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While mainly based on the use of fluorinated steroids, there is no standard management of anti-Ro/La-related congenital heart block (CHB). This is a report concerning two consecutive cases of anti-Ro/La-related second-degree block treated with betamethasone (4 mg/day), weekly plasmapheresis, and intravenous immunoglobulins (IVIGs; 1 g/kg) administered every 15 days, a therapy that was begun shortly after CHB was detected and continued until delivery. The newborns were also treated with IVIG (1 g/kg) soon after birth and continued fortnightly until the anti-Ro/La antibody levels became undetectable. In both cases second-degree AV block reverted to a stable sinus rhythm with a first-degree atrioventricular (AV) block. Moreover, there was no recurrence of CHB when therapy was suspended, as confirmed by a 29 month and an eight month follow-up, respectively. [ABSTRACT FROM AUTHOR]

Background: Pre-delivery maternal electrolyte derangements may reflect themselves in the newborn, since placental homeostasis determines electrolyte equilibrium between mother and fetus., Case Presentation: A term newborn, transferred to our Neonatal Intensive Care Unit 1 h after birth for an apnoea episode, presented with initially left-sided, and subsequently generalized tonic-clonic seizures due to severe hyponatremia (119 mmol/L). Seizures rapidly ceased after electrolyte correction plus a phenobarbital bolus. Deep hyponatremia was also detected in the mother (123 mmol/L)., Conclusions: As placental homeostasis determines electrolytes equilibrium between mother and fetus, obstetrics and neonatologists should be aware that any maternal dyselectrolytemia will reflect itself in the newborn; hence, it is fundamental to detect possible maternal electrolyte imbalances before delivery, in order to be prepared to timely correction of electrolyte derangements in the newborn.

Coenzyme Q10 deficiency is a clinically and genetically heterogeneous disorder, with manifestations that may range from fatal neonatal multisystem failure, to adult-onset encephalopathy. We report a patient who presented at birth with severe lactic acidosis, proteinuria, dicarboxylic aciduria, and hepatic insufficiency. She also had dilation of left ventricle on echocardiography. Her neurological condition rapidly worsened and despite aggressive care she died at 23 h of life. Muscle histology displayed lipid accumulation. Electron microscopy showed markedly swollen mitochondria with fragmented cristae. Respiratory-chain enzymatic assays showed a reduction of combined activities of complex I+III and II+III with normal activities of isolated complexes. The defect was confirmed in fibroblasts, where it could be rescued by supplementing the culture medium with 10 μM coenzyme Q10. Coenzyme Q10 levels were reduced (28% of controls) in these cells. We performed exome sequencing and focused the analysis on genes involved in coenzyme Q10 biosynthesis. The patient harbored a homozygous c.545T>G, p.(Met182Arg) alteration in COQ2, which was validated by functional complementation in yeast. In this case the biochemical and morphological features were essential to direct the genetic diagnosis. The parents had another pregnancy after the biochemical diagnosis was established, but before the identification of the genetic defect. Because of the potentially high recurrence risk, and given the importance of early CoQ10 supplementation, we decided to treat with CoQ10 the newborn child pending the results of the biochemical assays. Clinicians should consider a similar management in siblings of patients with CoQ10 deficiency without a genetic diagnosis.

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.

Premature newborns may be exposed to hyperoxia in the first postnatal period, but clinical and experimental works have raised the question of oxygen toxicity for the developing brain. However, specific analysis of hyperoxia exposure on neurogenesis is still lacking. Thus, the aim of the present study was to evaluate possible changes in the morphometric parameters of the main neurogenic sites in newborn rats exposed to 60 or 95 % oxygen for the first 14 postnatal days. The optical disector, a morphometric method based upon unbiased sampling principles of stereology, was applied to analyse cell densities, total volumes, and total cell numbers of the dentate gyrus (DG) and subventricular zone (SVZ). Apoptosis and proliferation were also studied by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling method and anti-ki67 immunohistochemistry, respectively. Severe hyperoxia increased the percentage of apoptotic cells in the DG. Moderate and severe hyperoxia induced a proliferative response both in the DG and SVZ, but the two neurogenic sites showed different changes in their morphometric parameters. The DG of both the hyperoxic groups showed lower volume and total cell number than that of the normoxic one. Conversely, the SVZ of newborn rats exposed to 95 % hyperoxia showed statistically significant higher volume and total cell number than SVZ of rats raised in normoxia. Our findings indicate that hyperoxia exposure in the first postnatal period affects both the neurogenic areas, although in different ways, i.e. reduction of DG and expansion of SVZ.

