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  1. Boo NY
    Malays J Pathol, 2016 Dec;38(3):223-227.
    PMID: 28028291 MyJurnal
    Necrotising enterocolitis (NEC) is the most commonly acquired gastrointestinal disease of neonates, particularly the very preterm (gestation <32 weeks) and/or very low birth weight (<1500g). It is associated with high morbidity and mortality. Despite improvement in neonatal care and increased use of expressed breast milk (EBM), the incidence remains high in many neonatal intensive care units (NICU), and even shows increasing trend in some countries. Numerous studies have pointed to the infective nature of NEC. Some investigators have reported an increase in the incidence of NEC in their NICU when the percentage of infants with pathogens isolated from their gut increased, and decreased when gut colonisation rate was low. Both bacteria and viruses have been reported to be associated with outbreaks of NEC. The majority (>90%) of the NEC cases occurred in neonates on enteral feeding. Studies have shown that milk (whether EBM or formula) fed to neonates was not sterile and were further contaminated during collection, transport, storage and/or feeding. Other investigators have reported a reduction in the incidence of NEC when they improved infection control measures and hygienic procedures in handling milk. It is, therefore, hypothesised that the most common cause of NEC is due to the feeding of neonates, particularly the vulnerable very preterm small neonates, with milk heavily contaminated during collection at source, transport, storage and/or feeding. Because of the immaturity of the immune system of the neonates, excessive inflammatory response to the pathogen load in the gut leads to the pathogenesis of NEC.
    Matched MeSH terms: Enterocolitis, Necrotizing/microbiology*
  2. Nah SA, Tan HL, Tamba RP, Aziz DA, Azzam N
    J Pediatr Surg, 2011 Feb;46(2):424-7.
    PMID: 21292104 DOI: 10.1016/j.jpedsurg.2010.11.045
    Necrotizing enterocolitis has a wide clinical spectrum of manifestation. We report a novel method of managing focal isolated perforation in necrotizing enterocolitis by using diagnostic laparoscopy to localize the site of perforation and by making a microincision over the perforation to perform exteriorization or limited resection and primary anastomosis.
    Matched MeSH terms: Enterocolitis, Necrotizing/diagnosis; Enterocolitis, Necrotizing/pathology; Enterocolitis, Necrotizing/surgery*
  3. Lee JK, Hern Tan LT, Ramadas A, Ab Mutalib NS, Lee LH
    PMID: 32977611 DOI: 10.3390/ijerph17196963
    The mortality rate of very preterm infants with birth weight <1500 g is as high as 15%. The survivors till discharge have a high incidence of significant morbidity, which includes necrotising enterocolitis (NEC), early-onset neonatal sepsis (EONS) and late-onset neonatal sepsis (LONS). More than 25% of preterm births are associated with microbial invasion of amniotic cavity. The preterm gut microbiome subsequently undergoes an early disruption before achieving bacterial maturation. It is postulated that bacterial gut colonisation at birth and postnatal intestinal dysbacteriosis precede the development of NEC and LONS in very preterm infants. In fact, bacterial colonization patterns in preterm infants greatly differ from term infants due to maternal chorioamnionitis, gestational age, delivery method, feeding type, antibiotic exposure and the environment factor in neonatal intensive care unit (NICU). In this regard, this review provides an overview on the gut bacteria in preterm neonates' meconium and stool. More than 50% of preterm meconium contains bacteria and the proportion increases with lower gestational age. Researchers revealed that the gut bacterial diversity is reduced in preterm infants at risk for LONS and NEC. Nevertheless, the association between gut dysbacteriosis and NEC is inconclusive with regards to relative bacteria abundance and between-sample beta diversity indices. With most studies show a disruption of the Proteobacteria and Firmicutes preceding the NEC. Hence, this review sheds light on whether gut bacteria at birth either alone or in combination with postnatal gut dysbacteriosis are associated with mortality and the morbidity of LONS and NEC in very preterm infants.
    Matched MeSH terms: Enterocolitis, Necrotizing/microbiology*; Enterocolitis, Necrotizing/mortality
  4. Seak CJ, Yen DH, Ng CJ, Wong YC, Hsu KH, Seak JC, et al.
    PLoS One, 2017;12(9):e0184813.
    PMID: 28915258 DOI: 10.1371/journal.pone.0184813
    OBJECTIVE: This study aims to evaluate the performance of Rapid Emergency Medicine Score (REMS), Rapid Acute Physiology Score (RAPS), and Modified Early Warning Score (MEWS) in ascertaining the severity of illness and predicting the mortality of adult hepatic portal venous gas (HPVG) patients presenting to the emergency department (ED). This will assist emergency physicians (EPs) in risk stratification.

