Biomarkers of gut injury in neonates – where are we in predicting necrotising enterocolitis?

Howarth, Claire; Banerjee, Jayanta; Eaton, Simon; Aladangady, Narendra

doi:10.3389/fped.2022.1048322

Cited by 12 publications

(7 citation statements)

References 116 publications

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“…Various biomarkers, including blood amyloid A, apolipoprotein C2, and stool calprotectin, have been suggested as potential indicators for predicting intestinal diseases in neonates [ 16 , 17 , 18 , 19 , 20 ]. However, in contrast to these biomarkers, which respond to inflammation or tissue injury, blood citrulline is more likely to mirror the actual intestinal function [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…Elevated amyloid A levels and reduced apolipoprotein C2 levels (197.1 μg/mL and 29.9 μg/mL, respectively) were observed in VLBWIs with sepsis or NEC compared to their healthy peers (32.7 μg/mL and 49.7 μg/mL, respectively) [ 17 ], although these biomarkers did not discriminate between NEC and nonabdominal sepsis [ 13 , 18 ]. Stool calprotectin, a protein derived from neutrophils, is a nonspecific biomarker of gut injury [ 19 ]. An approximately three-fold increase in stool calprotectin levels was observed in infants with NEC compared to those in their peers [ 20 ], although the positive predictive value to identify NEC remains at 0.20; neonates with NEC often do not pass stools, rendering this biomarker difficult to use in VLBWIs [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Antenatal Growth, Gestational Age, Birth, Enteral Feeding, and Blood Citrulline Levels in Very Low Birth Weight Infants

Obayashi,

Iwata,

Okuda

et al. 2024

Nutrients

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Early enteral nutrition using reliable biomarkers of intestinal function must be established to improve neurodevelopmental outcomes in very low birth weight infants (VLBWIs). Serum citrulline levels reflect the intestinal function in adults. To elucidate the relationship among antenatal growth, postnatal enteral nutrition, and blood citrulline levels, a retrospective single-center observational study was conducted on 248 VLBWIs born between April 2014 and March 2021. A mixed effect model and post hoc simple slope analysis were used to estimate the correlations between clinical variables and citrulline levels at Early (day 5.1) and Late (day 24.3) postnatal ages. Greater gestational age, birth weight, and amount of enteral nutrition at the time of blood sampling were associated with lower citrulline levels at the Early postnatal age and higher citrulline levels at the Late postnatal age. Provided that Early citrulline levels predominantly reflect the consequence of antenatal citrulline metabolism, it is suggested that fetal growth and maturation are likely to promote citrulline catabolism in utero and its synthesis after birth. With additional insights into the temporal transition point wherein the maturation-dependent balance of citrulline metabolism shifts from catabolism-dominant to synthesis-dominant, citrulline emerges as a potential biomarker for assessing intestinal function and gastrointestinal disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antenatal Growth, Gestational Age, Birth, Enteral Feeding, and Blood Citrulline Levels in Very Low Birth Weight Infants

Obayashi,

Iwata,

Okuda

et al. 2024

Nutrients

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“…The limitations include the choice of FCP as the sole marker of intestinal in ammation. We believe that fecal FCP was a pragmatic choice considering the limited information on other markers of intestinal in ammation (e.g., intestinal fatty acid binding protein, trefoil factor, volatile organic compounds) in very preterm infants [13,24,25]. Although FCP levels are considered as a reliable marker of intestinal in ammation, elevated levels are also reported with acute and cumulative pain or stress, feeding with mother's own milk, non-white race, and increasing severity of illness [24].…”

Section: Discussionmentioning

confidence: 99%

Effects of a live vs heat-inactivated probiotic Bifidobacterium spp in preterm infants (the ProPara study)- a randomized clinical trial