Objective: To evaluate whether a polyethylene total body wrapping (covering both the body and head) is more effective than conventional treatment (covering up to the shoulders) in reducing perinatal thermal losses in very preterm infants., Study Design: This was a multicenter, prospective, randomized, parallel 1:1, unblinded, controlled trial of infants<29 weeks' gestation age, comprising two study groups: experimental group (total body group; both the body and head covered with a polyethylene occlusive bag, with the face uncovered) and control group (only the body, up to the shoulders, covered with a polyethylene occlusive bag). The primary outcome was axillary temperature on neonatal intensive care unit admission immediately after wrap removal., Results: One hundred randomly allocated infants (50 in the total body group and 50 controls) completed the study. Mean axillary temperature on neonatal intensive care unit admission was similar in the two groups (36.5±0.6°C total body vs 36.4±0.8°C controls; P=.53). The rate of moderate hypothermia (temperature<36°C) was 12% in the total body group and 20% in the control group (P=.41). Three subjects in each group (6.0%) had an axillary temperature>37.5°C on admission, and one subject in control group had an axillary temperature>38°C., Conclusion: Total body wrapping is comparable with covering the body up to the shoulders in preventing postnatal thermal losses in very preterm infants., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The most important action in the resuscitation of a newborn in the delivery room is to establish effective assisted ventilation. The face mask and endotracheal tube are the devices used to achieve this goal. Laryngeal mask airways that fit over the laryngeal inlet have been shown to be effective for ventilating newborns at birth and should be considered as an alternative to facemask ventilation or endotracheal intubation among newborns weighing >2,000 g or delivered ≥34 weeks' gestation. A recent systematic review and meta-analysis of supraglottic airways in neonatal resuscitation reported the results of four randomized controlled trials (RCTs) stating that fewer infants in the group using laryngeal mask airways required endotracheal intubation (1.5%) compared to the group using face masks (12.0%). However, there were methodological concerns over all the RCTs including the fact that the majority of the operators in the trials were anesthesiologists.Our hypothesis is based on the assumption that ventilating newborns needing positive pressure ventilation with a laryngeal mask airway will be more effective than ventilating with a face mask in a setting where neonatal resuscitation is performed by midwives, nurses, and pediatricians. The primary aim of this study will be to assess the effectiveness of the laryngeal mask airway over the face mask in preventing the need for endotracheal intubation., Methods/design: This will be an open, prospective, randomized, single center, clinical trial. In this study, 142 newborns weighing >1,500 g or delivered ≥34 weeks gestation needing positive pressure ventilation at birth will be randomized to be ventilated with a laryngeal mask airway (LMA SupremeTM, LMA Company, UK - intervention group) or with a face mask (control group)., Primary Outcome: Proportion of newborns needing endotracheal intubation., Secondary Outcomes: Apgar score at 5 minutes, time to first breath, onset of the first cry, duration of resuscitation, death or moderate to severe hypoxic-ischemic encephalopathy within 7 days of life., Trial Registration: ClinicalTrials.gov identifier: NCT01963936 (October 11, 2013).

Background: Ibuprofen (IBU) has proved as effective as indomethacin in the pharmacological closure of hemodynamically significant patent ductus arteriosus (HsPDA), with an efficacy inversely related to gestational age (57-89%)., Objective: This study aimed to establish whether continuous infusions of IBU could be more effective in very low birth weight infants with no additional adverse effects and reduce the need for surgical ligation., Methods: A prospective, randomized, double-dummy study was conducted on 112 very low birth weight infants (mean gestational age 27.2 weeks, SD 2; birth weight 1,019 g, SD 330) with HsPDA, 56 of whom were given IBU in conventional 15-min intermittent boluses, while the other 56 were administered IBU as a 24-hour continuous infusion, both at standard doses (10/5/5 mg/kg). Extensive echocardiography was performed before and after treatment, and adverse effects were monitored., Results: Pharmacological PDA closure was achieved after 1 or 2 IBU courses in 36 of 56 infants (64.3%) after bolus administration and in 46 of 55 (83.6%) after continuous infusion (p = 0.020), and in 9 of 26 (34.6%) and 24 of 30 (80.0%), respectively, in the infants with a gestational age of 23-27 weeks (p = 0.006). Sustained pharmacological closure was observed in 38 of 56 infants (67.9%) after bolus IBU and in 47 of 55 (85.5%) after continuous infusion (p = 0.029). Surgical ligation was used less after continuous infusion than after bolus IBU (5.5 vs. 19.6%; p = 0.024). The continuous infusion group had fewer symptoms of necrotizing enterocolitis (NEC), especially in the more preterm infants, while other neonatal morbidity and mortality rates were similar., Conclusion: Continuous IBU infusion is more effective than standard boluses for sustained closure of HsPDA, with fewer NEC symptoms and less need for surgical ligation in very low birth weight infants., (© 2013 S. Karger AG, Basel.)