    METHODS: Data for 66 adult HPVG patients who visited the EDs of 2 research hospitals between October 1999 and April 2016 were analyzed. REMS, RAPS, and MEWS were calculated based on data in the ED, and probability of death was calculated for each patient based on these scores. The ability of REMS, RAPS, and MEWS to predict group mortality was assessed by using receiver operating characteristic (ROC) curve analysis and calibration analysis.

    RESULTS: The sensitivity, specificity, and accuracy for each scoring system were 92.1%, 89.3%, and 90.9% for REMS, 86.8%, 82.1%, and 84.8% for RAPS, and 78.9%, 89.3%, and 83.3% for MEWS respectively. In the ROC curve analysis, the areas under the curve for REMS, RAPS, and MEWS were 0.929, 0.877, and 0.856 respectively.

    CONCLUSION: Our study is the largest series performed in a population of adult HPVG patients in the ED. The results from this study demonstrate that REMS is superior in predicting the mortality of these patients compared to RAPS and MEWS. We therefore recommend that REMS be used for outcome prediction and risk stratification of adult HPVG in the ED.

    Matched MeSH terms: Enterocolitis, Necrotizing/diagnosis*; Enterocolitis, Necrotizing/therapy*
  5. Yeo KT, Kong JY, Sasi A, Tan K, Lai NM, Schindler T
    Cochrane Database Syst Rev, 2019 10 28;2019(10).
    PMID: 31684689 DOI: 10.1002/14651858.CD012888.pub2
    BACKGROUND: Feeding practices around the time of packed red blood cell transfusion have been implicated in the subsequent development of necrotising enterocolitis (NEC) in preterm infants. Specifically, it has been suggested that withholding feeds around the time of transfusion may reduce the risk of subsequent NEC. It is important to determine if withholding feeds around transfusion reduces the risk of subsequent NEC and associated mortality.

    OBJECTIVES: • To assess the benefits and risks of stopping compared to continuing feed management before, during, and after blood transfusion in preterm infants • To assess the effects of stopping versus continuing feeds in the following subgroups of infants: infants of different gestations; infants with symptomatic and asymptomatic anaemia; infants who received different feeding schedules, types of feed, and methods of feed delivery; infants who were transfused with different blood products, at different blood volumes, via different routes of delivery; and those who received blood transfusion with and without co-interventions such as use of diuretics • To determine the effectiveness and safety of stopping feeds around the time of a blood transfusion in reducing the risk of subsequent necrotising enterocolitis (NEC) in preterm infants SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 11), in the Cochrane Library; MEDLINE (1966 to 14 November 2018); Embase (1980 to 14 November 2018); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 14 November 2018). We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised controlled trials (RCTs), cluster-RCTs, and quasi-RCTs.

    SELECTION CRITERIA: Randomised and quasi-randomised controlled trials that compared stopping feeds versus continuing feeds around the time of blood transfusion in preterm infants.

    DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed trial quality, and extracted data from the included studies.

    MAIN RESULTS: The search revealed seven studies that assessed effects of stopping feeds during blood transfusion. However, only one RCT involving 22 preterm infants was eligible for inclusion in the review. This RCT had low risk of selection bias but high risk of performance bias, as care personnel were not blinded to the study allocation. The primary objective of this trial was to investigate changes in mesenteric blood flow, and no cases of NEC were reported in any of the infants included in the trial. We were unable to draw any conclusions from this single study. The overall GRADE rating for quality of evidence was very low.

    AUTHORS' CONCLUSIONS: Randomised controlled trial evidence is insufficient to show whether stopping feeds has an effect on the incidence of subsequent NEC or death. Large, adequately powered RCTs are needed to address this issue.

    Matched MeSH terms: Enterocolitis, Necrotizing/etiology; Enterocolitis, Necrotizing/prevention & control*
  6. Ibrahim NR, Van Rostenberghe H, Ho JJ, Nasir A
    Cochrane Database Syst Rev, 2021 Aug 19;8(8):CD012322.
    PMID: 34415568 DOI: 10.1002/14651858.CD012322.pub2
    BACKGROUND: There is presently no certainty about the ideal feeding intervals for preterm infants. Shorter feeding intervals of, for example, two hours, have the theoretical advantage of allowing smaller volumes of milk. This may have the potential to reduce the incidence and severity of gastro-oesophageal reflux. Longer feeding intervals have the theoretical advantage of allowing more gastric emptying between two feeds. This potentially provides periods of rest (and thus less hyperaemia) for an immature digestive tract.

    OBJECTIVES: To determine the safety of shorter feeding intervals (two hours or shorter) versus longer feeding intervals (three hours or more) and to compare the effects in terms of days taken to regain birth weight and to achieve full feeding.

    SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to run comprehensive searches in CENTRAL (2020, Issue 6) and Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions, and CINAHL on 25 June 2020. We searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs.