Athalye-Jape,

Esvaran,

Patole

et al. 2023

Preprint

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Background Heat-inactivated probiotics may provide an effective alternative to live probiotics by avoiding the risk of probiotic sepsis, altered immune responses and antimicrobial resistance while retaining probiotic benefits. Objective We assessed safety and efficacy of a heat-inactivated probiotic in very preterm (VP: gestation < 32 weeks) infants. Methods VP infants were recruited including a pre-planned subgroup of extremely preterm (EP: gestation < 28 weeks). Mixture of heat-inactivated (HP) or live probiotic (P) strains B. breve M-16V, B. longum subsp. infantis M-63, B. longum subsp. longum BB536 (Total 3 x109 CFU/day) assuring blinding. Primary outcomes included fecal calprotectin (FCP) levels and safety. Secondary outcomes included fecal microbiota assessed by 16S ribosomal RNA and shotgun sequencing and short chain fatty acid (SCFA) levels in samples collected after the 1st (T1) and 3rd (T2) week of supplementation. Results 86 VP (P:43; HP:43) infants were randomized. Median (range) FCP was lower at T2 vs T1 in both HP [75 (8-563) vs 109 (5.1–725) µg/g; p = 0.22] and P [80 (21–277) vs 105 (11–842) µg/g; p = 0.4] groups. Total FCP and SCFA were comparable between HP vs P groups at T1 and T2 (p > 0.05). Propionate was significantly raised in both groups, whilst butyrate was significantly raised in HP group (all p < 0.01). At T2, alpha diversity increased but was comparable and beta diversity showed significantly different community structures in both groups (all p < 0.01). Actinobacteria significantly increased and Bacteroidetes decreased at T2 vs T1 for both groups (p < 0.05). Bifidobacteriacae increased (p < 0.001) whilst Staphylococcaceae decreased (p < 0.05) for both groups. Bifidobacteriacae, B. longum subsp. infantis and B. longum subsp. longum levels were comparable. Clinical outcomes were comparable and there were no adverse events. Conclusions Heat-inactivated probiotic was safe and well tolerated, with an intestinal anti-inflammatory effect comparable to live probiotic. Adequately powered randomised trials are needed to assess its clinically significant effects in preterm infants. Trial Registration ID and URL Australian and New Zealand Clinical Trials Registry (ACTRN12618000489291); ANZCTR - Registration

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“…8 In addition, there have been several reports that anemic patients have elevated levels of VEGF, which is a marker of tissue hypoxia. 9 Moreover, it has been shown recently that the anemia of newborns induces EPO expression in the developing mouse retina. 10 EPO and VEGF are independently associated with proliferative diabetic retinopathy (PDR), and EPO is more strongly associated with PDR than VEGF.…”

Section: Anemia and Angiogenesis Inhibitorsmentioning

confidence: 99%

Anemia: A Potential Source of Bias in Clinical Trials of Angiogenesis Inhibitors: A Hypothesis

Rastmanesh¹

2023

Explor Res Hypothesis Med

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Although anemia may cause angiogenesis and neovascularization, especially in ocular situations, neither published nonrandomized clinical trials nor registered clinical trials have reported the anemia status as inclusion or exclusion criteria in their design. Increases in the circulating levels of erythropoietin and vascular endothelial growth factor are proportional to the levels of tissue hypoxia, which are influenced by hematocrit. Erythropoietin is a potent retinal angiogenic factor that is independent of endothelial growth factor and is capable of stimulating ischemia-induced retinal angiogenesis. We suggest that clinical trials investigating anti-vascular endothelial growth factor treatment for retinal neovascularization should measure appropriate variables such as serum erythropoietin, vascular endothelial growth factor, hemoglobin, and hematocrit to yield preliminary data for future trials of angiogenesis inhibitors. Ignoring the anemia status, serum erythropoietin, and/or vascular endothelial growth factor levels could create clinical uncertainty and subtle statistical bias in both systematic reviews and nonrandomized clinical trials that aim to evaluate the efficiency of angiogenesis inhibitors in several medical situations, including but not limited to ocular alterations, rheumatoid arthritis, and many types of cancer, just to mention a few. Implications of this type of bias could be involved in other disease situations in which angiogenesis inhibitors are used for medication, such as different carcinomas as well as metastases. In this hypothesis paper, we suggest that clinical trials of angiogenesis inhibitors should measure appropriate variables such as serum erythropoietin, hemoglobin, and hematocrit and match their participants by anemia and its severity to avoid a game-changing bias in their data analysis.

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Biomarkers of gut injury in neonates – where are we in predicting necrotising enterocolitis?

Cited by 12 publications

References 116 publications

Antenatal Growth, Gestational Age, Birth, Enteral Feeding, and Blood Citrulline Levels in Very Low Birth Weight Infants

Antenatal Growth, Gestational Age, Birth, Enteral Feeding, and Blood Citrulline Levels in Very Low Birth Weight Infants

Effects of a live vs heat-inactivated probiotic Bifidobacterium spp in preterm infants (the ProPara study)- a randomized clinical trial

Anemia: A Potential Source of Bias in Clinical Trials of Angiogenesis Inhibitors: A Hypothesis

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