergency department and underwent operation for severe peritonitis and sigmoid colonic perforation. Loop sigmoidostomy was performed. At postoperative 15th day, she was transferred to our clinic with necrotizing fasciitis and severe faecal peritonitis due to ostomy necrosis and detachment. Enteric effluent was removed from the OA wound by using the Flexi-Seal Fecal Management System (FMS) (ConvaTec) and pesser tube in deeply located colonic fistula in conjunction with Negative Pressure Therapy (NPT). Maturation of ostomy was facilitated by using second NPT on ostomy side. After source control, delayed abdominal closure was achieved by skin flap approximation.

Mode of Action of Shigella Toxin: Effects on Ribosome Structure and Function

DTIC Science & Technology

1988-05-01

1974. Sindrome hemolitico uremico: reporte de 60 casos asociados a una epidemia de enterocolitis hemorragica. Revista Colombiana de Ped. Puericult. 28...1518-1521. 34. Fong, J.S.C., J-P de Chadarevian and B.S. Kaplan. 1982. Hemolytic-uremic syndrome: current concepts and management. Ped. Clin. North Am

[Necrotizing Fasciitis: A comprehensive review].

PubMed

Carbonetti, F; Carusi, V; Guidi, M; David, V

Even though necrotizing fasciitis is considered a rare disease, the spreading of the predisposing factors such as diabetes and chronic diseases, contribute to increase the incidence of this infection. Thus, how to diagnose and treat this clinical pathology, which represents an emerging need. This infection could be fatal for patients if not early diagnosed and treated and it represents a challenge both for the clinicians both for the surgeons. From this consideration was born the idea to write this review article in order to furnish to the readers a helpful tool in the management of this disease starting from its clinical and epidemiological features leading to the diagnosis, both clinical and radiological, and concluding with the treatment both medical both surgical .This article reviews literature on PubMed/MEDLINE with key words "necrotizing", "fasciitis" and "necrotizing fasciitis" from 1967 to 2014, considering all the aspects of the disease. The authors attempt to draw comparisons to their own experience managing this condition to give an Italian perspective to the condition.

Abdominal ultrasonographic findings in typhoid fever: a comparison between typhoid patients and those with non-typhoidal Salmonella and Campylobacter jejuni enterocolitis.

PubMed

Kobayashi, Akira; Adachi, Yasuo; Iwata, Yoshinori; Sakai, Yoshiyuki; Shigemitu, Kazuaki; Todoroki, Miwako; Ide, Mituru

2012-03-01

Typhoid fever is a major health problem in many developing countries and its clinical features are similar to other types of bacterial enterocolitis. Definitive diagnosis by blood culture requires several days and is often unfeasible to perform in developing countries. More efficient and rapid diagnostic methods for typhoid are needed. We compared the pathological changes in the bowel and adjacent tissues of patients having typhoid fever with those having bacterial enterocolitis using ultrasonography. A characteristic of patients with non-typhoidal Salmonella and Campylobacter jejuni enterocolitis was mural thickening of the terminal ileum; only mild mural swelling or no swelling was observed in patients with typhoid fever. Mesenteric lymph nodes in patients with typhoid fever were significantly more enlarged compared to patients with other types of bacterial enterocolitis. Our findings suggest typhoid fever is not fundamentally an enteric disease but rather resembles mesenteric lymphadenopathy and ultrasound is a promising modality for diagnosing typhoid fever in developing countries.

Statin-induced necrotizing myositis - a discrete autoimmune entity within the "statin-induced myopathy spectrum".

PubMed

Hamann, Philip D H; Cooper, Robert G; McHugh, Neil J; Chinoy, Hector

2013-10-01

Statin-induced necrotizing myositis is increasingly being recognised as part of the "statin-induced myopathy spectrum". As in other immune-mediated necrotizing myopathies, statin-induced myositis is characterised by proximal muscle weakness with marked serum creatinine kinase elevations and histological evidence of myonecrosis, with little or no inflammatory cell infiltration. Unlike other necrotizing myopathies, statin-induced myopathy is associated with the presence of autoantibodies directed against 3-hydroxy-3-methylglutaryl- coenzyme A reductase (the enzyme target of statin therapies), and with Human Leukocyte Antigen-DRB1*11. This article summarises the clinical presentation, investigations and management of this rare, but serious complication of statin therapy. © 2013 Elsevier B.V. All rights reserved.

Raised serum lactate: a marker of necrotizing fasciitis?

PubMed

Murphy, George; Markeson, Daniel; Choa, Robert; Armstrong, Anthony

2013-12-01

Distinguishing necrotizing fasciitis from non-necrotizing soft-tissue infections remains a difficult clinical judgement call, with a paucity of diagnostic aids to the clinician. The aim of this study was to assess raised serum lactate as a point-of-care test to aid in differentiating necrotizing from non-necrotizing soft tissue infections. The authors performed a post-hoc analysis of a prospectively compiled database. All patients referred to a single surgeon (A.P.A.) as suspected cases of necrotizing fasciitis at one hospital between September 2000 and September 2010 were included. Serum lactate at presentation was recorded, along with demographic and outcome data. Using histological evidence of tissue necrosis as the 'gold standard', patients were divided into those with or without necrotizing fasciitis, and their serum lactate at presentation compared. Fifty three patients met the inclusion criteria. Twenty eight had histologically proven necrosis, 25 did not. Serum lactate (mean±SD) was 4.1±1.62 mmol/l in the necrotizing fasciitis group and 1.8±0.46 mmol/l in the non-necrotizing fasciitis group (p≤0.0001). A serum lactate level above 2.0 mmol/l had a sensitivity of 1.00 and a specificity of 0.76 for necrotizing fasciitis in this series. In this series of patients with suspected necrotizing soft tissue infection, serum lactate levels above 2.0 mmol/l at presentation were strongly associated with the presence of tissue necrosis. Although no test can be relied upon in isolation, our results suggest that serum lactate is a promising adjunct to the diagnosis of necrotizing infection, which could help to expedite appropriate management. Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Necrotizing fasciitis of the breast: a case managed without mastectomy.

PubMed

Soliman, M O; Ayyash, E H; Aldahham, A; Asfar, S

2011-01-01

To report a rare presentation of necrotizing fasciitis (NF) in the breast and its management. A 61-year-old non-diabetic lady presented with a painful swollen right breast and yellowish discharge associated with fever for the last few days. Based on clinical examination and haematological parameters, a provisional diagnosis of breast abscess was made that later proved to be a case of NF. She was managed conservatively with repeated debridement followed by split-skin grafting with preservation of the breast. This case showed that NF of the breast can present as a simple breast abscess which was managed conservatively. Copyright © 2011 S. Karger AG, Basel.

Necrotizing Fasciitis of Thoracic and Abdominal Wall with Emphysematous Pyelonephritis and Retroperitoneal Abscess

PubMed Central

Khaladkar, Sanjay Mhalasakant; Jain, Kunaal Mahesh; Kuber, Rajesh; Gandage, Sidappa

2018-01-01

Emphysematous pyelonephritis is a life-threatening severe form of pyelonephritis usually occurring in patients with diabetes mellitus with or without obstructive uropathies in whom there is necrotizing infection leading to the gas production of an unclear mechanism involving the renal parenchyma and the collecting system. Necrotizing fasciitis is characterized by progressive necrosis of fat and fascia due to deep-seated infection of subcutaneous tissue. It has a fulminant course with considerable mortality. Diabetes Mellitus is a common predisposing factor. The combined occurrence of emphysematous pyelonephritis and necrotizing fasciitis is extremely unusual. Early recognition and management is mandatory to avoid mortality. We report a case of a 53-year-old female, a known case of Type II diabetes mellitus, who presented with necrotizing fasciitis of thoracic and abdominal wall with emphysematous pyelonephritis in the left kidney with a retroperitoneal abscess. PMID:29541493

Cervical necrotizing fasciitis: Systematic review and analysis of 1235 reported cases from the literature.

PubMed

Gunaratne, Dakshika A; Tseros, Evan A; Hasan, Zubair; Kudpaje, Akshay S; Suruliraj, Anand; Smith, Mark C; Riffat, Faruque; Palme, Carsten E

2018-06-22

Cervical necrotizing fasciitis is a progressive soft tissue infection with significant morbidity and mortality. A case review of cervical necrotizing fasciitis managed at our institution (2007-2017) and a systematic review of PubMed, MEDLINE, and EMBASE databases using the algorithm "(cervical OR neck) AND necrotizing fasciitis." There were 1235 cases from 207 articles which were included in our clinical review. Mean age for cervical necrotizing fasciitis was 49.1 years (64.23% men). Etiology was odontogenic (47.04%), pharyngolaryngeal (28.34%), or tonsillar/peritonsillar (6.07%). There were 2 ± 0.98 organisms identified per patient; streptococci (61.22%), staphylococci (18.09%), and prevotella (10.87%). There were 2.5 ± 3.22 surgical debridements undertaken. Descending necrotizing mediastinitis occurred in 31.56% of patients. Mean length of stay in the hospital was 29.28 days and overall mortality was 13.36%. Physicians and surgeons must be vigilant of the diagnosis of cervical necrotizing fasciitis as early clinical findings may be subtle and prompt identification to facilitate aggressive intervention is required to preclude catastrophic local and systemic morbidity and mortality. © 2018 Wiley Periodicals, Inc.

Necrotizing Fasciitis - Report of ten cases and review of recent literature

PubMed Central

Al Shukry, S; Ommen, J

2013-01-01

Necrotizing fasciitis is an uncommon disease that results in gross morbidity and mortality if not diagnosed and treated in its early stages. At onset, however, it is difficult to differentiate from other superficial skin conditions such as cellulitis. Family physicians must have a high level of suspicion and low threshold for surgical referral when confronted with cases of pain, fever, and erythema. We present ten cases of necrotizing fasciitis managed in a provincial secondary hospital in Oman over 3 years ago. A review of recent literature is also presented. PMID:23904882

Long-term outcomes of twins based on the intended mode of delivery.

PubMed

Fox, Nathan S; Cohen, Natalie; Odom, Elizabeth; Gupta, Simi; Lam-Rachlin, Jennifer; Saltzman, Daniel H; Rebarber, Andrei

2018-08-01

Recent studies have shown that for twin pregnancies with a cephalic presenting first twin, planned vaginal delivery is not associated with adverse short-term neonatal outcomes, as compared to planned cesarean delivery. Our objective was to compare long-term outcomes in twins, based on planned mode of delivery. This was a prospective, observational cohort of twin pregnancies delivered by a single MFM practice. All the patients with a twin pregnancy >34 weeks delivered from 2005-2014 were surveyed regarding pediatric outcomes at or after 2 years of life. The survey was mail-based, with phone follow-up for nonresponses or for clarification of answers. Using chi-square, Student's t-tests, and regression analysis we compared outcomes between women who planned a vaginal (with active management of the second stage) versus cesarean delivery. The main outcome measures were: (1) a composite of major adverse outcomes (death, cerebral palsy, necrotizing enterocolitis, chronic renal, heart, or lung disease); (2) a composite of minor adverse outcomes (learning disability, speech therapy, occupational therapy, physical therapy). Five hundred and thirty-two women met inclusion criteria and 354 (66.5%) responded. 178 (50.3%) women planned to have a cesarean delivery (100% of whom had a cesarean delivery) and 176 (49.7%) women planned to have a vaginal delivery (83% of whom had a vaginal delivery). The average age of the children at the time of the survey was 5.9 years. There were no differences in any pediatric outcomes between the two groups. After controlling for maternal age, IVF, obesity, and preeclampsia, the planned mode of delivery was not associated with a composite of major adverse outcomes (aOR 0.673, 95% CI 0.228, 1.985), nor a composite of minor adverse outcomes (aOR 0.767, 95% CI 0.496, 1.188). Planned vaginal delivery with active management of the second stage of labor in twin pregnancies >34 weeks is not associated with adverse childhood outcomes.

Reduced Hospital Mortality With Surgical Ligation of Patent Ductus Arteriosus in Premature, Extremely Low Birth Weight Infants: A Propensity Score-matched Outcome Study.

PubMed

Tashiro, Jun; Perez, Eduardo A; Sola, Juan E

2016-03-01

To evaluate outcomes after surgical ligation (SL) of patent ductus arteriosus (PDA) in premature, extremely low birth weight (ELBW) infants. Optimal management of PDA in this specialized population remains undefined. Currently, surgical therapy is largely reserved for infants failing medical management. To date, a large-scale, risk-matched population-based study has not been performed to evaluate differences in mortality and resource utilization. Data on identified premature (<37 weeks) and ELBW (<1000  g) infants with PDA (International Classification of Diseases, 9th revision, Clinical Modification, 747.0) and respiratory distress (769) were obtained from Kids' Inpatient Database (2003-2009). Overall, 12,470 cases were identified, with 3008 undergoing SL. Propensity score-matched analysis of 1620 SL versus 1584 non-SL found reduced mortality (15% vs 26%) and more routine disposition (48% vs 41%) for SL (P < 0.001). SL had longer length of stay and higher total cost (P < 0.001). On multivariate analysis, SL mortality predictors were necrotizing enterocolitis (NEC; surgical odds ratio, 5.95; medical odds ratio, 4.42) and sepsis (3.43) (P < 0.006). Length of stay increased with bronchopulmonary dysplasia (BPD; 1.77), whereas total cost increased with surgical NEC (1.82) and sepsis (1.26) (P < 0.04). Non-SL mortality predictors were NEC (surgical, 76.3; medical, 6.17), sepsis (2.66), and intraventricular hemorrhage (1.97) (P < 0.005). Length of stay increased with BPD (2.92) and NEC (surgical, 2.04; medical, 1.28) (P < 0.03). Total cost increased with surgical NEC (2.06), medical NEC (1.57), sepsis (1.43), and BPD (1.30) (P < 0.001). Propensity score-matched analysis demonstrates reduced mortality in premature/ELBW infants with SL for PDA. NEC and sepsis are predictors of mortality and resource utilization.

Diffusion-weighted imaging is helpful in the accurate non-invasive diagnosis of breast abscess: correlation with necrotic breast cancer.

PubMed

Wang, Cuiyan; Eghtedari, Mohammad; Yang, Wei Tse; Dogan, Basak Erguvan

2018-03-22

Clinical differentiation of atypical breast abscesses from necrotic tumour in premenopausal women is challenging and may delay appropriate therapy. In this case report, we present a 36-year-old woman with signs, symptoms and conventional imaging features of malignancy who underwent breast MRI. On diffusion-weighted imaging (DWI), profoundly low apparent diffusion coefficient values were a distinguishing sign of breast abscess from necrotic breast cancer, and helped manage the patient conservatively. We present a companion case of necrotic breast tumour highlighting significant differences in DWI. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Severe forms of food allergy.

PubMed

Sarinho, Emanuel; Lins, Maria das Graças Moura

To guide the diagnostic and therapeutic management of severe forms of food allergy. Search in the Medline database using the terms "severe food allergy," "anaphylaxis and food allergy," "generalized urticaria and food allergy," and "food protein-induced enterocolitis syndrome" in the last ten years, searching in the title, abstract, or keyword fields. Food allergy can be serious and life-threatening. Milk, eggs, peanuts, nuts, walnuts, wheat, sesame seeds, shrimp, fish, and fruit can precipitate allergic emergencies. The severity of reactions will depend on associated cofactors such as age, drug use at the onset of the reaction, history and persistence of asthma and/or severe allergic rhinitis, history of previous anaphylaxis, exercise, and associated diseases. For generalized urticaria and anaphylaxis, intramuscular epinephrine is the first and fundamental treatment line. For the treatment in acute phase of food-induced enterocolitis syndrome in the emergency setting, prompt hydroelectrolytic replacement, administration of methylprednisolone and ondansetron IV are necessary. It is important to recommend to the patient with food allergy to maintain the exclusion diet, seek specialized follow-up and, in those who have anaphylaxis, to emphasize the need to carry epinephrine. Severe food allergy may occur in the form of anaphylaxis and food-protein-induced enterocolitis syndrome, which are increasingly observed in the pediatric emergency room; hence, pediatricians must be alert so they can provide the immediate diagnosis and treatment. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

A fatal case of necrotizing fasciitis caused by Serratia marcescens.

PubMed

Curtis, Christopher E; Chock, Stefan; Henderson, Terrance; Holman, Michael J

2005-03-01

A patient with a history of type II diabetes mellitus (DM), end stage renal disease (ESRD), and congestive heart failure (CHF) developed necrotizing fasciitis caused by Serratia marcescens after scraping his leg on rocks in a river while fishing. Aggressive management with surgical debridement, antibiotics, and pressure support was unsuccessful.

[Necrotizing cervico-facial cellulitis of dental origin in a developing country].

PubMed

Togo, S; Ouattara, M A; Saye, J; Sangaré, I; Touré, M; Maiga, I; Dakouo, D J; Xing, L; Guo, L; Zhou, A J; Koumaré, S; Koita, A K; Sanogo, Z Z; Yéna, S

2017-09-01

Necrotizing cellulitis of dental origin is a serious disease and requires prompt and effective management to avoid adverse outcomes. The purpose of this work is to describe the diagnostic and therapeutic difficulties encountered in this condition. This was a prospective study in the thoracic surgery department of Mali Hospital from January 2011 to February 2015. We collected consecutively 19 cases of complicating cervico-facial cellulitis of dental origin. The anatomical and clinical aspects, therapeutic modalities and difficulties are described. Dental pain and fever were the predominant symptoms followed by cervical edema. Chest CT-scan was the basis for the diagnosis in all cases. Cervicotomy with debridement was the most performed surgical procedure. Pleural drainage was performed in 6 cases. Three patients (15.8%) died. Necrotizing cellulitis of dental origin is a serious disease with high morbidity and mortality. The key radiological examination is the thoracic CT-scan. Early medico-surgical management by emergency care, tailored antibiotic therapy, removal of necrotizing tissues and drainage of collections are required to deliver a good outcome. Copyright © 2016 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Necrotizing pancreatitis: new definitions and a new era in surgical management.

PubMed

Rosenberg, Andrew; Steensma, Elizabeth A; Napolitano, Lena M

2015-02-01

Necrotizing pancreatitis is a challenging condition that requires surgical treatment commonly and is associated with substantial morbidity and mortality. Over the past decade, new definitions have been developed for standardization of severity of acute and necrotizing pancreatitis, and new management techniques have emerged based on prospective, randomized clinical trials. Review of English-language literature. A new international classification of acute pancreatitis has been developed by PANCREA (Pancreatitis Across Nations Clinical Research and Education Alliance) to replace the Atlanta Classification. It is based on the actual local (whether pancreatic necrosis is present or not, whether it is sterile or infected) and systemic determinants (whether organ failure is present or not, whether it is transient or persistent) of severity. Early management requires goal-directed fluid resuscitation (with avoidance of over-resuscitation and abdominal compartment syndrome), assessment of severity of pancreatitis, diagnostic computed tomography (CT) imaging to assess for necrotizing pancreatitis, consideration of endoscopic retrograde cholangiopancreatography (ERCP) for biliary pancreatitis and early enteral nutrition support. Antibiotic prophylaxis is not recommended. Therapeutic antibiotics are required for treatment of documented infected pancreatic necrosis. The initial treatment of infected pancreatic necrosis is percutaneous catheter or endoscopic (transgastric/transduodenal) drainage with a second drain placement as required. Lack of clinical improvement after these initial procedures warrants consideration of minimally invasive techniques for pancreatic necrosectomy including video-assisted retroperitoneal debridement (VARD), minimally invasive retroperitoneal pancreatectomy (MIRP), or transluminal direct endoscopic necrosectomy (DEN). Open necrosectomy is associated with substantial morbidity, but to date no randomized trial has documented superiority of either minimally invasive or open surgical technique. Additional trials are underway to address this. Severe acute and necrotizing pancreatitis requires a multi-disciplinary treatment strategy that must be individualized for each patient. Optimal treatment of necrotizing pancreatitis now requires a staged, multi-disciplinary, minimally invasive "step-up" approach that includes a team of interventional radiologists, therapeutic endoscopists, and surgeons.

Retroperitoneal Necrotizing Fasciitis Masquerading as Perianal Abscess - Rare and Perilous.

PubMed

Amaranathan, Anandhi; Sahoo, Ashok Kumar; Barathi, Deepak; Shankar, Gomathi; Sistla, Sarath Chandra

2017-01-17

Necrotizing fasciitis is one of the uncommon presentations of a rapidly spreading subcutaneous tissue infection. Although the actual cause is unclear in many cases, most of them are due to the rapid proliferation of microorganisms. Retroperitoneal necrotizing fasciitis is extremely rare. It is a potentially lethal infection that requires immediate and aggressive surgical care. Early diagnosis is the key to a better prognosis. The possibility of retroperitoneal necrotizing fasciitis should be suspected in patients with symptoms of sepsis that are disproportionate to clinical findings. The rapid deterioration of the patient also gives a clue towards the diagnosis. We report a 35-year-old male with perianal abscess who had been progressed to retroperitoneal necrotizing fasciitis. The patient was managed successfully with aggressive debridement and drainage after laparotomy. Appropriate antibiotics were used to combat the sepsis. The patient recovered well at follow up, three months after discharge. Another patient, a 45-year-old male with a retroperitoneal abscess, progressed to retroperitoneal necrotizing fasciitis, and extra peritoneal drainage and debridement was done. Antibiotics depending upon the culture and sensitivity were used to control sepsis. But the patient succumbed to death 45 days after surgery due to uncontrolled sepsis. Necrotizing fasciitis of any anatomical site needs aggressive surgical care with early intervention. But retroperitoneal necrotizing fasciitis needs an extra effort for diagnosis. After diagnosis, it needs timely surgical intervention and appropriate antibiotic therapy for the recovery of the patients.

Group B Streptococcal Cellulitis and Necrotizing Fasciitis in Infants: A Systematic Review.

PubMed

Wojtera, Monika; Cheng, Horace; Fiorini, Kyle; Coughlin, Kevin; Barton, Michelle; Strychowsky, Julie

2018-02-07

There is no consensus regarding approaches to infantile group B streptococcal (GBS) head and neck cellulitis and necrotizing fasciitis. We present a case of GBS necrotizing cellulitis and summarizes the literature regarding the presentation and management of infantile head and neck GBS cellulitis and necrotizing fasciitis. The literature was searched using PubMed, Web of Science, EMBASE, and Medline (inception to April 2017) by two independent review authors. Inclusion criteria encompassed case reports or case series of infants less than 12 months of age with GBS cellulitis of the head and neck, or with GBS necrotizing fasciitis without restriction to the head and neck. Data were extracted using tables developed a priori by two independent review authors, and discrepancies were resolved by consensus. An infant presenting at 33 days of age with GBS facial necrotizing fasciitis was successfully treated conservatively with antibiotics. Our literature search identified 40 infants with GBS head and neck cellulitis. Late-onset (98%), male gender (65%), and prematurity (58%) predominated. Penicillins were the main therapy used (97%). The 12 identified cases of necrotizing fasciitis were associated with polymicrobial etiology (36%) and broad-spectrum antibiotic use. Seventy-five percent required debridement, including four of five (80%) cases involving the head and neck. Skin and soft tissue involvement is an uncommon manifestation of late-onset GBS infection which requires antibiotic therapy and possibly surgical debridement cases with necrotizing fasciitis.

Revascularization and Apical Plug in an Immature Molar

PubMed Central

Roghanizadeh, Leyla; Fazlyab, Mahta

2018-01-01

Managing of necrotic permanent teeth with immature apices is a treatment challenges. Treatment of such teeth includes apexification, apical plug and more recently, revascularization technique with the probable advantage of continuation of root development. In the present case report the referred patient had discomfort with a necrotic immature mandibular first molar. Periapical radiography showed a rather large apical lesion around immature roots. Revascularization protocol using calcium-enriched mixture (CEM) cement was indicated for the mesial root. However, in distal canal apical plug technique was applied. At 2-year follow-up, both procedures were successful in relieving patient’s symptoms. Dentin formation and increase in length of the mesial root was obvious. Apical plug and revascularization technique proved to be successful in management of necrotic immature teeth; moreover, revascularization carried the advantage of continuation of root development. PMID:29692851

Peritoneal drainage or laparotomy for neonatal bowel perforation? A randomized controlled trial.

PubMed

Rees, Clare M; Eaton, Simon; Kiely, Edward M; Wade, Angie M; McHugh, Kieran; Pierro, Agostino

2008-07-01

To determine whether primary peritoneal drainage improves survival and outcome of extremely low birth weight (ELBW) infants with intestinal perforation. Optimal surgical management of ELBW infants with intestinal perforation is unknown. An international multicenter randomized controlled trial was performed between 2002 and 2006. Inclusion criteria were birthweight >or=1000 g and pneumoperitoneum on x-ray (necrotizing enterocolitis or isolated perforation). Patients were randomized to peritoneal drain or laparotomy, minimizing differences in weight, gestation, ventilation, inotropes, platelets, country, and on-site surgical facilities. Patients randomized to drain were allowed to have a delayed laparotomy after at least 12 hours of no clinical improvement. Sixty-nine patients were randomized (35 drain, 34 laparotomy); 1 subsequently withdrew consent. Six-month survival was 18/35 (51.4%) with a drain and 21/33 (63.6%) with laparotomy (P = 0.3; difference 12% 95% CI, -11, 34%). Cox regression analysis showed no significant difference between groups (hazard ratio for primary drain 1.6; P = 0.3; 95% CI, 0.7-3.4). Delayed laparotomy was performed in 26/35 (74%) patients after a median of 2.5 days (range, 0.4-21) and did not improve 6-month survival compared with primary laparotomy (relative risk of mortality 1.4; P = 0.4; 95% CI, 0.6-3.4). Drain was effective as a definitive treatment in only 4/35 (11%) surviving neonates, the rest either had a delayed laparotomy or died. Seventy-four percent of neonates treated with primary peritoneal drainage required delayed laparotomy. There were no significant differences in outcomes between the 2 randomization groups. Primary peritoneal drainage is ineffective as either a temporising measure or definitive treatment. If a drain is inserted, a timely "rescue" laparotomy should be considered. Trial registration number ISRCTN18282954; http://isrctn.org/

Methicillin-Resistant and Susceptible Staphylococcus aureus Bacteremia and Meningitis in Preterm Infants

PubMed Central

Hansen, Nellie I.; Stoll, Barbara J.; Bell, Edward F.; Sánchez, Pablo J.; Shankaran, Seetha; Laptook, Abbot R.; Das, Abhik; Walsh, Michele C.; Hale, Ellen C.; Newman, Nancy S.; Schrag, Stephanie J.; Higgins, Rosemary D.

2012-01-01

BACKGROUND: Data are limited on the impact of methicillin-resistant Staphylococcus aureus (MRSA) on morbidity and mortality among very low birth weight (VLBW) infants with S aureus (SA) bacteremia and/or meningitis (B/M). METHODS: Neonatal data for VLBW infants (birth weight 401–1500 g) born January 1, 2006, to December 31, 2008, who received care at centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network were collected prospectively. Early-onset (≤72 hours after birth) and late-onset (>72 hours) infections were defined by blood or cerebrospinal fluid cultures and antibiotic treatment of ≥5 days (or death <5 days with intent to treat). Outcomes were compared for infants with MRSA versus methicillin-susceptible S aureus (MSSA) B/M. RESULTS: Of 8444 infants who survived >3 days, 316 (3.7%) had SA B/M. Eighty-eight had MRSA (1% of all infants, 28% of infants with SA); 228 had MSSA (2.7% of all infants, 72% of infants with SA). No infant had both MRSA and MSSA B/M. Ninety-nine percent of MRSA infections were late-onset. The percent of infants with MRSA varied by center (P < .001) with 9 of 20 centers reporting no cases. Need for mechanical ventilation, diagnosis of respiratory distress syndrome, necrotizing enterocolitis, and other morbidities did not differ between infants with MRSA and MSSA. Mortality was high with both MRSA (23 of 88, 26%) and MSSA (55 of 228, 24%). CONCLUSIONS: Few VLBW infants had SA B/M. The 1% with MRSA had morbidity and mortality rates similar to infants with MSSA. Practices should provide equal focus on prevention and management of both MRSA and MSSA infections among VLBW infants. PMID:22412036

Enteral feeding during indomethacin and ibuprofen treatment of a patent ductus arteriosus

PubMed Central

Clyman, Ronald; Wickremasinghe, Andrea; Jhaveri, Nami; Hassinger, Denise C.; Attridge, Joshua T.; Sanocka, Ulana; Polin, Richard; Gillam-Krakauer, Maria; Reese, Jeff; Mammel, Mark; Couser, Robert; Mulrooney, Neil; Yanowitz, Toby D.; Derrick, Matthew; Jegatheesan, Priya; Walsh, Michele; Fujii, Alan; Porta, Nicolas; Carey, William A.; Swanson, Jonathan R.

2013-01-01

Objective To test the hypothesis that infants who are just being introduced to enteral feedings will advance to full enteral nutrition at a faster rate if they receive “trophic” (15 ml/kg/day) enteral feedings while receiving indomethacin or ibuprofen treatment for patent ductus arteriosus (PDA). Study design Infants were eligible for the study if they were 231/7 – 306/7 weeks gestation, weighed 401–1250 g at birth, received maximum enteral volumes ≤60 ml/kg/day and were about to be treated with indomethacin or ibuprofen. A standardized “feeding advance regimen” and guidelines for managing feeding intolerance were followed at each site (n=13). Results Infants (n=177; 26.3±1.9 wks (±SD) gestation) were randomized at 6.5±3.9 days to receive “trophic” feeds (“feeding” group, n=81: indomethacin=80%, ibuprofen=20%) or no feeds (“fasting (npo)” group, n=96: indomethacin=75%, ibuprofen=25%) during the drug administration period. Maximum daily enteral volumes prior to study entry were 14±15 ml/kg/day. After drug treatment, infants randomized to the “feeding” arm required fewer days to reach the study’s feeding volume endpoint (120 ml/kg/day). Although the enteral feeding endpoint was reached at an earlier postnatal age, the age at which central venous lines were removed did not differ between the two groups. There were no differences between the two groups in the incidence of infection, necrotizing enterocolitis, spontaneous intestinal perforation or other neonatal morbidities. Conclusion Infants required less time to reach the feeding volume endpoint if they were given “trophic” enteral feedings when they received indomethacin or ibuprofen treatments. PMID:23472765

Probiotics and Time to Achieve Full Enteral Feeding in Human Milk-Fed and Formula-Fed Preterm Infants: Systematic Review and Meta-Analysis

PubMed Central

Aceti, Arianna; Gori, Davide; Barone, Giovanni; Callegari, Maria Luisa; Fantini, Maria Pia; Indrio, Flavia; Maggio, Luca; Meneghin, Fabio; Morelli, Lorenzo; Zuccotti, Gianvincenzo; Corvaglia, Luigi

2016-01-01

Probiotics have been linked to a reduction in the incidence of necrotizing enterocolitis and late-onset sepsis in preterm infants. Recently, probiotics have also proved to reduce time to achieve full enteral feeding (FEF). However, the relationship between FEF achievement and type of feeding in infants treated with probiotics has not been explored yet. The aim of this systematic review and meta-analysis was to evaluate the effect of probiotics in reducing time to achieve FEF in preterm infants, according to type of feeding (exclusive human milk (HM) vs. formula). Randomized-controlled trials involving preterm infants receiving probiotics, and reporting on time to reach FEF were included in the systematic review. Trials reporting on outcome according to type of feeding (exclusive HM vs. formula) were included in the meta-analysis. Fixed-effect or random-effects models were used as appropriate. Results were expressed as mean difference (MD) with 95% confidence interval (CI). Twenty-five studies were included in the systematic review. In the five studies recruiting exclusively HM-fed preterm infants, those treated with probiotics reached FEF approximately 3 days before controls (MD −3.15 days (95% CI −5.25/−1.05), p = 0.003). None of the two studies reporting on exclusively formula-fed infants showed any difference between infants receiving probiotics and controls in terms of FEF achievement. The limited number of included studies did not allow testing for other subgroup differences between HM and formula-fed infants. However, if confirmed in further studies, the 3-days reduction in time to achieve FEF in exclusively HM-fed preterm infants might have significant implications for their clinical management. PMID:27483319

Probiotics and Time to Achieve Full Enteral Feeding in Human Milk-Fed and Formula-Fed Preterm Infants: Systematic Review and Meta-Analysis.

