Recent advances in understanding necrotizing enterocolitis

Alganabi, Mashriq; Lee, Carol; Bindi, Elena; Li, Bo; Pierro, Agostino

doi:10.12688/f1000research.17228.1

Cited by 125 publications

(110 citation statements)

References 79 publications

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“…Moreover, antenatal steroids are associated with a decrease in incidence of PDA, since these attenuate the sensitivity of the DA to PGE 2 and increase the PGE 2 catabolism. Robust evidence exists on the presence of an association between low GA and development of NEC [17]. In the current study, we identified GA as an independent predictor for the development of sNEC.…”

Section: Perinatal Variablesmentioning

confidence: 50%

Predictive factors for surgical treatment in preterm neonates with necrotizing enterocolitis: a multicenter case-control study

et al. 2020

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Necrotizing enterocolitis (NEC) is one of the most common and lethal gastrointestinal diseases in preterm infants. Early recognition of infants in need for surgical intervention might enable early intervention. In this multicenter case-control study, performed in nine neonatal intensive care units, preterm born infants (< 30 weeks of gestation) diagnosed with NEC (stage ≥ IIA) between October 2014 and August 2017 were divided into two groups: (1) medical (conservative treatment) and (2) surgical NEC (sNEC). Perinatal, clinical, and laboratory parameters were collected daily up to clinical onset of NEC. Univariate and multivariate logistic regression analyses were applied to identify potential predictors for sNEC. In total, 73 preterm infants with NEC (41 surgical and 32 medical NEC) were included. A low gestational age (p value, adjusted odds ratio [95%CI]; 0.001, 0.91 [0.86–0.96]), no maternal corticosteroid administration (0.025, 0.19 [0.04–0.82]), early onset of NEC (0.003, 0.85 [0.77–0.95]), low serum bicarbonate (0.009, 0.85 [0.76–0.96]), and a hemodynamically significant patent ductus arteriosus for which ibuprofen was administered (0.003, 7.60 [2.03–28.47]) were identified as independent risk factors for sNEC.Conclusions: Our findings may support the clinician to identify infants with increased risk for sNEC, which may facilitate early decisive management and consequently could result in improved prognosis. What is Known:• In 27–52% of the infants with NEC, a surgical intervention is indicated during its disease course.• Absolute indication for surgical intervention is bowel perforation, whereas fixed bowel loop or clinical deterioration highly suggestive of bowel perforation or necrosi, is a relative indication. What is New:• Lower gestational age, early clinical onset, and no maternal corticosteroids administration are predictors for surgical NEC.• Low serum bicarbonate in the 3 days prior clinical onset and patent ductus arteriosus for which ibuprofen was administered predict surgical NEC.

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Section: Perinatal Variablesmentioning

confidence: 50%

Predictive factors for surgical treatment in preterm neonates with necrotizing enterocolitis: a multicenter case-control study

et al. 2020

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“…Other morbidities in the neonatal intensive care unit (NICU) such as necrotizing enterocolitis (NEC) also have high mortality rates and have been associated with prolonged antibiotic exposure. 10,11 . Nevertheless, antibiotics remain the most commonly prescribed medication in the NICU 12,13 .…”

Section: Mainmentioning

confidence: 99%

Antibiotics and the developing intestinal microbiome, metabolome and inflammatory environment: a randomized trial of preterm infants

