Necrotizing enterocolitis (NEC) is the most devastating gastrointestinal emergency in preterm neonates. Research on early predictive biomarkers is fundamental. This is a systematic review of studies applying untargeted metabolomics and gut microbiota analysis to evaluate the differences between neonates affected by NEC (Bell’s stage II or III), and/or by spontaneous intestinal perforation (SIP) versus healthy controls. Five studies applying metabolomics (43 cases, 95 preterm controls) and 20 applying gut microbiota analysis (254 cases, 651 preterm controls, 22 term controls) were selected. Metabolomic studies utilized NMR spectroscopy or mass spectrometry. An early urinary alanine/histidine ratio >4 showed good sensitivity and predictive value for NEC in one study. Samples collected in proximity to NEC diagnosis demonstrated variable pathways potentially related to NEC. In studies applying untargeted gut microbiota analysis, the sequencing of the V3–V4 or V3 to V5 regions of the 16S rRNA was the most used technique. At phylum level, NEC specimens were characterized by increased relative abundance of Proteobacteria compared to controls. At genus level, pre-NEC samples were characterized by a lack or decreased abundance of Bifidobacterium. Finally, at the species level Bacteroides dorei, Clostridium perfringens and perfringens-like strains dominated early NEC specimens, whereas Clostridium butyricum, neonatale and Propionibacterium acnei those at disease diagnosis. Six studies found a lower Shannon diversity index in cases than controls. A clear separation of cases from controls emerged based on UniFrac metrics in five out of seven studies. Importantly, no studies compared NEC versus SIP. Untargeted metabolomics and gut microbiota analysis are interrelated strategies to investigate NEC pathophysiology and identify potential biomarkers. Expression of quantitative measurements, data sharing via biorepositories and validation studies are fundamental to guarantee consistent comparison of results.

Necrotizing enterocolitis (NEC) is the main gastrointestinal emergency of preterm infants for whom bowel rest and parenteral nutrition (PN) is essential. Despite the improvements in neonatal care, the incidence of NEC remains high (11% in preterm newborns with a birth weight <1500 g) and up to 20–50% of cases still require surgery. In this narrative review, we report how to optimize PN in severe NEC requiring surgery. PN should begin as soon as possible in the acute phase: close fluid monitoring is advocated to maintain volemia, however fluid overload and electrolytes abnormalities should be prevented. Macronutrients intake (protein, glucose, and lipids) should be adequately guaranteed and is essential in each phase of the disease. Composite lipid emulsion should be the first choice to reduce the risk of parenteral nutrition associated liver disease (PNALD). Vitamin and trace elements deficiency or overload are frequent in long-term PN, therefore careful monitoring should be planned starting from the recovery phase to adjust their parenteral intake. Neonatologists must be aware of the role of nutrition especially in patients requiring long-term PN to sustain growth, limiting possible adverse effects and long-term deficiencies.

Background: Necrotizing enterocolitis (NEC) is the most frightening gastrointestinal emergency in newborns. Despite being primarily a disease of premature infants, neonates with congenital heart disease (CHD) are at increased risk of development. Acute and chronic hemodynamic changes in this population may lead to mesenteric circulatory insufficiency. Objectives: In this narrative review, we describe monitoring tools, alone or in multimodal use, that may help in the early recognition of patients with CHD at major risk of NEC development. Methods: We focused on vital parameters, echocardiography, Doppler flowmetry, abdominal near-infrared spectroscopy (aNIRS), and abdominal ultrasound (aUS). Results: The number of studies on this topic is small and includes a wide range of patients’ ages and types of CHD. Peripheral oxygen saturation (SpO₂) and certain echocardiographic indices (antegrade and retrograde velocity time integral, cardiac output, etc.) do not seem to differentiate infants with further onset of NEC from those not developing it. Hypotensive events, persistent diastolic flow reversal in the descending aorta, and low mesenteric oxygen saturation (rsSO₂) measured by aNIRS appear to occur more frequently in infants who later develop NEC. aUS may be helpful in the diagnosis of cardiac NEC, potentially showing air contrast tracked to the right atrium in the presence of pneumatosis. Conclusions: This narrative review describes the current knowledge on bedside tools for the early prediction of cardiac NEC. Future research needs to further explore the use of easy-to-learn, reproducible instruments to assist patient status and monitor patient trends.