    SELECTION CRITERIA: We included RCTs and quasi-RCTs comparing short (e.g. one or two hours) versus long (e.g. three or four hours) feeding intervals in preterm infants of any birth weight, all or most of whom were less than 32 weeks' gestation. Infants could be of any postnatal age at trial entry, but eligible infants should not have received feeds before study entry, with the exception of minimal enteral feeding. We included studies of nasogastric or orogastric bolus feeding, breast milk or formula, in which the feeding interval is the intervention.

    DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We used the GRADE approach to assess the certainty of evidence. Our primary outcomes were days taken to achieve full enteral feeding and days to regain birth weight. Our other outcomes were duration of hospital stay, episodes of necrotising enterocolitis (NEC) and growth during hospital stay (weight, length and head circumference).

    MAIN RESULTS: We included four RCTs, involving 417 infants in the review. One study involving 350 infants is awaiting classification. All studies compared two-hourly versus three-hourly feeding interval. The risk of bias of the included studies was generally low, but all studies had high risk of performance bias due to lack of blinding of the intervention. Three studies were included in meta-analysis for the number of days taken to achieve full enteral feeding (351 participants). The mean days to achieve full feeds was between eight and 11 days. There was little or no difference in days taken to achieve full enteral feeding between two-hourly and three-hourly feeding, but this finding was of low certainty (mean difference (MD) ‒0.62, 95% confidence interval (CI) ‒1.60 to 0.36). There was low-certainty evidence that the days taken to regain birth weight may be slightly longer in infants receiving two-hourly feeding than in those receiving three-hourly feeding (MD 1.15, 95% CI 0.11 to 2.20; 3 studies, 350 participants). We are uncertain whether shorter feeding intervals have any effect on any of our secondary outcomes including the duration of hospital stay (MD ‒3.36, 95% CI ‒9.18 to 2.46; 2 studies, 207 participants; very low-certainty evidence) and the risk of NEC (typical risk ratio 1.07, 95% CI 0.54 to 2.11; 4 studies, 417 participants; low-certainty evidence). No study reported growth during hospital stay.

    AUTHORS' CONCLUSIONS: The low-certainty evidence we found in this review suggests that there may be no clinically important differences between two- and three-hourly feeding intervals. There is insufficient information about potential feeding complications and in particular NEC. No studies have looked at the effect of other feeding intervals and there is no long-term data on neurodevelopment or growth.

    Matched MeSH terms: Enterocolitis, Necrotizing/epidemiology; Enterocolitis, Necrotizing/prevention & control
  7. Mohd Amin AT, Zaki RA, Friedmacher F, Sharif SP
    Pediatr Surg Int, 2021 Jul;37(7):881-886.
    PMID: 33779823 DOI: 10.1007/s00383-021-04879-1
    PURPOSE: The role of hypoalbuminemia and raised C-reactive protein (CRP) levels in predicting critical prognosis has been described extensively in adult literature. However, there are limited studies in pediatrics, particularly neonates. The CRP/albumin (CRP/ALB) ratio is often associated with higher mortality, organ failure and prolonged hospital stay. We hypothesized that the serum CRP/ALB ratio has a prognostic value in predicting surgery and mortality in neonates with necrotizing enterocolitis (NEC).

    METHODS: Retrospective review of all neonates with clinical and radiological evidence of non-perforated NEC that were treated in a tertiary-level referral hospital between 2009 and 2018. General patient demographics, laboratory parameters and outcomes were recorded. Receiver operating characteristics analysis was performed to evaluated optimal cut-offs and area under the curve (AUC) with 95% confidence intervals (CI).

    RESULTS: A total of 191 neonates were identified. Of these, 103 (53.9%) were born at ≤ 28 weeks of gestation and 101 (52.9%) had a birth weight of ≤ 1000 g. Eighty-four (44.0%) patients underwent surgical intervention for NEC. The overall survival rate was 161/191 (84.3%). A CRP/ALB ratio of ≥ 3 on day 2 of NEC diagnosis was associated with a statistically significant higher likelihood for surgery [AUC 0.71 (95% CI 0.63-0.79); p 

