Patrizia Zaramella

Brain Auditory Activation Measured by Near-Infrared Spectroscopy (NIRS) in Neonates

This study presents a new measure of the hemodynamic changes to an auditory stimulus in newborns. Nineteen newborns born at 28-41 wk and aged 1 to 49 d were studied in waking and/or sleeping state, for a median time of 4 min 40 s before, 2 min 40 s during, and 3 min 5 s after an acustic stimulus (tonal sweep of frequency increasing from 2 to 4 kHz, intensity 90 dB SPL) originating 5 cm from the external auditory meatus. The emitter and detector optodes were placed over the left or right temporal region, corresponding to T3 or T4 EEG electrodes. The concentration changes in cerebral chromophores Δ[HbO2], Δ[Hb] and Δoxidized-reduced cytochrome aa3 were recorded every 5 s. Changes in cerebral blood volume were calculated from the changes in total Hb × 0.89/large vessel Hb concentration. Increased oxyhemoglobin, Δ[HbO2], total Hb, Δ[Hb sum], and cerebral blood volume, ΔCBV, were found in 13/19 neonates, with the exception of a neonate who only had increased in Δ[Hb], Δ[Hb sum] and ΔCBV. During the stimulation phase there was a significant increase in ΔCBV (t test, p = 0.00006) in the responsive newborns from a mean value of 0.006 (±0.02) mL/100 g in the pretest phase to 0.09 (±0.06) mL/100 g during the auditory stimulus. After the test ΔCBV decreased to 0.04 (±0.07) mL/100 g (t test, p = 0.01), so did Δ[Hb sum] (p = 0.02). Hemodynamic responses of the subjects who showed increases in Δ[Hb sum] and Δ[HbO2] were analyzed to study the Δ[Hb]. The responder subjects could be classified into two groups according to Δ[Hb] changes: 8/13 (61.5%) showed an increase of Δ[Hb] (pattern A), while 5/13 (38.4%) showed a decrease (pattern B) (t test, p = 0.03). These two patterns did not show differences related to Δ[HbO2] and Δ[Hb sum]. The ΔCBV changes in nonresponders presented a decrease during the test phase (t test, p = 0.04). CBV did not return to pretest values, suggesting a fronto-temporal brain pathway for storing unusual sounds. The increase in CBV followed the local increase in oxyhemoglobin and total Hb concentrations due to a greater use of oxygen in the homolateral temporal cortex of the newborns.

Foot pulse oximeter perfusion index correlates with calf muscle perfusion measured by near-infrared spectroscopy in healthy neonates.

OBJECTIVE:In critically ill neonates, peripheral perfusion and oxygenation assessment may provide indirect information on the circulatory failure of vital organs during circulatory shock. The development of pulse oximetry has recently made it possible to calculate the perfusion index (PI), obtained from the ratio between the pulsatile and nonpulsatile signals of absorbed light. The main goals of this study were: (1) to study foot PI; and (2) to evaluate the relationship between foot PI, obtained continuously by pulse oximetry, and a number of variables, i.e. blood flow (BF), oxygen delivery (DO2), oxygen consumption (VO2), and fractional oxygen extraction (FOE), measured indirectly by near-infrared spectroscopy (NIRS) on the calf in 43 healthy term neonates (weight 3474.6±466.9 g; gestational age 39.1±1.4 weeks).STUDY DESIGN:Calf BF, DO2 and VO2 were assessed by NIRS on short-lived venous and arterial occlusion maneuvers. PI was measured on the contralateral foot.RESULTS:Foot PI was 1.26±0.39. There was a positive correlation between foot PI and both calf BF (r=0.32, p=0.03) and DO2 (r=0.32, p=0.03), but no correlation was found between foot PI and calf FOE and between foot PI and VO2.CONCLUSIONS:In the neonatal intensive care unit, continuously measuring foot PI by pulse oximetry seems clinically more feasible for peripheral perfusion monitoring than spot measurements of the calf BF and/or VO2 by indirect NIRS.

Human amniotic fluid stem cells protect rat lungs exposed to moderate hyperoxia.

Treatment of bronchopulmonary dysplasia (BPD) remains as yet an unmet clinical need and recently stem cells have been proposed as a therapeutic tool in animal models. We investigated the role of amniotic fluid stem cells (AFS) in an adult rat model of hyperoxia lung injury.