Background: 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., Methods: Fifty Sprague-Dawley rats were, at birth, randomly exposed to moderate hyperoxia or room air for 14 days and a single dose of human amniotic fluid stem (hAFS) or human Fibroblasts (hF), cells was delivered intratracheally (P21). At P42 animals were euthanized and lung tissue examined using histology, immunohistochemistry, PCR, and ELISA. hAFS cells characterization and homing were studied by immunofluorescence., Results: In rats treated with hAFS and hF cells 16S human rRNA fragment was detected. Despite a low level of pulmonary hAFS cell retention (1.43 ± 0.2% anti-human-mitochondria-positive cells), the lungs of the treated animals revealed higher secondary crest numbers and lower mean linear intercept and alveolar size, than those exposed to hyperoxia, those left untreated or treated with hF cells. Except for those treated with hAFS cells, moderate hyperoxia induced an increase in protein content of IL-6, IL-1β, as well as IF-γ and TGF-1β in lung tissues. High VEGF expression and arrangement of capillary architecture in hAFS cell group were also detected., Conclusions: Treatment with hAFS cells has a reparative potential through active involvement of cells in alveolarization and angiogenesis. A downstream paracrine action was also taken into account, in order to understand the immunodulatory response., (© 2013 Wiley Periodicals, Inc.)

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., (Copyright © 2013 Elsevier B.V. All rights reserved.)

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.

Aim: In critically ill neonates, peripheral perfusion and oxygenation assessment may provide indirect information on circulatory failure in limb arterial thromboembolic emergencies. Aims of our study were: 1) to evaluate the changes on tissue oxygenation index, oxyhemoglobin, deoxyhemoglobin and blood volume obtained by near-infrared spectroscopy (NIRS) on the infants legs; 2) to compare them with ultrasonographic data., Methods: Tissue oxygenation index (TOI), oxyhemoglobin (O2Hb), deoxyhemoglobin (HHb) and blood volume (BV) differences were assessed by NIRS on the calf of 8 newborn infants (median weight 1995, range 585-3010 g; median gestational age 32.5, range 26-40 wks). An ultrasonographic scan of the arterial system was performed before the NIRS measurements, to validate the site of arterial occlusion., Results: A t-test for independent samples showed lower values in the affected limb for all NIRS measurements. TOI measurements displayed lower values in the thromboembolic limb (mean 44.79±12%) versus unaffected (mean 47.95±17.08%) (P=0.0001). Mean (SD) peak systolic velocity in the patent artery below the occlusion decreased from 108±25 cm/s in the normal limb to 25.6±28 cm/s in the thrombus site (P=0.02)., Conclusion: In neonatal intensive care units, measurement of limb peripheral perfusion and oxygenation seems to be clinically useful in arterial thromboembolic emergencies.

Fluoxetine shows controversial lung effects as it prevents pulmonary hypertension in adult rats but exposure during gestation causes pulmonary hypertension in neonatal rats. In the present study, we tested the null hypothesis that the antidepressant drug fluoxetine does not modify the development of bronchopulmonary dysplasia (BPD) in neonatal rats. Experimental categories included I: room air (controls) with daily injection of saline; II: room air with daily injection of 10 mg/kg fluoxetine, i.p., during two weeks; III: 60% oxygen with daily injection of saline; and IV: 60% oxygen with daily injection of 10 mg/kg fluoxetine, i.p., during two weeks. Hyperoxia resulted in significant reduction in alveolar density and an increase in pulmonary endocrine cells, as well as increases in muscle layer areas of bronchi and arteries. Fluoxetine treatment generated a further increase in muscularisation and did not significantly modify the hyperoxia-induced reductions in alveolar density and increases in the endocrine cells. In hyperoxia, Real-Time PCR showed a lower pulmonary expression of vascular endothelial growth factor (VEGF) with no significant changes in the expression of matrix metalloproteinases (MMP) 2 and 12. Fluoxetine did not affect VEGF or MMP-2 expression but it significantly increased MMP-12 mRNA in both normoxic and hyperoxic groups. Zymographic analysis of MMP-2 activity in bronchoalveolar fluid showed a significantly reduced MMP-2 activity in hyperoxia, while fluoxetine treatment restored MMP-2 activity to levels comparable with the normoxic group. In conclusion, our data show that fluoxetine may worsen bronchial and arterial muscularisation during development of BPD and may up-regulate MMP expression or activity.