PubMed

Aceti, Arianna; Gori, Davide; Barone, Giovanni; Callegari, Maria Luisa; Fantini, Maria Pia; Indrio, Flavia; Maggio, Luca; Meneghin, Fabio; Morelli, Lorenzo; Zuccotti, Gianvincenzo; Corvaglia, Luigi

2016-07-30

Probiotics have been linked to a reduction in the incidence of necrotizing enterocolitis and late-onset sepsis in preterm infants. Recently, probiotics have also proved to reduce time to achieve full enteral feeding (FEF). However, the relationship between FEF achievement and type of feeding in infants treated with probiotics has not been explored yet. The aim of this systematic review and meta-analysis was to evaluate the effect of probiotics in reducing time to achieve FEF in preterm infants, according to type of feeding (exclusive human milk (HM) vs. formula). Randomized-controlled trials involving preterm infants receiving probiotics, and reporting on time to reach FEF were included in the systematic review. Trials reporting on outcome according to type of feeding (exclusive HM vs. formula) were included in the meta-analysis. Fixed-effect or random-effects models were used as appropriate. Results were expressed as mean difference (MD) with 95% confidence interval (CI). Twenty-five studies were included in the systematic review. In the five studies recruiting exclusively HM-fed preterm infants, those treated with probiotics reached FEF approximately 3 days before controls (MD -3.15 days (95% CI -5.25/-1.05), p = 0.003). None of the two studies reporting on exclusively formula-fed infants showed any difference between infants receiving probiotics and controls in terms of FEF achievement. The limited number of included studies did not allow testing for other subgroup differences between HM and formula-fed infants. However, if confirmed in further studies, the 3-days reduction in time to achieve FEF in exclusively HM-fed preterm infants might have significant implications for their clinical management.

Early versus Delayed Human Milk Fortification in Very Low Birth Weight Infants-A Randomized Controlled Trial.

PubMed

Shah, Sanket D; Dereddy, Narendra; Jones, Tamekia L; Dhanireddy, Ramasubbareddy; Talati, Ajay J

2016-07-01

To compare the effect of initiating human milk fortification at 2 different feeding volumes on feeding intolerance and the time to reach full feeding volume. Very low birth weight infants (n = 100) were prospectively randomized to early fortification (EF) (beginning at a feeding volume of 20 mL/kg/d) or delayed fortification (at a feeding volume of 100 mL/kg/d). We employed a standardized feeding protocol and parenteral nutrition guidelines for the nutritional management of all study infants. The median days to reach full feeding volumes were equivalent in the 2 groups (20 vs 20, P = .45). No significant difference was observed in the total number of episodes of feeding intolerance (58 vs 57). Two cases of necrotizing enterocolitis (Bell stage ≥2) and deaths occurred in each group. Median daily protein intake (g/kg/d) was higher in EF group in week 1 (3.3 [3.2, 3.5] vs 3.1 [2.9, 3.3], P < .001), week 2 (3.6 [3.5, 3.8] vs 3.2 [2.9, 3.4], P < .001), and week 3 (3.7 [3.4, 3.9] vs 3.5 [2.8, 3.8], P = .006). Cumulative protein intake (g/kg) in the first 4 weeks of life was higher in EF group (98.6 [93.8, 104] vs 89.6 [84.2, 96.4], P < .001). Very early human milk fortification may improve early protein intake in very low birth weight infants without increasing frequencies of adverse events. ClinicalTrials.gov: NCT01988792. Copyright © 2016 Elsevier Inc. All rights reserved.

Validating bifidobacterial species and subspecies identity in commercial probiotic products.

PubMed

Lewis, Zachery T; Shani, Guy; Masarweh, Chad F; Popovic, Mina; Frese, Steve A; Sela, David A; Underwood, Mark A; Mills, David A

2016-03-01

The ingestion of probiotics to attempt to improve health is increasingly common; however, quality control of some commercial products can be limited. Clinical practice is shifting toward the routine use of probiotics to aid in prevention of necrotizing enterocolitis in premature infants, and probiotic administration to term infants is increasingly common to treat colic and/or prevent atopic disease. Since bifidobacteria dominate the feces of healthy breast-fed infants, they are often included in infant-targeted probiotics. We evaluated 16 probiotic products to determine how well their label claims describe the species of detectable bifidobacteria in the product. Recently developed DNA-based methods were used as a primary means of identification, and were confirmed using culture-based techniques. We found that the contents of many bifidobacterial probiotic products differ from the ingredient list, sometimes at a subspecies level. Only 1 of the 16 probiotics perfectly matched its bifidobacterial label claims in all samples tested, and both pill-to-pill and lot-to-lot variation were observed. Given the known differences between various bifidobacterial species and subspecies in metabolic capacity and colonization abilities, the prevalence of misidentified bifidobacteria in these products is cause for concern for those involved in clinical trials and consumers of probiotic products.

A comparison of Wisconsin neonatal intensive care units with national data on outcomes and practices.

PubMed

Hagen, Erika W; Sadek-Badawi, Mona; Albanese, Aggie; Palta, Mari

2008-11-01

Improvements in neonatal care over the past 3 decades have increased survival of infants at lower birthweights and gestational ages. However, outcomes and practices vary considerably between hospitals. To describe maternal and infant characteristics, neonatal intensive care units (NICU) practices, morbidity, and mortality in Wisconsin NICUs, and to compare outcomes in Wisconsin to the National Institute of Child Health and Human Development network of large academic medical center NICUs. The Newborn Lung Project Statewide Cohort is a prospective observational study of all very low birthweight (< or =1500 grams) infants admitted during 2003 and 2004 to the 16 level III NICUs in Wisconsin. Anonymous data were collected for all admitted infants (N=1463). Major neonatal morbidities, including bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and retinopathy of prematurity (ROP) were evaluated. The overall incidence of BPD was 24% (8%-56% between NICUs); IVH incidence was 23% (9%-41%); the incidence of NEC was 7% (0%-21%); and the incidence of grade III or higher ROP was 10% (0%-35%). The incidence rates of major neonatal morbidities in Wisconsin were similar to those of a national network of academic NICUs.

Conflicts in wound classification of neonatal operations.

PubMed

Vu, Lan T; Nobuhara, Kerilyn K; Lee, Hanmin; Farmer, Diana L

2009-06-01

This study sought to determine the reliability of wound classification guidelines when applied to neonatal operations. This study is a cross-sectional web-based survey of pediatric surgeons. From a random sample of 22 neonatal operations, participants classified each operation as "clean," "clean-contaminated," "contaminated," or "dirty or infected," and specified duration of perioperative antibiotics as "none," "single preoperative," "24 hours," or ">24 hours." Unweighted kappa score was calculated to estimate interrater reliability. Overall interrater reliability for wound classification was poor (kappa = 0.30). The following operations were classified as clean: pyloromyotomy, resection of sequestration, resection of sacrococcygeal teratoma, oophorectomy, and immediate repair of omphalocele; as clean-contaminated: Ladd procedure, bowel resection for midgut volvulus and meconium peritonitis, fistula ligation of tracheoesophageal fistula, primary esophageal anastomosis of esophageal atresia, thoracic lobectomy, staged closure of gastroschisis, delayed repair and primary closure of omphalocele, perineal anoplasty and diverting colostomy for imperforate anus, anal pull-through for Hirschsprung disease, and colostomy closure; and as dirty: perforated necrotizing enterocolitis. There is poor consensus on how neonatal operations are classified based on contamination. An improved classification system will provide more accurate risk assessment for development of surgical site infections and identify neonates who would benefit from antibiotic prophylaxis.

ORACLE--antibiotics for preterm prelabour rupture of the membranes: short-term and long-term outcomes.

PubMed

Kenyon, S; Taylor, D J; Tarnow-Mordi, W O

2002-01-01

Preterm prelabour rupture of the foetal membranes (pPROM) is the most common antecedent of preterm birth and can lead to death, neonatal disease and long-term disability. Previous small trials of antibiotics for pPROM suggested some health benefits for the neonate, but the results were inconclusive. A large, randomized, multicentre trial was undertaken to try to resolve this issue. In total, 4826 women with pPROM were randomized to one of four treatments: 325 mg co-amoxiclav plus 250 mg erythromycin, co-amoxiclav plus erythromycin placebo, erythromycin plus co-amoxiclav placebo, or co-amoxiclav placebo plus erythromycin placebo, four times daily for 10 d or until delivery. The primary outcome measure was a composite of neonatal death, chronic lung disease or major cerebral abnormality on ultrasonography before discharge from hospital. The analysis was undertaken by intention to treat. Indications of short-term respiratory function, chronic lung disease and major neonatal cerebral abnormality were reduced with the prescription of erythromycin. In contrast, the use of co-amoxiclav was associated with a significant increase in the occurrence of neonatal necrotizing enterocolitis. Prophylactic antibiotics can play a role in preterm prelabour rupture of the membranes in reducing infant morbidity.

Protothecosis as a cause of chronic diarrhoea in a dog.

PubMed

Sapierzyński, R; Jaworska, O

2008-01-01

The clinical form of the protothecosis in animals is most commonly observed in countries with a warm and moist climate, only a few reports describing cases of this infection in cooler areas of the word exist. In the case of large bowel infection in dogs, organisms colonise the lamina propria and submucosa causing severe necrotizing ulcerative or haemorrhagic enterocolitis. In this report the intestinal form of protothecosis in 1.5-year-old, male, mongrel dog with chronic hemorrhagic diarrhoea is described. History revealed that the dog spent some time in the countryside and afterwards diarrhoea with fresh blood appeared. The results of morphological and biochemical blood analysis were normal and stool examination did not reveal the presence of parasites. Treatment with anti-inflammatory doses of prednisone, metronidazole and enrofloxacin followed by sulphasalazine resulted in a short period of improvement, but was followed by deep deterioration of animal status. Because of the relapse diagnostic laparotomy was performed and tissue samples of the colon and jejunum were obtained for histopathology. On the basis of the clinical signs, exploratory laparotomy findings and histopathology the diagnosis of canine intestinal prototecosis was made and medical treatment was recommended.

[Probiotics: innocuousness, prevention and risks].

PubMed

Brunser, Oscar

2017-01-01

Probiotics have been defined as live microorganisms which, when ingested in adequate numbers, confer health benefits to the host. They are currently consumed without any age restrictions and adverse effects such as sepsis, a marker of the risk of invasion of the bloodstream, are extremely infrequent. However, some health professionals express doubts about probiotics being truly innocuous. This review discusses the incidence of sepsis secondary to probiotics use, mainly lactobacilli and bifidobacteria, evaluated through molecular biology or classic culture techniques, showing that sepsis in large numbers of individuals along decennia is extremely low, of the order of 0,02% en some centers or as low as 1 case/million population in France. These data are important considering the use different species and strains of these microorganisms. Few studies which have reported other adverse effects but many of these have problems with their design that cast doubt about the validity of their results. On the contrary, it has been shown that probiotic microorganisms exert positive stimulatory effects on innate and acquired immunity, with decrease of the manifestations of atopy and eczema. These positive effects are further evidenced by the beneficial effects of many species of probiotics in preventing necrotizing enterocolitis in patients as functionally labile as premature-born babies.

Probiotics to counteract biofilm-associated infections: promising and conflicting data

PubMed Central

Vuotto, Claudia; Longo, Francesca; Donelli, Gianfranco

2014-01-01

Altered bowel flora is currently thought to play a role in a variety of disease conditions, and the use of Bifidobacterium spp. and Lactobacillus spp. as probiotics has been demonstrated to be health-promoting, even if the success of their administration depends on the applied bacterial strain(s) and the targeted disease. In the last few decades, specific probiotics have been shown to be effective in the treatment or the prevention of acute viral gastroenteritis, pediatric post-antibiotic-associated diarrhea, some pediatric allergic disorders, necrotizing enterocolitis in preterm infants, inflammatory bowel diseases and postsurgical pouchitis. The potential application of probiotics is continuously widening, with new evidence accumulating to support their effect on the prevention and treatment of other disease conditions, including several oral diseases, such as dental caries, periodontal diseases and oral malodor, as well as genitourinary and wound infections. Considering the increasingly widespread ability of pathogens to generate persistent biofilm-related infections, an even more attractive proposal is to administer probiotics to prevent or counteract biofilm development. The response of biofilm-based oral, intestinal, vaginal and wound infections to probiotics treatment will be reviewed here in light of the most recent results obtained in this field. PMID:25257882

Epigenetic effects of human breast milk.

PubMed

Verduci, Elvira; Banderali, Giuseppe; Barberi, Salvatore; Radaelli, Giovanni; Lops, Alessandra; Betti, Federica; Riva, Enrica; Giovannini, Marcello

2014-04-24

A current aim of nutrigenetics is to personalize nutritional practices according to genetic variations that influence the way of digestion and metabolism of nutrients introduced with the diet. Nutritional epigenetics concerns knowledge about the effects of nutrients on gene expression. Nutrition in early life or in critical periods of development, may have a role in modulating gene expression, and, therefore, have later effects on health. Human breast milk is well-known for its ability in preventing several acute and chronic diseases. Indeed, breastfed children may have lower risk of neonatal necrotizing enterocolitis, infectious diseases, and also of non-communicable diseases, such as obesity and related-disorders. Beneficial effects of human breast milk on health may be associated in part with its peculiar components, possible also via epigenetic processes. This paper discusses about presumed epigenetic effects of human breast milk and components. While evidence suggests that a direct relationship may exist of some components of human breast milk with epigenetic changes, the mechanisms involved are still unclear. Studies have to be conducted to clarify the actual role of human breast milk on genetic expression, in particular when linked to the risk of non-communicable diseases, to potentially benefit the infant's health and his later life.

Isolation of Enterobacter sakazakii from ass' milk in Sicily: case report, safety and legal issues.

PubMed

Conte, F; Passantino, A

2008-07-01

Enterobacter sakazakii (Es) infections are likely to involve newborns and infants, causing meningitis and necrotizing enterocolitis and sepsis. Contamination of infant formulae milk during factory production or bottle preparation is implicated. Es has been isolated from environmental sources and from food other than infant formula and milk powder, but why it is associated only with the consumption of infant formulae, is unclear. According to Regulation (EC) No. 2073/2005 on the microbiological criteria for foodstuffs, Es is considered a microorganisms of greatest concern in infant formulae and follow-on formulae. Es is included between "safety criteria". The isolation of two strains of Es from 50 samples of ass' milk in Sicily is described. The antibiotic resistance profile of the isolates revealed a multiple resistance profile, including fluoroquinolones, commonly used to treat the infections. The authors underline the importance of survey because in Italy ass' milk is considered one of the solutions for infants suffering from hypersensitivity to milk protein of some animal species. There is scarce information about the ecology and the uncertainty concerning the source of infection in the children and adults; the authors are concerned that ass' milk could become a high-risk food.

Identification of potential virulence factors of Cronobacter sakazakii isolates by comparative proteomic analysis.

PubMed

Ye, Yingwang; Li, Hui; Ling, Na; Han, Yongjia; Wu, Qingping; Xu, Xiaoke; Jiao, Rui; Gao, Jina

2016-01-18

Cronobacter is a group of important foodborne pathogens associated with neonatal meningitis, septicemia, and necrotizing enterocolitis. Among Cronobacter species, Cronobacter sakazakii is the most common species in terms of isolation frequency. However, the molecular basis involved in virulence differences among C. sakazakii isolates is still unknown. In this study, based on the determination of virulence differences of C. sakazakii G362 (virulent isolate) and L3101 (attenuated isolate) through intraperitoneal injection, histopathologic analysis (small intestine, kidney, and liver) further confirmed virulence differences. Thereafter, the potential virulence factors were determined using two-dimensional electrophoresis (2-DE) coupled with MALDI/TOP/TOF mass spectrometry. Among a total of 36 protein spots showing differential expression (fold change>1.2), we identified 31 different proteins, of which the expression abundance of 22 was increased in G362. These up-regulated proteins in G362 mainly contained DNA starvation/stationary phase protection protein Dps, OmpA, LuxS, ATP-dependent Clp protease ClpC, and ABC transporter substrate-binding proteins, which might be involved in virulence of C. sakazakii. This is the first report to determine the potential virulence factors of C. sakazakii isolates at the proteomic levels. Copyright © 2015 Elsevier B.V. All rights reserved.

Rapid Detection and Simultaneous Genotyping of Cronobacter spp. (formerly Enterobacter sakazakii) in Powdered Infant Formula Using Real-time PCR and High Resolution Melting (HRM) Analysis

PubMed Central

Cai, Xian-Quan; Yu, Hai-Qiong; Ruan, Zhou-Xi; Yang, Lei-Liang; Bai, Jian-Shan; Qiu, De-Yi; Jian, Zhi-Hua; Xiao, Yi-Qian; Yang, Jie-Yang; Le, Thanh Hoa; Zhu, Xing-Quan

2013-01-01

Cronobacter spp. is an emerging pathogen that causes meningitis, sepsis, bacteremia, and necrotizing enterocolitis in neonates and children. The present study developed an assay integrating real-time PCR and high resolution melting (HRM) analysis targeting the OmpA gene for the specific detection and rapid identification of Cronobacter spp. (formerly Enterobacter sakazakii) in powdered infant formula. Eleven Cronobacter field isolates and 25 reference strains were examined using one pair of primers, having the accuracy of 100% in reference to conventional methods. The assay was proved to be highly sensitive with a detection limit of 102 CFU/ml without pre-enrichment, and highly concordant (100%) when compared with ISO-IDF 22964 in 89 actual samples. The method performed for Cronobacter spp. detection was less than 24 h, drastically shortened, compared to several days using standard culturing method, it is probe-free and reduces a risk of PCR carryover. Moreover, all Cronobacter strains examined in this study were genotyped into two species according to their HRM profiles. The established method should provide a molecular tool for direct detection and simultaneous genotyping of Cronobacter spp. in powdered infant formula. PMID:23825624

Rapid detection and simultaneous genotyping of Cronobacter spp. (formerly Enterobacter sakazakii) in powdered infant formula using real-time PCR and high resolution melting (HRM) analysis.

PubMed

Cai, Xian-Quan; Yu, Hai-Qiong; Ruan, Zhou-Xi; Yang, Lei-Liang; Bai, Jian-Shan; Qiu, De-Yi; Jian, Zhi-Hua; Xiao, Yi-Qian; Yang, Jie-Yang; Le, Thanh Hoa; Zhu, Xing-Quan

2013-01-01

Cronobacter spp. is an emerging pathogen that causes meningitis, sepsis, bacteremia, and necrotizing enterocolitis in neonates and children. The present study developed an assay integrating real-time PCR and high resolution melting (HRM) analysis targeting the OmpA gene for the specific detection and rapid identification of Cronobacter spp. (formerly Enterobacter sakazakii) in powdered infant formula. Eleven Cronobacter field isolates and 25 reference strains were examined using one pair of primers, having the accuracy of 100% in reference to conventional methods. The assay was proved to be highly sensitive with a detection limit of 10(2) CFU/ml without pre-enrichment, and highly concordant (100%) when compared with ISO-IDF 22964 in 89 actual samples. The method performed for Cronobacter spp. detection was less than 24 h, drastically shortened, compared to several days using standard culturing method, it is probe-free and reduces a risk of PCR carryover. Moreover, all Cronobacter strains examined in this study were genotyped into two species according to their HRM profiles. The established method should provide a molecular tool for direct detection and simultaneous genotyping of Cronobacter spp. in powdered infant formula.

Occurrence and Characterization of Cronobacter spp. in Dehydrated Rice Powder from Chinese Supermarket

PubMed Central

Huang, Yan; Pang, Yiheng; Wang, Hong; Tang, Zhengzhu; Zhou, Yan; Zhang, Weiyu; Li, Xiugui; Tan, Dongmei; Li, Jian; Lin, Ying; Liu, Xiaoling; Huang, Weiyi; Shi, Yunliang

2015-01-01

Cronobacter spp. are emerging food-borne pathogens and have been identified as causative agents of meningitis and necrotizing enterocolitis in infants. Dehydrated rice is popular with a wide range of people and it is frequently used as a substitute for infant milk powder to baby older than four months. The occurrence of Cronobacter spp. was investigated in 1,012 samples of dehydrated rice powder collected from 14 manufacturers in China during 2010 to 2012. The isolates were identified using fusA allele sequencing and subtyped using pulsed-field gel electrophoresis. Seventy-six samples (7.5%) contained Cronobacter spp. The prevalence among manufacturers ranged from 0-28.8%. The 76 isolates included 4 species [Cronobacter sakazakii (52 isolates) Cronobacter malonaticus (14 isolates), Cronobacter dublinensis (7 isolates), and Cronobacter muytjensii (3 isolates)]. Twenty-three unique fusA alleles and sixty-six PFGE-patterns were detected. All isolated strains were observed to be sensitive or to show intermediate susceptibility to eight tested antimicrobial agents. The study revealed serious contamination of dehydrated rice powder by Cronobacter spp., with prevalence varying among manufacturers in China. Identified Cronobacter species, fusA alleles, and subtypes were diverse. PMID:26132635

Transcriptome analysis of Cronobacter sakazakii ATCC BAA-894 after interaction with human intestinal epithelial cell line HCT-8.

PubMed

Jing, Chun-e; Du, Xin-jun; Li, Ping; Wang, Shuo

2016-01-01

Cronobacter spp. are opportunistic pathogens that are responsible for infections including severe meningitis, septicemia, and necrotizing enterocolitis in neonates and infants. To date, questions still remain regarding the mechanisms of pathogenicity and virulence determinants for each bacterial strain. In this study, we established an in vitro model for Cronobacter sakazakii ATCC BAA-894 infection of HCT-8 human colorectal epithelial cells. The transcriptome profile of C. sakazakii ATCC BAA-894 after interaction with HCT-8 cells was determined using high-throughput whole-transcriptome sequencing (RNA sequencing (RNA-seq)). Gene expression profiles indicated that 139 genes were upregulated and 72 genes were downregulated in the adherent C. sakazakii ATCC BAA-894 strain on HCT-8 cells compared to the cultured bacteria in the cell-free medium. Expressions of some flagella genes and virulence factors involved in adherence were upregulated. High osmolarity and osmotic stress-associated genes were highly upregulated, as well as genes responsible for the synthesis of lipopolysaccharides and outer membrane proteins, iron acquisition systems, and glycerol and glycerophospholipid metabolism. In sum, our study provides further insight into the mechanisms underlying C. sakazakii pathogenesis in the human gastrointestinal tract.

[First case of lung abscess due to Yersinia pseudotuberculosis in Japan].

PubMed

Takahashi, Yoshinori; Sasabe, Jun; Maeda, Hikaru; Fujiwara, Atsushi; Yuda, Hisamichi; Yoshida, Masamichi; Taguchi, Osamu

2014-07-01

A 63-year-old previously healthy man was admitted to our hospital with diarrhea that had lasted for about 4 weeks, high fever and dyspnea. Chest computed tomography showed consolidation with a low-density area in the right middle lobe and small nodules with feeding vessels in the right upper lobe. On Day 8, a cavity was observed in the consolidation, and the lymph nodes in the mediastinum became necrotic. Yersinia pseudotuberculosis (serotype 4b) was cultured from blood, bronchial washing fluid, and lung tissue specimens. We diagnosed the lung lesions as septic pulmonary embolism caused by enterocolitis. We started treatment with tazobactam/piperacillin. It has been reported that high-dose ceftriaxone (CTRX) is effective, but CTRX at normal doses and other beta-lactams are less effective or even ineffective. Therefore, we changed to CTRX (4g/day) on Day 5, CTRX (2g/day) on Day 8, and oral cefditoren pivoxil (600 mg/day; a third-generation cephalosporin) on Day 18. Antibiotic therapy resulted in a favorable response. The patient was discharged from our hospital on day 25 in good health. To the best of our knowledge, this is the first case of a lung abscess caused by Y. pseudotuberculosis reported in Japan.

Strategies for prevention of feed intolerance in preterm neonates: a systematic review.

PubMed

Patole, Sanjay

2005-07-01

Postnatal growth restriction and failure to thrive have been recently identified as a major issue in preterm, especially extremely-low-birth-weight neonates. An increased length of time to reach full enteral feedings is also significantly associated with a poorer mental outcome in preterm neonates at 24 months corrected age. Optimization of enteral nutrition without increasing the risk of necrotizing enterocolitis (NEC) has thus become a priority in preterm neonates. A range of feeding strategies currently exists for preventing/minimizing feed intolerance in preterm neonates reflecting the dilemma surrounding the definition and significance of signs of feed intolerance due to ileus of prematurity and the fear of NEC. The results of a systematic review of current strategies for preventing/minimizing feed intolerance in preterm neonates are discussed. The need for clinical research in the area of signs of feed intolerance is emphasized to develop a scientific basis to feeding strategies. Only large pragmatic trials based on such strategies will reveal whether the benefits (improved growth and long term neurodevelopmental outcomes) of aggressive enteral nutrition can outweigh the risks of a potentially devastating illness like NEC, and of prolonged parenteral nutrition in preterm neonates.

Update on infection control challenges in special pediatric populations.

PubMed

Balkhy, Hanan H; Zingg, Walter

2014-08-01

Compared with adults, neonatal and pediatric populations are especially vulnerable patients who have specific diagnostic and therapeutic differences; therefore, the standard infection control practices designed for adults are sometimes not effective or need modifications to work. This review focuses on the recent literature addressing the challenges and successes in preventing healthcare-associated infections (HAIs) in children. Improving the implementation of pediatric versions of preventive bundles focusing on proper catheter insertion and maintenance, mainly as a part of a larger multimodal strategy, is effective in reducing the central-line-associated bloodstream infections in neonatal and pediatric populations including oncology patients. Appropriate feeding, antimicrobial stewardship, and infection control measures should be combined in reducing necrotizing enterocolitis in preterm neonates. Implementing a multimodal bundle strategy adapted for pediatric population is successful in preventing ventilator-associated pneumonia. Appropriate use of antimicrobial prophylaxis remains the cornerstone for preventing surgical-site infections irrespective of age, with few additional effective adjuvant preventive practices in specific pediatric patients. Several evidence-based practices are effective in reducing the incidence and the impact of HAIs in children; however, proper implementation remains a challenge. Additionally, several adult preventive practices are still unestablished in children and need further thorough examination.

Beyond Building Better Brains: Bridging the Docosahexaenoic acid (DHA) Gap of Prematurity

PubMed Central

Harris, William

2014-01-01

Long chain polyunsaturated fatty acids (LCPUFA) including docosahexaenoic acid (DHA), are essential for normal vision and neurodevelopment. DHA accretion in utero occurs primarily in the last trimester of pregnancy to support rapid growth and brain development. Premature infants, born before this process is complete, are relatively deficient in this essential fatty acid. Very low birth weight (VLBW) infants remain deficient for a long period of time due to ineffective conversion from precursor fatty acids, lower fat stores, and a limited nutritional provision of DHA after birth. In addition to long- term visual and neurodevelopmental risks, VLBW infants have significant morbidity and mortality from diseases specific to premature birth, including bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and retinopathy of prematurity (ROP). There is increasing evidence that DHA has protective benefits against these disease states. The aim of this article is to identify the unique needs of premature infants, review the current recommendations for LCPUFA provision in infants, and discuss the caveats and innovative new ways to overcome the DHA deficiency through postnatal supplementation, with the long term goal of improving morbidity and mortality in this at risk population. PMID:25357095

Intestinal flora in very low-birth weight infants.

PubMed

Björkström, Markus V; Hall, Lina; Söderlund, Stina; Håkansson, Eva Grahn; Håkansson, Stellan; Domellöf, Magnus

2009-11-01

To study the early faecal microbiota in very low-birth weight infants (VLBW, <1500 g), possible associations between faecal microbiota and faecal calprotectin (f-calprotectin) and to describe the faecal microbiota in cases with necrotizing enterocolitis (NEC) before diagnosis. Stool samples from the first weeks of life were analysed in 48 VLBW infants. Bacterial cultures were performed and f-calprotectin concentrations were measured. In three NEC cases, cultures were performed on stool samples obtained before diagnosis. Bifidobacteria and lactobacilli were often identified in the first stool sample, 55% and 71% of cases, respectively within the first week of life. A positive correlation between lactic acid bacteria (LAB) and volume of enteral feed was found. Other bacteria often identified were Escherichia coli, Enterococcus and Staphyloccus sp. F-calprotectin was not associated with any bacterial species. All NEC cases had an early colonization of LAB. Prior to onset of disease, all cases had a high colonization of non-E. coli Gram-negative species. In contrast to the previous studies in VLBW infants, we found an early colonization with LAB. We speculate that this may be due to early feeding of non-pasteurized breast milk.

Role of Gut Microbiota in Early Infant Development

PubMed Central

Wall, R; Ross, R.P; Ryan, C.A; Hussey, S; Murphy, B; Fitzgerald, G.F; Stanton, C

2009-01-01

Early colonization of the infant gastrointestinal tract is crucial for the overall health of the infant, and establishment and maintenance of non-pathogenic intestinal microbiota may reduce several neonatal inflammatory conditions. Much effort has therefore been devoted to manipulation of the composition of the microbiota through 1) the role of early infant nutrition, particularly breast milk, and supplementation of infant formula with prebiotics that positively influence the enteric microbiota by selectively promoting growth of beneficial bacteria and 2) oral administration of probiotic bacteria which when administered in adequate amounts confer a health benefit on the host. While the complex microbiota of the adult is difficult to change in the long-term, there is greater impact of the diet on infant microbiota as this is not as stable as in adults. Decreasing excessive use of antibiotics and increasing the use of pre- and probiotics have shown to be beneficial in the prevention of several important infant diseases such as necrotizing enterocolitis and atopic eczema as well as improvement of short and long-term health. This review addresses how the composition of the gut microbiota becomes established in early life, its relevance to infant health, and dietary means by which it can be manipulated. PMID:23818794

Noninvasive monitoring of gas in the lungs and intestines of newborn infants using diode lasers: feasibility study.

PubMed

Lundin, Patrik; Svanberg, Emilie Krite; Cocola, Lorenzo; Lewander Xu, Märta; Somesfalean, Gabriel; Andersson-Engels, Stefan; Jahr, John; Fellman, Vineta; Svanberg, Katarina; Svanberg, Sune

2013-12-01

Preterm newborn infants have a high morbidity rate. The most frequently affected organs where free gas is involved are the lungs and intestines. In respiratory distress syndrome, both hyperexpanded and atelectatic (collapsed) areas occur, and in necrotizing enterocolitis, intramural gas may appear in the intestine. Today, these conditions are diagnosed with x-ray radiography. A bed-side, rapid, nonintrusive, and gas-specific technique for in vivo gas sensing would improve diagnosis. We report the use of noninvasive laser spectroscopy, for the first time, to assess gas content in the lungs and intestines of three full-term infants. Water vapor and oxygen were studied with two low-power diode lasers, illuminating the skin and detecting light a few centimeters away. Water vapor was easily detected in the intestines and was also observed in the lungs. The relatively thick chest walls of the infants prevented detection of the weaker oxygen signal in this study. However, results from a previous phantom study, together with scaling of the results presented here to the typical chest-wall thickness of preterm infants, suggest that oxygen also should be detectable in their lungs.

Noninvasive monitoring of gas in the lungs and intestines of newborn infants using diode lasers: feasibility study

NASA Astrophysics Data System (ADS)

Lundin, Patrik; Svanberg, Emilie Krite; Cocola, Lorenzo; Xu, Märta Lewander; Somesfalean, Gabriel; Andersson-Engels, Stefan; Jahr, John; Fellman, Vineta; Svanberg, Katarina; Svanberg, Sune

2013-12-01

Preterm newborn infants have a high morbidity rate. The most frequently affected organs where free gas is involved are the lungs and intestines. In respiratory distress syndrome, both hyperexpanded and atelectatic (collapsed) areas occur, and in necrotizing enterocolitis, intramural gas may appear in the intestine. Today, these conditions are diagnosed with x-ray radiography. A bed-side, rapid, nonintrusive, and gas-specific technique for in vivo gas sensing would improve diagnosis. We report the use of noninvasive laser spectroscopy, for the first time, to assess gas content in the lungs and intestines of three full-term infants. Water vapor and oxygen were studied with two low-power diode lasers, illuminating the skin and detecting light a few centimeters away. Water vapor was easily detected in the intestines and was also observed in the lungs. The relatively thick chest walls of the infants prevented detection of the weaker oxygen signal in this study. However, results from a previous phantom study, together with scaling of the results presented here to the typical chest-wall thickness of preterm infants, suggest that oxygen also should be detectable in their lungs.

Neonatal necrotizing fasciitis of the scrotum caused by Streptococcus agalactiae.