Influence of ventilation mode on neonatal cerebral blood flow and volume

BACKGROUND Cerebral hemodynamics is supposed to be influenced by the different ventilation approach. Ventilation support can be classified as non-invasive (N-CPAP) or invasive (SIMV and HFV), the last known to induce endotrauma. Our aim was the non-invasive NIRS assessment of neonatal absolute cerebral blood flow (CBF) and relative cerebral blood volume changes (DeltaCBV) during synchronized intermittent ventilation (SIMV), or high frequency ventilation (HFV) and nasal continuous positive airways pressure (CPAP). METHODS An observational study in a tertiary referral NICU. CBF and DeltaCBV changes were assessed in 41 preterm newborn infants with respiratory distress syndrome treated using mechanical ventilation or the CPAP device. RESULTS Basal chromophore traces enabled DeltaCBV (mL/100 g) changes to be calculated. CBF was calculated in mL/100 g/min from the saturation rise integral and rate of rise [O(2)Hb-HHb]. Median DeltaCBV was 0.07 (range 0.01-0.13) in SIMV group, 0.07 (0.01-0.19) in HFV group and 0.13 (0.10-1.28) in CPAP group. Median CBF was 14.44 (2.70-32.10), 9.20 (2.94-19.58) and 31.69 (13.59-34.93) respectively. A multiple regression model showed a significant correlation between DeltaCBV or CBF and ventilation approach. CONCLUSION In the light of our results, we might speculate that, assuming that hemodynamic autoregulation is safe and arterial blood pressure is preserved, ventilation per se influences brain circulation.

Neonatal meningitis due to a vertical transmission of Pasteurella multocida

of domestic animals, such as cats and dogs, and can be transmitted to humans from bites or scratches. Human diseases caused by P. multocida include: (i) cellulitis and lymphadenitis; (ii) chronic respiratory infections in patients with pulmonary disorders; and (iii) P. multocida often acts as an opportunistic pathogen with a predilection for causing bacteremia in patients with liver dysfunction, septic arthritis in damaged joints, central nervous system infections and meningitis in the very elderly or young, especially the newborn. Cases of neonatal meningitis acquired by vertical transmission are very unusual. We describe a case of neonatal infection acquired intrapartum from the mother’s vagina. Table 1 summarizes the literature regarding neonatal infections caused by P. multocida.1–20

Untargeted Metabolomic Analysis of Amniotic Fluid in the Prediction of Preterm Delivery and Bronchopulmonary Dysplasia

Objective Bronchopulmonary dysplasia (BPD) is a serious complication associated with preterm birth. A growing body of evidence suggests a role for prenatal factors in its pathogenesis. Metabolomics allows simultaneous characterization of low molecular weight compounds and may provide a picture of such a complex condition. The aim of this study was to evaluate whether an unbiased metabolomic analysis of amniotic fluid (AF) can be used to investigate the risk of spontaneous preterm delivery (PTD) and BPD development in the offspring. Study design We conducted an exploratory study on 32 infants born from mothers who had undergone an amniocentesis between 21 and 28 gestational weeks because of spontaneous preterm labor with intact membranes. The AF samples underwent untargeted metabolomic analysis using mass spectrometry combined with ultra-performance liquid chromatography. The data obtained were analyzed using multivariate and univariate statistical data analysis tools. Results Orthogonally Constrained Projection to Latent Structures-Discriminant Analysis (oCPLS2-DA) excluded effects on data modelling of crucial clinical variables. oCPLS2-DA was able to find unique differences in select metabolites between term (n = 11) and preterm (n = 13) deliveries (negative ionization data set: R2 = 0.47, mean AUC ROC in prediction = 0.65; positive ionization data set: R2 = 0.47, mean AUC ROC in prediction = 0.70), and between PTD followed by the development of BPD (n = 10), and PTD without BPD (n = 11) (negative data set: R2 = 0.48, mean AUC ROC in prediction = 0.73; positive data set: R2 = 0.55, mean AUC ROC in prediction = 0.71). Conclusions This study suggests that amniotic fluid metabolic profiling may be promising for identifying spontaneous preterm birth and fetuses at risk for developing BPD. These findings support the hypothesis that some prenatal metabolic dysregulations may play a key role in the pathogenesis of PTD and the development of BPD.