Background: Moderate normobaric hyperoxia causes alveolar and vascular lung derangement in the newborn rat. Endogenous nitric oxide (NO), which promotes lung growth, is produced from the metabolism of L-arginine to L-citrulline in endothelial cells. We investigated whether administering L-citrulline by raising the serum levels of L-arginine and enhancing NO endogenous synthesis attenuates moderate hyperoxia-induced lung injury., Methods: Newborn rats were exposed to FiO(2) = 0.6 or room air for 14 days to induce lung derangement and then were administered L-citrulline or a vehicle (sham). Lung histopathology was studied with morphometric features. Lung tissues and bronchoalveolar lavage fluid (BALF) were collected for analysis. Lung vascular endothelial growth factor (VEGF), nitric oxide synthase (eNOS), and matrix metalloproteinase 2 (MMP2) gene and protein expressions were assessed., Results: Serum L-arginine rose in the L-citr + hyperoxia group (p = 0.05), as well as the Von Willebrand factor stained vessels count (p = 0.0008). Lung VEGF immune staining, localized on endothelial cells, was weaker in the sections under hyperoxia than the L-citr + hyperoxia and room air groups. This pattern was comparable with the VEGF gene and protein expression profiles. Mean alveolar size increased in the untreated hyperoxia and sham-treated groups compared with the groups reared in room air or treated with L-citrulline under exposure to hyperoxia (p = 0.0001). Lung VEGF and eNOS increased in the L-citrulline-treated rats, though this treatment did not change MMP2 gene expression but regulated the MMP2 active protein, which rose in BALF (p = 0.003)., Conclusions: We conclude that administering L: -citrulline proved effective in improving alveolar and vascular growth in a model of oxygen-induced pulmonary damage, suggesting better lung growth and matrix regulation than in untreated groups.

Aim: To evaluate the impact of endothelial progenitor cells (EPCs), a subset of committed circulatory stem cells, on the development of bronchopulmonary dysplasia (BPD) and other short term outcomes in a cohort of extremely premature newborns., Methods: Progenitor cells were quantified by flow cytometry at birth in 36 neonates born <=28 weeks of gestation and at 36 postmenstrual weeks in 18 of them. Cells expressing the stemness markers CD34, CD133, or both were defined as circulating progenitor cells (CPCs). EPCs were defined as CPCs co-expressing the endothelial marker KDR., Results: Mean (SD) gestational age and birth weight of the infants studied were 26.2(1.5) weeks and 761.6(171.8) grams, respectively. EPC levels at birth did not differ between infants who subsequently developed BPD (n=9) and those who did not (n=24) [CD34(+)KDR(+) EPCs: 81(34-41) vs 80(56-110), p=0.7] and were not correlated with the duration of mechanical ventilation or O2-dependence, nor with the need of surfactant replacement. Infants with a hemodynamically significant patent ductus arteriosus (PDA) (n=22) had significantly lower EPC levels at birth than those with no PDA (n=11) [CD34(+)KDR(+) cells: 47(34-92) vs 142(84.5-221), p=0.008]. Data from the 18 infants studied both at birth and at 36 postmenstrual weeks showed that, while CPCs sharply decline over time, levels of all EPCs phenotypes are preserved after delivery., Conclusions: Levels of EPCs at birth did not affect the risk of developing BPD in our group of extremely premature neonates. However, the association between low EPC counts at birth and PDA may be clinically relevant, and deserves further studies., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

We measured circulating ADMA concentrations in a group of very premature newborns at birth and during the first week of life. ADMA levels resulted significantly higher in infants born to mothers with histologic chorioamnionitis than in infants delivered for other maternal or fetal indications, both at birth and through the first week of life. We speculate that ADMA might be involved in the complex biological events associated with fetal exposure to chorioamnionitis., (2010 Elsevier Ltd. All rights reserved.)

The objective of the study is to describe safety and effects of protein C concentrate (PCConc) administration in neonates with sepsis-induced coagulopathy. Eighteen neonates (12 preterm and 6 full term) aged between 1 and 28 days who have severe sepsis (n = 6) or septic shock (n = 12), with coagulopathy and acquired protein C (PC) deficiency received PCConc (i.v. bolus of 100 IU/kg, followed by 50 IU/kg every 6 h for 72 h). Platelet counts, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, D-dimer, C-reactive protein (CRP), antithrombin (AT), PC, CRP, and neonatal therapeutic intervention scoring system (NTISS) were assessed before and 24, 48, and 72 h after the study entry. According to Clinical Risk Index for Babies II score (CRIB II score), the expected mortality in preterms was 10%. After 24 h of treatment, PC activity levels increased from an average of 19% to 57%, and they were within normal limits before the last PCConc bolus. During the treatment period, a shortening of PT (P = 0.04) and activated partial thromboplastin time (P = 0.02), and an increase in antithrombin levels (P < 0.0001) were observed, along with a reduction in CRP (P = 0.005) and NTISS values (P = 0.003). No adverse events were observed. This pilot study shows that in neonatal severe sepsis, normalization of PC levels is safe and probably effective in modulating the inflammatory response and in controlling coagulopathy. However, for the potential beneficial effects of PCConc administration on morbidity and mortality, a placebo-controlled, double-blind study is required.