PubMed

Kuroda, Junpei; Inoue, Nobuaki; Satoh, Hiroyuki; Fukuzawa, Ryuji; Terakawa, Toshiro; Hasegawa, Yukihiro

2015-04-01

We herein describe the case of a 27-day-old male infant who was brought to the emergency room for intermittent crying, and swelling of the left scrotum. Based on the clinical findings, necrotizing fasciitis was suspected, and surgical intervention was successfully completed within a few hours of admission. Streptococcus agalactiae type Ia was cultured from the drained abscess, and was considered the causative pathogen. To our knowledge, this is the first report of neonatal necrotizing fasciitis caused by S. agalactiae. Prompt diagnosis and immediate surgical debridement are crucial in the initial management of this disease. © 2015 Japan Pediatric Society.

Cervical necrotizing fasciitis of nonodontogenic origin: case report and review of literature.

PubMed

Suárez, Aldo; Vicente, Mario; Tomás, Jose A; Floría, Luis M; Delhom, José; Baquero, Mari C

2014-11-01

Cervical necrotizing fasciitis (CNF) is a potentially fatal infection characterized by generalized necrosis of the cervical fascia that progresses rapidly. The incidence of this entity corresponds to 2.6% of all infections of the head and neck. The most frequent primary origin is dental infection, although other causes exist that should be evaluated.Delay in the diagnosis of this entity may lead to rapid progression and fatal outcome. Patients often present immunosuppression or systemic diseases that predispose them to this pathology. Cervical necrotizing fasciitis is associated with mortality rates of 7% to 20% depending on the extension of the cervical lesion. The highest rates correspond to cases that progress to mediastinitis or septic shock, which are the main and most frequent complications. Early detection and adequate emergency treatment are critical in the management of these patients and may reduce morbimortality and improve survival. The emergency services should be prepared to manage such cases efficiently, through a multidisciplinary treatment by coordinating emergency surgery with critical support and clinical stabilization of patients.We present a case of CNF of non odontogenic origin managed in our hospital.

Management and Novel Adjuncts of Necrotizing Soft Tissue Infections

PubMed Central

Cocanour, Christine S.; Chang, Phillip; Huston, Jared M.; Adams, Charles A.; Diaz, Jose J.; Wessel, Charles B.; Falcione, Bonnie A.; Bauza, Graciela M.; Forsythe, Raquel A.

2017-01-01

Abstract Necrotizing soft tissue infections (NSTI) have been recognized for millennia and continue to impose considerable burden on both patient and society in terms of morbidity, death, and the allocation of resources. With improvements in the delivery of critical care, outcomes have improved, although disease-specific therapies are lacking. The basic principles of early diagnosis, of prompt and broad antimicrobial therapy, and of aggressive debridement have remained unchanged. Clearly novel and new therapeutics are needed to combat this persistently lethal disease. This review emphasizes the pillars of NSTI management and then summarizes the contemporary evidence supporting the incorporation of novel adjuncts to the pharmacologic and operative foundations of managing this disease. PMID:28375805

Latest Insights on Food Protein-Induced Enterocolitis Syndrome: An Emerging Medical Condition.

PubMed

Vila Sexto, L

2018-01-01

Food protein-induced enterocolitis syndrome (FPIES) is a type of non-IgE-mediated gastrointestinal food hypersensitivity characterized by profuse vomiting that is frequently associated with pallor or/and lethargy and appears within 1 to 3 hours after ingestion of the offending food. A less frequent chronic form of FPIES is characterized by protracted vomiting, diarrhea, or both accompanied by poor growth. Although FPIES is considered a rare allergic disorder, increasing reports in recent years point to a real increase in incidence, or at least an increased awareness of this condition by pediatricians. The foods most frequently implicated are cow's milk, soy formula, grains, and fish, depending on the geographic area. Diagnosis is based on clinical manifestations and requires a high index of suspicion, since we still lack a diagnostic laboratory tool. Early recognition of FPIES and removal of the offending food are mandatory. International consensus guidelines on diagnosis and management have been published. Prognosis is usually good, with most children tolerating foods before 6 years of age.

Review of 58 patients with necrotizing fasciitis in the Netherlands.

PubMed

van Stigt, Sander F L; de Vries, Janneke; Bijker, Jilles B; Mollen, Roland M H G; Hekma, Edo J; Lemson, Susan M; Tan, Edward C T H

2016-01-01

Necrotizing fasciitis is a rare, life threatening soft tissue infection, primarily involving the fascia and subcutaneous tissue. In a large cohort of patients presenting with Necrotizing fasciitis in the Netherlands we analysed all available data to determine the causative pathogens and describe clinical management and outcome. We conducted a retrospective, multicentre cohort study of patients with a necrotizing fasciitis between January 2003 and December 2013 in an university medical hospital and three teaching hospitals in the Netherlands. We only included patients who stayed at the Intensive Care Unit for at least one day. Fifty-eight patients were included. The mortality rate among those patients was 29.3 %. The central part of the body was affected in 28 patients (48.3 %) and in 21 patients (36.2 %) one of the extremities. Most common comorbidity was cardio vascular diseases in 39.7 %. Thirty-nine patients (67.2 %) were operated within 24 h after presentation. We found a type 1 necrotizing fasciitis in 35 patients (60.3 %) and a type 2 in 23 patients (39.7 %). Our study, which is the largest study in Europe, reaffirmed that Necrotizing fasciitis is a life threatening disease with a high mortality. Early diagnosis and adequate treatment are necessary to improve the clinical outcome. Clinical awareness off necrotizing fasciitis remains pivotal.

Fatal neutropenic enterocolitis due to clostridium septicum.

PubMed

Shah, B K; KC, R

2011-10-01

We describe a case of Clostridium septicum enterocolitis in a patient with pre-B acute lymphoblastic leukaemia undergoing autologous stem cell transplant. In the setting of neutropenia, Clostridium septicum should be suspected in patients who develop signs and symptoms of acute abdomen.

[Retrograde pancreatic duct imaging and surgical tactics in hemorrhagic necrotizing pancreatitis. Preliminary report].

PubMed

Gebhardt, C; Gall, F P; Lux, G; Riemann, J; Link, W

1983-12-01

In patients with haemorrhagic necrotizing pancreatitis who are scheduled for surgery we have been carrying out a preoperative retrograde investigation of the pancreatic duct system for the past months. The results in, to date, ten patients revealed four different morphological findings of importance for the surgical tactic: 1. A normal pancreatic duct system with no signs of fistulae: only peripancreatic necrosectomy is required. - 2. Contrast medium leaks via a ductal fistula: left resection including the removal of the fistulous area must be done. - 3. Normal duct system with complete segmental parenchymal staining, representing total necrosis in this region: left resection of the pancreas. - 4. Duodenoscopically demonstrable perforation into the duodenum of a necrotic cavity in the head of the pancreas: conservative management only, no surgery, since this lesion resulting in drainage of the necrotic cavity into the bowel permits self-healing, while the site of the perforation within the necrotic wall cannot be dealt with by surgery. - The experience gained so far indicates that the surgical tactic can be determined with greater selectivity by the use of ERP.

Non-IgE-mediated gastrointestinal food allergies.

PubMed

Biermé, Priscille; Nowak-Wegrzyn, Anna; Caubet, Jean-Christoph

2017-12-01

We focus on recent advances regarding the epidemiology, physiopathology, diagnosis and managements of non-IgE-mediated gastrointestinal food allergies (non-IgE-GI-FAs), particularly food protein-induced enterocolitis syndrome (FPIES). The first international FPIES diagnostic and management guidelines have been recently published. Although FPIES largely remains a diagnosis of exclusion, it may be more prevalent than previously thought. Ondansetron has emerged as a major tool for the treatment of FPIES acute reactions. Recent data also suggest an important role for innate immune cells in FPIES pathogenesis. Despite major advances in the diagnosis and management of non-IgE-GI-FAs, particularly FPIES, the lack of specific diagnostic tests and biomarkers to guide clinical management remains challenging.

Necrotizing Fasciitis: An Emergency Medicine Simulation Scenario.

PubMed

Galust, Henrik; Oliverio, Matthew H; Giorgio, Daniel J; Espinal, Alexis M; Ahmed, Rami

2016-08-31

Necrotizing fasciitis (NF) is a rare and rapidly progressing life-threatening infectious process. By progressing through a simulation involving a patient with NF and participating in a post-scenario debriefing, learners will gain the necessary skills and knowledge to properly diagnose and manage patients with NF. Learners are taught to initiate appropriate and timely treatment and to advocate on behalf of their patient after inappropriate pushback from consultants to improve outcomes.

[Fulminant isolated necrotizing fasciitis of the chest wall, complicating thoracic empyema].

PubMed

Kovács, Ottó; Szántó, Zoltán; Krasznai, Géza

2016-03-01

Authors introduce the case of a 64-year-old male patient with fulminant isolated necrotizing fasciitis of the chest wall, complicating empyema thoracis of unknown origin. The patient's co-morbidities were hypertension, ischaemic heart disease, atrial fibrillation with oral anticoagulation. The real etiology was revealed post mortem, due to the rapid progression. The autopsy demonstrated that the fasciitis was caused by a small blunt thoracic trauma (haematoma), not emerged from patient's history and was not visible during physical examination. Authors review diagnostic pitfalls, leading to delayed recognition in addition to this very case. After quick diagnosis surgical debridement, targeted wide spectrum antibiotics and maximal intensive care are the basic pillars of the management of necrotizing fasciitis.

[Postoperative necrotizing fasciitis: a rare and fatal complication].

PubMed

Ghezala, Hassen Ben; Feriani, Najla

2016-01-01

Postoperative parietal complications can be exceptionally severe and serious threatening vital prognosis. Necrotizing fasciitis is a rare infection of the skin and deep subcutaneous tissues, spreading along fascia and adipose tissue. It is mainly caused by group A streptococcus (streptococcus pyogenes) but also by other bacteria such as Vibrio vulnificus, Clostridium perfringens or Bacteroides fragilis. Necrotizing fasciitis is a real surgical and medical emergency. We report, in this study, a very rare case of abdominal parietal gangrene occurring in a 75-year-old woman on the fifth day after surgery for an ovarian cyst. Evolution was marked by occurrence of a refractory septic shock with a rapidly fatal course on the third day of management.

Necrotizing Fasciitis of the lower extremity: a case report and current concept of diagnosis and management

PubMed Central

Naqvi, GA; Malik, SA; Jan, W

2009-01-01

Necrotizing fasciitis is a severe soft tissue infection characterized by rapidly progressing necrosis, involving subcutaneous tissues. This rare condition carries high mortality rate and require prompt diagnosis and urgent treatment with radical debridement and antibiotics. We describe a case of 21-year old man who presented with the history of trivial injury to the knee. Initially he was admitted and treated for septic arthritis but later was diagnosed as necrotizing fasciitis which was successfully treated with no ill effects what so ever from this devastating condition. This rare condition has been reported in literature but still early diagnosis, which is a key for successful treatment, remains a challenge. PMID:19527519

Use of negative pressure wound therapy with instillation in the management of cervical necrotizing fasciitis.

PubMed

Frankel, Jonathan K; Rezaee, Rod P; Harvey, Donald J; McBeath, Evan R; Zender, Chad A; Lavertu, Pierre

2015-11-01

Cervical necrotizing fasciitis is an aggressive infection that can be rapidly fatal if aggressive therapies are not initiated early. Negative pressure wound therapy has been established as an effective tool in promoting wound healing, but its use in the acutely infected wound has been avoided because it limits frequent irrigations and standard dressing changes. We discuss a novel application of negative pressure wound therapy with instillation in an immunocompromised patient with extensive cervical necrotizing fasciitis. The negative pressure wound therapy with instillation provided pain relief by minimizing the frequency of dressing changes, increased the speed of healing, helped to control infection, and facilitated the development of a healthy wound bed sufficient for reconstruction with a split thickness skin graft. The role of negative pressure wound therapy with instillation continues to expand and can be used in the management of both acute and chronic wounds in the head and neck. © 2015 Wiley Periodicals, Inc.

Poultry management: a useful tool for the control of necrotic enteritis in poultry.

PubMed

Tsiouris, Vasilios

2016-06-01

The intestinal ecosystem of poultry has been inevitably changed as a result of the ban of antimicrobial growth promoters. The re-emergence of necrotic enteritis has been the most significant threat for the poultry industry, which, in clinical form, causes high mortality and in subclinical forms, affects growth and feed conversion. It is one of the most common and economically devastating bacterial diseases in modern broiler flocks in terms of performance, welfare and mortality. Necrotic enteritis is a multi-factorial disease process, in which a number of co-factors are usually required to precipitate an outbreak of the disease. Although, Clostridium perfringens has been identified as the aetiological agent of the disease, the predisposing factors that lead to over-proliferation of C. perfringens and the subsequent progression to disease are poorly understood. Any factor that causes stress in broiler chicks could suppress the immune system and disturb the balance of the intestinal ecosystem, in such a way that the risk of a necrotic enteritis (NE) outbreak increases. Poultry management could significantly affect the pathogenesis of NE. In particular, feed restriction and coccidiosis vaccination can protect against NE, while extreme house temperature, feed mycotoxins and high stocking density predispose to NE. It becomes really important to understand the pathogenesis of the disease, as well as to clarify the interactions between husbandry, nutritional and infectious factors and the outbreak of necrotic enteritis. This is necessary and extremely important in order to develop managerial strategies at the farm level to control the incidence and severity of the disease in the post-antibiotic era.

Surgical Management of Complicated Necrotizing Pneumonia in Children.

PubMed

Lai, Jin-Yao; Yang, Wendy; Ming, Yung-Ching

2017-08-01

There are no well-established indications for the surgical management of acute necrotizing pneumonitis in children. This study presents our experience regarding this challenging topic. Between 2002 and 2009, 56 necrotizing pneumonitis patients with empyema were treated surgically. The outcomes were analyzed retrospectively. Computed tomography findings of massive lung necrosis or large cavities involving more than 50% of the involved lobe were deemed to be complicated necrotizing pneumonitis. Patients without the above indications were considered uncomplicated. Thirty-one cases were uncomplicated and 25 were complicated. Operative procedures included 38 decortications (31 uncomplicated and seven complicated), 14 wedge resections, and four lobectomies (complicated only). Preoperatively, patients with complicated necrotizing pneumonia had a higher incidence of pneumothorax (32% vs. 14.3%; p = 0.001), endotracheal intubation (44% vs. 9.7%; p = 0.008), and hemolytic uremic syndrome (20% vs. 3.2%; p = 0.01). These patients also had higher incidences of intraoperative transfusion (68% vs. 9.7%; p = 0.03), major postoperative complications (16% vs. 0%; p = 0.02), reoperations (16% vs. 0%; p = 0.02), and longer postoperative stay (19.8 ± 24.2 days vs. 11.2 ± 5.8 days; p = 0.03). Four complicated patients, who initially had decortications and limited resections, underwent reoperations. Compared with uncomplicated patients, those who underwent decortications and wedge resection required longer postoperative stays (23.6 ± 9.9 days, p < 0.01 and 21.1 ± 30.7 days, p = 0.04, respectively), whereas patients who had lobectomy had a similar duration of recovery (9.0 ± 2.1 days, p = 0.23). All patients improved significantly at follow-up. Children with complicated necrotizing pneumonitis have more preoperative morbidities, more major postoperative complications, and require longer postoperative stays. Aggressive surgical treatment results in significant clinical improvement. Lobectomy in patients with complicated necrotizing pneumonitis may shorten the postoperative course and avoid subsequent surgery. Copyright © 2016. Published by Elsevier B.V.

Transanal rectal mucosectomy and partial internal anal sphincterectomy for Hirschsprung's disease.

PubMed

Zhang, Jin-Shan; Li, Long; Hou, Wen-Ying; Liu, Shu-Li; Diao, Mei; Zhang, Jun; Ming, An-Xiao; Cheng, Wei

2014-05-01

Hirschsprung-associated enterocolitis (HAEC) is a serious complication of Hirschsprung's disease (HD), with generalized sepsis and high mortality rate. Although the surgical correction of HD is mostly successful, challenges remain in the management of children with repeated episodes of enterocolitis. The authors describe a novel modification of transanal rectal mucosectomy and partial internal anal sphincterectomy (TRM-PIAS) for HD. One hundred twenty-seven HD children aged from 8 days to 16 years who successfully underwent TRM-PIAS were reviewed. TRM-PIAS was carried out circumferentially along the anorectal line. Anterior dissection was conducted between the rectal submuscosal layer and the rectal muscular sleeve. The posterior dissection was performed along the plane between internal and external anal sphincters. Normal colon was pulled through and anastomosed to anal mucosa. Aganglionic segment, rectal mucosa, part of internal anal sphincter and posterior rectal muscular cuff were removed. Twenty-five age-matched children without defecation dysfunction were used as the control group in the study of anal resting pressure. Patients were followed up for 6-12 years (median: 8.2 years). The median age at last follow-up was 12.2 years (7.2-20.1 years). The incidence of enterocolitis decreased from 33.9% (43/127) preoperatively to 1.6% (2/127) postoperatively (P<0.01). The incidence of constipation decreased from 100% (127/127) preoperatively to 2.4% (3/127) postoperatively (P<0.01). Soiling rate on postoperative 1 month was 32.3%. It gradually decreased to 1.6% 6 months later. Anorectal manometries showed that mean anal resting pressure was significantly reduced from 37.9±12.5 mm Hg preoperatively to 20.2±6.4 mm Hg on postoperative 1 month and 24.8±9.9 mm Hg on postoperative 6 months, which were similar to age-matched normal controls (27.9±9.6 mm Hg, P>0.05). TRM-PIAS is effective in treatment of HD. It is associated with low postoperative HD-associated enterocolitis. Copyright © 2014 Elsevier Inc. All rights reserved.

Vacuum-assisted closure as a surgical assistant in life-threatening necrotizing fasciitis in children

PubMed Central

Al-Subhi, FS; Zuker, RM; Cole, WG

2010-01-01

Necrotizing fasciitis is a severe soft tissue infection that can involve skin, subcutaneous fat, fascia and muscle. It can result in devastating sequelae including tissue necrosis, sepsis, toxic shock syndrome, cardiopulmonary collapse and death. To control rapidly spreading necrosis, early diagnosis and aggressive surgical treatment with extensive radical debridement of the affected areas is necessary, as well as systemic administration of broad-spectrum antimicrobials and, very often, intensive care support. The subatmospheric negative pressure dressing has been previously used in acute and complex wounds management. The concept of using vacuum-assisted closure dressing as another management component is presented in the current article. PMID:22131841

Streptococcus bovis septicemia and meningitis associated with chronic radiation enterocolitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jadeja, L.; Kantarjian, H.; Bolivar, R.

1983-12-01

We describe the first patient with simultaneous S bovis septicemia and meningitis associated with chronic radiation enterocolitis. This case underlines the value of a thorough gastrointestinal evaluation of all patients with S bovis infection, and the need for a neurologic investigation even with minor neurologic manifestations.

Prevalence and associated risk factors of necrotic enteritis on broiler farms in the United Kingdom; a cross-sectional survey.

PubMed

Hermans, P G; Morgan, K L

2007-02-01

In order to determine the prevalence and risk factors for necrotic enteritis in broilers, a cross-sectional survey was conducted among 857 farms, rearing broilers for nine UK poultry companies. The main data collection tool was a postal questionnaire directed at farm managers. Additional information on disease occurrence on the farm was collected from veterinary postmortem reports. The response rate to the questionnaire was 75%, ranging from 54% to 90% within companies. During 2001, 32.8% of the respondents indicated that they had observed a case of necrotic enteritis (95% confidence interval, 29.1 to 36.8) in at least one flock. The disease was most often reported during the months October to February. The point prevalence (necrotic enteritis occurrence in the most recently reared flock) reported by farm managers was 12.3% (95% confidence interval, 9.8 to 15.2). Multilevel logistic regression was performed with the poultry company as the random effect, using the occurrence of necrotic enteritis in the farm's most recently reared flock as the dependent variable. Strong associations were found between the outcome variable and the occurrence of wet litter (odds ratio, 2.39; 95% confidence interval, 1.27 to 4.52; P = 0.007) and coccidiosis (odds ratio, 4.68; 95% confidence interval, 1.74 to 12.55; P = 0.002). In addition, the use of ammonia as a disinfectant for coccidial oocysts appeared to be an independent risk factor (odds ratio, 3.44; 95% confidence interval, 1.53 to 7.71; P = 0.003). Finally, the positive association between the use of plasterboard walls in poultry houses and the occurrence of necrotic enteritis might point to an important role of cleaning and disinfection in the epidemiology of this disease (odds ratio, 3.72; 1.38 to 10.00; P = 0.009).

Necrotizing Fasciitis: An Emergency Medicine Simulation Scenario

PubMed Central

Galust, Henrik; Oliverio, Matthew H; Giorgio, Daniel J; Espinal, Alexis M

2016-01-01

Necrotizing fasciitis (NF) is a rare and rapidly progressing life-threatening infectious process. By progressing through a simulation involving a patient with NF and participating in a post-scenario debriefing, learners will gain the necessary skills and knowledge to properly diagnose and manage patients with NF. Learners are taught to initiate appropriate and timely treatment and to advocate on behalf of their patient after inappropriate pushback from consultants to improve outcomes. PMID:27733963

IAP/APA evidence-based guidelines for the management of acute pancreatitis.

PubMed

2013-01-01

There have been substantial improvements in the management of acute pancreatitis since the publication of the International Association of Pancreatology (IAP) treatment guidelines in 2002. A collaboration of the IAP and the American Pancreatic Association (APA) was undertaken to revise these guidelines using an evidence-based approach. Twelve multidisciplinary review groups performed systematic literature reviews to answer 38 predefined clinical questions. Recommendations were graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The review groups presented their recommendations during the 2012 joint IAP/APA meeting. At this one-day, interactive conference, relevant remarks were voiced and overall agreement on each recommendation was quantified using plenary voting. The 38 recommendations covered 12 topics related to the clinical management of acute pancreatitis: A) diagnosis of acute pancreatitis and etiology, B) prognostication/predicting severity, C) imaging, D) fluid therapy, E) intensive care management, F) preventing infectious complications, G) nutritional support, H) biliary tract management, I) indications for intervention in necrotizing pancreatitis, J) timing of intervention in necrotizing pancreatitis, K) intervention strategies in necrotizing pancreatitis, and L) timing of cholecystectomy. Using the GRADE system, 21 of the 38 (55%) recommendations, were rated as 'strong' and plenary voting revealed 'strong agreement' for 34 (89%) recommendations. The 2012 IAP/APA guidelines provide recommendations concerning key aspects of medical and surgical management of acute pancreatitis based on the currently available evidence. These recommendations should serve as a reference standard for current management and guide future clinical research on acute pancreatitis. Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Relationship of maternal mean platelet volume with fetal Doppler parameters and neonatal complications in pregnancies with and without intrauterine growth restriction.

PubMed

Ureyen, Isin; Ozyuncu, Ozgur; Sahin-Uysal, Nihal; Kara, Ozgur; Basaran, Derman; Turgal, Mert; Deren, Ozgur

2017-02-01

In this study, we investigated the relationship of mean platelet volume (MPV) with the presence and the severity of intrauterine growth restriction (IUGR) and with neonatal complications. The pregnancies with and without IUGR, that were followed-up in our hospital between 2003 and 2009 were analyzed retrospectively. Pregnancies which resulted in birth of a newborn with a birthweight less than 10th percentile for the gestational age were selected for IUGR group. IUGR cases were divided into three groups according to the Doppler parameters. There was no significant difference between the MPV values in the groups. There was no association between MPV and Doppler parameters that can be used in predicting the severity of IUGR. There was no significant relation between MPV and the perinatal complications such as intracranial hemorrhage (ICH), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), the development of sepsis, postpartum exitus (PPEX) and intrauterine exitus (IUEX). Higher MPV values were associated with hospitalization in the neonatal intensive care unit (NICU) and respiratory distress syndrome (RDS) in the IUGR group. Analysis of MPV is a simple and readily available laboratory test. Prospective researches employing standard measurement technics are required to clarify the relationship between MPV and IUGR.

Role of cyclooxygenase-2 in intestinal injury in neonatal rats.

PubMed

Lu, Hui; Zhu, Bing

2014-11-01

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in premature neonates. The pathogenesis of NEC remains poorly understood. The present study aimed to investigate the dynamic change and role of cyclooxygenase-2 (COX-2) in neonatal rats with intestinal injury. Wistar rats, <24 h in age, received an intraperitoneal injection with 5 mg/kg lipopolysaccharide (LPS). Ileal tissues were collected at 1, 3, 6, 12 and 24 h following the LPS challenge for histological evaluation of NEC and for measurements of COX-2 mRNA. The correlation between the degree of intestinal injury and expression of COX-2 mRNA was determined. The LPS-injected pups showed a significant increase in injury scores compared to the control, and the most deteriorating change was at 12 h. COX-2 mRNA expression was upregulated following LPS injection. There was a significantly positive correlation between COX-2 mRNA and the grade of intestinal injury within 12 h, whereas COX-2 mRNA expression had a significantly negative correlation with the severity of intestinal injury at 24 h. COX-2 plays an important role in LPS-induced intestinal injury and the repair processes. Caution should be exerted concerning the potential therapeutic uses of COX-2 inhibitors or promoters in NEC.

Enhanced Probiotic Potential of Lactobacillus reuteri When Delivered as a Biofilm on Dextranomer Microspheres That Contain Beneficial Cargo

PubMed Central

Navarro, Jason B.; Mashburn-Warren, Lauren; Bakaletz, Lauren O.; Bailey, Michael T.; Goodman, Steven D.

2017-01-01

As with all orally consumed probiotics, the Gram-positive bacterium Lactobacillus reuteri encounters numerous challenges as it transits through the gastrointestinal tract of the host, including low pH, effectors of the host immune system, as well as competition with commensal and pathogenic bacteria, all of which can greatly reduce the availability of live bacteria for therapeutic purposes. Recently we showed that L. reuteri, when adhered in the form of a biofilm to a semi-permeable biocompatible dextranomer microsphere, reduces the incidence of necrotizing enterocolitis by 50% in a well-defined animal model following delivery of a single prophylactic dose. Herein, using the same semi-permeable microspheres, we showed that providing compounds beneficial to L. reuteri as diffusible cargo within the microsphere lumen resulted in further advantageous effects including glucosyltransferase-dependent bacterial adherence to the microsphere surface, resistance of bound bacteria against acidic conditions, enhanced adherence of L. reuteri to human intestinal epithelial cells in vitro, and facilitated production of the antimicrobial compound reuterin and the anti-inflammatory molecule histamine. These data support continued development of this novel probiotic formulation as an adaptable and effective means for targeted delivery of cargo beneficial to the probiotic bacterium. PMID:28396655

Arginine depletion increases susceptibility to serious infections in preterm newborns

PubMed Central

Badurdeen, Shiraz; Mulongo, Musa; Berkley, James A.

2015-01-01

Preterm newborns are highly susceptible to bacterial infections. This susceptibility is regarded as being due to immaturity of multiple pathways of the immune system. However, it is unclear whether a mechanism that unifies these different, suppressed pathways exists. Here, we argue that the immune vulnerability of the preterm neonate is critically related to arginine depletion. Arginine, a “conditionally essential” amino acid, is depleted in acute catabolic states, including sepsis. Its metabolism is highly compartmentalized and regulated, including by arginase-mediated hydrolysis. Recent data suggest that arginase II-mediated arginine depletion is essential for the innate immune suppression that occurs in newborn models of bacterial challenge, impairing pathways critical for the immune response. Evidence that arginine depletion mediates protection from immune activation during first gut colonization suggests a regulatory role in controlling gut-derived pathogens. Clinical studies show that plasma arginine is depleted during sepsis. In keeping with animal studies, small clinical trials of L-arginine supplementation have shown benefit in reducing necrotizing enterocolitis in premature neonates. We propose a novel, broader hypothesis that arginine depletion during bacterial challenge is a key factor limiting the neonate's ability to mount an adequate immune response, contributing to the increased susceptibility to infections, particularly with respect to gut-derived sepsis. PMID:25360828

Incidence of retinopathy of prematurity in the United States: 1997 through 2005.

PubMed

Lad, Eleonora M; Hernandez-Boussard, Tina; Morton, John M; Moshfeghi, Darius M

2009-09-01

To determine the incidence of retinopathy of prematurity (ROP) based on a national database and to identify baseline characteristics, demographic information, comorbidities, and surgical interventions. Retrospective study based on the National Inpatient Sample from 1997 through 2005. The National Inpatient Sample was queried for all newborn infants with and without ROP. Multivariate logistic regression was used to predict risk factors for ROP. Thirty-four million live births were recorded during the study period. The total ROP incidence was 0.17% overall and 15.58% for premature infants with length of stay of more than 28 days. Our results conclusively demonstrated the importance of low birth weight as a risk for ROP development in infants with length of stay of more than 28 days, as well as association with respiratory conditions, fetal hemorrhage, intraventricular hemorrhage, and blood transfer. An interesting finding was the protective effect conferred by hypoxia, necrotizing enterocolitis, and hemolytic disease of the newborn. Infants with ROP had a higher incidence of undergoing laser photocoagulation therapy, pars plana vitrectomy, and scleral buckle surgery. The current study represents a large, retrospective analysis of newborns with ROP. The multivariate analysis emphasizes the role of birth weight in extended-stay infants, as well as respiratory conditions, fetal hemorrhage, intraventricular hemorrhage, and blood transfer.

Probiotics and prebiotics in prevention and treatment of diseases in infants and children.

PubMed

Vandenplas, Yvan; Veereman-Wauters, Genevieve; De Greef, Elisabeth; Peeters, Stefaan; Casteels, Ann; Mahler, Tania; Devreker, Thierry; Hauser, Bruno

2011-01-01

To evaluate the impact of probiotics and prebiotics on the health of children. MEDLINE and LILACS were searched for relevant English and French-language articles. Human milk is rich in prebiotic oligosaccharides and may contain some probiotics. No data suggest that addition of probiotics to infant formula may be harmful, but evidence of its efficacy is insufficient for its recommendation. Since data suggest that addition of specific prebiotic oligosaccharides may reduce infections and atopy in healthy infants, their addition to infant formula seems reasonable. Long-term health benefits of pro- and prebiotics on the developing immune system remain to be proven. Selected probiotics reduce the duration of infectious diarrhea by 1 day, but evidence in prevention is lacking, except in antibiotic-associated diarrhea. Some specific probiotics prevent necrotizing enterocolitis, and other microorganisms may be beneficial in Helicobacter pylori gastritis and in infantile colic. Evidence is insufficient to recommend probiotics in prevention and treatment of atopic dermatitis. The use of probiotics in constipation, irritable bowel syndrome, inflammatory bowel disease, and extra-intestinal infections requires more studies. Duration of administration, microbial dosage, and species used need further validation for both pro- and prebiotics. Unjustified health claims are a major threat for the pro- and prebiotic concept.

Probiotics: their role in the treatment and prevention of disease.

PubMed

Doron, Shira; Gorbach, Sherwood L

2006-04-01

A probiotic is a "live microbial food ingredients that, when ingested in sufficient quantities, exerts health benefits on the consumer". Probiotics exert their benefits through several mechanisms; they prevent colonization, cellular adhesion and invasion by pathogenic organisms, they have direct antimicrobial activity and they modulate the host immune response. The strongest evidence for the clinical effectiveness of probiotics has been in their use for the prevention of symptoms of lactose intolerance, treatment of acute diarrhea, attenuation of antibiotic-associated gastrointestinal side effects and the prevention and treatment of allergy manifestations. More research needs to be carried out to clarify conflicting findings on the use of probiotics for prevention of travelers' diarrhea, infections in children in daycare and dental caries, and elimination of nasal colonization with potentially pathogenic bacteria. Promising ongoing research is being conducted on the use of probiotics for the treatment of Clostridium difficile colitis, treatment of Helicobacter pylori infection, treatment of inflammatory bowel disease and prevention of relapse, treatment of irritable bowel syndrome, treatment of intestinal inflammation in cystic fibrosis patients, and prevention of necrotizing enterocolitis in premature infants. Finally, areas of future research include the use of probiotics for the treatment of rheumatoid arthritis, prevention of cancer and the treatment of graft-versus-host disease in bone marrow transplant recipients.

Human milk, a concrete risk for infection?