Russell

Ruoss

Cruz

et al. 2020

Preprint

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15Antibiotic use in neonates can have detrimental effects on the developing gut microbiome, 16increasing the risk of morbidity. A majority of preterm neonates receive antibiotics after birth 17 without clear evidence to guide this practice. Increasing evidence suggests associations between 18 early-life antibiotic use, intestinal dysbiosis, and morbidity that challenge the efficacy of this 19 common neonatal practice. Here we present microbiome and metabolomic results from the 20 Routine Early Antibiotic use in Symptomatic preterm Neonates (REASON) study, which is the 21 first trial to randomize symptomatic preterm neonates to receive or not receive antibiotics in the 22 first 48 hours after birth. Using 16S rRNA sequencing of stool samples collected longitudinally 23for 91 neonates, we show that antibiotics alter trends in microbiome diversity and development 24 between randomized neonates and illustrate that type of nutrition helps shape the early infant gut 25 microbiome. Integrating multi-omic data for the gut microbiome, stool immune markers, stool 26 metabolites, and inferred metabolic pathways, we identified an association between Veillonella 27 and the neurotransmitter gamma-aminobutyric acid (GABA). Our results suggest early antibiotic 28 use may impact the gut-brain axis with the potential for consequences in early life development. 29 Main 30Premature infants are particularly susceptible to infections secondary to increased need for 31 invasive procedures and immaturity of the immune system, skin, and gastrointestinal tract1-3. 32Increasingly, there is growing concern that risk factors for mortality may originate from 33underlying pathologies that could also be responsible for premature birth4. Symptoms of 34 prematurity are difficult to discern from symptoms of infection which, compounded by the 35 3 increased risk of infection, have led to most premature infants being exposed to antibiotics early 36 in life5-7. Despite high mortality rates, the incidence of culture positive early onset sepsis (EOS) 37 is relatively low, between 0.2-0.6%8. In the absence of a positive culture, a majority of preterm 38 infants receive antibiotics immediately after birth based on maternal risk factors (e.g. intra-39 amniotic infection) or laboratory abnormalities (e.g. elevated serum C-reactive protein (CRP) 40 because of the risk of mortality8. Given the low incidence of culture positive EOS in this 41 population, it is possible that such high rates of antibiotic use are unnecessary and may increase 42 morbidity in these infants9. Other morbidities in the neonatal intensive care unit (NICU) such as 43 necrotizing enterocolitis (NEC) also have high mortality rates and have been associated with 44 prolonged antibiotic exposure.10,11. Nevertheless, antibiotics remain the most commonly 45 prescribed medication in the NICU12,13. 46The gut microbiome comprises a highly volatile community structure early in life14. Microbial 47Randomized clinical trials have the advantage of controlling for the numerous covariates that 58 cou...

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“…NEC involves derangement of intestinal microcirculation that leads to poor blood flow, which may induce an inflammatory cascade, resulting in intestinal injury. 20 In this study, we hypothesized that in NEC, the intestinal injury leads to release of mtDNA from the necrotic intestinal epithelial cells. The increased levels of mtDNA could enhance the inflammatory injury trough activation of TLR-9 receptors while mtDNA released in the circulation triggers injury in remote organs.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA: A Biomarker of Disease Severity in Necrotizing Enterocolitis

Bindi

Zhou

et al. 2019

Eur J Pediatr Surg

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Introduction There is a need to develop sensitive markers to diagnose or monitor the severity of intestinal damage in necrotizing enterocolitis (NEC). Mitochondrial deoxyribonucleic acid (mtDNA) is increased in the intestine and blood of adults in response to intestinal ischemia and can trigger secondary organ damage. We hypothesize that mtDNA is increased during experimental NEC and that mtDNA levels are correlated to the degree of intestinal injury. Materials and Methods NEC was induced in C57BL/6 mice (n = 18) (approval: 44032) by gavage feeding with hyperosmolar formula, hypoxia, and lipopolysaccharide administration from postnatal day (P) 5 to 9. Breastfed pups served as control (n = 15). Blood was collected by cardiac puncture and terminal ileum was harvested on P9. Reverse transcription quatitative polymerase chain reaction was used to measure mtDNA (markers COX3, CYTB, ND1) and inflammatory cytokines (interleukin 6 [IL-6] and tumor necrosis factor-α[TNF-α]) in blood and ileum. Intestinal injury was scored blindly by four investigators and classified as no/minor injury (score 0 or 1) or NEC (score ≥2). Results mtDNA is significantly increased in gut and blood of NEC mice (p < 0.05). Furthermore, mtDNA increases in intestine and blood proportionally to the degree of intestinal injury as indicated by a positive correlation with histological scoring and inflammation (r = 0.6; p < 0.05) (expression of IL-6 and TNF-α). Conclusion Following NEC intestinal injury, mtDNA is released from the intestine into circulation. The blood level of mtDNA is related to the degree of intestinal injury. mtDNA can be a novel marker of intestinal injury and can be useful for monitoring the progression of NEC.

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Recent advances in understanding necrotizing enterocolitis

Cited by 125 publications

References 79 publications

Predictive factors for surgical treatment in preterm neonates with necrotizing enterocolitis: a multicenter case-control study

Predictive factors for surgical treatment in preterm neonates with necrotizing enterocolitis: a multicenter case-control study

Antibiotics and the developing intestinal microbiome, metabolome and inflammatory environment: a randomized trial of preterm infants

Mitochondrial DNA: A Biomarker of Disease Severity in Necrotizing Enterocolitis

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