The reticulocyte count reflects the erythropoietic activity of the bone marrow and is thus useful in both the diagnosis of anemias and in monitoring bone marrow response to therapy. Starting in the mid-1990s, automated flow-cytometric analysis has replaced traditional microscopic quantitation of reticulocytes. Reticulocyte analysis now includes measurements mRNA content and the maturity of reticulocytes, cell volume, hemoglobin concentration and content. The immature reticulocyte fraction is a reliable early predictor of hematopoietic engraftment following allogeneic stem cell transplantation, while the reticulocyte hemoglobin content provides an indirect measure of the functional iron available for new red blood cell production over the previous 3-4 days. Especially in anemic newborns, reticulocyte analysis is useful to help clinicians follow erythropoietic changes, to monitor response to recombinant human erythropoietin therapy, to gauge transfusion needs, and to evaluate jaundice. Despite improved accuracy and precision, significant problems still persist in maintaining adequate levels of precision and comparability across different laboratories. In the absence of better laboratory standardization, having a single reference range for the parameters provided by flow-cytometric studies of reticulocytes remains problematic.

Background: Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide (NO) formation inhibitor, has emerged as a promising biomarker of NO-associated endothelial dysfunction in cardiovascular diseases as well in chronic renal failure. The interest in potentially fundamental role of this metabolite, in basic and clinical research, led to the development of numerous analytical methods for the quantitative determination of ADMA and dimethylarginines in biological systems, notably plasma, serum and urine., Objectives: The aim of this work was to present a simple, fast and accurate UPLC-tandem-MS-based method for the simultaneous determination and quantification of arginine, ADMA, SDMA, NMMA, homo-arginine and citrulline. This method is designed for high sample throughput of only 10 μL of human plasma, serum or urine., Methods: The analysis time is reduced to 1.9 min by an ultrahigh-performance liquid chromatography run coupled with electrospray ionization (ESI) in the positive mode tandem mass spectrometry detection., Results: The method was validated in plasma, serum and urine. Correlation coefficients (r(2)) of the calibration curves in all matrices considered ranged from 0.9810 to 0.9993. Inter- and intra-assay precision, accuracy, recovery and carry-over were evaluated for validation. The LOD was 0.01 μM for all compounds in water, plasma and serum and 0.1 μM in urine. The LOQ was 0.05 μM for ADMA, SDMA, NMMA and H-Arg and 0.5 μM for Arg and Cit in water, plasma and serum; while in urine was 0.1 μM for ADMA, SDMA, NMMA and H-Arg and 0.5 μM for Arg and Cit. The precision was ranged from 1% to 15% expressed as CV% and the accuracy (bias %) was <±7% for all added concentrations with the exception of NMMA (-10%). ADMA mean plasma levels, measured in healthy adults and newborns, were in accord with literature data published: (M±SD) 0.56±0.10 μM and 0.84±0.21 μM, respectively, showing that ADMA levels in plasma decreased with age. In serum we have similar data (0.54±0.18 μM and 1.14±0.36 μM), while in neonatal urine ADMA was 11.98±7.13 μmol mmol(-1) creatinine., Conclusions: Data from calibration curves and method validation reveal that the method is accurate and precise. The fast run time, the feasibility of high sample throughput and the small amount of sample required make this method very suitable for routine analysis in the clinical setting., (Copyright © 2010 Elsevier B.V. All rights reserved.)

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.

In the last few years some studies have shown the possibility of deriving progenitors with various potential from the amniotic fluid. Amniocentesis is a widely accepted method for prenatal diagnosis; it is associated with low risk both for the mother and the fetus and overcomes the ethical problems commonly associated to other sources. Recently we have described that amniotic fluid stem (AFS) cells, for their ability to differentiate to various lineages, could represent a good candidate for therapeutic applications. For gene therapy purposes human AFS (hAFS) cells should be genetically modified with a therapeutic gene and delivered systematically or injected directly into the tissue of interest. The aim of this study was to investigate the feasibility of transducing hAFS cells with adenoviral vectors and to determine whether transduced stem cells retain the ability to differentiate into different lineages. Herein, we showed that hAFS cells could be efficiently infected by first generation adenovirus vectors. In addition, we demonstrated that infection and expression of two different marker genes, LacZ and EGFP, have no effect on cells phenotype and differentiation potential. In particular, on undifferentiated status, hAFS cells continued to express both the transgenes and stemness cell markers OCT4 and SSEA4. When cultured under mesenchymal conditions, infected cells could still differentiate into osteocytes and adipocytes expressing lineage specific genes. These preliminary findings suggest that adenovirus may be useful to engineer populations of pluripotent stem cells, which may be used in a wide range of gene therapy treatments.

