Necrotizing enterocolitis: a potential protective role for intestinal alkaline phosphatase as lipopolysaccharide detoxifying enzyme.

Introduction: Necrotizing enterocolitis (NEC) is a life-threatening inflammatory disease. Its onset might be triggered by Toll-Like Receptor 4 (TLR4) activation via bacterial lipopolysaccharide (LPS). We hypothesize that a deficiency of intestinal alkaline phosphatase (IAP), an enzyme secreted by enterocytes that dephosphorylates LPS, may contribute to NEC development. Methods: In this prospective pilot study, we analyzed intestinal resection specimens from surgical NEC patients, and from patients undergoing Roux-Y reconstruction for hepatobiliary disease as controls. We assessed IAP activity via enzymatic stainings and assays and explored IAP and TLR4 co-localization through immunofluorescence. Results: The study population consisted of five NEC patients (two Bell's stage IIb and three-stage IIIb, median (IQR) gestational age 25 (24-28) weeks, postmenstrual age at diagnosis 28 (26-31) weeks) and 11 controls (unknown age). There was significantly lower IAP staining in NEC resection specimens [49 (41-50) U/g of protein] compared to controls [115 (76-144), P = 0.03]. LPS-dephosphorylating activity was also lower in NEC patients [0.06 (0-0.1)] than in controls [0.3 (0.2-0.5), P = 0.003]. Furthermore, we observed colocalization of IAP and TLR4 in NEC resection specimens. Conclusion: This study suggests a significantly lower IAP level in resection specimens of NEC patients compared to controls. This lower IAP activity suggests a potential role of IAP as a protective agent in the gut, which needs further confirmation in larger cohorts.

Ischemia modified albumin as a marker of hypoxia in preterm infants in the first week after birth.

BACKGROUND: Tissue hypoxia remains a leading cause of morbidity and mortality in preterm infants. Current biomarkers often detect irreversible hypoxic cellular injury (i.e. lactate) and are non-specific. A new biomarker is needed which detects tissue hypoxia before irreversible damage occurs. AIMS: To investigate the relation between serum ischemia modified albumin (IMA), a marker of hypoxia; and analytic variables, patient related variables and conditions associated with hypoxia, in preterm infants. STUDY DESIGN: Retrospective cohort study. SUBJECTS: Infants with a gestational age < 30 weeks and/or birth weight < 1000 g. OUTCOME MEASURES: We collected two remnant blood samples in the first week after birth and measured IMA. IMA/albumin ratio (IMAR) was used to adjust for albumin. We assessed correlations between IMA(R) and analytic variables (albumin, lipemia- and haemolysis index); mean-2 h SpO2; mean-2 h variability of regional splanchnic oxygen saturation (rsSO2), measured using near-infrared spectroscopy; and patent ductus arteriosus (PDA). RESULTS: Sixty-five infants were included. Albumin, the lipemia- and haemolysis index correlated negatively with IMA (r:-0.620, P<0.001; r:-0.458, P<0.001; and r:-0.337, P=0.002). IMAR correlated negatively with SpO2 (rho:-0.614, P<0.001). Lower rsSO2 variability correlated with higher IMAR values (rho:-0.785, n=14, P=0.001 and rho:-0.773, n=11, P=0.005). Infants with a hemodynamic significant PDA (hsPDA) had higher IMAR values than infants without PDA (0.13 [0.11-0.28], n=16 vs. 0.11 [0.08-0.20], n=29, P=0.005 and 0.11 [0.09-0.18], n=13 vs. 0.09 [0.06-0.17], n=37, P=0.026). CONCLUSIONS: When adjusted for albumin, the lipemia- and haemolysis index, IMAR has potential value as a marker for systemic hypoxia in preterm infants, considering the associations with SpO2, variability of rsSO2, and hsPDA.

Core Outcome Set for Necrotizing Enterocolitis Treatment Trials.

BACKGROUND AND OBJECTIVES: Variability in outcome reporting in necrotizing enterocolitis (NEC) treatment trials hinders conducting meta-analyses and implementing novel treatments. We aimed to develop a core outcome set (COS) for NEC treatment trials including outcome measures most relevant to patients and physicians, from NEC diagnosis to adulthood. METHODS: Clinicians and/or researchers from low-middle- and high-income countries were approached based on their scientific contributions to NEC literature, and patients and parents through local organizations. We presented participants with 45 outcomes used in NEC research, identified through a systematic review. To achieve consensus, outcomes were rated on a scale of 1 to 9 in 3 online Delphi rounds, and discussed at a final consensus meeting. RESULTS: Seventy-one participants from 25 countries completed all Delphi rounds, including 15 patients and family representatives. Thirteen outcomes reached consensus in one of the stakeholder groups and were included in the consensus meeting, 6 outcomes reached consensus in both groups. Twenty-seven participants from both high- and low-middle-income countries attended the online consensus meeting, including family representatives and NEC patients. After discussion and a final vote, 5 outcomes reached consensus to be included: mortality, NEC-related mortality, short bowel syndrome, quality of life, and neurodevelopmental impairment. CONCLUSIONS: This NEC COS includes 5 predominantly long-term outcomes agreed upon by clinicians, patients, and family representatives. Use of this international COS will help standardize outcome selection in clinical trials, ensure these are relevant to those most affected by NEC care, and, ultimately, improve the care of infants with NEC.