    Matched MeSH terms: Enterocolitis, Necrotizing/blood*; Enterocolitis, Necrotizing/mortality; Enterocolitis, Necrotizing/surgery
  8. Wariki WM, Mori R, Boo NY, Cheah IG, Fujimura M, Lee J, et al.
    J Paediatr Child Health, 2013 Jan;49(1):E23-7.
    PMID: 23282105 DOI: 10.1111/jpc.12054
    The study aims to determine the risk factors associated with mortality and necrotising enterocolitis (NEC) among very low birthweight infants in 95 neonatal intensive care units in the Asian Network on Maternal and Newborn Health.
    Matched MeSH terms: Enterocolitis, Necrotizing/etiology*; Enterocolitis, Necrotizing/epidemiology
  9. Boo NY, Cheah IG
    Singapore Med J, 2012 Dec;53(12):826-31.
    PMID: 23268157
    This study aimed to identify the risk factors associated with necrotising enterocolitis (NEC) in very low birth weight (VLBW; weight < 1,501 g) infants in Malaysian neonatal intensive care units (NICUs).
    Matched MeSH terms: Enterocolitis, Necrotizing/etiology; Enterocolitis, Necrotizing/epidemiology*
  10. Liau LL, Al-Masawa ME, Koh B, Looi QH, Foo JB, Lee SH, et al.
    Front Pediatr, 2020;8:591693.
    PMID: 33251167 DOI: 10.3389/fped.2020.591693
    Mesenchymal stromal cells (MSCs) can be derived from various tissue sources, such as the bone marrow (BMSCs), adipose tissue (ADSCs), umbilical cord (UC-MSCs) and umbilical cord blood (UCB-MSCs). Clinical trials have been conducted to investigate the potential of MSCs in ameliorating neonatal diseases, including bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH) and necrotizing enterocolitis (NEC). In preclinical studies, MSC therapy has been tested for the treatment of various neonatal diseases affecting the heart, eye, gut, and brain as well as sepsis. Up to date, the number of clinical trials using MSCs to treat neonatal diseases is still limited. The data reported thus far positioned MSC therapy as safe with positive outcomes. However, most of these trials are still preliminary and generally smaller in scale. Larger trials with more appropriate controls and a longer follow-up period need to be conducted to prove the safety and efficacy of the therapy more conclusively. This review discusses the current application of MSCs in treating neonatal diseases, its mechanism of action and future direction of this novel therapy, including the potential of using MSC-derived extracellular vesicles instead of the cells to treat various clinical conditions in the newborn.
    Matched MeSH terms: Enterocolitis, Necrotizing
  11. Yu, Victor Y.H.
    MyJurnal
    ANTENATAL CORTICOSTEROID THERAPY. Benefits. In 1969, the first study was published which showed that prematurely delivered lambs exposed prenatally to corticosteroids survived longer than placebo-treated control animals.' A randomised clinical trial (RCT) followed which demonstrated that antenatal corticosteroid therapy significantly reduced the incidence of respiratory distress syndrome (RDS) in infants born before 2 weeks gestation and reduced mortality in those born before 37 weeks.2 A meta-analysis has been published on 12 RCTs involving over 3000 women in preterm labour, using primarily 24mg of betamethasone or dexamethasone given in 2-6 divided doses over a 48-hour period.' It showed that antenatal corticosteroid therapy is associated with a significant reduction in the risk of RDS (a) if the infant is born > 24 hours or < 7 days of the treatment, (b) in both male and female infants and (c) even in infants < 31 weeks gestation. It also significantly reduces mortality rate and morbidity such as intraventricular haemorrhage (IVH) and necrotising enterocolitis (NEC), shortens the duration of hospitalisation and reduces treatment costs. The improvement in survival rate in infants born
    Matched MeSH terms: Enterocolitis, Necrotizing
  12. Norrakiah Abdullah Sani, Masomeh Ghassem, Abdul Salam Babji, Uma Priya Kupusamy, Norizan Jaafar
    Sains Malaysiana, 2014;43:1855-1863.
    Enterobacter sakazakii previously known as 'yellow-pigmented E. cloacae' has been classified as a new genus 'Cronobacter' based on taxonomic analysis and geno-and phenotypic evaluation. This pathogenic organism has been associated with rare form of infant meningitis and necrotizing enterocolitis (NEC) with high mortality rate (40-80%). Some cases have been linked to the consumption of contaminated powdered infant formula milk (PIF). The objective of this study was to determine the presence of Cronobacter spp. in PIF sold in Malaysia. A selective chromogenic agar, Brilliance Enterobacter sakazakii (DFI, Oxoid), was used for detection of Cronobacter strains. Presumptive Cronobacter isolates were identified using biochemical tests (API 20E and MicrogenTM) and molecular assays (SYBR Green Real-time PCR and 16S ribosomal DNA sequencing). All presumptive Cronobacter strains produced typical blue-green colonies and non-Cronobacter strains produced yellow colonies on Brilliance Enterobacter sakazakii agar (DFI formulation). A total of 12 presumptive isolates were selected from DFI agar and identified with biochemical and molecular tests. The results indicated prevalence of 12.5% C. sakazakii contamination from 72 PIF samples. Molecular detection methods such as Real-time PCR and 16S rDNA proved to have higher identification percentage compared to the biochemical tests. In this study, it was observed that molecular assays were suitable means for sensitive identification of Cronobacter strains in PIF samples.
    Matched MeSH terms: Enterocolitis, Necrotizing
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