Background: The availability of a score for predicting neonatal outcome prior to discharge may help us to define the risk of developmental disorders in very low birth weight infants., Aim: To compare Scheiner's Perinatal Risk Inventory (PERI) with Brazy's Neurobiological Risk Score (NBRS) when applied at discharge, in predicting developmental delay at 24 months of age., Study Design: To evaluate the predictive power of the two tests, we measured their sensitivity and specificity in predicting outcome (Mental Development Index, MDI, Psychomotor Development Index, PDI, and Amiel-Tison Neurological Examination) in an observational study., Subjects: 102 very low birth weight infants (BW <1,500 g) admitted to our NICU at the Pediatric Department of Padova University., Results: In the cohort studied, 75.5% of the patients had a normal MDI, while 24.5% showed a delayed performance (8.8% mildly and 15.7% severely so); the PDI was normal in 74.5% patients, whilst 25.5% had a delayed performance (9.8% mildly and 15.7% severely so). According to the Amiel-Tison test, neurological performance was normal in 66% patients, impaired without disability in 19% and impaired with disability in 15%. NBRS showed a sensitivity and specificity respectively of 0.96 and 0.23 (MDI), 0.96 and 0.24 (PDI), 0.94 and 0.25 (Amiel-Tison test); for PERI were 0.88 and 0.54 (MDI), 0.77 and 0.51 (PDI), 0.82 and 0.57 (Amiel-Tison test). The PERI and NBRS can predict the MDI with an AUC >0.8 and the PDI or Amiel-Tison findings with an AUC of 0.7-0.8. No significant differences were found between the areas under the ROC curves using the NBRS and the PERI., Conclusions: : In assessing the prognosis for individual babies, the physician can choose either the PERI or the NBRS to predict PDI, MDI or Amiel-Tison performance.

Background: In the debate on the best cord clamping time in newborn infants, we hypothesized that late cord clamping enables an increased volemia due to blood transfer to the newborn from the placenta., Aim: To assess whether clamping time can affect limb perfusion and heart hemodynamics in a group of 22 healthy term newborn infants., Study Design: A case-control study., Subjects: Eleven early-clamped (at 30 s) vaginally-delivered newborn infants were compared with eleven late-clamped (at 4 min) newborns., Outcome Measures: The two groups were studied using near-infrared spectroscopy and M-mode echocardiography., Results: Late cord clamping coincided with a higher hematocrit (median 62% versus 54%) and hemoglobin concentration (median 17.2 versus 15 g/dL), whilst there were no changes in bilirubin level. Echocardiography showed a larger end-diastolic left ventricle diameter (1.7 cm median value versus 1.5) coupled with unvaried shortening and ejection fraction values. There were no changes in calf blood flow, oxygen delivery, oxygen consumption or fractional oxygen extraction calculated from the NIRS measurements, or in foot perfusion index., Conclusions: Our results demonstrated that late cord clamping coincides with an increased placental transfusion, expressed by higher hematocrit and hemoglobin values, and larger left ventricle diameter at the end of the diastole, with no changes in peripheral perfusion or oxygen metabolism.

Objective: To investigate how the mode of delivery affects the level oxidative stress in newborns., Design and Methods: 15-F(2t)-isoprostane, as index of oxidative stress, was measured in umbilical cord plasma samples from 37 infants born after vaginal delivery or caesarian section, using specific immuno-affinity extraction and immunoassay., Results: 15-F(2t)-isoprostane levels were higher in infants born after vaginal delivery (n=18) compared to those delivered by elective caesarian section (n=19)., Conclusions: 15-F(2t)-isoprostane is a sensitive biomarker of fetal oxidative stress during labor.

Background: Diagnostic tools of birth asphyxia provide only an uncertain prediction of neurological outcome., Aims: To assess whether TOI and DeltaCBV, combined with a set of biochemical and neurophysiological variables, have any diagnostic and prognostic value in birth depression or asphyxia., Study Design: Case control study at the nursery and NICU of the Padova University Children's Hospital., Subjects: 22 term neonates with an Apgar score < or = 6 at 5', a 1-h umbilical artery pH value < or = 7.25 with an increased base deficit and a gestational age > or = 36 weeks; 15 healthy term infants with an Apgar score > or = 9 at 5'., Outcome Measures: Troponin I and NIRS measurements (TOI and DeltaCBV) were assessed in both groups. Blood gases, neurological evaluation, US, NIRS, EEG and SEP were evaluated in the infants with depression or asphyxia., Results: Troponin I was higher in the study group than in controls (p=0.04), showing a correlation with base excess values. In the depressed/asphyxiated neonates with an abnormal outcome at 1 year, TOI rose to 80.1% vs 66.4% in controls (p=0.04) and 74.7% in infants with a normal 1-year outcome. A multiple regression model showed a significant multiple correlation coefficient, R=0.79, p<0.001, where the predictive variables significantly associated with outcome were SEP and BE., Conclusions: Troponin I is a useful short-term index of birth asphyxia or perinatal depression. An increased TOI suggests a risk of abnormal neurological outcome at 1 year. Among the cotside variables, BE and evoked potential abnormalities were the best predictors of abnormal outcome in this study.