PubMed

Lanari, M; Sogno Valin, P; Natale, F; Capretti, M G; Serra, L

2012-10-01

Breastfeeding should be considered a public health issue and the reference normative standards for infant feeding at least to the 6th month of life, with continuation of breastfeeding for 1 year or longer as mutually desired by mother and infant. Numerous studies demonstrate that breastfeeding results in improved infant and maternal health. Moreover the reduction of the risk of severe retinopathy of prematurity, sepsis and necrotizing enterocolitis is particularly evident in preterm infants. There are a limited number of medical conditions in which breastfeeding is contraindicated, including some maternal infectious diseases. During breastfeeding the baby can be infected by mother's pathogens with several routes of transmission that can be considered, such as respiratory secretions and droplets (e.g. Adenovirus, Influenza virus, Respiratory Syncytial Virus, Haemophilus, Mycoplasma) direct contact with lesions in the breast and nipple (e.g. HSV 1-2, VZV, Treponema) and breast milk. Frequently, in case of infection, different routes of transmission are contemporary implicated. The basic assumption is that breastfeeding is rarely contraindicated during maternal infections, a few exceptions are HTVL-I and HIV in industrialized country. The theoretic risk for transmission trough breast milk should be discussed and balanced with the benefits of breast milk, so the mother and parents can make an informed decision concerning infant feeding.

Anti-inflammatory mechanisms of bioactive milk proteins in the intestine of newborns.

PubMed

Chatterton, Dereck E W; Nguyen, Duc Ninh; Bering, Stine Brandt; Sangild, Per Torp

2013-08-01

The human newborn infant is susceptible to gut inflammatory disorders. In particular, growth-restricted infants or infants born prematurely may develop a severe form of intestinal inflammation known as necrotizing enterocolitis (NEC), which has a high mortality. Milk provides a multitude of proteins with anti-inflammatory properties and in this review we gather together some recent significant advances regarding the isolation and proteomic identification of these minor constituents of both human and bovine milk. We introduce the process of inflammation, with a focus on the immature gut, and describe how a multitude of milk proteins act against the inflammatory process according to both in vitro and in vivo studies. We highlight the effects of milk proteins such as caseins, and of whey proteins such as alpha-lactalbumin, beta-lactoglobulin, lactoferrin, osteopontin, immunoglobulins, trefoil factors, lactoperoxidase, superoxide dismutase, platelet-activating factor acetylhydrolase, alkaline phosphatase, and growth factors (TGF-β, IGF-I and IGF-II, EGF, HB-EGF). The effects of milk fat globule proteins, such as TLR-2, TLR-4, sCD14 and MFG-E8/lactadherin, are also discussed. Finally, we indicate how milk proteins could be useful for the prophylaxis and therapy of intestinal inflammation in infants and children. Copyright © 2013 Elsevier Ltd. All rights reserved.

Multiplexed Lateral Flow Test for Detection and Differentiation of Cronobacter sakazakii Serotypes O1 and O2

PubMed Central

Scharinger, Eva J.; Dietrich, Richard; Wittwer, Tobias; Märtlbauer, Erwin; Schauer, Kristina

2017-01-01

The ubiquitous and opportunistic pathogen Cronobacter sakazakii is responsible for severe meningitis, sepsis, and necrotizing enterocolitis in neonates and infants associated with ingestion of contaminated powdered infant formula (PIF). The current ISO method for isolation and detection of Cronobacter spp. is laborious, time-consuming and expensive. In this study, a multiplexed lateral flow test strip was developed to rapidly detect and simultaneously serotype O1 and O2 C. sakazakii serotypes. The assay is based on two monoclonal antibodies (MAb) that specifically bind to the lipopolysaccharides (LPS) of these pathogens. The test strip provides results very quickly; C. sakazakii could be detected in pure culture within 15 min with a sensitivity of 107 CFU/ml. After non-selective enrichment for 18 h as low as one Cronobacter cell per g PIF could be detected. Moreover, the established lateral flow assay (LFA) offers excellent specificity showing no cross-reactivity with other C. sakazakii serotypes, Cronobacter species or Enterobacteriaceae tested. These characteristics, together with several advantages such as speed, simplicity in performance, low analysis cost, and no requirement of specialized skills or sophisticated equipment make the developed multiplexed LFA suitable for reliable detection and serotyping of C. sakazakii serotypes O1 and O2. PMID:28979257

Rapid inactivation of Cronobacter sakazakii on copper alloys following periods of desiccation stress.

PubMed

Elguindi, Jutta; Alwathnani, Hend A; Rensing, Christopher

2012-04-01

Cronobacter spp. have been identified as the causative agent in meningitis and necrotizing enterocolitis in premature infants which can be linked to the bacterium's desiccation resistance and persistence in powdered infant formula. In this study we examined the efficacy of copper cast alloys in contact killing of Cronobacter sakazakii following periods of desiccation stress. Cronobacter sakazakii cells suspended in Tryptic Soy Broth (TSB) were killed within 10 min while kept moist on 99.9% copper alloys and within 1 min of drying on 99.9% copper alloys. Survival times were unchanged after cells suspended in TSB were desiccated for 33 days. Cronobacter sakazakii cells suspended in infant formula were killed within 30 min under moist conditions and within 3 min of drying on 99.9% copper alloys. However, when desiccated in infant formula for 45 days, survival times decreased to 10 and 1 min in moist and dry conditions, respectively. In contrast, no decrease in viable cells was noted on stainless steel surfaces under the experimental conditions employed in this study. Cronobacter sakazakii was rapidly killed on copper alloys under all testing conditions of this study indicating that desiccation and copper ion resistance do not prolong survival. These results could have important implications for the utilization of copper in the production and storage of powdered infant formula.

Multiplexed Lateral Flow Test for Detection and Differentiation of Cronobacter sakazakii Serotypes O1 and O2.

PubMed

Scharinger, Eva J; Dietrich, Richard; Wittwer, Tobias; Märtlbauer, Erwin; Schauer, Kristina

2017-01-01

The ubiquitous and opportunistic pathogen Cronobacter sakazakii is responsible for severe meningitis, sepsis, and necrotizing enterocolitis in neonates and infants associated with ingestion of contaminated powdered infant formula (PIF). The current ISO method for isolation and detection of Cronobacter spp. is laborious, time-consuming and expensive. In this study, a multiplexed lateral flow test strip was developed to rapidly detect and simultaneously serotype O1 and O2 C. sakazakii serotypes. The assay is based on two monoclonal antibodies (MAb) that specifically bind to the lipopolysaccharides (LPS) of these pathogens. The test strip provides results very quickly; C. sakazakii could be detected in pure culture within 15 min with a sensitivity of 10 7 CFU/ml. After non-selective enrichment for 18 h as low as one Cronobacter cell per g PIF could be detected. Moreover, the established lateral flow assay (LFA) offers excellent specificity showing no cross-reactivity with other C. sakazakii serotypes, Cronobacter species or Enterobacteriaceae tested. These characteristics, together with several advantages such as speed, simplicity in performance, low analysis cost, and no requirement of specialized skills or sophisticated equipment make the developed multiplexed LFA suitable for reliable detection and serotyping of C. sakazakii serotypes O1 and O2.

Putative Inv Is Essential for Basolateral Invasion of Caco-2 Cells and Acts Synergistically with OmpA To Affect In Vitro and In Vivo Virulence of Cronobacter sakazakii ATCC 29544

PubMed Central

Chandrapala, Dilini; Kim, Kyumson; Choi, Younho; Senevirathne, Amal; Kang, Dong-Hyun; Ryu, Sangryeol

2014-01-01

Cronobacter sakazakii is an opportunistic pathogen that causes neonatal meningitis and necrotizing enterocolitis. Its interaction with intestinal epithelium is important in the pathogenesis of enteric infections. In this study, we investigated the involvement of the inv gene in the virulence of C. sakazakii ATCC 29544 in vitro and in vivo. Sequence analysis of C. sakazakii ATCC 29544 inv revealed that it is different from other C. sakazakii isolates. In various cell culture models, an Δinv deletion mutant showed significantly lowered invasion efficiency, which was restored upon genetic complementation. Studying invasion potentials using tight-junction-disrupted Caco-2 cells suggested that the inv gene product mediates basolateral invasion of C. sakazakii ATCC 29544. In addition, comparison of invasion potentials of double mutant (ΔompA Δinv) and single mutants (ΔompA and Δinv) provided evidence for an additive effect of the two putative outer membrane proteins. Finally, the importance of inv and the additive effect of putative Inv and OmpA were also proven in an in vivo rat pup model. This report is the first to demonstrate two proteins working synergistically in vitro, as well as in vivo in C. sakazakii pathogenesis. PMID:24549330

Strategies for the Identification and Tracking of Cronobacter Species: An Opportunistic Pathogen of Concern to Neonatal Health

PubMed Central

Yan, Qiongqiong; Fanning, Séamus

2015-01-01

Cronobacter species are emerging opportunistic food-borne pathogens, which consists of seven species, including C. sakazakii, C. malonaticus, C. muytjensii, C. turicensis, C. dublinensis, C. universalis, and C. condimenti. The organism can cause severe clinical infections, including necrotizing enterocolitis, septicemia, and meningitis, predominately among neonates <4 weeks of age. Cronobacter species can be isolated from various foods and their surrounding environments; however, powdered infant formula (PIF) is the most frequently implicated food source linked with Cronobacter infection. This review aims to provide a summary of laboratory-based strategies that can be used to identify and trace Cronobacter species. The identification of Cronobacter species using conventional culture method and immuno-based detection protocols were first presented. The molecular detection and identification at genus-, and species-level along with molecular-based serogroup approaches are also described, followed by the molecular sub-typing methods, in particular pulsed-field gel electrophoresis and multi-locus sequence typing. Next generation sequence approaches, including whole genome sequencing, DNA microarray, and high-throughput whole-transcriptome sequencing, are also highlighted. Appropriate application of these strategies would contribute to reduce the risk of Cronobacter contamination in PIF and production environments, thereby improving food safety and protecting public health. PMID:26000266

Putative Inv is essential for basolateral invasion of Caco-2 cells and acts synergistically with OmpA to affect in vitro and in vivo virulence of Cronobacter sakazakii ATCC 29544.

PubMed

Chandrapala, Dilini; Kim, Kyumson; Choi, Younho; Senevirathne, Amal; Kang, Dong-Hyun; Ryu, Sangryeol; Kim, Kwang-Pyo

2014-05-01

Cronobacter sakazakii is an opportunistic pathogen that causes neonatal meningitis and necrotizing enterocolitis. Its interaction with intestinal epithelium is important in the pathogenesis of enteric infections. In this study, we investigated the involvement of the inv gene in the virulence of C. sakazakii ATCC 29544 in vitro and in vivo. Sequence analysis of C. sakazakii ATCC 29544 inv revealed that it is different from other C. sakazakii isolates. In various cell culture models, an Δinv deletion mutant showed significantly lowered invasion efficiency, which was restored upon genetic complementation. Studying invasion potentials using tight-junction-disrupted Caco-2 cells suggested that the inv gene product mediates basolateral invasion of C. sakazakii ATCC 29544. In addition, comparison of invasion potentials of double mutant (ΔompA Δinv) and single mutants (ΔompA and Δinv) provided evidence for an additive effect of the two putative outer membrane proteins. Finally, the importance of inv and the additive effect of putative Inv and OmpA were also proven in an in vivo rat pup model. This report is the first to demonstrate two proteins working synergistically in vitro, as well as in vivo in C. sakazakii pathogenesis.

Preparation and handling of powdered infant formula: a commentary by the ESPGHAN Committee on Nutrition.

PubMed

Agostoni, Carlo; Axelsson, Irene; Goulet, Olivier; Koletzko, Berthold; Michaelsen, Kim F; Puntis, John W L; Rigo, Jacques; Shamir, Raanan; Szajewska, Hania; Turck, Dominique; Vandenplas, Yvan; Weaver, Lawrence T

2004-10-01

Powdered infant formulae are not sterile and may contain pathogenic bacteria. In addition, milk products are excellent media for bacterial proliferation. Multiplication of Enterobacter sakazakii in prepared formula feeds can cause devastating sepsis, particularly in the first 2 months of life. In approximately 50 published case reports of severe infection, there are high rates of meningitis, brain abscesses and necrotizing enterocolitis, with an overall mortality from 33% to 80%. Breast feeding provides effective protection against infection, one of the many reasons why it deserves continued promotion and support. To minimize the risk of infection in infants not fully breastfed, recommendations are made for preparation and handling of powdered formulae for children younger than 2 months of age. In the home setting, powdered infant formulae should be freshly prepared for each feed. Any milk remaining should be discarded rather than used in the following feed. Infant feeds should never be kept warm in bottle heaters or thermoses. In hospitals and other institutions written guidelines for preparation and handling of infant formulae should be established and their implementation monitored. If formula needs to be prepared in advance, it should be prepared on a daily basis and kept at 4 degrees C or below. Manufacturers of infant formulae should make every effort to minimize bacterial contamination of powdered products.

Bifidobacterium longum subspecies infantis: champion colonizer of the infant gut

PubMed Central

Underwood, Mark A.; German, J. Bruce; Lebrilla, Carlito B.; Mills, David A.

2015-01-01

Oligosaccharides are abundant in human milk. Production of these highly diverse structures requires significant energy expenditure by the mother and yet these human milk oligosaccharides offer no direct nutritive value to her infant. A primary function of human milk oligosaccharides is to shape the infant’s intestinal microbiota with life-long consequences. Bifidobacterium longum subspecies infantis (B. infantis) is unique among gut bacteria in its prodigious capacity to digest and consume any human milk oligosaccharide structure, the result of a large repertoire of bacterial genes encoding an array of glycosidases and oligosaccharide transporters not found in other bacterial species. In vitro, B. infantis grows better than other bacterial strains in the presence of human milk oligosaccharides, displays anti-inflammatory activity in premature intestinal cells, and decreases intestinal permeability. In premature infants, B. infantis given in combination with human milk increases B. infantis and decreases Enterobacteriaceae in the feces. Probiotics containing B. infantis decrease the risk of necrotizing enterocolitis in premature infants. Colonization with B. infantis is also associated with increased vaccine responses. Probiotic organisms have historically been selected based on ease of production and stability. The advantages of B. infantis, selected through coevolution with human milk glycans, present an opportunity for focused manipulation of the infant intestinal microbiota. PMID:25303277

The Human Neonatal Gut Microbiome: A Brief Review

PubMed Central

Gritz, Emily C.; Bhandari, Vineet

2015-01-01

The field of genomics has expanded into subspecialties such as metagenomics over the course of the last decade and a half. The development of massively parallel sequencing capabilities has allowed for increasingly detailed study of the genome of the human microbiome, the microbial super organ that resides symbiotically within the mucosal tissues and integumentary system of the human host. The gut microbiome, and particularly the study of its origins in neonates, has become subtopics of great interest within the field of genomics. This brief review seeks to summarize recent literature regarding the origins and establishment of the neonatal gut microbiome, beginning in utero, and how it is affected by neonatal nutritional status (breastfed versus formula fed) and gestational age (term versus preterm). We also explore the role of dysbiosis, a perturbation within the fragile ecosystem of the microbiome, and its role in the origin of select pathologic states, specifically, obesity and necrotizing enterocolitis (NEC) in preterm infants. We discuss the evidence supporting enteral pre- and pro-biotic supplementation of commensal organisms such as Bifidobacterium and Lactobacillus in the neonatal period, and their role in the prevention and amelioration of NEC in premature infants. Finally, we review directions to consider for further research to promote human health within this field. PMID:25798435

Immunogold Nanoparticles for Rapid Plasmonic Detection of C. sakazakii.

PubMed

Aly, Mohamed A; Domig, Konrad J; Kneifel, Wolfgang; Reimhult, Erik

2018-06-25

Cronobacter sakazakii is a foodborne pathogen that can cause a rare, septicemia, life-threatening meningitis, and necrotizing enterocolitis in infants. In general, standard methods for pathogen detection rely on culture, plating, colony counting and polymerase chain reaction DNA-sequencing for identification, which are time, equipment and skill demanding. Recently, nanoparticle- and surface-based immunoassays have increasingly been explored for pathogen detection. We investigate the functionalization of gold nanoparticles optimized for irreversible and specific binding to C. sakazakii and their use for spectroscopic detection of the pathogen. We demonstrate how 40-nm gold nanoparticles grafted with a poly(ethylene glycol) brush and functionalized with polyclonal antibodies raised against C. sakazakii can be used to specifically target C. sakazakii . The strong extinction peak of the Au nanoparticle plasmon polariton resonance in the optical range is used as a label for detection of the pathogens. Individual binding of the nanoparticles to the C. sakazakii surface is also verified by transmission electron microscopy. We show that a high degree of surface functionalization with anti- C. sakazakii optimizes the detection and leads to a detection limit as low as 10 CFU/mL within 2 h using a simple cuvette-based UV-Vis spectrometric readout that has great potential for further optimization.

Patent ductus arteriosus: patho-physiology, hemodynamic effects and clinical complications.

PubMed

Capozzi, Giovanbattista; Santoro, Giuseppe

2011-10-01

During fetal life, patent arterial duct diverts placental oxygenated blood from the pulmonary artery into the aorta by-passing lungs. After birth, decrease of prostacyclins and prostaglandins concentration usually causes arterial duct closure. This process may be delayed, or may even completely fail in preterm infants with arterial duct still remaining patent. If that happens, blood flow by-pass of the systemic circulation through the arterial duct results in pulmonary overflow and systemic hypoperfusion. When pulmonary flow is 50% higher than systemic flow, a hemodynamic "paradox" results, with an increase of left ventricular output without a subsequent increase of systemic output. Cardiac overload support neuro-humoral effects (activation of sympathetic nervous system and renin-angiotensin system) that finally promote heart failure. Moreover, increased pulmonary blood flow can cause vascular congestion and pulmonary edema. However, the most dangerous effect is cerebral under-perfusion due to diastolic reverse-flow and resulting in cerebral hypoxia. At last, blood flow decreases through the abdominal aorta, reducing perfusion of liver, gut and kidneys and may cause hepatic failure, renal insufficiency and necrotizing enterocolitis. Conclusions Large patent arterial duct may cause life-threatening multi-organ effects. In pre-term infant early diagnosis and timely effective treatment are cornerstones in the prevention of cerebral damage and long-term multi-organ failure.

Development of fine motor skills in preterm infants.

PubMed

Bos, Arend F; Van Braeckel, Koenraad N J A; Hitzert, Marrit M; Tanis, Jozien C; Roze, Elise

2013-11-01

Fine motor skills are related to functioning in daily life and at school. We reviewed the status of knowledge, in preterm children, on the development of fine motor skills, the relation with gross motor skills, and risk factors for impaired fine motor skills. We searched the past 15 years in PubMed, using ['motor skills' or 'fine motor function' and 'preterm infant'] as the search string. Impaired gross and fine motor skills are among the most frequently occurring problems encountered by preterm children who do not develop cerebral palsy. The prevalence is around 40% for mild to moderate impairment and 20% for moderate impairment. Fine motor skill scores on the Movement Assessment Battery for Children are about 0.62 of a standard deviation lower compared with term children. Risk factors for fine motor impairments include moderately preterm birth (odds ratio [OR] 2.0) and, among very preterm children (<32 wk gestation), intra-uterine growth restriction (ORs 2-3), inflammatory conditions (late-onset sepsis and necrotizing enterocolitis, ORs 3-5), and dexamethasone therapy for bronchopulmonary dysplasia (OR 2.7). A better understanding of factors that play a role in the development of and recovery from brain injury could guide future intervention attempts aimed at improving fine motor skills of preterm children. © The Authors. Developmental Medicine & Child Neurology © 2013 Mac Keith Press.

The Infant Intestinal Microbiome: Friend or Foe?

PubMed Central

Mshvildadze, Maka; Neu, Josef

2013-01-01

During the course of mammalian evolution there has been a close relationship between microbes residing in the gastrointestinal (GI) tract and the mammalian host. Interactions of resident intestinal microbes with the luminal contents and the mucosal surface play important roles in normal intestinal development, nutrition and adaptive innate immunity. The GI tract of the premature infant has a large but fragile surface area covered by a thin monolayer of epithelial cells that overlies a highly immunoreactive submucosa. Interactions in the lumen between microbes, nutrients and the intestinal mucosa can range from a healthy homeostasis to an uncontrolled systemic inflammatory response syndrome (SIRS) that leads to multiple organ system failure and death. Recent advances in molecular microbiota analytic methodology that stem from advances in high throughput sequencing technology have provided us with the tools to determine the GI microbiota in great depth, including the nearly 80 % of microbes in the intestine that are very difficult if not impossible to culture by current methodology. Application of these techniques to derive a better understanding of the developing intestinal ecosystem in the premature neonate may hold the key to understand and eventually prevent several important diseases including necrotizing enterocolitis (NEC) and late onset neonatal sepsis that may be acquired via translocation through the GI tract. PMID:20116944

Greater mortality and morbidity in extremely preterm infants fed a diet containing cow milk protein products.

PubMed

Abrams, Steven A; Schanler, Richard J; Lee, Martin L; Rechtman, David J

2014-01-01

Provision of human milk has important implications for the health and outcomes of extremely preterm (EP) infants. This study evaluated the effects of an exclusive human milk diet on the health of EP infants during their stay in the neonatal intensive care unit. EP infants <1,250 g birth weight received a diet consisting of either human milk fortified with a human milk protein-based fortifier (HM) (n=167) or a diet containing variable amounts of milk containing cow milk-based protein (CM) (n=93). Principal outcomes were mortality, necrotizing enterocolitis (NEC), growth, and duration of parenteral nutrition (PN). Mortality (2% versus 8%, p=0.004) and NEC (5% versus 17%, p=0.002) differed significantly between the HM and CM groups, respectively. For every 10% increase in the volume of milk containing CM, the risk of sepsis increased by 17.9% (p<0.001). Growth rates were similar between groups. The duration of PN was 8 days less in the subgroup of infants receiving a diet containing <10% CM versus ≥10% CM (p<0.02). An exclusive human milk diet, devoid of CM-containing products, was associated with lower mortality and morbidity in EP infants without compromising growth and should be considered as an approach to nutritional care of these infants.

Association of the gut microbiota mobilome with hospital location and birth weight in preterm infants.

PubMed

Ravi, Anuradha; Estensmo, Eva Lena F; Abée-Lund, Trine M L'; Foley, Steven L; Allgaier, Bernhard; Martin, Camilia R; Claud, Erika C; Rudi, Knut

2017-11-01

BackgroundThe preterm infant gut microbiota is vulnerable to different biotic and abiotic factors. Although the development of this microbiota has been extensively studied, the mobilome-i.e. the mobile genetic elements (MGEs) in the gut microbiota-has not been considered. Therefore, the aim of this study was to investigate the association of the mobilome with birth weight and hospital location in the preterm infant gut microbiota.MethodsThe data set consists of fecal samples from 62 preterm infants with and without necrotizing enterocolitis (NEC) from three different hospitals. We analyzed the gut microbiome by using 16S rRNA amplicon sequencing, shot-gun metagenome sequencing, and quantitative PCR. Predictive models and other data analyses were performed using MATLAB and QIIME.ResultSThe microbiota composition was significantly different between NEC-positive and NEC-negative infants and significantly different between hospitals. An operational taxanomic unit (OTU) showed strong positive and negative correlation with NEC and birth weight, respectively, whereas none showed significance for mode of delivery. Metagenome analyses revealed high levels of conjugative plasmids with MGEs and virulence genes. Results from quantitative PCR showed that the plasmid signature genes were significantly different between hospitals and in NEC-positive infants.ConclusionOur results point toward an association of the mobilome with hospital location in preterm infants.

Gender dependent association between perinatal morbidity and estrogen receptor-alpha Pvull polymorphism.

PubMed

Derzbach, László; Treszl, András; Balogh, Adám; Vásárhelyi, Barna; Tulassay, Tivadar; Rigó J, János

2005-01-01

Assuming the importance of estrogen in perinatal physiology, we tested the association of an estrogen receptor-alpha (ER-alpha) gene Pvull pP polymorphism with perinatal morbidity in premature infants. The ER-alpha Pp genotype was determined in 69 low-birth weight (LBW) boys and 72 LBW girls, 86 term boys and 81 term girls. The association between risk factors, genotype, gender and perinatal morbidity was tested with binary logistic regression analysis. Boys carrying "p" allele were at lower risk for necrotizing enterocolitis (OR [95% Cl]: 0.24 [0.07-0.83]) and patent ductus arteriosus (OR [95% Cl]: 0.24 [0.05-0.97]). The carrier state of the "p" allele was associated with a 34-h shorter period of oxygen supplementation on average (P=0.0018). Boys with pp genotype were at greater risk for intraventricular hemorrhage (OR [95% Cl]: 4.39 [1.15-16.82]). No association between ER-alpha Pvull polymorphism and morbidity was present in girls. Since homozygocity for any Pvull alleles (i.e. having PP or pp genotype) increases the risk for at least one of the most common perinatal complications, it is likely that the heterozygous carrier state of Pvull genotypes has a protective effect, which is gender-dependent.

The role of patent ductus arteriosus ligation in bronchopulmonary dysplasia: reexamining a randomized controlled trial.

PubMed

Clyman, Ronald; Cassady, George; Kirklin, James K; Collins, Monica; Philips, Joseph B

2009-06-01

To reexamine data from a randomized controlled trial of prophylactic ductus ligation to determine whether ligation contributes directly to the development of bronchopulmonary dysplasia (BPD) in extremely low birth weight infants. The control group underwent ligation only if they had development of a symptomatic patent ductus arteriosus (PDA). The Prophylactic Ligation group underwent ligation within 24 hours of birth regardless of the presence or absence of symptoms of a PDA. We hypothesized that the incidence of BPD would be higher in the prophylactic ligation group because more ligations were performed than in the control group. Prophylactic ligation significantly increased the incidence of BPD (defined as a supplemental oxygen requirement at 36 weeks postmenstrual age) and the incidence of mechanical ventilation at 36 weeks. The groups were statistically similar in gestation, sex, race, fluid administration, intraventricular hemorrhage, pulmonary air leaks, and survival to 36 weeks. The lower incidence of BPD in the control group occurred despite the fact that the incidence of necrotizing enterocolitis (a known risk factor for BPD) was significantly elevated in the control group. Only infants who had previously undergone a PDA ligation had development of BPD in the control group. Prophylactic ligation, while eliminating the PDA, increases the risk for BPD.

Determinants of outcomes in patients with simple gastroschisis.

PubMed

Youssef, Fouad; Laberge, Jean-Martin; Puligandla, Pramod; Emil, Sherif

2017-05-01

We analyzed the determinants of outcomes in simple gastroschisis (GS) not complicated by intestinal atresia, perforation, or necrosis. All simple GS patients enrolled in a national prospective registry from 2005 to 2013 were studied. Patients below the median for total parenteral nutrition (TPN) duration (26days) and hospital stay (34days) were compared to those above. Univariate and multivariate logistic and linear regression analyses were employed using maternal, patient, postnatal, and treatment variables. Of 700 patients with simple GS, representing 76.8% of all GS patients, 690 (98.6%) survived. TPN was used in 352 (51.6%) and 330 (48.4%) patients for ≤26 and >26days, respectively. Hospital stay for 356 (51.9%) and 330 (48.1%) infants was ≤34 and >34days, respectively. Univariate analysis revealed significant differences in several patient, treatment, and postnatal factors. On multivariate analysis, prenatal sonographic bowel dilation, older age at closure, necrotizing enterocolitis, longer mechanical ventilation, and central-line associated blood stream infection (CLABSI) were independently associated with longer TPN duration and hospital stay, with CLABSI being the strongest predictor. Prenatal bowel dilation is associated with increased morbidity in simple GS. CLABSI is the strongest predictor of outcomes. Bowel matting is not an independent risk factor. 2c. Copyright © 2017 Elsevier Inc. All rights reserved.

The importance of ERCP for the surgical tactic in haemorrhagic necrotizing pancreatitis (preliminary report).

PubMed

Gebhardt, C; Riemann, J F; Lux, G

1983-03-01

In patients with haemorrhagic necrotizing pancreatitis who are scheduled for surgery, we have been carrying out a preoperative retrograde investigation of the pancreatic duct system for the past 3 months. The results in, to date, ten patients, all of whom survived their severe illness, revealed four different morphological findings of importance for the surgical tactic. 1. A normal pancreatic duct system with no signs of fistulae: only peripancreatic necrosectomy is required. 2. Contrast medium leaks via a ductal fistula: left resection, including the removal of the fistulous area, must be done. 3. Normal duct system with complete segmental parenchymal staining, representing total necrosis in this region: left resection of the pancreas. 4. Duodenoscopically demonstrable perforation into the duodenum of a necrotic cavity in the head of the pancreas: conservative management only, no surgery, since this lesions, resulting in drainage of the necrotic cavity into the bowel, permits self-healing, while the site of the perforation within the necrotic wall cannot be dealt with by surgery. The experience gained so far indicates that the surgical tactic can be determined with greater selectivity by the use of ERCP.

Recurring Necrotic Enteritis Outbreaks in Commercial Broiler Chicken Flocks Strongly Influence Toxin Gene Carriage and Species Richness in the Resident Clostridium perfringens Population

PubMed Central

Gaucher, Marie-Lou; Perron, Gabriel G.; Arsenault, Julie; Letellier, Ann; Boulianne, Martine; Quessy, Sylvain

2017-01-01

Extensive use of antibiotic growth promoters (AGPs) in food animals has been questioned due to the globally increasing problem of antibiotic resistance. For the poultry industry, digestive health management following AGP withdrawal in Europe has been a challenge, especially the control of necrotic enteritis. Much research work has focused on gut health in commercial broiler chicken husbandry. Understanding the behavior of Clostridium perfringens in its ecological niche, the poultry barn, is key to a sustainable and cost-effective production in the absence of AGPs. Using polymerase chain reaction and pulsed-field gel electrophoresis, we evaluated how the C. perfringens population evolved in drug-free commercial broiler chicken farms, either healthy or affected with recurring clinical necrotic enteritis outbreaks, over a 14-month period. We show that a high genotypic richness was associated with an increased risk of clinical necrotic enteritis. Also, necrotic enteritis-affected farms had a significant reduction of C. perfringens genotypic richness over time, an increase in the proportion of C. perfringens strains harboring the cpb2 gene, the netB gene, or both. Thus, necrotic enteritis occurrence is correlated with the presence of an initial highly diverse C. perfringens population, increasing the opportunity for the selective sweep of particularly virulent genotypes. Disease outbreaks also appear to largely influence the evolution of this bacterial species in poultry farms over time. PMID:28567032

Necrotizing odontogenic fasciitis of head and neck extending to anterior mediastinum in elderly patients: innovative treatment with a review of the literature.

PubMed

Cortese, Antonio; Pantaleo, Giuseppe; Borri, Antonio; Amato, Massimo; Claudio, Pier Paolo

2017-02-01

Necrotizing fasciitis (NF) of odontogenic origin affecting the head and neck region is a rare but serious clinical condition, which, if diagnosed late, can lead to a fatal outcome. The early diagnosis of necrotizing fasciitis can be difficult. Delay in diagnosis leads to increase in the area of necrosis with a resulting increase in cosmetic deformity and life-threatening complication. In this study, we present two cases of elderly patients with aggressive NF affecting the neck and anterior mediastinum, which were of odontogenic origin. In the two patients selected necrotic skin and soft tissue were removed and wide exposure was achieved with debridement of the neck at the level of the affected layer of superficial cervical fascia. Saline solution was used as irrigation to treat the patients with acute necrotizing fasciitis. Difficulties in managing this condition with NF extent to deep anterior mediastinum is related to clavicle osteotomy or thoracotomy need with high surgical risks. In our technique, by gentle suction in anterior mediastinum, necrotic tissue resection was possible without any osteotomy need. Suctioning resection technique associated with hyperbaric, metabolic rebalance, and amino acid support in association with three types antibiotic therapy are fundamental points for correct therapy strategy, leading to full recovery and healing of NF patients even if in very unfavorable conditions. Multidisciplinary approach is paramount for proper treatment of this disease.

Detection of cytomegalovirus DNA in fecal samples as a method for CMV enterocolitis diagnosis after allogeneic stem cell transplantation.