Postnatal Hyperoxia Exposure Differentially Affects Hepatocytes and Liver Haemopoietic Cells in Newborn Rats

Premature newborns are frequently exposed to hyperoxic conditions and experimental data indicate modulation of liver metabolism by hyperoxia in the first postnatal period. Conversely, nothing is known about possible modulation of growth factors and signaling molecules involved in other hyperoxic responses and no data are available about the effects of hyperoxia in postnatal liver haematopoiesis. The aim of the study was to analyse the effects of hyperoxia in the liver tissue (hepatocytes and haemopoietic cells) and to investigate possible changes in the expression of Vascular Endothelial Growth Factor (VEGF), Matrix Metalloproteinase 9 (MMP-9), Hypoxia-Inducible Factor-1α (HIF-1α), endothelial Nitric Oxide Synthase (eNOS), and Nuclear Factor-kB (NF-kB). Experimental design of the study involved exposure of newborn rats to room air (controls), 60% O2 (moderate hyperoxia), or 95% O2 (severe hyperoxia) for the first two postnatal weeks. Immunohistochemical and Western blot analyses were performed. Severe hyperoxia increased hepatocyte apoptosis and MMP-9 expression and decreased VEGF expression. Reduced content in reticular fibers was found in moderate and severe hyperoxia. Some other changes were specifically produced in hepatocytes by moderate hyperoxia, i.e., upregulation of HIF-1α and downregulation of eNOS and NF-kB. Postnatal severe hyperoxia exposure increased liver haemopoiesis and upregulated the expression of VEGF (both moderate and severe hyperoxia) and eNOS (severe hyperoxia) in haemopoietic cells. In conclusion, our study showed different effects of hyperoxia on hepatocytes and haemopoietic cells and differential involvement of the above factors. The involvement of VEGF and eNOS in the liver haemopoietic response to hyperoxia may be hypothesized.

Lethal Effect of a Single Dose of Rasburicase in a Preterm Newborn Infant

This case report describes a preterm newborn infant who was treated with a single dose of rasburicase for an increase in uric acid level. He died on the third day as a result of complications of hemolysis, which appeared to be precipitated by rasburicase. The patient’s death was preceded by progressive respiratory insufficiency, lactic acidosis, and hyperbilirubinemia, culminating in refractory hypoxia and hypotension. A postmortem assay for glucose-6-phosphate dehydrogenase showed deficiency and the glucose-6-phosphate dehydrogenase Mediterranean genotype.

Analysis and interpretation of acylcarnitine profiles in dried blood spot and plasma of preterm and full-term newborns

Background:Acylcarnitines are biomarkers of fatty acid metabolism, and examining their patterns in preterm newborn may reveal metabolic changes associated with particular conditions related to prematurity. Isomeric acylcarnitines in dried blood spots (DBS) and plasma have never been assessed in preterm infants.Methods:We studied 157 newborn divided into four groups by weeks of gestational age (GA), as follows: 22–27 wk in group 1; 28–31 wk in group 2; 32–36 wk in group 3; and 37–42 wk in group 4. Samples were collected on the third day of life. Acylcarnitines were separated and quantified using ultra-performance liquid chromatography tandem mass spectrometry.Results:Acylcarnitine concentrations correlated significantly with GA and birth weight in both DBS and plasma samples. Concentrations were lower in preterm newborn, except for acylcarnitines derived from branched-chain amino acids, which were higher and correlated with enteral feeding. On day 3 of life, no correlations emerged with gender, respiratory distress syndrome, bronchopulmonary dysplasia, surfactant administration, or mechanical ventilation.Conclusion:We established GA-based reference ranges for isomeric acylcarnitine concentrations in preterm newborn, which could be used to assess nutritional status and the putative neuroprotective role of acylcarnitines.

Cyclosporine and hyperoxia-induced lung damage in neonatal rats ☆

Cyclosporine effects on hyperoxia-induced histopathological and functional changes in the rat adult lung are controversial and the newborn lung has not been studied. Thus, we evaluated the effects of cyclosporine in young rats after 60% hyperoxia exposure postnatally. Experimental categories included: (1) room air for the first 5 postnatal weeks with daily subcutaneous injections of saline from postnatal day (PN)15 to PN35; (2) room air with daily injections of cyclosporine from PN15 to PN35; (3) 60% oxygen from PN0 to PN14 and then daily saline injections during the following three weeks; (4) 60% oxygen from PN0 to PN14 followed by cyclosporine treatment from PN15 to PN35. Hyperoxia significantly reduced the number of secondary crests and microvessel density, and it increased the mean alveolar size and septa thickness. Cyclosporine treatment did not significantly modify the hyperoxia-induced changes. Conversely, in normoxia, cyclosporine reduced microvessel density and the number of secondary crests. In conclusion, cyclosporine did not modify alveolar and microvascular parameters in hyperoxia exposure, although it caused some changes in normoxia.