Congenital intrapericardial teratoma can present in the fetal and neonatal period, but prenatal diagnosis is difficult. Its clinical course, similar to that of an anterior mediastinal mass, may be fatal if the tumor is not promptly excised. We report the case of a fetus with a large anterior mediastinal mass associated with hydramnios, pleural effusion, and ascites. Perinatal surgical removal is the only lifesaving therapy; any conservative approach in these neonates should be avoided even if critically symptomatic.

Objective: We compared neonatal helmet continuous positive airway pressure (CPAP) and the conventional nasal Infant Flow driver (IFD) CPAP in the noninvasive assessment of absolute cerebral blood flow (CBF) and relative cerebral blood volume changes (DeltaCBV) by near-infrared spectroscopy., Design and Setting: A randomized crossover study in a tertiary referral NICU., Patients and Interventions: Assessment of CBF and DeltaCBV in 17 very low birth weight infants with respiratory distress (median age 5 days) treated with two CPAP devices at a continuous distending pressure of 4 mbar., Measurements and Results: Neonates were studied for two consecutive 60-min periods with helmet CPAP and with IFD CPAP. Basal chromophore traces enabled DeltaCBV changes to be calculated. CBF was calculated in milliliters per 100 grams per minute from the saturation rise integral and rate of rise O(2)Hb-HHb. Median (range) CBF with helmet CPAP was 27.37 (9.47-48.20) vs. IFD CBF 34.74 (13.59-60.10)(p=0.049) and DeltaCBV 0.15 (0.09-0.28) with IFD and 0.13 (0.07-0.27) with helmet CPAP (NS). Using helmet and IFD CPAP, the neonates showed no difference in mean physiological parameters (transcutaneous carbon dioxide and oxygen tension, pulse oximetry saturation, heart rate, breathing rate, mean arterial blood pressure, desaturation rate, axillary temperature)., Conclusion: Assessing CBF and DeltaCBV measured by near-infrared spectroscopy with two CPAP devices revealed no differences in relative blood volume, but CBF was lower with helmet CPAP. Greater active vasoconstriction and/or passive capillary and/or venous vessel compression seem the most likely reason, due to a positive pressure around the head, neck, and shoulders by comparison with the airway pressure.

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 (DO(2)), oxygen consumption (VO(2)), 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, DO(2) and VO(2) 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 DO(2) (r = 0.32, p = 0.03), but no correlation was found between foot PI and calf FOE and between foot PI and VO(2)., 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 VO(2) by indirect NIRS.

Despite improvements in prenatal diagnosis and neonatal intensive care, the Congenital Diaphragmatic Hernia (CDH) Registry still records a 64% survival rate. Many reports demonstrate, however, that approximately 80% of CDH patients with no other malformations may survive if managed with permissive hypercapnia, gentle ventilation, high-frequency oscillatory ventilation (HFOV), surfactant, inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO), and delayed surgical repair. We wished to define the evolving outcome of CDH newborns using a protocol approach to management, which includes surgery in the neonatal intensive care unit (NICU) or operating room (OR). From January 1996, data were collected prospectively on 42 consecutive live-born infants with CDH. Newborns symptomatic at birth were sedated and paralyzed in the delivery room, and treated with elective HFOV, iNO, surfactant, and ECMO as necessary, delaying surgical repair until their clinical conditions were stable. Once the CDH newborn was stabilized, a trial on conventional ventilation was started at least 24 hours before surgery; however, if the patient was unstable, therapy was switched back to HFOV and surgery was performed in the NICU. Demographic and clinical parameters were compared between CDH newborns who underwent surgery in the NICU and in the OR. The two groups were comparable in terms of clinical characteristics and baseline ventilatory and blood gas values. Mean age at surgery was 3 +/- 2 days. After surgery, the NICU group had more infectious complications. However, the survival rate of uncomplicated CDH was 78% and a low rate of chronic lung disease was reported. A prolonged phase of presurgery stabilization is proposed and strict control of infection is recommended for the CDH newborns who might benefit from an exclusive HFOV and NICU surgery.