PubMed

Zavrelova, Alzbeta; Radocha, Jakub; Pliskova, Lenka; Paterova, Pavla; Vejrazkova, Eva; Cyrany, Jiri; Gabalec, Filip; Podhola, Miroslav; Zak, Pavel

2018-05-16

Cytomegalovirus enterocolitis is a rare but potentially life threatening complication after allogeneic stem cell transplantation. Its early diagnosis and treatment are essential for a successful outcome. To determine the potential benefit of fecal CMV DNA detection in the diagnosis of CMV colitis among stem cell transplant recipients. Biopsies from the lower gastrointestinal tract, taken during 69 episodes of diarrhea, were compared with fecal samples previously examined for CMV DNA in 45 patients after allogeneic stem cell transplantation. Six confirmed cases of CMV colitis were observed, with 16 out of 69 (23%) fecal samples proving positive for CMV DNA. Only one positive sample correlated with histologically confirmed CMV colitis, and 15 samples were evaluated as false positive. These results provide a 16.7% sensitivity and 76.2% specificity in the diagnosis of CMV enterocolitis. The examination of fecal samples for the presence of CMV DNA has very low potential in the diagnosis of CMV enterocolitis after allogeneic stem cell transplantation; therefore, a biopsy of the gastrointestinal mucosa is still warranted for correct diagnosis.

Chronic food protein-induced enterocolitis syndrome caused by cow's milk proteins passed through breast milk.

PubMed

Miceli Sopo, Stefano; Monaco, Serena; Greco, Monica; Scala, Guglielmo

2014-01-01

We describe 2 cases of food protein-induced enterocolitis syndrome (FPIES) caused by cow's milk (CM) passed through breast milk. The onset in both cases was characterized by chronic symptoms (regurgitation, colic, diarrhea, failure to thrive); in one patient, two acute episodes due to the direct consumption of CM formula by the infant were also reported. The diagnosis of FPIES through breast milk can be easily overlooked, especially in milder cases. We also discuss some important issues concerning the general management of the disease. In conclusion, (1) the diagnosis of chronic FPIES should be taken into account even in exclusively breast-fed infants who present suggestive symptoms such as persistent regurgitation, small amounts of vomiting, lethargy, failure to thrive, dehydration, diarrhea (sometimes bloody) and abdominal distention. A 2-week maternal elimination diet should be considered even in apparently mild cases. (2) CM seems to be the most frequently reported culprit food. (3) In those cases in which acute FPIES is elicited by the direct consumption of the culprit food in breast-fed infants, maternal diet may be unrestricted. © 2014 S. Karger AG, Basel.

Toward improving mucosal barrier defenses: rhG-CSF plus IgG antibody.

PubMed

Simmonds, Aryeh; LaGamma, Edmund F

2006-11-01

Epithelial cell functions ultimately define the ability of the extremely low birth weight human fetus to survive outside of the uterus. These specialized epithelial cell capacities manage all human interactions with the ex utero world including: (i) lung mechanics, surface chemistry and gas exchange, (ii) renal tubular balance of fluid and electrolytes, (iii) barrier functions of the intestine and skin for keeping bacteria out and water in, plus enabling intestinal digestion, as well as (iv) maintaining an intact neuroepithelium lining of the ventricles of the brain and retina. In Part I of this two part review, the authors describe why the gut barrier is a clinically relevant model system for studying the complex interplay between innate and adaptive immunity, dendritic &epithelial cell interactions, intraepithelial lymphocytes, M-cells, as well as the gut associated lymphoid tissues where colonization after birth, clinician feeding practices, use of antibiotics as well as exposure to prebiotics, probiotics and maternal vaginal flora all program the neonate for a life-time of immune competence distinguishing "self" from foreign antigens. These barrier defense capacities become destructive during disease processes like necrotizing enterocolitis (NEC) when an otherwise maturationally normal, yet dysregulated and immature, immune defense system is associated with high levels of certain inflammatory mediators like TNFa. In Part II the authors discuss the rationale for why rhG-CSF has theoretical advantages in managing NEC or sepsis by augmenting neonatal neutrophil number, neutrophil expression of Fcg and complement receptors, as well as phagocytic function and oxidative burst. rhG-CSF also has potent anti-TNFa functions that may serve to limit extension of tissue destruction while not impairing bacterial killing capacity. Healthy, non-infected neutropenic and septic neonates differ in their ability to respond to rhG-CSF; however, no neonatal clinical trials to date have identified a clear clinical benefit of rhG-CSF therapy. This manuscript will review the literature and evidence available for identifying the ideal subject for cytokine treatment using NEC as the model disease target.

Comparison between minimally invasive and open surgical treatment in necrotizing pancreatitis.

PubMed

Wroński, Marek; Cebulski, Włodzimierz; Witkowski, Bartosz; Jankowski, Mieczysław; Kluciński, Andrzej; Krasnodębski, Ireneusz W; Słodkowski, Maciej

2017-04-01

Minimal access techniques have gained popularity for the management of necrotizing pancreatitis, but only a few studies compared open necrosectomy with a less invasive treatment. The aim of this study was to evaluate the outcomes of minimally invasive treatment for necrotizing pancreatitis in comparison with open necrosectomy. This retrospective study included 70 patients who underwent minimally invasive intervention or open surgical debridement for necrotizing pancreatitis between January 2007 and December 2014. Data were analyzed for postoperative morbidity and outcome. Of 70 patients, 22 patients underwent primary open necrosectomy and 48 patients were treated with minimally invasive techniques. Percutaneous and endoscopic drainage were successful in 34.9% and 75.0% of patients, respectively. The rates of postoperative new-onset organ failure and intensive care unit stay were significantly lower in the minimally invasive group (25.0% versus 54.5%; P = 0.016, and 29.2% versus 54.5%; P = 0.041, respectively). Gastrointestinal fistulas occurred more frequently after primary open necrosectomy (36.4% versus 10.4%; P = 0.009). Mortality was comparable in both groups (18.6% versus 27.3%; P = 0.420). Mortality for salvage open necrosectomy was similar to that for primary open debridement (28.6% versus 27.3%; P = 0.924). The independent risk factors for major postoperative complications were primary open necrosectomy (P = 0.028) and shorter interval to first intervention (P = 0.020). Mortality was independently associated only with older age (P = 0.009). Minimally invasive treatment should be preferred over open necrosectomy for initial management of necrotizing pancreatitis. Copyright © 2016 Elsevier Inc. All rights reserved.

Neutropenic enterocolitis (typhlitis) associated with infectious mononucleosis.

PubMed

Siğirci, Ahmet; Akinci, Ayşehan; Ozgen, Unsal; Ozen, Metehan

2006-02-01

Neutropenic enterocolitis (typhlitis) is an unusual acute complication of neutropenia, most often associated with leukaemia and lymphoma and characterized by segmental caecal and ascending colonic ulceration that may progress to necrosis, perforation, and septicaemia. We present a unique case of an 8-year-old girl with recently diagnosed infectious mononucleosis having findings consistent with typhlitis on abdominal CT.

Are there any reasons to change our behavior in necrotizing fasciitis with the advent of new antibiotics?

PubMed

Menichetti, Francesco; Giuliano, Simone; Fortunato, Simona

2017-04-01

The treatment of necrotizing fasciitis requires a multifaceted approach, consisting of surgical source control with immediate surgical debridement along with life support, clinical monitoring, and antimicrobial therapy. Many drugs are now available for the treatment of this life-threatening infectious disease, and the purpose of this review is to provide the reader with an updated overview of the newest therapeutic options. Because most necrotizing soft tissue infections are polymicrobial, broad-spectrum coverage is advisable. Acceptable monotherapy regimens include piperacillin-tazobactam or a carbapenem. However, drugs such as ceftolozane-tazobactam, ceftazidime-avibactam in association with an antianaerobic agent (metronidazole or clindamycin) are currently available as valuable alternatives. The new cephalosporins active against methicillin-resistant Staphylococcus aureus (MRSA), ceftaroline, and ceftobiprole share similar antibacterial activity against Gram-positive cocci, and they might be considered as an alternative to nonbetalactam anti-MRSA agents for necrotizing fasciitis management. Two new long-acting lypoglycopeptides - oritavancin and dalbavancin - share the indications for acute bacterial skin and skin structure infections and had similar activity against Gram-positive cocci including MRSA and streptococci. Carbapenem-sparing agents are particularly suitable for antimicrobial stewardship strategy. The new long-acting lypoglycopeptides are very effective in treating necrotizing fasciitis and are uttermost attractive for patients requiring short hospital stays and early discharge.

Loss of tolerance for fishes previously tolerated in children with fish food protein induced enterocolitis syndrome.

PubMed

Miceli Sopo, S; Fantacci, C; Bersani, G; Romano, A; Monaco, S

We describe two case reports presenting some novel information on fish FPIES. Fish FPIES to one fish does not always start at the same time to other fish. Additionally, development of tolerance to the index fish do not necessarily imply tolerance to other reactive fish. This reflects on the best management of children with FPIES fish. Copyright © 2017 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

Relationship between parietal blood flow studies in the left colon and the rectum in dogs. Colonic pressure and blood flow.

PubMed

Arhan, P; Bouchoucha, M; Martelli, H; Rimbert, J N; Berdeaux, A; Gallix, P; Héro, M; Barritault, L; Pellerin, D; Devroede, G

1988-01-01

An animal model was proposed to clarify the difference in occurrence of enterocolitis in congenital aganglionosis. When gaseous distention of the colon was localized to the rectosigmoid area, enterocolitis never occurred. On the contrary, when it involved the left colon, enterocolitis occurred in 13 of 15 patients. Intestinal blood flow rates were simultaneously measured in the left colon and rectum of six dogs by using labeled microspheres and expressed in function of the intraluminal pressure. Results show that for elevated values of intraluminal pressure, blood flow was significantly lower in the left colon than in the rectum. These results may explain why ischemia and necrosis occurred more frequently in the left colon than in the rectum.

Necrotizing fasciitis as a complication of odontogenic infection: a review of management and case series.

PubMed

Bayetto, K; Cheng, A; Sambrook, P

2017-09-01

The aims of the present study were to establish the incidence of head and neck necrotizing fasciitis (NF) in the Adelaide Oral and Maxillofacial Surgery Unit; review the current literature regarding the management of head and neck NF; and determine the evidence for the role of hyperbaric oxygen therapy in the management of NF. A retrospective audit of all patients admitted to the Royal Adelaide Hospital Oral and Maxillofacial Surgery Unit 2006-2015 with severe odontogenic infections was carried out. Patient demographics were recorded and treatment details were collected and analysed. A total of 672 patients were admitted for management of severe odontogenic infections. Of these, three were identified as NF. One case was treated using hyperbaric oxygen as an adjunct to conventional surgical and medical management. Two cases were managed using aggressive surgical management alone. Two patients survived. The incidence of head and neck NF in South Australia is 48/100 000 infections per year. The first-line treatment of severe odontogenic infections remains conventional surgical and medical management; however, hyperbaric oxygen therapy may have an additional role in the management of NF and other rare severe infections in medically complex patients. © 2017 Australian Dental Association.

Probiotics for human health –new innovations and emerging trends

PubMed Central

2012-01-01

The role of the gut microbiome in human health and disease with a particular emphasis on therapeutic use of probiotics under specific medical conditions was mainly highlighted in 1st Annual conference of Probiotic Association of India (PAi) and International Symposium on “Probiotics for Human Health - New Innovations and Emerging Trends” held on 27th-28th August, 2012 at New Delhi, India. There is increasing recognition of the fact that dysbiosis or alteration of this gut microbiome may be implicated in gastro-intestinal disorders including diarrheal diseases, ulcerative colitis, inflammatory bowel diseases, life style diseases viz. Diabetes Mellitus-2 and obesity etc. This report summarizes the proceedings of the conference and the symposium comprehensively. Although, research on probiotics has been continuing for the past few decades, the subject has been currently the major focus of attention across the world due to recent advances and new developments in genomics, transcriptomics, proteomics, metabolomics and emergence of new generation of high through put sequencing technologies that have immensely helped in understanding the probiotic functionality and mode of action from nutritional and health perspectives. There is now sufficient evidence backed up with good quality scientific clinical data to suggest that probiotic interventions could indeed be effective in various types of diarrheal diseases, other chronic gastrointestinal inflammatory disorders like pouchitis, necrotizing entero-colitis, allergic responses and lactose intolerance etc. This report makes a modest attempt to give all the stake holders involved in development of probiotic based functional/health foods an overview of the current status of probiotics research at the Global and National level. The most crucial issues that emerged from the lead talks delivered by the eminent speakers from India and abroad were the major focus of discussions in different plenary and technical sessions. By discussing some of these issues from scientific perspectives, the conference could achieve its prime objective of disseminating the current knowledge on the prospects of probiotics as potential biotherapeutics in the management of human health and diseases. PMID:23181893

[Nasal CPAP versus mechanical ventilation in 28 to 32-week preterm infants with early surfactant administration].

PubMed

Pérez, Luis Alfonso; González, Diana Marcela; Álvarez, Karen Margarita de Jesús; Díaz-Martínez, Luis Alfonso

2014-01-01

Continuous positive airway pressure (CPAP) is useful in low birth weight infants with respiratory distress, but it is not known if it is a better alternative to mechanical ventilation after early pulmonary surfactant administration. To compare the incidence of adverse events in 28 to 32-week newborns with respiratory distress managed with mechanical ventilation or CPAP after early surfactant administration. In total, 176 newborns were treated with CPAP and 147 with mechanical ventilation, all with Apgar scores >3 at five minutes and without apnea. The incidence of CPAP failure was 6.5% (95% CI: 11.3-22.8%); 29 patients died: 7 with CPAP (4.0%) and 22 with mechanical ventilation (15.0%, p<0.001). The relative risk of dying with CPAP versus mechanical ventilation was 0.27 (95% CI: 0.12-0.61), but after adjusting for confounding factors, CPAP use did not imply a higher risk of dying (RR=0.60; 95% CI: 0.29-1.24). Mechanical ventilation fatality rate was 5.70 (95% CI: 3.75-8.66) deaths/1,000 days-patient, while with CPAP it was 1.37 (95% CI: 0.65-2.88, p<0.001). Chronic lung disease incidence was lower with CPAP than with mechanical ventilation (RR=0.71; 95% CI: 0.54-0.96), as were intracranial hemorrhage (RR=0.28, 95% CI: 0.09-0.84) and sepsis (RR=0.67; 95%CI: 0.52-0.86), and it was similar for air leaks (RR=2.51; 95% CI: 0.83-7.61) and necrotizing enterocolitis (RR=1.68, 95% CI: 0.59-4.81). CPAP exposure of premature infants with respiratory distress syndrome is protective against chronic lung disease, intraventricular hemorrhage and sepsis compared to mechanical ventilation. No differences were observed regarding air leak syndrome or death.

Gabapentin therapy for pain and irritability in a neurologically impaired infant.

PubMed

Haney, A Lauren; Garner, Sandra S; Cox, Toby H

2009-08-01

Gabapentin is a gamma-aminobutyric acid analog used for numerous neurologic conditions, including neuropathic pain and epilepsy. We describe a 39-week gestational age, male infant with hypotonicity, functional short gut, and microduplication of chromosome 22 who was treated with gabapentin to control pain and irritability. During his hospitalization, the infant experienced multiple complications including respiratory distress, persistent pulmonary hypertension of the newborn, hypocalcemia, hypoglycemia, hyperbilirubinemia, gastroesophageal reflux, necrotizing enterocolitis, and cholestatic jaundice. Pain associated with related invasive procedures and surgeries was treated with intermittent and scheduled morphine. In addition to postoperative and procedural pain, the infant continued to experience pain and irritability attributed to neurologic impairment, presumably secondary to his chromosomal abnormality. Trials of scheduled lorazepam along with intermittent morphine and phenobarbital were unsuccessful in managing these symptoms. After failure of nonpharmacologic treatment and continued trials of sedatives and analgesics, gabapentin 5 mg/kg at bedtime was started on day of life 98. Improvement in the infant's tone and disposition was noted by numerous health care professionals and the infant's mother. In addition, the infant's pain scores, using the Pain Assessment in Neonates Scale, showed marked improvement. The infant continued to receive gabapentin; the dosage was increased to 10 mg/kg at bedtime after 6 days, then to 5 mg/kg in the morning and 10 mg/kg at bedtime 10 days later. When the infant was 7 months old, his mother requested that gabapentin be discontinued. He was slowly weaned, and the drug was discontinued when he was 11 months old. The infant tolerated gabapentin well except for experiencing nystagmus, which was noted 31 days after starting the drug and resolved after drug discontinuation. Clinicians should be aware of gabapentin as an alternative treatment for pain and irritability in neurologically impaired infants. Further study is needed, however, to verify the drug's safety and efficacy in neonates and infants. Standardized pain scales along with close patient monitoring will help to guide clinicians in dosage titration to optimize therapy.

Why do four NICUs using identical RBC transfusion guidelines have different gestational age-adjusted RBC transfusion rates?

PubMed

Henry, E; Christensen, R D; Sheffield, M J; Eggert, L D; Carroll, P D; Minton, S D; Lambert, D K; Ilstrup, S J

2015-02-01

To compare neonatal red blood cell (RBC) transfusion rates in four large Intermountain Healthcare NICUs, all of which adhere to the same RBC transfusion guidelines. This retrospective analysis was part of a transfusion-management quality-improvement project. De-identified data included RBC transfusions, clinical and laboratory findings, the anemia-prevention strategies in place in each NICU, and specific costs and outcomes. Of 2389 NICU RBC transfusions given during the 4-year period studied, 98.9 ± 2.1% (mean ± S.D.) were compliant with our transfusion guidelines, with no difference in compliance between any of the four NICUs. However, RBC transfusion rates varied widely between the four, with averages ranging from 4.6 transfusions/1000 NICU days to 21.7/1000 NICU days (P < 0.00001). Gestational age-adjusted transfusion rates were correspondingly discordant (P < 0.00001). The lower-transfusing NICUs had written anemia-preventing guidelines, such as umbilical cord milking at very low birth weight delivery, use of cord blood for admission laboratory studies, and darbepoetin dosing for selected neonates. Rates of Bell stage ⩾ 2 necrotizing enterocolitis and grade ⩾ 3 intraventricular hemorrhage were lowest in the two lower-transfusing NICUs (P < 0.0002 and P < 0.0016). Average pharmacy costs for darbepoetin were $84/dose, with an average pharmacy cost of $269 per transfusion averted. With a cost of $900/RBC transfusion, the anemia-preventing strategies resulted in an estimated cost savings to Intermountain Healthcare of about $6970 per 1000 NICU days, or about $282,300 annually. Using transfusion guidelines has been shown previously to reduce practice variability, lower transfusion rates and diminish transfusion costs. Based on our present findings, we maintain that even when transfusion guidelines are in place and adhered to rigorously, RBC transfusion rates are reduced further if anemia-preventing strategies are also in place.

Endosonography guided management of pancreatic fluid collections

PubMed Central

Vilmann, Andreas S; Menachery, John; Tang, Shou-Jiang; Srinivasan, Indu; Vilmann, Peter

2015-01-01

The revised Atlanta classification of acute pancreatitis was adopted by international consensus, and is based on actual local and systemic determinants of disease severity. The local determinant is pancreatic necrosis (sterile or infected), and the systemic determinant is organ failure. Local complications of pancreatitis can include acute peri-pancreatic fluid collection, acute necrotic collection, pseudocyst formation, and walled-off necrosis. Interventional endoscopic ultrasound (EUS) has been increasing utilized in managing these local complications. After performing a PubMed search, the authors manually applied pre-defined inclusion criteria or a filter to identify publications relevant to EUS and pancreatic collections (PFCs). The authors then reviewed the utility, efficacy, and risks associated with using therapeutic EUS and involved EUS devices in treating PFCs. Due to the development and regulatory approval of improved and novel endoscopic devices specifically designed for transmural drainage of fluid and necrotic debris (access and patency devices), the authors predict continuing evolution in the management of PFCs. We believe that EUS will become an indispensable part of procedures used to diagnose PFCs and perform image-guided interventions. After draining a PFC, the amount of tissue necrosis is the most important predictor of a successful outcome. Hence, it seems logical to classify these collections based on their percentage of necrotic component or debris present when viewed by imaging methods or EUS. Finally, the authors propose an algorithm for managing fluid collections based on their size, location, associated symptoms, internal echogenic patterns, and content. PMID:26557008

Complications of chronic necrotizing pulmonary aspergillosis: review of published case reports

PubMed Central

Barac, Aleksandra; Vukicevic, Tatjana Adzic; Ilic, Aleksandra Dudvarski; Rubino, Salvatore; Zugic, Vladimir; Stevanovic, Goran

2017-01-01

ABSTRACT Chronic necrotizing pulmonary aspergillosis (CNPA), a form of chronic pulmonary aspergillosis (CPA), affects immunocompetent or mildly immunocompromised persons with underlying pulmonary disease. These conditions are associated with high morbidity and mortality and often require long-term antifungal treatment. The long-term prognosis for patients with CNPA and the potential complications of CNPA have not been well documented. The aim of this study was to review published papers that report cases of CNPA complications and to highlight risk factors for development of CNPA. The complications in conjunction associated with CNPA are as follows: pseudomembranous necrotizing tracheobronchial aspergillosis, ankylosing spondylarthritis, pulmonary silicosis, acute respiratory distress syndrome, pulmonary Mycobacterium avium complex (MAC) disease, superinfection with Mycobacterium tuberculosis, and and pneumothorax. The diagnosis of CNPA is still a challenge. Culture and histologic examinations of bronchoscopically identified tracheobronchial mucus plugs and necrotic material should be performed in all immunocompromised individuals, even when the radiographic findings are unchanged. Early detection of intraluminal growth of Aspergillus and prompt antifungal therapy may facilitate the management of these patients and prevent development of complications. PMID:28423094

Management of necrotizing myositis in a field hospital: a case report

PubMed Central

Bharathi, Ramanathan Saranga; Sharma, Vinay; Sood, Rohit; Chakladar, Arunava; Singh, Pragnya; Raman, Deep Kumar

2009-01-01

Necrotizing myositis is a rare and fatal disease of skeletal muscles caused by group A beta hemolytic streptococci (GABHS). Its early detection by advanced imaging forms the basis of current management strategy. Paucity of advanced imaging in field/rural hospitals necessitates adoption of management strategy excluding imaging as its basis. Such a protocol, based on our experience and literature, constitutes: i. Prompt recognition of the clinical triad: disproportionate pain; precipitous course; and early loss of power- in a swollen limb with/without preceding trauma. ii. Support of clinical suspicion by 2 ubiquitous laboratory tests: gram staining- of exudates from bullae/muscles to indicate GABHS infection; and CPK estimation- to indicate myonecrosis. iii. Replacement of empirical antibiotics with high intravenous doses of sodium penicillin and clindamycin iv. Exploratory fasciotomy: to confirm myonecrosis without suppuration- its hallmark v. Emergent radical debridement vi. Primary closure with viable flaps – unconventional, if need be. PMID:19374768

Severe soft tissue infections.

PubMed

Napolitano, Lena M

2009-09-01

Severe skin and soft tissue infections (SSTIs) frequently require management in the ICU, in part related to associated septic shock or toxic shock syndrome or associated organ failure. Four fundamental management principles are key to a successful outcome in caring for patients who have severe SSTIs, including (1) early diagnosis and differentiation of necrotizing versus nonnecrotizing SSTI, (2) early initiation of appropriate empiric broad-spectrum antimicrobial therapy with consideration of risk factors for specific pathogens and mandatory coverage for methicillin-resistant Staphylococcus aureus (MRSA), (3) source control (ie, early aggressive surgical intervention for drainage of abscesses and debridement of necrotizing soft tissue infections), and (4) pathogen identification and appropriate de-escalation of antimicrobial therapy. MRSA has emerged as the most common identifiable cause of severe SSTIs; therefore, initiation of empiric anti-MRSA antimicrobials is warranted in all cases of severe SSTIs. In addition, appropriate critical care management-including fluid resuscitation, organ support and nutritional support-is a necessary component in treating severe SSTIs.

Group A streptococcal toxic shock syndrome secondary to necrotizing pelvic inflammatory disease in a postmenopausal woman.

PubMed

Paulson, Qiwei; Douglass, Elizabeth; Moreno, Alejandro; Aydelotte, Jayson

2016-01-01

Group A β-hemolytic streptococcus (GAS) is well known to cause upper respiratory tract or cutaneous infections, but some more virulent species of GAS can lead to a rapidly progressive life threatening soft tissue necrotizing infection and streptococcal toxic shock syndrome (STSS). In the modern era, GAS infections within the female reproductive tract leading to STSS are unusual and are often the result of retained products of conception or intrauterine devices. This report describes a case of GAS necrotizing pelvic infection in a previously healthy menopausal woman with no obvious portal of entry. Her clinical course rapidly progressed to septic shock and multiorgan failure. She required multiple surgeries in addition to targeted antimicrobials and aggressive management of shock and organ failures. After a prolonged hospital stay, she had a full recovery.

Necrotizing pancreatitis: challenges and solutions.

PubMed

Bendersky, Victoria A; Mallipeddi, Mohan K; Perez, Alexander; Pappas, Theodore N

2016-01-01

Acute pancreatitis is a common disease that can progress to gland necrosis, which imposes significant risk of morbidity and mortality. In general, the treatment for pancreatitis is a supportive therapy. However, there are several reasons to escalate to surgery or another intervention. This review discusses the pathophysiology as well as medical and interventional management of necrotizing pancreatitis. Current evidence suggests that patients are best served by delaying interventions for at least 4 weeks, draining as a first resort, and debriding recalcitrant tissue using minimally invasive techniques to promote or enhance postoperative recovery while reducing wound-related complications.

Breast milk-derived exosomes promote intestinal epithelial cell growth.

PubMed

Hock, Alison; Miyake, Hiromu; Li, Bo; Lee, Carol; Ermini, Leonardo; Koike, Yuhki; Chen, Yong; Määttänen, Pekka; Zani, Augusto; Pierro, Agostino

2017-05-01

Breast milk administration prevents necrotizing enterocolitis (NEC). However, the mechanism remains unclear. Exosomes are cell-derived vesicles highly present in human milk and regulate intercellular signaling, inflammation, and immune response. We hypothesized that milk-derived exosomes beneficially affect intestinal epithelial cells. Rat milk was collected, and exosomes were isolated using ExoQuick reagent and visualized by Nanoparticle Tracking Analysis. Protein was extracted from encapsulating exosomes, and concentration was measured. 2×10 4 intestinal epithelial cells (IEC-18) were treated for five hours with 0.5-μg/μl exosomes, an equal volume of exosome-free milk, or control solution (PBS). IEC-18 viability was measured using a colorimetric assay (MTT), and gene expression was analyzed by qRT-PCR. Data were compared using one-way ANOVA with Bonferroni post-test. Rat milk was collected, and exosome isolation was confirmed. Compared to control, treatment with exosomes significantly increased IEC viability, proliferation, and stem cell activity (all p<0.05). However, administration of exosome-free milk had less significant effects. Rat milk-derived exosomes promote IEC viability, enhance proliferation, and stimulate intestinal stem cell activity. These findings provide insight into the mechanism of action of breast milk in the intestines. Exosome administration is a promising prevention method for infants at risk of developing NEC when breastfeeding is not tolerated. Copyright © 2017 Elsevier Inc. All rights reserved.

Animal models of ischemia-reperfusion-induced intestinal injury: progress and promise for translational research

PubMed Central

Gonzalez, Liara M.; Moeser, Adam J.

2014-01-01

Research in the field of ischemia-reperfusion injury continues to be plagued by the inability to translate research findings to clinically useful therapies. This may in part relate to the complexity of disease processes that result in intestinal ischemia but may also result from inappropriate research model selection. Research animal models have been integral to the study of ischemia-reperfusion-induced intestinal injury. However, the clinical conditions that compromise intestinal blood flow in clinical patients ranges widely from primary intestinal disease to processes secondary to distant organ failure and generalized systemic disease. Thus models that closely resemble human pathology in clinical conditions as disparate as volvulus, shock, and necrotizing enterocolitis are likely to give the greatest opportunity to understand mechanisms of ischemia that may ultimately translate to patient care. Furthermore, conditions that result in varying levels of ischemia may be further complicated by the reperfusion of blood to tissues that, in some cases, further exacerbates injury. This review assesses animal models of ischemia-reperfusion injury as well as the knowledge that has been derived from each to aid selection of appropriate research models. In addition, a discussion of the future of intestinal ischemia-reperfusion research is provided to place some context on the areas likely to provide the greatest benefit from continued research of ischemia-reperfusion injury. PMID:25414098

Human perinatal immunity in physiological conditions and during infection.

PubMed

van Well, Gijs T J; Daalderop, Leonie A; Wolfs, Tim; Kramer, Boris W

2017-12-01

The intrauterine environment was long considered sterile. However, several infectious threats are already present during fetal life. This review focuses on the postnatal immunological consequences of prenatal exposure to microorganisms and related inflammatory stimuli. Both the innate and adaptive immune systems of the fetus and neonate are immature, which makes them highly susceptible to infections. There is good evidence that prenatal infections are a primary cause of preterm births. Additionally, the association between antenatal inflammation and adverse neonatal outcomes has been well established. The lung, gastrointestinal tract, and skin are exposed to amniotic fluid during pregnancy and are probable targets of infection and subsequent inflammation during pregnancy. We found a large number of studies focusing on prenatal infection and the host response. Intrauterine infection and fetal immune responses are well studied, and we describe clinical data on cellular, cytokine, and humoral responses to different microbial challenges. The link to postnatal immunological effects including immune paralysis and/or excessive immune activation, however, turned out to be much more complicated. We found studies relating prenatal infectious or inflammatory hits to well-known neonatal diseases such as respiratory distress syndrome, bronchopulmonary dysplasia, and necrotizing enterocolitis. Despite these data, a direct link between prenatal hits and postnatal immunological outcome could not be undisputedly established. We did however identify several unresolved topics and propose questions for further research.

Paracetamol versus ibuprofen for the treatment of patent ductus arteriosus in preterm neonates: a meta-analysis of randomized controlled trials.

PubMed

Huang, Xintao; Wang, Fang; Wang, Kai

2018-08-01

Paracetamol has been suggested as an effective treatment for patent ductus arteriosus (PDA). However, the comparative efficacy and safety between paracetamol and ibuprofen were not determined. A meta-analysis of randomized controlled trials (RCTs) was performed. Relevant studies were identified via database searching. A fixed or random effect model was applied depending on the extent of heterogeneity. Five RCTs with 677 neonates were included. The efficacies for the primary (risk ratio [RR]: 1.03, p = .56) and overall PDA closure were comparable between the two medications (RR: 1.02, p = .62). Neonates of the two groups were comparable for the incidence of PDA complications, including necrotizing enterocolitis (RR: 0.86, p = .70), intraventricular hemorrhage (RR: 0.84, p = .55), bronchopulmonary dysplasia (RR: 0.69, p = .16), and retinopathy of prematurity (RR: 0.58, p = .15), and the risks of sepsis (RR = 0.88, p = .48) and death (RR: 1.45, p = .45) within hospitalization. However, treatment with paracetamol was associated with a trend of reduced risk of renal failure (RR: 0.20, p = .07), and a significantly reduced risk of gastrointestinal bleeding (RR: 0.28, p = .009). Paracetamol may confer comparable treatment efficacy for the closure of PDA as ibuprofen, although paracetamol is associated with lower risk of adverse events.

Effect of Digestion and Storage of Human Milk on Free Fatty Acid Concentration and Cytotoxicity

PubMed Central

Penn, Alexander H.; Altshuler, Angelina E.; Small, James W.; Taylor, Sharon F.; Dobkins, Karen R.; Schmid-Schönbein, Geert W.

2014-01-01

Objectives Fat is digested in the intestine into free fatty acids (FFAs), which are detergents and therefore toxic to cells at micromolar concentration. The mucosal barrier protects cells in the adult intestine, but this barrier may not be fully developed in premature infants. Lipase-digested infant formula, but not fresh human milk, has elevated FFAs and is cytotoxic to intestinal cells, and therefore could contribute to intestinal injury in necrotizing enterocolitis (NEC). But even infants exclusively fed breast milk may develop NEC. Our objective was to determine if stored milk and milk from donor milk banks (DM) could also become cytotoxic, especially after digestion. Methods We exposed cultured rat intestinal epithelial cells or human neutrophils to DM and milk collected fresh and stored at 4 or −20 °C for up to 12 weeks and then treated for 2 hours (37°C) with 0.1 or 1 mg/ml pancreatic lipase and/or trypsin and chymotrypsin. Results DM and milk stored 3 days (at 4 or −20 °C) and then digested were cytotoxic. Storage at −20 °C for 8 and 12 weeks resulted in an additional increase in cytotoxicity. Protease digestion decreased, but did not eliminate cell death. Conclusions Current storage practices may allow milk to become cytotoxic and contribute to intestinal damage in NEC. PMID:24840512

Parenteral Fish-Oil Lipid Emulsions in the Prevention of Severe Retinopathy of Prematurity: A Systematic Review and Meta-Analysis.