Background: The premature-born adult population is set to grow significantly, and prematurity has emerged as an important cardiovascular risk factor. We aimed to comprehensively assess cardiac mechanics and function in a cohort of ex-preterm preschoolers. Methods: Ex-preterm children (<30 weeks of gestation), aged 2 to 5 years, underwent transthoracic 2D, speckle-tracking, and 4D echocardiography. The findings were compared with 19 full-term children. Results: Our cohort of 38 children with prematurity history showed a normal morpho-functional echocardiographic assessment. However, compared to controls, the indexed 3D end-diastolic volumes of ventricular chambers were reduced (left ventricle 58.7 ± 11.2 vs. 67.2 ± 8.5 mL/m²; right ventricle 50.3 ± 10.4 vs. 57.7 ± 11 mL/m²; p = 0.02). Left ventricle global and longitudinal systolic function were worse in terms of fraction shortening (32.9% ± 6.8 vs. 36.5% ± 5.4; p = 0.05), ejection fraction (59.2% ± 4.3 vs. 62.3% ± 3.7; p = 0.003), and global longitudinal strain (−23.6% ± 2.4 vs. −25.5% ± 1.7; p = 0.003). Finally, we found a reduced left atrial strain (47.4% ± 9.7 vs. 54.9% ± 6.8; p = 0.004). Conclusions: Preschool-aged ex-preterm children exhibited smaller ventricles and subclinical impairment of left ventricle systolic and diastolic function compared to term children. Long-term follow-up is warranted to track the evolution of these findings.

Very preterm neonates are more prone to experience hyper and hypo-glycaemia after birth. To date, there is no available evidence on the local brain hemodynamic response to these glycemic changes. This study uses continuous glucose monitoring (CGM) and diffuse optical tomography (DOT) to investigate this issue. Sixty very preterm neonates were recruited and continuously monitored after birth with CGM and DOT for several days. Patients with only mild (Sensor glucose concentration (SGC) ≥ 48 mg/dL & ≤ 72 mg/dL) or severe (SGC ≤ 47 mg/dL) hypoglycaemia (N=17) were then selected for analysis. DOT data were reconstructed in three 10-minute windows throughout each hypoglycemic event: at the beginning of the event, after the minimum of hypoglycemia, and at the end of the event. Correlations and spatial consistencies were found between changes in blood volume and SGC during these time windows, suggesting a coupling between SGC and brain hemodynamics in very preterm newborns after birth.

SignificanceVery preterm infants are prone to large fluctuations in their blood glucose concentration (BGC), i.e., they can experience episodes of hyper- and hypoglycemia, due to impaired glucose control. To date, the relationship among how specific regions of the brain respond to glycemic events has not been fully explored, and characterizing how glucose fluctuations affect region-specific functional connectivity at birth may provide insight into neurodevelopment and could help identify early biomarkers of brain vulnerability in very preterm infants.AimThe aim is to evaluate whether the differences in task-free functional connectivity (tfFC) patterns before and after experiencing several days of BGC fluctuations were correlated with changes in the glucose profile during this time interval.ApproachWe continuously monitored both glucose concentration with a continuous glucose monitoring device and brain hemodynamics with diffuse optical tomography in a group of very preterm newborns to conduct tfFC analysis (N=12).ResultsChanges in tfFC patterns between the left frontal and left parietal regions were found to be correlated with the standard deviation of the glucose profile, whereas changes between the central prefrontal cortex and the right prefrontal region were found to be correlated with the maximum value of glucose concentration.ConclusionsWe suggest that changes in the coupling of these brain areas during rest are dependent on and occur during exposures to glycemic changes in the preterm brain.