PubMed

Vayalthrikkovil, Sakeer; Bashir, Rani A; Rabi, Yacov; Amin, Harish; Spence, Jill-Marie; Robertson, Helen Lee; Lodha, Abhay

2017-06-01

Objective  Omega-3 fatty acids are vital for brain and retinal maturation. It is not clear if early use of ω-3 fatty acids in the form of fish-oil lipid emulsions (FLEs) prevents retinopathy of prematurity (ROP) in preterm infants. The aim of this meta-analysis is to evaluate whether early administration of parenteral FLEs reduces ROP requiring laser therapy or severe ROP ≥stage 3 in preterm infants. Methods  A literature search was performed to identify studies comparing parenteral FLEs with soybean-based lipid emulsions (SLEs) in preventing ROP. The main outcome was incidence of severe ROP or ROP requiring laser therapy. Results  Studies met the inclusion criteria (four RCTs and two observational studies). The pooled relative risk of ROP requiring laser therapy or severe ROP ≥ stage 3 in FLEs group was 0.47 [95% CI: 0.24-0.90] and 0.40 [95% CI: 0.22-0.76] in RCTs and observational studies, respectively. FLEs also reduced cholestasis; however, other secondary outcomes of bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), sepsis, intraventricular hemorrhage (IVH), and mortality were similar. Conclusion  The use of FLEs may reduce the incidence of severe ROP or need for laser therapy in preterm infants. A large multicenter RCT is required to confirm this. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Relationship of Assisted Reproductive Technology on Perinatal Outcomes in Triplet Gestations.

PubMed

Shah, Jaimin S; Roman, Tania; Viteri, Oscar A; Haidar, Ziad A; Ontiveros, Alejandra; Sibai, Baha M

2018-06-08

 To assess whether assisted reproductive technology (ART) is associated with increased risk of adverse perinatal outcomes in triplet gestations compared with spontaneous conception.  Secondary analysis of a multicenter randomized trial for the prevention of preterm birth in multiple gestations. Triplets delivered at ≥ 24 weeks were studied. The primary outcome was the rate of composite neonatal morbidity (CNM) that included one or more of the following: bronchopulmonary dysplasia, respiratory distress syndrome, necrotizing enterocolitis, culture proven sepsis, pneumonia, retinopathy of prematurity, intraventricular hemorrhage, periventricular leukomalacia, or perinatal death.  There were 381 triplets (127 women) of which 89 patients conceived via ART and 38 patients spontaneously. Women with ART were more likely to be older, Caucasian, married, nulliparous, have higher level of education, and develop pre-eclampsia. Spontaneously conceived triplets were more likely to delivery at an earlier gestation (31.2 ± 3.5 vs 32.8 ± 2.7 weeks) ( p  = 0.009) with a lower birth weight ( p  < 0.001). After adjusting for confounders, no differences were noted in culture proven sepsis, perinatal death, CNM, respiratory distress syndrome, or Apgar score < 7 at 5 minutes. All remaining perinatal outcomes were similar.  Triplets conceived by ART had similar perinatal outcomes compared with spontaneously conceived triplets. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Individualized fortification of breast milk in 41 Extremely Low Birth Weight (ELBW) preterm infants.

PubMed

Reali, Alessandra; Greco, Francesca; Marongiu, Guido; Deidda, Federica; Atzeni, Simona; Campus, Roberta; Dessì, Angelica; Fanos, Vassilios

2015-12-07

The use of breast milk presents numerous early and long-term advantages for ELBW preterms. However, breast milk without fortification does not cover the high nutritional needs of such patients. The aim of our study was to assess the effect of individualized fortification of breast milk on the growth of ELBWs hospitalized in a neonatal intensive care unit (NICU). Retrospective single-center observational study. We assessed the growth of 41 consecutive ELBWs (21 females, 20 males) with gestational ages between 23 and 30 weeks (mean GA 26.31±1.8) fed with breast milk in an individualized way. The rate of growth as the mean weight increase with breast milk fortification was 16.04±3.13 g/kg/day, more than the growth of the fetus in the uterus (~15 g/kg/day). This result was confirmed also among the ELBWs of lower GA. However, only 24.4% of all the ELBWs at the time of discharge from the NICU presented an appropriate weight for their gestational age. No cases of Necrotizing Enterocolitis (NEC) were observed. Despite high growth velocity, the ELBWs failed to remain in the same percentiles of birth and, at discharge, only 27.7% had a weight of >10 centiles. Further studies are needed to improve growth during early critical phases of development. Copyright © 2015 Elsevier B.V. All rights reserved.

Economic Benefits and Costs of Human Milk Feedings: A Strategy to Reduce the Risk of Prematurity-Related Morbidities in Very-Low-Birth-Weight Infants123

PubMed Central

Johnson, Tricia J.; Patel, Aloka L.; Bigger, Harold R.; Engstrom, Janet L.; Meier, Paula P.

2014-01-01

Infants born at very low birth weight (VLBW; birth weight <1500 g) are at high risk of mortality and are some of the most expensive patients in the hospital. Additionally, VLBW infants are susceptible to prematurity-related morbidities, including late-onset sepsis, bronchopulmonary dysplasia (BPD), necrotizing enterocolitis, and retinopathy of prematurity, which have short- and long-term economic consequences. The incremental cost of these morbidities during the neonatal intensive care unit (NICU) hospitalization is high, ranging from $10,055 (in 2009 US$) for late-onset sepsis to $31,565 for BPD. Human milk has been shown to reduce both the incidence and severity of some of these morbidities and, therefore, has an indirect impact on the cost of the NICU hospitalization. Furthermore, human milk may also directly reduce NICU hospitalization costs, independent of the indirect impact on the incidence and/or severity of these morbidities. Although there is an economic cost to both the mother and institution for providing human milk during the NICU hospitalization, these costs are relatively low. This review describes the total cost of the initial NICU hospitalization, the incremental cost associated with these prematurity-related morbidities, and the incremental benefits and costs of human milk feedings during critical periods of the NICU hospitalization as a strategy to reduce the incidence and severity of these morbidities. PMID:24618763

Research Opportunities to Improve Neonatal Red Blood Cell Transfusion

PubMed Central

Patel, Ravi M.; Meyer, Erin K.; Widness, John A.

2016-01-01

Red blood cell (RBC) transfusion is a common and lifesaving therapy for anemic neonates and infants, particularly among those born prematurely or undergoing surgery. However, evidence-based indications for when to administer RBCs and adverse effects of RBC transfusion on important outcomes including necrotizing enterocolitis, survival and long-term neurodevelopmental impairment remain uncertain. In addition, blood-banking practices for preterm and term neonates and infants have been largely developed using studies from older children and adults. Use of and refinements in emerging technologies and advances in biomarker discovery and neonatal-specific RBC transfusion databases may allow clinicians to better define and tailor RBC transfusion needs and practices to individual neonates. Decreasing the need for RBC transfusion and developing neonatal-specific approaches in the preparation of donor RBCs has potential for reducing resource utilization and cost, improving outcomes, and assuring blood safety. Finally, large donor-recipient linked cohort studies can provide data to better understand the balance of the risks and benefits of RBC transfusion in neonates. These studies may also guide the translation of new research into best practices that can rapidly be integrated into routine care. This review highlights key opportunities in transfusion medicine and neonatology for improving the preparation and transfusion of RBCs into neonates and infants. We focus on timely, currently addressable knowledge gaps that can increase the safety and efficacy of preterm and term neonatal and infant RBC transfusion practices. PMID:27424006

Economic benefits and costs of human milk feedings: a strategy to reduce the risk of prematurity-related morbidities in very-low-birth-weight infants.

PubMed

Johnson, Tricia J; Patel, Aloka L; Bigger, Harold R; Engstrom, Janet L; Meier, Paula P

2014-03-01

Infants born at very low birth weight (VLBW; birth weight <1500 g) are at high risk of mortality and are some of the most expensive patients in the hospital. Additionally, VLBW infants are susceptible to prematurity-related morbidities, including late-onset sepsis, bronchopulmonary dysplasia (BPD), necrotizing enterocolitis, and retinopathy of prematurity, which have short- and long-term economic consequences. The incremental cost of these morbidities during the neonatal intensive care unit (NICU) hospitalization is high, ranging from $10,055 (in 2009 US$) for late-onset sepsis to $31,565 for BPD. Human milk has been shown to reduce both the incidence and severity of some of these morbidities and, therefore, has an indirect impact on the cost of the NICU hospitalization. Furthermore, human milk may also directly reduce NICU hospitalization costs, independent of the indirect impact on the incidence and/or severity of these morbidities. Although there is an economic cost to both the mother and institution for providing human milk during the NICU hospitalization, these costs are relatively low. This review describes the total cost of the initial NICU hospitalization, the incremental cost associated with these prematurity-related morbidities, and the incremental benefits and costs of human milk feedings during critical periods of the NICU hospitalization as a strategy to reduce the incidence and severity of these morbidities.

Placental transfusion in preterm neonates of 30-33 weeks' gestation: a randomized controlled trial.

PubMed

Das, Bikramjit; Sundaram, Venkataseshan; Tarnow-Mordi, William; Ghadge, Alpana; Dhaliwal, Lakhbir Kaur; Kumar, Praveen

2018-02-06

To compare effect of placental transfusion by delayed cord clamping (DCC) or cord milking (CM) with early cord clamping (ECC) on a composite of mortality or abnormal neurological status at 40 weeks' post-menstrual age (PMA) and 24-30 months' chronological age in neonates of 30-33 weeks' gestation. Randomized, controlled trial. A composite of mortality or abnormal neurological status at 40 weeks PMA and survival free of neurodevelopmental abnormalities at 24-30 months' chronological age. A total of 461 neonates were randomized to placental transfusion (n = 233) or to ECC (n = 228). Among those assigned to placental transfusion group, 173 underwent DCC while in the remaining 60, CM was done. Incidence of mortality or abnormal neurological status at 40 weeks PMA (43 (18%) vs 35 (15%), RR (95% CI) 1.2 (0.8, 1.8), p = 0.4) and survival free of neurodevelopmental impairment at 24-30 months of chronological age (99 (47%) vs. 100 (50%); RR (95% CI): 0.9 (0.8, 1.2); P = 0.9) was similar between the study groups. The placental transfusion group showed a trend towards lower incidence of necrotizing enterocolitis. In 30-33 weeks' gestation preterm neonates, placental transfusion as compared to early cord clamping resulted in similar mortality or abnormal neurological status at 40 weeks PMA and at 24-30 months of chronological age.

Perinatal outcomes associated with intrahepatic cholestasis of pregnancy.

PubMed

Herrera, Christina Annette; Manuck, Tracy A; Stoddard, Gregory J; Varner, Michael W; Esplin, Sean; Clark, Erin A S; Silver, Robert M; Eller, Alexandra G

2018-07-01

The objective of this study is to examine perinatal outcomes associated with cholestasis of pregnancy according to bile acid level and antenatal testing practice. Retrospective cohort study of women with symptoms and bile acid testing from 2005 to 2014. Women were stratified by bile acid level: no cholestasis (<10 μmol/L), mild (10-39 μmol/L), moderate (40-99 μmol/L), and severe (≥100 μmol/L). The primary outcome was composite neonatal morbidity (hypoxic ischemic encephalopathy, severe intraventricular hemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis, or death). 785 women were included; 487 had cholestasis (347 mild, 108 moderate, 32 severe) and 298 did not. After controlling for gestational age (GA), severe cholestasis was associated with the composite neonatal outcome (aRR 5.6, 95% CI 1.3-23.5) and meconium-stained fluid (aRR 4.82, 95%CI 1.6-14.2). Bile acid levels were not correlated with the frequency of testing (p = .50). Women who underwent twice weekly testing were delivered earlier (p = .016) than women tested less frequently, but the difference in GA was ≤4 d. Abnormal testing prompting delivery was uncommon. Among women with cholestasis, there were three stillbirths. One of these women was undergoing antenatal testing, which was normal 1 d prior to the fetal demise. Severe cholestasis is associated with neonatal morbidity which antenatal testing may not predict.

Sensitive determination of D-lactic acid and L-lactic acid in urine by high-performance liquid chromatography-tandem mass spectrometry.

PubMed

Henry, H; Marmy Conus, N; Steenhout, P; Béguin, A; Boulat, O

2012-04-01

D-lactic acid in urine originates mainly from bacterial production in the intestinal tract. Increased D-lactate excretion as observed in patients affected by short bowel syndrome or necrotizing enterocolitis reflects D-lactic overproduction. Therefore, there is a need for a reliable and sensitive method able to detect D-lactic acid even at subclinical elevation levels. A new and highly sensitive method for the simultaneous determination of L- and D-lactic acid by a two-step procedure has been developed. This method is based on the concentration of lactic acid enantiomers from urine by supported liquid extraction followed by high-performance liquid chromatography-tandem mass spectrometry. The separation was achieved by the use of an Astec Chirobiotic™ R chiral column under isocratic conditions. The calibration curves were linear over the ranges of 2-400 and 0.5-100 µmol/L respectively for L- and D-lactic acid. The limit of detection of D-lactic acid was 0.125 µmol/L and its limit of quantification was 0.5 µmol/L. The overall accuracy and precision were well within 10% of the nominal values. The developed method is suitable for production of reference values in children and could be applied for accurate routine analysis. Copyright © 2011 John Wiley & Sons, Ltd.

Morbidity and Mortality in Small for Gestational Age Infants at 22 to 29 Weeks' Gestation.

PubMed

Boghossian, Nansi S; Geraci, Marco; Edwards, Erika M; Horbar, Jeffrey D

2018-02-01

To identify the relative risks of mortality and morbidities for small for gestational age (SGA) infants in comparison with non-SGA infants born at 22 to 29 weeks' gestation. Data were collected (2006-2014) on 156 587 infants from 852 US centers participating in the Vermont Oxford Network. We defined SGA as sex-specific birth weight <10th centile for gestational age (GA) in days. Binomial generalized additive models with a thin plate spline term on GA by SGA were used to calculate the adjusted relative risks and 95% confidence intervals for outcomes by GA. Compared with non-SGA infants, the risk of patent ductus arteriosus decreased for SGA infants in early GA and then increased in later GA. SGA infants were also at increased risks of mortality, respiratory distress syndrome, necrotizing enterocolitis, late-onset sepsis, severe retinopathy of prematurity, and chronic lung disease. These risks of adverse outcomes, however, were not homogeneous across the GA range. Early-onset sepsis was not different between the 2 groups for the majority of GAs, although severe intraventricular hemorrhage was decreased among SGA infants for only gestational week 24 through week 25. SGA was associated with additional risks to mortality and morbidities, but the risks differed across the GA range. Copyright © 2018 by the American Academy of Pediatrics.

Improving Growth for Infants ≤1250 Grams Receiving an Exclusive Human Milk Diet.

PubMed

Huston, Robert K; Markell, Andrea M; McCulley, Elizabeth A; Gardiner, Stuart K; Sweeney, Sean L

2018-02-16

An exclusive human milk diet (EHM) fortified with human milk-based fortifier decreases necrotizing enterocolitis (NEC) compared to maternal milk supplemented with preterm formula and bovine fortifier (PTF). Growth has been less with EHM and also maternal milk supplemented with donor human milk and bovine fortifier (HMBF). The objective was to evaluate the effect of a standardized feeding protocol on the growth of infants ≤1250 g birth weight supported with EHM and HMBF. The effect on the incidence of NEC was also evaluated. A retrospective study of growth before and after implementation of a feeding protocol for infants who received either EHM or HMBF. Primary outcomes were weight, length, and head circumference gain velocities from birth to discharge. The incidence of NEC was also recorded. Analysis of covariance for 379 total infants showed that earlier day of life for fortification to 24 Kcal/oz was associated with increased weight gain (p = 0.0166) and length gain (p = 0.0064). Implementation of the feeding protocol was associated with increased head circumference gain (p = 0.006). EHM was associated with decreased incidence of NEC (p = 0.0302). Implementation of a standardized feeding protocol including earlier fortification of maternal milk was associated with improved growth for infants receiving human milk feedings. EHM significantly decreased NEC. Earlier fortification had no effect on NEC. © 2018 American Society for Parenteral and Enteral Nutrition.

Outcomes of Left Ventricular Function According to Treatment Response for a Patent Ductus Arteriosus in Preterm Infants.

PubMed

Kang, Soo Jung; Cho, Young Sun; Hwang, Seo Jung; Kim, Hyo Jin

2017-12-01

To evaluate the outcomes of left ventricular (LV) function according to treatment response for a hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants. Echocardiograms of 21 preterm infants born at gestational age < 31 weeks obtained at term-equivalent age were retrospectively studied. Among preterm infants with a hsPDA, 9 underwent ligation after failure of pharmacological closure (ligation group) and 6 experienced successful pharmacological closure (medication group). Six preterm infants without hsPDA (no-hsPDA group) were studied as controls. LV peak longitudinal systolic strain (ε) of each infant was retrospectively obtained from echocardiograms using velocity vector imaging, along with neonatal outcomes. Pharmacological closures were attempted at postnatal day 2-3. In the ligation group, the median postnatal age at ligation was 20 days. In the ligation group, LV peak longitudinal systolic ε was significantly decreased at term-equivalent age compared to the other groups. Between the medication and no-hsPDA groups, LV peak longitudinal systolic ε did not differ significantly. Among the neonatal outcomes, infants who experienced necrotizing enterocolitis (NEC) showed significantly decreased LV peak longitudinal systolic ε compared to the infants who did not experience NEC . We speculate that in preterm infants with an hsPDA, in cases of medical treatment failure, early PDA ligation at less than 20 days of postnatal age would be beneficial for preserving LV systolic function.

Early neurodevelopmental outcomes of infants with intestinal failure.

PubMed

So, Stephanie; Patterson, Catherine; Gold, Anna; Rogers, Alaine; Kosar, Christina; de Silva, Nicole; Burghardt, Karolina Maria; Avitzur, Yaron; Wales, Paul W

2016-10-01

The survival rate of infants and children with intestinal failure is increasing, necessitating a greater focus on their developmental trajectory. To evaluate neurodevelopmental outcomes in children with intestinal failure at 0-15months corrected age. Analysis of clinical, demographic and developmental assessment results of 33 children followed in an intestinal rehabilitation program between 2011 and 2014. Outcome measures included: Prechtl's Assessment of General Movements, Movement Assessment of Infants, Alberta Infant Motor Scale and Mullen Scales of Early Learning. Clinical factors were correlated with poorer developmental outcomes at 12-15months corrected age. Thirty-three infants (17 males), median gestational age 34weeks (interquartile range 29.5-36.0) with birth weight 1.98kg (interquartile range 1.17-2.50). Twenty-nine (88%) infants had abnormal General Movements. More than half had suspect or abnormal scores on the Alberta Infant Motor Scale and medium to high-risk scores for future neuromotor delay on the Movement Assessment of Infants. Delays were seen across all Mullen subscales, most notably in gross motor skills. Factors significantly associated with poorer outcomes at 12-15months included: prematurity, low birth weight, central nervous system co-morbidity, longer neonatal intensive care admission, necrotizing enterocolitis diagnosis, number of operations and conjugated hyperbilirubinemia. Multiple risk factors contribute to early developmental delay in children with intestinal failure, highlighting the importance of close developmental follow-up. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Appropriate fluid regimens to prevent bronchopulmonary dysplasia.

PubMed

Tammela, O K

1995-01-01

Pulmonary oedema is an important problem in premature neonates with surfactant deficiency because of fluid accumulation in the lung interstitium and reduced urine output. Some retrospective reports suggest that excessive early hydration might increase the risk of bronchopulmonary dysplasia (BPD). Only three prospective studies evaluating low or conventional fluid administration regimens to very low birth weight infants have been published. According to their results no significant differences in the incidence of BPD have been shown. However, fluid restriction seems to improve the outcome of the infants because of decreased incidence of haemodynamically significant patent ductus arteriosus, necrotizing enterocolitis, pulmonary air leaks and decreased mortality. The appropriate amount of sodium in the intravenous fluids during the first days of life needs further evaluation. In tiny infants with birth weights from 500 to 800g intensive monitoring of fluid balance is essential to control the extremely high fluid losses due to evaporation. Undernutrition is a risk factor of BPD and therefore it is important to start parenteral nutrition early. The benefit of the use of colloids as volume expanders is controversial. According to some retrospective reports there might be an association with increased use of colloidal fluids during the first days of life and the development of BPD. Early excessive fluid administration might constitute a potential risk for low birth weight infants with hyaline membrane disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth inhibition of Cronobacter spp. strains in reconstituted powdered infant formula acidified with organic acids supported by natural stomach acidity.

PubMed

Zhu, S; Schnell, S; Fischer, M

2013-09-01

Cronobacter is associated with outbreaks of rare, but life-threatening cases of meningitis, necrotizing enterocolitis, and sepsis in newborns. This study was conducted to determine the effect of organic acids on growth of Cronobacter in laboratory medium and reconstituted powdered infant formula (PIF) as well as the bacteriostatic effect of slightly acidified infant formula when combined with neonatal gastric acidity. Inhibitory effect of seven organic acids on four acid sensitive Cronobacter strains was determined in laboratory medium with broth dilution method at pH 5.0, 5.5 and 6.0. Acetic, butyric and propionic acids were most inhibitive against Cronobacter in the laboratory medium. The killing effect of these three acids was partially buffered in reconstituted PIF. Under neonatal gastric acid condition of pH 5.0, the slightly acidified formula which did not exert inhibition effect solely reduced significantly the Cronobacter populations. A synergistic effect of formula moderately acidified with organic acid combined with the physiological infant gastric acid was visible in preventing the rapid growth of Cronobacter in neonatal stomach. The study contributed to a better understanding of the inhibitory effect of organic acids on Cronobacter growth in different matrixes and provided new ideas in terms of controlling bacteria colonization and translocation by acidified formula. Copyright © 2013 Elsevier Ltd. All rights reserved.

Implementation of an Automatic Stop Order and Initial Antibiotic Exposure in Very Low Birth Weight Infants.

PubMed

Tolia, Veeral N; Desai, Sujata; Qin, Huanying; Rayburn, Polli D; Poon, Grace; Murthy, Karna; Ellsbury, Dan L; Chiruvolu, Arpitha

2017-01-01

Objective  To evaluate if an antibiotic automatic stop order (ASO) changed early antibiotic exposure (use in the first 7 days of life) or clinical outcomes in very low birth weight (VLBW) infants. Study Design  We compared birth characteristics, early antibiotic exposure, morbidity, and mortality data in VLBW infants (with birth weight <= 1500 g) born 2 years before (pre-ASO group, n  = 313) to infants born in the 2 years after (post-ASO, n  = 361) implementation of an ASO guideline. Early antibiotic exposure was quantified by days of therapy (DOT) and antibiotic use > 48 hours. Secondary outcomes included mortality, early mortality, early onset sepsis (EOS), and necrotizing enterocolitis. Results  Birth characteristics were similar between the two groups. We observed reduced median antibiotic exposure (pre-ASO: 6.5 DOT vs. Post-ASO: 4 DOT; p  < 0.001), and a lower percentage of infants with antibiotic use > 48 hours (63.4 vs. 41.3%; p  < 0.001). There were no differences in mortality (12.1 vs 10.2%; p  = 0.44), early mortality, or other reported morbidities. EOS accounted for less than 10% of early antibiotic use. Conclusion  Early antibiotic exposure was reduced after the implementation of an ASO without changes in observed outcomes. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

[Viral cause and management of necrotizing herpetic retinopathies].

PubMed

Tran, T H C; Bodaghi, B; Rozenberg, F; Cassoux, N; Fardeau, C; LeHoang, P

2004-03-01

To study the viral cause and present the management of necrotizing herpetic retinopathies. Charts of patients presenting with acute retinal necrosis (ARN) or progressive outer retinal necrosis (PORN) diagnosed between March 1997 and June 2001 were retrospectively reviewed. Intraocular specimens were obtained in 33 cases to determine the viral cause using polymerase chain reaction-based assays and/or detection of intraocular antibody production. The mean age was 43.4 Years. Herpesvirus genome was identified in 29 patients (80.5%). In the ARN group (32 patients, 38 eyes), herpes simplex virus (HSV) DNA was found in 11 patients (34.4%), varicella-zoster virus (VZV) in nine patients (28.1%), and cytomegalovirus (CMV) in four patients (12.5%). One patient (3.1%) presented an Epstein-Barr virus (EBV) infection. ARN was bilateral at initial examination in six patients and secondary bilateralization was observed in four patients. In the PORN group (four patients, eight eyes), the retinitis was bilateral and VZV DNA was detected in all cases. Two patients were treated with intravenous acyclovir, six with foscarnet alone, ten with intravenous foscarnet + acyclovir, 18 with intravenous foscarnet and intravitreous ganciclovir injections. Complications of necrotizing herpetic retinitis were cataract (26%), optic nerve atrophy (23.9%), and retinal detachment (17.4%). Final visual acuity was less or equal to 20/200 in 47.8% of cases. It is important to determine the specific viral etiology since progression and prognosis may be different in herpetic necrotizing retinitis caused by HSV, VZV, or CMV. Visual prognosis is improved by intensive antiviral therapy, but remains poor if complications occur.

Dens invaginatus with necrotic pulp in a right maxillary lateral incisor with preserved vitality.

PubMed

Alessandro, Lanza; Fabrizio, Di Francesco; Gennaro, De Marco; Dario, Di Stasio; Eugenio, Guidetti; Letizia, Perillo; Luigi, Femiano; Felice, Femiano

2018-01-01

Dens invaginatus (DI) is a dental malformation occurring in several morphologic types. Consequently, treatment of teeth affected by DI can get complicated because of the complex root canal anatomy. The aim is to describe how to manage a rare report of a DI with necrotic pulp held within the vital pulp of a maxillary lateral incisor. Oral fistula was found on the buccal mucosa of the apex of the vital maxillary lateral incisor with a DI having necrotic pulp. Endodontic treatment of the maxillary lateral incisor and of the tract canal of DI was realized. Clinical disappearance of oral sinus tract was observed after 10 days. On the contrary, the disappearance of radiolucent area occurred after 6 months. A proper and prompt diagnosis is necessary to carry out effective prevention protocols or prevent consequences generating nonrecoverable endo-perio diseases.

Necrotizing fasciitis in a patient with type 2 diabetes mellitus.

PubMed

Kanuck, David M; Zgonis, Thomas; Jolly, Gary Peter

2006-01-01

Necrotizing fasciitis is a soft-tissue infection characterized by extensive necrosis of subcutaneous fat, neurovascular structures, and fascia. In general, fascial necrosis precedes muscle and skin involvement, hence its namesake. Initially, this uncommon and rapidly progressive disease process can present as a form of cellulitis or superficial abscess. However, the high morbidity and mortality rates associated with necrotizing fasciitis suggest a more serious, ominous condition. A delay in diagnosis can result in progressive advancement highlighted by widespread infection, multiple-organ involvement, and, ultimately, death. We present a case of limb salvage in a 52-year-old patient with type 2 diabetes mellitus and progressive fascial necrosis. A detailed review of the literature is presented, and current treatment modalities are described. Aggressive surgical debridement, comprehensive medical management of the sepsis and comorbidities, and timely closure of the resultant wound or wounds are essential for a successful outcome.

Antibiotic-Associated Apoptotic Enterocolitis in the Absence of a Defined Pathogen: The Role of Intestinal Microbiota Depletion*

PubMed Central

Wurm, Philipp; Spindelboeck, Walter; Krause, Robert; Plank, Johannes; Fuchs, Gottfried; Bashir, Mina; Petritsch, Wolfgang; Halwachs, Bettina; Langner, Cord; Högenauer, Christoph

2017-01-01

Objective: Antibiotic therapy is a major risk factor for the development of diarrhea and colitis with varying severity. Often the origin of antibiotic-associated gastrointestinal deterioration remains elusive and no specific infectious agents could be discerned. Patients: We represent three cases of intractable high-volume diarrhea associated with combined antibiotic and steroid therapy in critically ill patients not fitting into established disease entities. Cases presented with severe apoptotic enterocolitis resembling acute intestinal graft-versus-host-disease. Microbiologic workup precluded known enteropathogens, but microbiota analysis revealed a severely depleted gut microbiota with concomitant opportunistic pathogen overgrowth. Interventions: Fecal microbiota transplantation, performed in one patient, was associated with correction of dysbiosis, rapid clinical improvement, and healing of enterocolitis. Conclusions: Our series represents a severe form of antibiotic-associated colitis in critically ill patients signified by microbiota depletion, and reestablishment of a physiologic gastrointestinal microbiota might be beneficial for this condition. PMID:28333760

The pathogenesis of Hirschsprung's disease-associated enterocolitis.

PubMed

Austin, Kelly Miller

2012-11-01

Hirschsprung's disease-associated enterocolitis (HAEC) remains the most life-threatening complication in Hirschsprung disease (HD) patients. The pathogenesis of HAEC has not been determined and many hypotheses regarding the etiology of HAEC have been proposed. These include a possible causal relationship between the abnormal enteric nervous system development in HD and the development of enterocolitis. Based on the complex genetic causes of HD that have been discovered and the resultant heterogeneous group of patients that exists, the causes of HAEC are likely multiple. New insights regarding the relationship of the role of the enteric nervous system and its interaction between intestinal barrier function, innate host immunity, and commensal microflora have been discovered, which may shed light on this perplexing problem. This review presents current known risk factors of HAEC and the proposed theories and supporting evidence for the potential etiologies of HAEC. Copyright © 2012. Published by Elsevier Inc.

Development of a Gestational Age-Specific Case Definition for Neonatal Necrotizing Enterocolitis.

PubMed

Battersby, Cheryl; Longford, Nick; Costeloe, Kate; Modi, Neena

2017-03-01

Necrotizing enterocolitis (NEC) is a major cause of neonatal morbidity and mortality. Preventive and therapeutic research, surveillance, and quality improvement initiatives are hindered by variations in case definitions. To develop a gestational age (GA)-specific case definition for NEC. We conducted a prospective 34-month population study using clinician-recorded findings from the UK National Neonatal Research Database between December 2011 and September 2014 across all 163 neonatal units in England. We split study data into model development and validation data sets and categorized GA into groups (group 1, less than 26 weeks' GA; group 2, 26 to less than 30 weeks' GA; group 3, 30 to less than 37 weeks' GA; group 4, 37 or more weeks' GA). We entered GA, birth weight z score, and clinical and abdominal radiography findings as candidate variables in a logistic regression model, performed model fitting 1000 times, averaged the predictions, and used estimates from the fitted model to develop an ordinal NEC score and cut points to develop a dichotomous case definition based on the highest area under the receiver operating characteristic curves [AUCs] and positive predictive values [PPVs]. Abdominal radiography performed to investigate clinical concerns. Ordinal NEC likelihood score, dichotomous case definition, and GA-specific probability plots. Of the 3866 infants, the mean (SD) birth weight was 2049.1 (1941.7) g and mean (SD) GA was 32 (5) weeks; 2032 of 3663 (55.5%) were male. The total included 2978 infants (77.0%) without NEC and 888 (23.0%) with NEC. Infants with NEC in group 1 were less likely to present with pneumatosis (31.1% vs 47.2%; P = .01), blood in stool (11.8% vs 29.6%; P < .001), or mucus in stool (2.1% vs 5.6%; P = .048) but more likely to present with gasless abdominal radiography findings (6.3% vs 0.9%; P = .009) compared with infants with NEC in group 3. In the ordinal NEC score analysis, we allocated 3 points to pneumatosis, 2 points to blood in stool, and 1 point each to abdominal tenderness and abdominal discoloration; 1 point was assigned if 1 or more of pneumoperitoneum, fixed loop, and portal venous gas were present, and 1 point was assigned if both increased and/or bilious aspirates and abdominal distension were present. The cutoff scores for the dichotomous GA-specific case definition were 2 or greater for infants in groups 1 and 2, 3 or greater for infants in group 3, and 4 or greater for infants in group 4. The ordinal NEC score and dichotomous case definition discriminated well between infants with (AUC, 87%) and without (AUC, 80%) NEC. The case definition has a sensitivity of 66.2% (95% CI, 63.0-69.4), a specificity of 94.4% (95% CI, 93.2-95.4), an AUC of 80.0% (95% CI, 79-82), and a PPV of 85.5% (95% CI, 82.6-88.1). Applying the cut points to the 431 infants who underwent a laparotomy yielded a sensitivity of 76.5% (95% CI, 70.0-82.1), a specificity of 74.4% (95% CI, 68.3-80.0), an AUC of 75.0% (95% CI, 71.0- 80.0), and a PPV of 72.9% (95% CI, 66.4-78.7). The risk of NEC and clinical presentation are associated with GA. Adoption of a consistent GA-specific case definition would strengthen global efforts to reduce the population burden of this devastating neonatal disease.

[Food allergy or food intolerance?].

PubMed

Maître, S; Maniu, C-M; Buss, G; Maillard, M H; Spertini, F; Ribi, C

2014-04-16

Adverse food reactions can be classified into two main categories depending on wether an immune mechanism is involved or not. The first category includes immune mediated reactions like IgE mediated food allergy, eosinophilic oesophagitis, food protein-induced enterocolitis syndrome and celiac disease. The second category implies non-immune mediated adverse food reactions, also called food intolerances. Intoxications, pharmacologic reactions, metabolic reactions, physiologic, psychologic or reactions with an unknown mechanism belong to this category. We present a classification of adverse food reactions based on the pathophysiologic mechanism that can be useful for both diagnostic approach and management.

Necrotizing fasciitis: strategies for diagnosis and management.

PubMed

Taviloglu, Korhan; Yanar, Hakan

2007-08-07

Necrotizing fasciitis (NF) is uncommon and difficult to diagnose, and it cause progressive morbidity until the infectious process is diagnosed and treated medically and surgically. The literature addressed NF contains confusing information, inaccurate bacteriologic data, and antiquated antibiotic therapy. A delay in diagnosis is associated with a grave prognosis and increased mortality. The main goal of the clinician must be to establish the diagnosis and initially treat the patient within the standard of care. This review is planned as a guide for the clinician in making an early diagnosis of NF and initiating effective medical and surgical therapy.

Surgical management of necrotizing sialometaplasia of palate.

PubMed

Balaji, S M; Balaji, Preetha

2015-01-01

Necrotizing sialometaplasia (NSM) is a rare benign, inflammatory disease of both major and minor salivary glands, although more commonly reported in the minor glands of the palate. The characteristic clinical presentation can perplex the clinician and may be mistaken for a malignant neoplasm, such as mucoepidermoid carcinoma, as well as invasive squamous cell carcinoma. The clinical and histological similarity between this entity and a malignant lesion may result in unnecessary or mis-treatment. Though clinically mimics malignancy, NSM is considered to be a self-limiting disease, and takes about 3-12 weeks to resolve. Majority of the case resolves itself or by supportive and symptomatic treatment. Surgical intervention is rarely required in NSM except the diagnostic biopsy. Herein we report the clinical, histopathological feature and surgical management of a case of NSM of hard palate in a young adult male.

Necrotizing fasciitis – a diagnostic dilemma: two case reports

PubMed Central

2014-01-01

Introduction Necrotizing soft tissue infections can affect various tissue planes. Although predisposing etiologies are many, they mostly center on impaired immunity occurring directly or indirectly and loss of integrity of protective barriers which predispose to infection. The nonspecific presentation may delay diagnosis and favor high mortality. Case presentation Two case vignettes are presented. The first patient, a 44-year-old healthy South Asian man with a history of repeated minor traumatic injury presented to a primary health care center with a swollen left lower limb. He was treated with antibiotics with an initial diagnosis of cellulitis. Because he deteriorated rapidly and additionally developed intestinal obstruction, he was transferred to our hospital which is a tertiary health care center for further evaluation and management. Prompt clinical diagnosis of necrotizing soft tissue infection was made and confirmed on magnetic resonance imaging as necrotizing fasciitis. Urgent debridement was done, but the already spread infection resulted in rapid clinical deterioration with resultant mortality. The second patient was a 35-year-old South Asian woman with systemic lupus erythematous receiving immunosuppressive therapy who developed left lower limb pain and fever. Medical attention was sought late as she came to the hospital after 4 days. Her condition deteriorated rapidly as she developed septic shock and died within 2 days. Conclusions Necrotizing fasciitis can be fatal when not recognized and without early intervention. Clinicians and surgeons alike should have a greater level of suspicion and appreciation for this uncommon yet lethal infection. PMID:24965382

Prevalence of necrotizing ulcerative gingivitis and associated factors in Koranic boarding schools in Senegal.

PubMed

Diouf, M; Cisse, D; Faye, A; Niang, P; Seck, I; Faye, D; Lo, C M M

2012-06-01

Necrotizing ulcerative gingivitis is the most common clinical syndrome preceding noma. It is found in developing countries and in malnourished children and especially in deprived groups such as children at Koranic boarding schools. The objective of this study was to determine the prevalence of necrotizing ulcerative gingivitis and factors associated with its occurrence in a boarding school population. This was a cross-sectional study of children in Koranic boarding schools in the city of Touba, Senegal. A multistage sampling strategy was used and 8 out of 17 schools were selected. The variables collected were gender, age, oral hygiene habits, duration of residence, presence of ulcerative gingivitis and plaque, and gingival bleeding index. A logistic regression analysis with R software using the manual procedure down was used to identify factors associated with the dependent variables. There were 501 participants and boys made up 92% of the study group. The mean age was 9.3 (sd 4.0) years. The mean of duration residence was 3.4 (sd 1.5) years. The prevalence of necrotizing ulcerative gingivitis was 37% and 81% of children did not use a toothbrush or a chewing-stick. The length of residence, school size, hygiene habits and plaque and bleeding indices were significantly associated with necrotizing gingivitis after adjustment for other variables. It is necessary to develop oral hygiene programs, to establish policies to manage the oral health of children and to improve health and nutrition at Koranic boarding-schools.

Secondary plastic closure of gastroschisis is associated with a lower incidence of mechanical ventilation.

PubMed

Dariel, Anne; Poocharoen, Wannisa; de Silva, Nicole; Pleasants, Hazel; Gerstle, Justin Ted

2015-02-01

Nonsurgical closure after primary silo placement, secondary plastic closure (SPC), has been used as an alternative to secondary surgical closure (SSC) in gastroschisis. The benefits described were closure without formal surgical procedure, cosmetic aspect, and minimization of intra-abdominal pressures. This study compared requirements for mechanical ventilation and general anesthesia, nutritional care, and outcomes between SPC and SSC. We included patients with primary staged-silo reduction with a 1-year minimum follow-up. SPC was performed at bedside with sedation using a nonadherent dressing. SSC was performed in operating room under general anesthesia using standard surgical techniques. This retrospective study included 64 patients, 23 SPC and 41 SSC. The characteristics of the two groups were comparable. Mechanical ventilation was used for 15 SPC and 41 SSC (p=0.0001) with a comparable median duration (5.5 and 6.0 days, not significant [NS]). General anesthesia was required for 9 SPC and 41 SSC (p<0.0001). Complications included one SPC and six SSC with necrotizing enterocolitis, zero SPC and four SSC with intestinal atresia, two SPC and four SSC with small bowel obstruction, zero SPC and one SSC with abdominal compartment syndrome resulting in a short bowel syndrome (NS). Median duration of parenteral nutrition (30 and 27 days), time to first feeds (14 and 14 days), time at or above minimal enteral feeding (22 and 17 days), time to full feeds (31 and 28 days), length of stay (LOS) in neonatal intensive care unit (24 and 23.5 days) and overall hospital LOS (37 and 36 days) were not statistically different between SPC and SSC patients without complications, respectively. These data were comparable for SPC and SSC patients with complications. Five SPC and six SSC developed an umbilical hernia (NS); two patients in each group required a surgical repair (NS). Plastic closure of gastroschisis after primary silo reduction is simple, safe, reproducible, and associated with a significant lower incidence of mechanical ventilation. Nutritional management and length of hospital stay were similar to conventional surgical closure for patients. Plastic closure allows nonoperative management without general anesthesia at patient's bedside, in comparison with surgical closure that must be performed under general anesthesia in the operating room. Plastic closure does not appear to be associated with more umbilical hernias in this retrospective study. Georg Thieme Verlag KG Stuttgart · New York.

Current Concepts in the Management of Necrotizing Fasciitis

PubMed Central

Misiakos, Evangelos P.; Bagias, George; Patapis, Paul; Sotiropoulos, Dimitrios; Kanavidis, Prodromos; Machairas, Anastasios

2014-01-01

Necrotizing fasciitis (NF) is a severe, rare, potentially lethal soft tissue infection that develops in the scrotum and perineum, the abdominal wall, or the extremities. The infection progresses rapidly, and septic shock may ensue; hence, the mortality rate is high (median mortality 32.2%). Prognosis becomes poorer in the presence of co-morbidities, such as diabetes mellitus, immunosuppression, chronic alcohol disease, chronic renal failure, and liver cirrhosis. NF is classified into four types, depending on microbiological findings. Most cases are polymicrobial, classed as type I. The clinical status of the patient varies from erythema, swelling, and tenderness in the early stage to skin ischemia with blisters and bullae in the advanced stage of infection. In its fulminant form, the patient is critically ill with signs and symptoms of severe septic shock and multiple organ dysfunction. The clinical condition is the most important clue for diagnosis. However, in equivocal cases, the diagnosis and severity of the infection can be secured with laboratory-based scoring systems, such as the laboratory risk indicator for necrotizing fasciitis score or Fournier’s gangrene severity index score, especially in regard to Fournier’s gangrene. Computed tomography or ultrasonography can be helpful, but definitive diagnosis is attained by exploratory surgery at the infected sites. Management of the infection begins with broad-spectrum antibiotics, but early and aggressive drainage and meticulous debridement constitute the mainstay of treatment. Postoperative management of the surgical wound is also important for the patient’s survival, along with proper nutrition. The vacuum-assisted closure system has proved to be helpful in wound management, with its combined benefits of continuous cleansing of the wound and the formation of granulation tissue. PMID:25593960

Evaluation of a therapy for Idiopathic Chronic Enterocolitis in rhesus macaques (Macaca mulatta) and linked microbial community correlates

PubMed Central

Baker, Kate; Lauder, Abigail; Kim, Dorothy; Bailey, Aubrey; Wu, Gary D.; Collman, Ronald G.; Doyle-Meyers, Lara; Russell-Lodrigue, Kasi; Blanchard, James; Bushman, Frederic D.; Bohm, Rudolf

2018-01-01

Idiopathic chronic enterocolitis (ICE) is one of the most commonly encountered and difficult to manage diseases of captive rhesus macaques (Macaca mulatta). The etiology is not well understood, but perturbations in gut microbial communities have been implicated. Here we evaluated the effects of a 14-day course of vancomycin, neomycin, and fluconazole on animals affected with ICE, comparing treated, untreated, and healthy animals. We performed microbiome analysis on duodenal and colonic mucosal samples and feces in order to probe bacterial and/or fungal taxa potentially associated with ICE. All treated animals showed a significant and long-lasting improvement in stool consistency over time when compared to untreated and healthy controls. Microbiome analysis revealed trends associating bacterial community composition with ICE, particularly lineages of the Lactobacillaceae family. Sequencing of DNA from macaque food biscuits revealed that fungal sequences recovered from stool were dominated by yeast-derived food additives; in contrast, bacteria in stool appeared to be authentic gut residents. In conclusion, while validation in larger cohorts is needed, the treatment described here was associated with significantly improved clinical signs; results suggested possible correlates of microbiome structure with disease, though no strong associations were detected between single microbes and ICE. PMID:29666764

Proliferative Enterocolitis Associated with Dual Infection with Enteropathogenic Escherichia coli and Lawsonia intracellularis in Rabbits

PubMed Central

Schauer, David B.; McCathey, Sonya N.; Daft, Barbara M.; Jha, Sharda S.; Tatterson, Lisa E.; Taylor, Nancy S.; Fox, James G.

1998-01-01

Both enteropathogenic Escherichia coli (EPEC) and an obligate intracellular bacterium, previously referred to as an intracellular Campylobacter-like organism and now designated Lawsonia intracellularis, have been reported as causes of enterocolitis in rabbits. An outbreak of enterocolitis in a group of rabbits, characterized by an unusually high rate of mortality, was found to be associated with dual infection with EPEC and L. intracellularis. The EPEC strain was found to have eaeA gene homology but was negative for afrA homology. The absence of the afrA gene, which encodes the structural subunit for the AF/R1 pilus, indicates that this rabbit EPEC strain is distinct from the prototypic RDEC-1 strain. This finding suggests that rabbit EPEC strains widely reported in Western Europe, which lack AF/R1 pili, are also present in rabbits in the United States. Dual infection with these two pathogens in rabbits has not been previously reported and may have contributed to the unusually high mortality observed in this outbreak. PMID:9620403

Thrips-transmitted Viruses Infect a Number of Florida Crops

USDA-ARS?s Scientific Manuscript database

The ilarviruses Tomato necrotic streak virus and Tobacco streak virus are present in south Florida. Both species cause economically significant disease in vegetable crop. Control of these viruses makes use of integrated pest management approaches....

Fournier's Gangrene: Current Practices

PubMed Central

Mallikarjuna, M. N.; Vijayakumar, Abhishek; Patil, Vijayraj S.; Shivswamy, B. S.

2012-01-01

Fournier's gangrene is an acute, rapidly progressive, and potentially fatal, infective necrotizing fasciitis affecting the external genitalia, perineal or perianal regions, which commonly affects men, but can also occur in women and children. There has been an increase in number of cases in recent times. Despite advanced management mortality is still high and averages 20–30%. Early diagnosis using Laboratory Risk Indicator for Necrotizing Fasciitis score and stratification of patients into high risk category using Fournier's Gangrene Severity Index score help in early initiation of treatment. Triple antibiotic combined with radical debridement is the mainstay of treatment. There have been many advances in management of Fournier gangrene including use of vaccum assisted closure and hyperbaric oxygen therapy. With introduction of newer devices like Flexi-Seal, fecal diversion can be done, avoiding colostomy. Reconstruction of perineal defects using skin grafts, flaps, and urethral reconstruction using gracilis flaps can reduce the morbidity associated with FG and provide acceptable functional and aesthetic outcomes. PMID:23251819

Older age at diagnosis of Hirschsprung disease decreases risk of postoperative enterocolitis, but resection of additional ganglionated bowel does not.

PubMed

Haricharan, Ramanath N; Seo, Jeong-Meen; Kelly, David R; Mroczek-Musulman, Elizabeth C; Aprahamian, Charles J; Morgan, Traci L; Georgeson, Keith E; Harmon, Carroll M; Saito, Jacqueline M; Barnhart, Douglas C

2008-06-01

This study was conducted to determine the effect of age at diagnosis and length of ganglionated bowel resected on postoperative Hirschsprung-associated enterocolitis (HAEC). Children who underwent endorectal pull-through (ERPT) between January 1993 and December 2004 were retrospectively reviewed. t Test, analysis of variance, Kaplan-Meier, and Cox's proportional hazards analyses were performed. Fifty-two children with Hirschsprung disease (median age, 25 days; range, 2 days-16 years) were included. Nineteen (37%) had admissions for HAEC. Proportional hazards regression showed that HAEC admissions decreased by 30% with each doubling of age at diagnosis (P = .03) and increased 9-fold when postoperative stricture was present (P < .01), after controlling for type of ERPT, trisomy 21, transition zone level, and preoperative enterocolitis. Thirty-six children, with age at initial operation less than 6 months, were grouped based on length of ganglionated bowel excised (A [5 cm] and B [>5 cm]). No significant difference in the number of HAEC admissions during initial 2 years post-ERPT was seen between groups A (n = 18) and B (n = 18). The study had a power of 0.8 to detect a difference of 1 admission over 2 years. Children diagnosed with Hirschsprung disease at younger ages are at a greater risk for postoperative enterocolitis. Excising a longer margin of ganglionated bowel (>5 cm) does not seem to be beneficial in decreasing HAEC admissions.

Orbital compressed air and petroleum injury mimicking necrotizing fasciitis.

PubMed

Mellington, Faye E; Bacon, Annette S; Abu-Bakra, Mohammed A J; Martinez-Devesa, Pablo; Norris, Jonathan H

2014-09-01

Orbital injury secondary to petroleum-based products is rare. We report the first case, to our knowledge, of a combined compressed air and chemical orbital injury, which mimicked necrotizing fasciitis. A 58-year-old man was repairing his motorcycle engine when a piston inadvertently fired, discharging compressed air and petroleum-based carburetor cleaner into his left eye. He developed surgical emphysema, skin necrosis, and a chemical cellulitis, causing an orbital compartment syndrome. He was treated initially with antibiotics and subsequently with intravenous steroid and orbital decompression surgery. There was almost complete recovery by 4 weeks postsurgery. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Petroleum-based products can cause severe skin irritation and necrosis. Compressed air injury can cause surgical emphysema. When these two mechanisms of injury are combined, the resulting orbitopathy and skin necrosis can mimic necrotizing fasciitis and cause diagnostic confusion. A favorable outcome is achievable with aggressive timely management. Copyright © 2014 Elsevier Inc. All rights reserved.

[Lung abscess and necrotizing pneumonia: chest tube insertion or surgery?].

PubMed

Pagès, P-B; Bernard, A

2012-04-01

Lung abscesses and necrotizing pneumonia are rare complications of community-acquired pneumonia since the advent of antibiotics. Their management leans first of all on the antibiotic treatment adapted on the informed germs. However, in 11 to 20% of the cases of lung abscesses, this treatment is insufficient, and drainage, either endoscopic or percutaneous, must be envisaged. In first intention, we shall go to less invasive techniques: endoscopic or percutaneous radio-controlled. In case of failure of these techniques, a percutaneous surgical drainage by minithoracotomy will be performed. In the necrotizing pneumonia, because of the joint obstruction of the bronchus and blood vessels corresponding to a lung segment, the systemic antibiotic treatment will be poor effective. In case of failure of this one we shall propose, a percutaneous surgical drainage, especially if the necrosis limits itself to a single lobe. The surgical treatment will be reserved: in the failures of the strategy of surgical drainage, in the necroses extending in several lobes. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Quantitative Analysis of Periodic Breathing and Very Long Apnea in Preterm Infants

NASA Astrophysics Data System (ADS)

Mohr, Mary A.

Electronic signals from bedside monitors in University of Virginia's Neonatal Intensive Care Unit (NICU) are routinely collected and stored. The overall goal of our research is predictive monitoring: we seek patterns in signals that give early warning of impending pathology. This work focuses on apnea (pauses in regular respiration), and on periodic breathing (regular cycles of breathing and apnea). Our examination of apnea events revealed a disturbing number of cases in which the cessation of breathing lasted at least 60 seconds. These observations were validated, clinical correlations of these events were identified, and a theory was developed that partially explains how they occur. Periodic breathing in neonates is a normal developmental phenomenon. It arises when there is instability in the respiratory control system. A mathematical model of periodic breathing was developed to analyze the stability of the control system in infants. Periodic breathing has long been thought to be benign, however, exaggerated durations of periodic breathing may be an indicator of pathology. Characterization of periodic breathing has previously been limited to short monitoring times in small numbers of infants. An automated system for measurement and characterization of periodic breathing was developed and applied to 5 years of data from the NICU. The amount of periodic breathing that infants had was found to increase with gestational age (up to 32 weeks). Also, times of excessive periodic breathing were recorded and clinical correlations were sought. A significant increase in periodic breathing in the 24 hours before diagnosis of necrotizing enterocolitis was found.

Mucosal injury induced by ischemia and reperfusion in the piglet intestine: Influences of age and feeding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crissinger, K.D.; Granger, D.N.

1989-10-01

The pathogenesis of neonatal necrotizing enterocolitis is unknown, but enteral alimentation, infectious agents, and mesenteric ischemia have been frequently invoked as primary initiators of the disease. To define the vulnerability of the intestinal mucosa to ischemia and reperfusion in the developing piglet, we evaluated changes in mucosal permeability using plasma-to-lumen clearance of chromium 51-labeled ethylenediaminetetraacetic acid in the ileum of anesthetized 1-day-, 3-day-, 2-wk-, and 1-mo-old piglets as a function of (a) duration of intestinal ischemia (20, 40, or 60 min of total superior mesenteric artery occlusion), (b) feeding status (fasted or nursed), and (c) composition of luminal perfusate (balancedmore » salt solution vs. predigested cow milk-based formula). Baseline chromium 51-labeled ethylenediaminetetraacetic acid clearance was not significantly altered by ischemia, irrespective of duration, or feeding in all age groups. However, clearances were significantly elevated during reperfusion after 1 h of total intestinal ischemia in all age groups, whether fasted or fed. Reperfusion-induced increases in clearance did not differ among age groups when the bowel lumen was perfused with a balanced salt solution. However, luminal perfusion with formula resulted in higher clearances in 1-day-old piglets compared with all older animals. Thus, the neonatal intestine appears to be more vulnerable to mucosal injury induced by ischemia and reperfusion in the presence of formula than the intestine of older animals.« less

The Effect of Birth Order on Neonatal Morbidity and Mortality in Very Preterm Twins.

PubMed

Mei-Dan, Elad; Shah, Jyotsna; Lee, Shoo; Shah, Prakesh S; Murphy, Kellie E

2017-07-01

Objective  This retrospective cohort study examined the effect of birth order on neonatal morbidity and mortality in very preterm twins. Study Design  Using 2005 to 2012 data from the Canadian Neonatal Network, very preterm twins born between 24 0/7 and 32 6/7 weeks of gestation were included. Odds of morbidity and mortality of second-born cotwins compared with first-born cotwins were examined by matched-pair analysis. Outcomes were neonatal death, severe brain injury (intraventricular hemorrhage grade 3 or 4 or persistent periventricular echogenicity), bronchopulmonary dysplasia, severe retinopathy of prematurity (ROP) (> stage 2), necrotizing enterocolitis (≥ stage 2), and respiratory distress syndrome (RDS). Multivariable analysis was performed adjusting for confounders. Result  There were 6,636 twins (3,318 pairs) included with a mean gestational age (GA) of 28.9 weeks. A higher rate of small for GA occurred in second-born twins (10 vs. 6%). Mortality was significantly lower for second-born twins (4.3 vs. 5.3%; adjusted odds ratio: 0.75; 95% confidence interval [CI]: 0.59-0.95). RDS (66 vs. 60%; adjusted odds ratio: 1.40; 95% CI: 1.29-1.52) and severe retinopathy (9 vs. 7%; adjusted odds ratio: 1.46; 95% CI: 1.07-2.01) were significantly higher in second-born twins. Conclusion  Thus, while second-born twins had reduced odds of mortality, they also had increased odds of RDS and ROP. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Volvulus without malposition--a single-center experience.

PubMed

Kargl, Simon; Wagner, Oliver; Pumberger, Wolfgang

2015-01-01

This is a single-center case series about the rare condition of volvulus without malposition and/or malrotation (VWM) in preterm babies. We focus on diagnostic difficulties, and our results should help to distinguish VWM as a distinct entity different from classical volvulus and segmental volvulus. Medical chart review of infants with VWM from 2003-2012 was used. A total of 15 patients were identified. All of them had volvulus in the absence of intestinal malposition or other associated intestinal pathologies. All patients were born prematurely. Emergency laparotomy was necessary in all 15 patients. Two groups were identified. Group 1 includes four patients with typical signs of meconium obstruction of prematurity (MOP). Small bowel resection was only necessary in one of these four patients, all survived without residual intestinal lesions. Group 2 consists of 11 patients without signs of MOP-small bowel resection and temporary enterostomy were necessary in all these children. Four patients presented with pneumatosis intestinalis on the abdominal plain film, suggesting necrotizing enterocolitis. Although two infants died, the survivors showed complete recovery. VWM is a distinct disease of prematurity. When associated with MOP, VWM has a favorable outcome of treatment. In contrast, VWM occurring in the absence of signs of meconium obstruction requires small bowel resection. VWM primarily affects the top of the midgut (ileum). Because of absent malposition, presentation of VWM may be uncharacteristic. Pneumatosis intestinalis in advanced VWM may lead to diagnostic difficulties and a delay in treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

Role of Insulinlike Growth Factor 1 in Fetal Development and in the Early Postnatal Life of Premature Infants

PubMed Central

Hellström, Ann; Ley, David; Hansen-Pupp, Ingrid; Hallberg, Boubou; Ramenghi, Luca A.; Löfqvist, Chatarina; Smith, Lois E. H.; Hård, Anna-Lena

2018-01-01

The neonatal period of very preterm infants is often characterized by a difficult adjustment to extrauterine life, with an inadequate nutrient supply and insufficient levels of growth factors, resulting in poor growth and a high morbidity rate. Long-term multisystem complications include cognitive, behavioral, and motor dysfunction as a result of brain damage as well as visual and hearing deficits and metabolic disorders that persist into adulthood. Insulinlike growth factor 1 (IGF-1) is a major regulator of fetal growth and development of most organs especially the central nervous system including the retina. Glucose metabolism in the developing brain is controlled by IGF-1 which also stimulates differentiation and prevents apoptosis. Serum concentrations of IGF-1 decrease to very low levels after very preterm birth and remain low for most of the perinatal development. Strong correlations have been found between low neonatal serum concentrations of IGF-1 and poor brain and retinal growth as well as poor general growth with multiorgan morbidities, such as intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, and necrotizing enterocolitis. Experimental and clinical studies indicate that early supplementation with IGF-1 can improve growth in catabolic states and reduce brain injury after hypoxic/ischemic events. A multicenter phase II study is currently underway to determine whether intravenous replacement of human recombinant IGF-1 up to normal intrauterine serum concentrations can improve growth and development and reduce prematurity-associated morbidities. PMID:27603537

[Effect of oral administration of probiotics on intestinal colonization with drug-resistant bacteria in preterm infants].

PubMed

Hua, Xin-Tian; Tang, Jun; Mu, De-Zhi

2014-06-01

To evaluate the effect of oral administration of probiotics on intestinal colonization with drug-resistant bacteria among preterm infants in the neonatal intensive care unit (NICU). A double-blind, randomized, placebo-controlled trial was carried out in the preterm infants who were transferred to the NICU immediately after birth. These infants were stratified by whether they were breastfed and then randomized into test group and control group. The test group was given probiotics from the day when enteral feeding began, while the control group was treated conventionally without probiotics. The two groups were compared in terms of the colonization with extended-spectrum beta-lactamase-producing bacteria, as assessed by rectal swabs on days 1, 3, 7, and 14 after birth, and the incidence of diseases. Rectal colonization with drug-resistant bacteria was found in the test group (n=119) and control group (n=138) on days 1, 3, 7, and 14 after birth. There were no significant differences in the incidence of late-onset sepsis and necrotizing enterocolitis between the two groups (P>0.05). Among non-breastfed infants, the test group had significantly decreased rectal colonization with drug-resistant bacteria compared with the control group on day 14 after birth (71.1% vs 88.9%; P=0.04). No probiotic-related adverse events were observed in the study. Oral administration of probiotics may reduce rectal colonization with drug-resistant bacteria in preterm infants under certain conditions and shows good safety.

A point prevalence survey of health care-associated infections in Canadian pediatric inpatients.

PubMed

Rutledge-Taylor, Katie; Matlow, Anne; Gravel, Denise; Embree, Joanne; Le Saux, Nicole; Johnston, Lynn; Suh, Kathryn; Embil, John; Henderson, Elizabeth; John, Michael; Roth, Virginia; Wong, Alice; Shurgold, Jayson; Taylor, Geoff

2012-08-01

Health care-associated infections (HAIs) cause considerable morbidity and mortality to hospitalized patients. The objective of this point prevalence study was to assess the burden of HAIs in the Canadian pediatric population, updating results reported from a similar study conducted in 2002. A point prevalence survey of pediatric inpatients was conducted in February 2009 in 30 pediatric or combined adult/pediatric hospitals. Data pertaining to one 24-hour period were collected, including information on HAIs, microorganisms isolated, antimicrobials prescribed, and use of additional (transmission based) precautions. The following prevalent infections were included: pneumonia, urinary tract infection, bloodstream infection, surgical site infection, viral respiratory infection, Clostridium difficile infection, viral gastroenteritis, and necrotizing enterocolitis. One hundred eighteen patients had 1 or more HAI, corresponding to a prevalence of 8.7% (n = 118 of 1353, 95% confidence interval: 7.2-10.2). Six patients had 2 infections. Bloodstream infections were the most frequent infection in neonates (3.0%), infants (3.1%), and children (3.5%). Among all patients surveyed, 16.3% were on additional precautions, and 40.1% were on antimicrobial agents, whereas 40.7% of patients with a HAI were on additional precautions, and 89.0% were on antimicrobial agents. Overall prevalence of HAI in 2009 has remained similar to the prevalence reported from 2002. The unchanged prevalence of these infections nonetheless warrants continued vigilance on their prevention and control. Copyright © 2012 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.

Birth at 22 gestational weeks: case report of cognitive resilience.

PubMed

Hopp, Crista A; Baron, Ida Sue

2017-02-01

Children delivered at the edge of viability are at greatest risk of medical and neuropsychological disability, their adverse outcomes overshadowing extremely preterm survivors with more optimal outcomes. We aimed to describe an exceptionally early-born extremely preterm (EEEP) preschooler whose neurobiological, familial, and socioeconomic factors likely influenced her unexpected cognitive resilience. Baby G was a 3-years 10-months-old, English-speaking, Caucasian, singleton girl born weighing 435 g at 22 5/7  weeks' gestation to well-educated married parents. Neonatal complications of extremely premature birth included sepsis, severe respiratory distress syndrome, patent ductus arteriosus requiring ligation, necrotizing enterocolitis not requiring surgical intervention, and retinopathy of prematurity. Intellectual and neuropsychological testing was administered. Baby G performed age-appropriately in nearly all domains and did not exhibit intellectual deficits. Her general conceptual ability was above average for both her chronological and adjusted ages. She had below average performance on tests of motor function, working memory, and delayed recall of spatial locations. Standardized parental behavioral questionnaires indicated no concern in emotional or attentional functioning except in relation to mental shifting capacity and signs of anxiety. Report of persistent adverse neurodevelopmental/neuropsychological disabilities following EEEP birth is a counterpoint to the more optimal outcomes in some vulnerable EEEP survivors. This case emphasizes that decisions about aggressive resuscitation and prognostication for infants born EEEP may be enhanced by consideration of individual variability, and of pertinent medical, socioeconomic, and sociodemographic variables that may be more predictive of neuropsychological outcomes than birth weight and gestational age.

The ELGAN study of the brain and related disorders in extremely low gestational age newborns.

PubMed

O'Shea, T M; Allred, E N; Dammann, O; Hirtz, D; Kuban, K C K; Paneth, N; Leviton, A

2009-11-01

Extremely low gestational age newborns (ELGANs) are at increased risk for structural and functional brain abnormalities. To identify factors that contribute to brain damage in ELGANs. Multi-center cohort study. We enrolled 1506 ELGANs born before 28 weeks gestation at 14 sites; 1201 (80%) survived to 2 years corrected age. Information about exposures and characteristics was collected by maternal interview, from chart review, microbiologic and histological examination of placentas, and measurement of proteins in umbilical cord and early postnatal blood spots. Indicators of white matter damage, i.e. ventriculomegaly and echolucent lesions, on protocol cranial ultrasound scans; head circumference and developmental outcomes at 24 months adjusted age, i.e., cerebral palsy, mental and motor scales of the Bayley Scales of Infant Development, and a screen for autism spectrum disorders. ELGAN Study publications thus far provide evidence that the following are associated with ultrasongraphically detected white matter damage, cerebral palsy, or both: preterm delivery attributed to preterm labor, prelabor premature rupture of membranes, or cervical insufficiency; recovery of microorganisms in the placenta parenchyma, including species categorized as human skin microflora; histological evidence of placental inflammation; lower gestational age at delivery; greater neonatal illness severity; severe chronic lung disease; neonatal bacteremia; and necrotizing enterocolitis. In addition to supporting a potential role for many previously identified antecedents of brain damage in ELGANs, our study is the first to provide strong evidence that brain damage in extremely preterm infants is associated with microorganisms in placenta parenchyma.

Segmental pancreatic allograft survival in baboons treated with combined irradiation and cyclosporine: a preliminary report

DOE Office of Scientific and Technical Information (OSTI.GOV)

du Toit, D.F.; Heydenrych, J.J.; Smit, B.

1985-04-01

The present study was undertaken to evaluate the effectiveness of cyclosporine (CS) alone, total lymphoid irradiation (TLI) alone, and CS in combination with total body irradiation (TBI) in suppressing segmental pancreatic allograft rejection in totally pancreatectomized outbred chacma baboons. The administration of CS 25 mg/kg/day and 50 mg/ kg/day resulted in mean graft survival of 21.5 days and 24.5 days, respectively. CS 85 mg/kg/day resulted in median graft survival of 9 days. There was a wide daily fluctuation of CS serum trough levels exhibited between primates receiving the same oral dose. TBI in excess of 300 rads resulted in irreversiblemore » bone marrow suppression. Modest results were achieved in recipients of TBI-76 rads (38 x 2 rads), with median graft survival of 21 days, results not different from recipients treated with CS. TLI recipients of 600 rads (150 x 4 rads) resulted in median pancreatic graft survival of 16 days. TBI together with oral CS administration exhibited no synergistic or additive effect and a single peroperative donor-specific blood transfusion did not enhance pancreatic allograft survival in this model. However, of 10 primates receiving TBI 100 rads (50 x 2 rads) and CS 25 mg/kg/day administered orally indefinitely, four remained normoglycemic for more than 60 days. TBI 100 rads (50 x 2 rads) together with oral and parenteral CS resulted in necrotizing enterocolitis in four of six recipients.« less

Transforming growth factor-β2 is sequestered in preterm human milk by chondroitin sulfate proteoglycans

PubMed Central

Namachivayam, Kopperuncholan; Coffing, Hayley P.; Sankaranarayanan, Nehru Viji; Jin, Yingzi; MohanKumar, Krishnan; Frost, Brandy L.; Blanco, Cynthia L.; Patel, Aloka L.; Meier, Paula P.; Garzon, Steven A.; Desai, Umesh R.

2015-01-01

Human milk contains biologically important amounts of transforming growth factor-β2 isoform (TGF-β2), which is presumed to protect against inflammatory gut mucosal injury in the neonate. In preclinical models, enterally administered TGF-β2 can protect against experimental necrotizing enterocolitis, an inflammatory bowel necrosis of premature infants. In this study, we investigated whether TGF-β bioactivity in human preterm milk could be enhanced for therapeutic purposes by adding recombinant TGF-β2 (rTGF-β2) to milk prior to feeding. Milk-borne TGF-β bioactivity was measured by established luciferase reporter assays. Molecular interactions of TGF-β2 were investigated by nondenaturing gel electrophoresis and immunoblots, computational molecular modeling, and affinity capillary electrophoresis. Addition of rTGF-β2 (20–40 nM) to human preterm milk samples failed to increase TGF-β bioactivity in milk. Milk-borne TGF-β2 was bound to chondroitin sulfate (CS) containing proteoglycan(s) such as biglycan, which are expressed in high concentrations in milk. Chondroitinase treatment of milk increased the bioactivity of both endogenous and rTGF-β2, and consequently, enhanced the ability of preterm milk to suppress LPS-induced NF-κB activation in macrophages. These findings provide a mechanism for the normally low bioavailability of milk-borne TGF-β2 and identify chondroitinase digestion of milk as a potential therapeutic strategy to enhance the anti-inflammatory effects of preterm milk. PMID:26045614

Survival and morbidity outcomes for very low birth weight infants with Down syndrome.

PubMed

Boghossian, Nansi S; Hansen, Nellie I; Bell, Edward F; Stoll, Barbara J; Murray, Jeffrey C; Laptook, Abbot R; Shankaran, Seetha; Walsh, Michele C; Das, Abhik; Higgins, Rosemary D

2010-12-01

Our objective was to compare survival and neonatal morbidity rates between very low birth weight (VLBW) infants with Down syndrome (DS) and VLBW infants with non-DS chromosomal anomalies, nonchromosomal birth defects (BDs), and no chromosomal anomaly or major BD. Data were collected prospectively for infants weighing 401 to 1500 g who were born and/or cared for at one of the study centers participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network in 1994-2008. Risk of death and morbidities, including patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC), late-onset sepsis (LOS), retinopathy of prematurity, and bronchopulmonary dysplasia (BPD), were compared between VLBW infants with DS and infants in the other groups. Infants with DS were at increased risk of death (adjusted relative risk: 2.47 [95% confidence interval: 2.00-3.07]), PDA, NEC, LOS, and BPD, relative to infants with no BDs. Decreased risk of death (relative risk: 0.40 [95% confidence interval: 0.31-0.52]) and increased risks of NEC and LOS were observed when infants with DS were compared with infants with other non-DS chromosomal anomalies. Relative to infants with nonchromosomal BDs, infants with DS were at increased risk of PDA and NEC. The increased risk of morbidities among VLBW infants with DS provides useful information for counseling parents and for anticipating the need for enhanced surveillance for prevention of these morbidities.

Improved survival and neurodevelopmental outcomes among extremely premature infants born near the limit of viability.

PubMed

Younge, Noelle; Smith, P Brian; Gustafson, Kathryn E; Malcolm, William; Ashley, Patricia; Cotten, C Michael; Goldberg, Ronald N; Goldstein, Ricki F

2016-04-01

Infants born near the limit of viability are at high risk for death or adverse neurodevelopmental outcomes. It is unclear whether these outcomes have improved over the past 15 years. To determine if death and neurodevelopmental impairment have declined over the past 15 years in infants born at 22 to 24 weeks' gestation. Retrospective cohort study. We identified infants born at 22 to 24 weeks' gestation in our center in two epochs: 1998-2004 (Epoch 1) and 2005-2011 (Epoch 2). The primary outcome, death or neurodevelopmental impairment, was evaluated at 17-25 months' corrected gestational age with neurologic exams and Bayley Scales of Infant Development. Perinatal characteristics, major morbidities, and outcomes were compared between epochs. Birth weight and gestational age were similar between 170 infants in Epoch 1 and 187 infants in Epoch 2. Mortality was significantly lower in Epoch 2, 55% vs. 42% (p=0.02). Among surviving infants, late-onset sepsis (p<0.01), bronchopulmonary dysplasia (p<0.01), and surgical necrotizing enterocolitis (p=0.04) were less common in Epoch 2. Neurodevelopmental impairment among surviving infants declined from 68% in Epoch 1 to 47% in Epoch 2, p=0.02. Odds of death or NDI were significantly lower in Epoch 2 vs. Epoch 1, OR=0.31 (95% confidence interval; 0.16, 0.58). Risk of death or neurodevelopmental impairment decreased over time in infants born at 22 to 24 weeks' gestation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

How I transfuse red blood cells and platelets to infants with the anemia and thrombocytopenia of prematurity

PubMed Central

Strauss, Ronald G.

2010-01-01

Many aspects of hematopoiesis are either incompletely developed in preterm infants or still functioning to serve the fetus (i.e., the intrauterine counterpart to a liveborn preterm neonate). This delayed development and/or slow adaptation to extrauterine life diminishes the capacity of the neonate to produce red blood cells (RBCs), platelets (PLTs), and neutrophils—particularly during the stress of life-threatening illnesses encountered after preterm birth such as sepsis, severe pulmonary dysfunction, necrotizing enterocolitis, and immune cytopenias. The serious medical and/or surgical problems of preterm birth can be further complicated by phlebotomy blood losses, bleeding, hemolysis, and consumptive coagulopathy. To illustrate, some preterm infants, especially those with birth weight less than 1.0 kg and respiratory distress, are given numerous RBC transfusions early in life owing to several interacting factors. Neonates delivered before 28 weeks of gestation (birth weight, <1.0 kg) are born before the bulk of iron transport has occurred from mother to fetus via the placenta and before the onset of marked erythropoietic activity of fetal marrow during the third trimester. Soon after preterm birth, severe respiratory disease can lead to repeated blood sampling for laboratory studies and, consequently, to replacement RBC transfusions. Additionally, preterm infants are unable to mount an effective erythropoietin (EPO) response to decreasing numbers of RBCs, and this factor contributes to the diminished ability to compensate for anemia—thus enhancing need for RBC transfusions. PMID:18194380

Impact of Intended Mode of Delivery on Outcomes in Preterm Growth-Restricted Fetuses.

PubMed

Baalbaki, Sima H; Kuper, Spencer G; Wang, Michelle J; Steele, Robin A; Biggio, Joseph R; Harper, Lorie M

2018-06-01

 Scheduled cesarean is frequently performed for fetal growth restriction due to concerns for fetal intolerance of labor.  We compared neonatal outcomes in preterm growth-restricted fetuses by intended mode of delivery.  We performed a retrospective cohort study of indicated preterm births with prenatally diagnosed growth restriction from 2011 to 2014 at a single institution. Patients were classified by intended mode of delivery. The primary outcome was a composite of adverse neonatal outcomes, including perinatal death, cord blood acidemia, chest compressions during neonatal resuscitation, seizures, culture-proven sepsis, necrotizing enterocolitis, and grade III-IV intraventricular hemorrhage. Secondary analysis was performed examining the impact of umbilical artery Dopplers.  Of 101 fetuses with growth restriction, 75 underwent planned cesarean deliveries. Of those induced, 46.2% delivered vaginally. Delivery by scheduled cesarean was not associated with a decreased risk of the composite outcome (adjusted odds ratio [aOR], 1.61; 95% confidence interval [CI], 0.45-5.78), even when only those with abnormal umbilical artery Dopplers were considered (aOR, 2.8; 95% CI, 0.40-20.2).  In this cohort, planned cesarean was not associated with a reduction in neonatal morbidity, even when considering only those with abnormal umbilical artery Dopplers. In otherwise appropriate candidates for vaginal delivery, fetal growth restriction should not be considered a contraindication to trial of labor. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Outcomes of Medically Indicated Preterm Births Differ by Indication.

PubMed

Wang, Michelle J; Kuper, Spencer G; Steele, Robin; Sievert, Rachel A; Tita, Alan T; Harper, Lorie M

2018-07-01

 We aim to examine whether outcomes of preterm birth (PTB) are further modified by the indication for delivery.  We performed a retrospective cohort study of all singletons delivered at 23 to 34 weeks from 2011 to 2014. Women were classified by their primary indication for delivery: maternal (preeclampsia) or fetal/obstetric (growth restriction, nonreassuring fetal status, and vaginal bleeding). The primary neonatal outcome was a composite of neonatal death, cord pH <7 or base excess < - 12, 5-minute Apgar ≤3, C-reactive protein during resuscitation, culture-proven sepsis, intraventricular hemorrhage, and necrotizing enterocolitis. Secondary outcomes included the individual components of the primary outcome. Groups were compared using Student's t -test and chi-squared tests. Logistic regression was used to adjust for confounding variables.  Of 528 women, 395 (74.8%) were delivered for maternal and 133 (25.2%) for fetal/obstetric indications. Compared with those delivered for a maternal indication, those with a fetal/obstetric indication for delivery had an increased risk of the composite neonatal outcome (adjusted odds ratio [AOR]: 1.9, 95% confidence interval [CI]: 1.13-3.21) and acidemia at birth (AOR: 4.2, 95% CI: 1.89-9.55).  Preterm infants delivered for fetal/obstetric indications have worsened outcomes compared with those delivered for maternal indications. Additional research is needed to further tailor counseling specific to the indication for delivery. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Probiotic Supplementation in Preterm Infants Does Not Affect the Risk of Bronchopulmonary Dysplasia: A Meta-Analysis of Randomized Controlled Trials

PubMed Central

Mosca, Fabio; Kramer, Boris

2017-01-01

Probiotic supplementation reduces the risk of necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) in preterm infants, but it remains to be determined whether this reduction translates into a reduction of other complications. We conducted a systematic review and meta-analysis to evaluate the possible role of probiotics in altering the risk of bronchopulmonary dysplasia (BPD). Fifteen randomized controlled trials (4782 infants; probiotics: 2406) were included. None of the included studies assessed BPD as the primary outcome. Meta-analysis confirmed a significant reduction of NEC (risk ratio (RR) 0.52, 95% confidence interval (CI) 0.33 to 0.81, p = 0.004; random effects model), and an almost significant reduction of LOS (RR 0.82, 95% CI 0.65 to 1.03, p = 0.084). In contrast, meta-analysis could not demonstrate a significant effect of probiotics on BPD, defined either as oxygen dependency at 28 days of life (RR 1.01, 95% CI 0.91 to 1.11, p = 0.900, 6 studies) or at 36 weeks of postmenstrual age (RR 1.07, 95% CI 0.96 to 1.20, p = 0.203, 12 studies). Meta-regression did not show any significant association between the RR for NEC or LOS and the RR for BPD. In conclusion, our results suggest that NEC and LOS prevention by probiotics does not affect the risk of developing BPD in preterm infants. PMID:29088103

Impact of iron and vitamin C-containing supplements on preterm human milk: in vitro.

PubMed

Friel, James K; Diehl-Jones, William L; Suh, Miyoung; Tsopmo, Apollinaire; Shirwadkar, Vaibhav P

2007-05-15

Stress due to reactive oxygen species (ROS) may lead to neonatal diseases, such as necrotizing enterocolitis and respiratory distress. Enteral supplements for premature infants (PREM) added to human milk (HM) to increase nutrient content may induce lipid oxidation due to free radical formation via Fenton chemistry. We hypothesized that ferrous iron and vitamin C-containing supplements added to HM in vitro cause oxidation of milk fats, affect intracellular redox balance, and induce DNA damage. Lipid peroxidation in HM was measured by FOX-2 and TBARS assays; fatty acid composition of supplemented HM was measured by gas chromatography. Two cell culture bioassays were used for assessing either intracellular oxidative stress or DNA damage: the former involved Caco-2BBe cells, a secondary differentiated cell line, and the latter utilized FHS-74 Int cells, a primary fetal small intestinal culture. Lipid oxidation products of HM increased after the addition of iron alone, iron and vitamin C, or iron and a vitamin C-containing supplement (Trivisol, TVS). A reduced content of mono and polyunsaturated fatty acids in HM was also observed. Iron, not iron+vitamin C, but iron+TVS induced significant intracellular oxidative stress in FHS-74 Int cells. In contrast, iron, either alone or in combination with TVS or vitamin C, increased DNA damage in Caco-2BBE cells. Iron supplementation may increase oxidative stress in PREM infants and should be given separately from vitamin C-containing supplements.

Identification and Characterization of Cronobacter Iron Acquisition Systems

PubMed Central

Grim, C. J.; Kothary, M. H.; Gopinath, G.; Jarvis, K. G.; Beaubrun, J. Jean-Gilles; McClelland, M.; Tall, B. D.

2012-01-01

Cronobacter spp. are emerging pathogens that cause severe infantile meningitis, septicemia, or necrotizing enterocolitis. Contaminated powdered infant formula has been implicated as the source of Cronobacter spp. in most cases, but questions still remain regarding the natural habitat and virulence potential for each strain. The iron acquisition systems in 231 Cronobacter strains isolated from different sources were identified and characterized. All Cronobacter spp. have both the Feo and Efe systems for acquisition of ferrous iron, and all plasmid-harboring strains (98%) have the aerobactin-like siderophore, cronobactin, for transport of ferric iron. All Cronobacter spp. have the genes encoding an enterobactin-like siderophore, although it was not functional under the conditions tested. Furthermore, all Cronobacter spp. have genes encoding five receptors for heterologous siderophores. A ferric dicitrate transport system (fec system) is encoded specifically by a subset of Cronobacter sakazakii and C. malonaticus strains, of which a high percentage were isolated from clinical samples. Phylogenetic analysis confirmed that the fec system is most closely related to orthologous genes present in human-pathogenic bacterial strains. Moreover, all strains of C. dublinensis and C. muytjensii encode two receptors, FcuA and Fct, for heterologous siderophores produced by plant pathogens. Identification of putative Fur boxes and expression of the genes under iron-depleted conditions revealed which genes and operons are components of the Fur regulon. Taken together, these results support the proposition that C. sakazakii and C. malonaticus may be more associated with the human host and C. dublinensis and C. muytjensii with plants. PMID:22706064

Hospitalized Premature Infants Are Colonized by Related Bacterial Strains with Distinct Proteomic Profiles

PubMed Central

Xiong, Weili; Olm, Matthew R.; Thomas, Brian C.; Baker, Robyn; Firek, Brian; Morowitz, Michael J.; Hettich, Robert L.

2018-01-01

ABSTRACT During the first weeks of life, microbial colonization of the gut impacts human immune system maturation and other developmental processes. In premature infants, aberrant colonization has been implicated in the onset of necrotizing enterocolitis (NEC), a life-threatening intestinal disease. To study the premature infant gut colonization process, genome-resolved metagenomics was conducted on 343 fecal samples collected during the first 3 months of life from 35 premature infants housed in a neonatal intensive care unit, 14 of whom developed NEC, and metaproteomic measurements were made on 87 samples. Microbial community composition and proteomic profiles remained relatively stable on the time scale of a week, but the proteome was more variable. Although genetically similar organisms colonized many infants, most infants were colonized by distinct strains with metabolic profiles that could be distinguished using metaproteomics. Microbiome composition correlated with infant, antibiotics administration, and NEC diagnosis. Communities were found to cluster into seven primary types, and community type switched within infants, sometimes multiple times. Interestingly, some communities sampled from the same infant at subsequent time points clustered with those of other infants. In some cases, switches preceded onset of NEC; however, no species or community type could account for NEC across the majority of infants. In addition to a correlation of protein abundances with organism replication rates, we found that organism proteomes correlated with overall community composition. Thus, this genome-resolved proteomics study demonstrated that the contributions of individual organisms to microbiome development depend on microbial community context. PMID:29636439

Human milk oligosaccharides: every baby needs a sugar mama.

PubMed

Bode, Lars

2012-09-01

Human milk oligosaccharides (HMOs) are a family of structurally diverse unconjugated glycans that are highly abundant in and unique to human milk. Originally, HMOs were discovered as a prebiotic "bifidus factor" that serves as a metabolic substrate for desired bacteria and shapes an intestinal microbiota composition with health benefits for the breast-fed neonate. Today, HMOs are known to be more than just "food for bugs". An accumulating body of evidence suggests that HMOs are antiadhesive antimicrobials that serve as soluble decoy receptors, prevent pathogen attachment to infant mucosal surfaces and lower the risk for viral, bacterial and protozoan parasite infections. In addition, HMOs may modulate epithelial and immune cell responses, reduce excessive mucosal leukocyte infiltration and activation, lower the risk for necrotizing enterocolitis and provide the infant with sialic acid as a potentially essential nutrient for brain development and cognition. Most data, however, stem from in vitro, ex vivo or animal studies and occasionally from association studies in mother-infant cohorts. Powered, randomized and controlled intervention studies will be needed to confirm relevance for human neonates. The first part of this review introduces the pioneers in HMO research, outlines HMO structural diversity and describes what is known about HMO biosynthesis in the mother's mammary gland and their metabolism in the breast-fed infant. The second part highlights the postulated beneficial effects of HMO for the breast-fed neonate, compares HMOs with oligosaccharides in the milk of other mammals and in infant formula and summarizes the current roadblocks and future opportunities for HMO research.

Surveillance and molecular typing of Cronobacter spp. in commercial powdered infant formula and follow-up formula from 2011 to 2013 in Shandong Province, China.

PubMed

Zhang, Huaning; Hou, Peibin; Lv, Hui; Chen, Yuzhen; Li, Xinpeng; Ren, Yanyan; Wang, Mei; Tan, Hailian; Bi, Zhenwang

2017-05-01

Infection with Cronobacter spp. leads to neonatal meningitis, necrotizing enterocolitis and bacteremia. Cronobacter spp. are reported to comprise an important pathogen contaminating powdered infant formula (PIF) and follow-up formula (FUF), although little is known about the contamination level of Cronobacter spp. in PIFs and FUFs in China. In total, 1032 samples were collected between 2011 and 2013. Forty-two samples were positive, including 1.6% in PIFs and 6.5% in FUFs. The strains were susceptible to most antibiotics except for cefoxitin. Pulsed-field gel electrophoresis after XbaI digestion produced a total of 36 banding patterns. The 38 strains were found in 27 sequence types (STs), of which nine types (ST454 to ST462) had not been reported in other countries. The clinically relevant strains obtained from the 38 isolates in the present study comprised three ST3, two ST4, two ST8 and one ST1. The contamination rate in the PIF and FUF has stayed at a relatively high level. The contamination rate of PIF was significantly lower than FUF. The isolates had high susceptibility to the antibiotics tested, except cefoxitin. There were polymorphisms between the Cronobacter spp. as indicated by pulsed-field gel electrophoresis and multilocus sequence typing. Therefore, contamination with Cronobacter spp. remains a current issue for commercial infant formulas in China. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

A new way of thinking about complications of prematurity.

PubMed

Moore, Tiffany A; Berger, Ann M; Wilson, Margaret E

2014-01-01

The morbidity and mortality of preterm infants are impacted by their ability to maintain physiologic homeostasis using metabolic, endocrine, and immunologic mechanisms independent of the mother's placenta. Exploring McEwen's allostatic load model in preterm infants provides a new way to understand the altered physiologic processes associated with frequently occurring complications of prematurity such as bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, and retinopathy of prematurity. The purpose of this article is to present a new model to enhance understanding of the altered physiologic processes associated with complications of prematurity. The model of allostatic load and complications of prematurity was derived to explore the relationship between general stress of prematurity and complications of prematurity. The proposed model uses the concepts of general stress of prematurity, allostasis, physiologic response patterns (adaptive-maladaptive), allostatic load, and complications of prematurity. These concepts are defined and theoretical relationships in the proposed model are interpreted using the four maladaptive response patterns of repeated hits, lack of adaptation, prolonged response, and inadequate response. Empirical evidence for cortisol, inflammation, and oxidative stress responses are used to support the theoretical relationships. The proposed model provides a new way of thinking about physiologic dysregulation in preterm infants. The ability to describe and understand complex physiologic mechanisms involved in complications of prematurity is essential for research. Advancing the knowledge of complications of prematurity will advance clinical practice and research and lead to testing of interventions to reduce negative outcomes in preterm infants.

Clinical Outcomes among Diagnostic Subgroups of Infants with Severe Bronchopulmonary Dysplasia through 2 Years of Age.

PubMed

Akangire, Gangaram; Manimtim, Winston; Nyp, Michael F; Noel-MacDonnell, Janelle; Kays, Allyssa N; Truog, William E; Taylor, Jane B

2018-05-31

 This article aimed to identify readmission risk factors through 2 years of life for infants with severe bronchopulmonary dysplasia (BPD) who do not require tracheostomy and ventilatory support after neonatal intensive care unit (NICU) discharge. It also aimed to identify if clinical differences exist between the subcategories of severe BPD.  A retrospective chart review was performed on 182 infants with severe BPD born between 2010 and 2015. A total of 130 infants met the inclusion criteria and were stratified into three groups based on their respiratory status at 36 weeks of gestational age: group A-oxygen (O 2 ), group B-assisted ventilation (AV), group C-both O 2 and AV. NICU clinical risk factors for readmission were assessed at set time points (6/12/18/24 months). Reasons for readmission were assessed for the entire cohort and severe BPD subgroups.  An NICU diagnosis of neurologic abnormality, necrotizing enterocolitis, invasive NICU infection, dysphagia, and O 2 at NICU discharge differed between the three subgroups of severe BPD. The most common cause of readmission was viral respiratory tract infection. Inhaled steroid use remained stable over time, while oxygen use and diuretic use declined over time. Risk factors for readmission in the entire cohort included g-tube, O 2 use, and diuretic use at 12 months. There was no significant difference in readmission rates between the three BPD subgroups. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Short communication: Effects of high-pressure processing on the inactivity of Cronobacter sakazakii in whole milk and skim milk samples.

PubMed

Jiao, Rui; Gao, Jina; Li, Yinxiang; Zhang, Xiyan; Zhang, Maofeng; Ye, Yingwang; Wu, Qingping; Fan, Hongying

2016-10-01

Powdered infant formula is considered as the main transmission vehicle for Cronobacter sakazakii infections including meningitis, septicemia, and necrotizing enterocolitis. The effects of high-pressure processing treatment on inactivation of C. sakazakii ranging from 100 to 400 MPa for 3.0, 5.0, and 7.0 min in whole milk and skim milk were studied. Significant differences in inactivation of C. sakazakii were observed in milk samples under different pressures for 3 to 7 min compared with untreated samples, and C. sakazakii was not detected after 400 MPa for 3 min. The lethality rates of C. sakazakii cells in whole and skim milk with an initial level of 10(4) cfu/mL after 100 and 200 MPa treatments were not significantly different, but relatively higher lethality rates were found in whole milk after 300 MPa treatment than in skim milk. Finally, the scanning electron micrographs indicated that cellular envelope and intracellular damage of C. sakazakii cells were apparent after 300 and 400 MPa for 5.0 min compared with the untreated cells, and a progressive increase of injured cells with increased pressure treatment was found. It was concluded that C. sakazakii was sensitive to high-pressure processing treatment and that high-pressure processing treatment with 400 MPa for 3.0 min can be used to control C. sakazakii contamination in milk samples. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

NEONATAL SURGERY, A STUDY OF TWO YEARS AT NELSON MANDELA ACADEMIC HOSPITAL, MTHATHA, EASTERN CAPE.

PubMed

Delgado, A; Cejas, A; Bangasa, D

2017-09-01

Advances in diagnostic techniques and perioperative care have greatly improved the outcome of neonatal surgery. Despite this, disparity still exists in the outcome of neonatal surgery between developed and developing countries. We performed a prospective study of neonates admitted and treated due to surgical congenital diseases and other conditions in our hospital from April 2015 to April 2017. There were 19 (28,7%) females and 47 (70,3%) males in this group. It was found that 41 neonates had 7 days after birth or less by a 62% and 25 with more than 7 days by 38%. The Anorectal malformations (ARM) were the most frequent congenital anomaly in 21 patients (47%), followed by Gastroquises with 7 neonates (10,6%), Omphalocele with 8 (12%), and Oesophagus Atresia in 5 neonates (7,5%). Intestinal Malrotation with midgut volvulus, Pyloric Stenoses and Duodenal Atresia in 4 neonates (6,2 % each). Others alterations such as, Ileal Atresia, Strangulated Inguinal Hernia, Limb Gangrene, Necrotizing Enterocolitis, Sacro Coxigeal Theratoma, Megacolon Aganglionic, Colon perforation, Gastric perforation and Hydromethrocolpus accounted in 13 neonates by 19,7% from the total of patients. Ten babies died (15%). We conclude that Anorectal Malformations, Gastroquises and Omphalocele were the most frequent malformations. Considering the mortality is above the average of developed countries this could be improved by increasing the knowledge about the neonatal surgery characteristics among medical doctors and improving the necessary facilities and back up.

Breast-feeding improves gut maturation compared with formula feeding in preterm babies.

PubMed

Reisinger, Kostan W; de Vaan, Loes; Kramer, Boris W; Wolfs, Tim G A M; van Heurn, L W Ernest; Derikx, Joep P M

2014-12-01

The incidence of necrotizing enterocolitis (NEC) is higher in formula-fed babies than in breast-fed babies, which may be caused by breast-feeding-induced gut maturation. The effect of breast-feeding on gut maturation has been widely studied in animal models. This study aimed to assess the effects of breast-feeding on intestinal maturation in prematurely born babies by evaluating postnatal changes in urinary intestinal fatty acid binding protein (I-FABP) levels, a specific enterocyte marker. Gut maturation in 40 premature babies (<37 weeks of gestation) without gastrointestinal morbidity was studied, of whom 21 were exclusively breast-fed and 19 were formula-fed infants. Urinary I-FABP levels as the measure of gut maturation were measured at 5, 12, 19, and 26 days after birth. In breast-fed infants, there was a significant increase in median urinary I-FABP levels between 5 and 12 days after birth (104 [78-340] pg/mL to 408 [173-1028] pg/mL, P = 0.002), whereas I-FABP concentration in formula-fed infants increased between 12 and 19 days after birth (105 [44-557] pg/mL, 723 [103-1670] pg/mL, P = 0.004). Breast-fed babies had significantly higher median urinary I-FABP levels at postnatal day 12 (P = 0.01). The time course of the postnatal increase in urinary I-FABP levels reflecting gut maturation was significantly delayed in formula-fed babies, suggesting a delayed physiological response in formula-fed compared with breast-fed infants.

Mandatory Closure Versus Nonintervention for Patent Ductus Arteriosus in Very Preterm Infants.

PubMed

Sung, Se In; Chang, Yun Sil; Chun, Ji Young; Yoon, Shin Ae; Yoo, Hye Soo; Ahn, So Yoon; Park, Won Soon

2016-10-01

To determine whether a nonintervention approach for treating hemodynamically significant patent ductus arteriosus (PDA) is associated with decreased mortality and/or morbidity compared with a mandatory closure approach in extremely low birth weight infants. We reviewed the medical records of 178 infants of 23-26 weeks' gestational age with PDA, requiring ventilator treatment, and with hemodynamically significant PDA ≥2 mm in size. Mandatory closure was used during period I (July 2009 to December 2011, n = 81), and nonintervention was used during period II (January 2012 to June 2014, n = 97). During period I, 64% of infants were first treated with indomethacin, and 82% were ultimately ligated surgically. During period II, no infant was treated with indomethacin and/or ligation. The average postnatal day of PDA closure was day 13 and day 44 during periods I and II, respectively. There was significantly more use of diuretics and fluid restriction during period II compared with period I. There was no difference in mortality or morbidities such as necrotizing enterocolitis or intraventricular hemorrhage. The incidence of bronchopulmonary dysplasia (BPD) and the propensity score adjusted OR of BPD were significantly lower during period II compared with period I. Despite longer PDA exposure, nonintervention was associated with significantly less BPD compared with mandatory closure. Additional study is warranted to determine the benefits and risks of non-intervention for the hemodynamically significant PDA in extremely low birth weight infants. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Outcomes of Left Ventricular Function According to Treatment Response for a Patent Ductus Arteriosus in Preterm Infants

PubMed Central

Cho, Young Sun; Hwang, Seo Jung; Kim, Hyo Jin

2017-01-01

Background To evaluate the outcomes of left ventricular (LV) function according to treatment response for a hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants. Methods Echocardiograms of 21 preterm infants born at gestational age < 31 weeks obtained at term-equivalent age were retrospectively studied. Among preterm infants with a hsPDA, 9 underwent ligation after failure of pharmacological closure (ligation group) and 6 experienced successful pharmacological closure (medication group). Six preterm infants without hsPDA (no-hsPDA group) were studied as controls. LV peak longitudinal systolic strain (ε) of each infant was retrospectively obtained from echocardiograms using velocity vector imaging, along with neonatal outcomes. Results Pharmacological closures were attempted at postnatal day 2–3. In the ligation group, the median postnatal age at ligation was 20 days. In the ligation group, LV peak longitudinal systolic ε was significantly decreased at term-equivalent age compared to the other groups. Between the medication and no-hsPDA groups, LV peak longitudinal systolic ε did not differ significantly. Among the neonatal outcomes, infants who experienced necrotizing enterocolitis (NEC) showed significantly decreased LV peak longitudinal systolic ε compared to the infants who did not experience NEC . Conclusion We speculate that in preterm infants with an hsPDA, in cases of medical treatment failure, early PDA ligation at less than 20 days of postnatal age would be beneficial for preserving LV systolic function. PMID:29333220

Vital signs and their cross-correlation in sepsis and NEC: a study of 1,065 very-low-birth-weight infants in two NICUs.

PubMed

Fairchild, Karen D; Lake, Douglas E; Kattwinkel, John; Moorman, J Randall; Bateman, David A; Grieve, Philip G; Isler, Joseph R; Sahni, Rakesh

2017-02-01

Subtle changes in vital signs and their interactions occur in preterm infants prior to overt deterioration from late-onset septicemia (LOS) or necrotizing enterocolitis (NEC). Optimizing predictive algorithms may lead to earlier treatment. For 1,065 very-low-birth-weight (VLBW) infants in two neonatal intensive care units (NICUs), mean, SD, and cross-correlation of respiratory rate, heart rate (HR), and oxygen saturation (SpO 2 ) were analyzed hourly (131 infant-years' data). Cross-correlation (cotrending) between two vital signs was measured allowing a lag of ± 30 s. Cases of LOS and NEC were identified retrospectively (n = 186) and vital sign models were evaluated for ability to predict illness diagnosed in the ensuing 24 h. The best single illness predictor within and between institutions was cross-correlation of HR-SpO 2 . The best combined model (mean SpO 2 , SDHR, and cross-correlation of HR-SpO 2 ,) trained at one site with ROC area 0.695 had external ROC area of 0.754 at the other site, and provided additive value to an established HR characteristics index for illness prediction (Net Reclassification Improvement: 0.205; 95% confidence interval (CI): 0.113, 0.328). Despite minor inter-institutional differences in vital sign patterns of VLBW infants, cross-correlation of HR-SpO 2 and a 3-variable vital sign model performed well at both centers for preclinical detection of sepsis or NEC.