Aim: The aim of this paper was to study the evolution of ventriculomegaly, the treatment and the developmental problems of a group of very low birth weight infants (VLBWI) born between 1985 and 1999 who met Levene's percentiles for post-hemorrhagic ventricular dilatation (PHVD)., Methods: A retrospective hospital-based study of a cohort of 66 VLBWI who fulfilled the diagnostic criteria for PHVD was performed. Measures of neurodevelopmental outcome were evaluated by analyzing neurosensorial patterns as well as mental and behavioral adjustment up to pre-school age in 35 survivors., Results: The PHVDs initially (1985-1989) were due to a grade 4 intraventricular hemorrhage (IVH) (71.4%), and in the latter period (1995-1999) to IVH grade 2 (36.4%), grade 3 (31.8%) and grade 4 (31.8%). Acetazolamide has been used since the 90's in neonates with progressive PHVD. The 90s were characterized by an increasing incidence of tiny babies and rapidly-progressive PHVD. Taps were more frequent in the arrested dilatation group. Similarly, taps and acetazolamide were administered to newborns with persistent, slowly-progressive ventricular dilatation (PHVD > 4 weeks). The highest correlation was found for gestational age with the mental and psychomotor developmental indexes. Delayed performance and/or mental retardation were diagnosed in 71.4% of the survivors., Conclusion: Acetazolamide and lumbar puncture, associated with other risk variables (severity of IVH, PHVD evolution and associated parenchymal lesions) are harmful in terms of development, but they have a role in the short-term arrested and slowly progressive PHVD of the surviving babies, and not in the mortality incidence. Our retrospective data demonstrated that lower gestational age at birth increased the risk of lower mental and psychomotor developmental indexes.

Objectives: To survey current practice and to compare the opinion of paediatricians and anaesthesiologists regarding laryngeal mask airway (LMA) in neonatal resuscitation., Design: A structured postal questionnaire on the use of the laryngeal mask airway in neonatal resuscitation was sent to the heads of department of the paediatric and anaesthesiology services., Setting: Forty-three hospitals in the Veneto Region, Italy., Results: During the year 2000, 1526 out of 33708 (4.5%) neonates in our region needed resuscitation. Of these cases, 101 (6.6%) were ventilated using the LMA. Laryngeal mask airway availability was significantly greater in the anaesthesiology department compared to the paediatric department (90% versus 50%; P = 0.002). However, 52% of anaesthesiologists and 72% of paediatricians had never used the laryngeal mask airway in their practice. The laryngeal mask airway was considered as an essential device more frequently by the anaesthesiologists than by the paediatricians (27% versus 5%; P = 0.015); both groups considered the laryngeal mask airway particularly useful in specific situations. Interestingly, while 16% of the paediatricians described the laryngeal mask airway as having no value, none of the anaesthesiologists did (P = 0.002). Staff competence was considered low by 70% of anaesthesiology heads of department compared with 90% of their pediatric colleagues. In both specialties, use of the laryngeal mask airway was limited to medical staff. With regard to training, 35% of anaesthesiologists and 22.5% of paediatricians had attended a course on laryngeal mask airway use., Conclusions: Laryngeal mask airway availability and perceived value were higher amongst anaesthesiologists than their paediatric colleagues. However, educational level, competence and utilization rates of the LMA in neonatal resuscitation were low in both groups.

Ethical problems related to intensive care of extremely preterm newborns of < or = 25 weeks' gestational age and at risk of disability have been extensively debated. The Bioethical Committee of the Department of Paediatrics of the University Hospital of Padua organized and started a multidisciplinary group to release guidelines to help staff facing problems related to prematurity. The vitality limit, survival, outcome, and ethical aspects were analyzed. Consequently, we suggest the following: at 22 weeks' gestational age, the deliverance of comfort care only; at 23 weeks, in the presence of detectable vital signs, the practice of immediate intubation, respiratory support, and a reassessment of the neonatal conditions; and at 24 weeks, the provision of intubation, ventilatory support, and cardiovascular resuscitation. If the clinical age and anamnestic gestational age are different, we proceed according to the more advanced one. The importance of providing parents with correct information and the role of comfort care are outlined.

Unlabelled: Indomethacin (INDO) and, more recently, ibuprofen (IBU) have been used to treat haemodynamically significant patent ductus arteriosus (PDA) in preterm infants. Both are cyclo-oxygenase blockers, but seem to have a different influence on regional circulation. In a prospective, randomised, controlled study, we compared INDO and IBU with regard to efficacy and safety for the early non-invasive treatment of PDA. Doppler echocardiography was used to study 232 preterm infants (gestational age 23-34 weeks) with respiratory distress syndrome of whom 175 had persistent, haemodynamically significant PDA at 48-72 h of life. They were randomised to receive three intravenous doses of either INDO (0.2 mg/kg, at 12 h intervals) or IBU (a first 10 mg/kg dose followed by two doses of 5 mg/kg at 24 h intervals), recording rate of ductal closure, need for additional treatment, side-effects and clinical course. The efficacy of the pharmacological treatment was similar in the two groups (56/81, 69% INDO; 69/94, 73% IBU). Patients treated with INDO showed a significant increase in serum creatinine (89 +/- 24 versus 82 +/- 20 mmol/l, P = 0.03) and a near-significant tendency for a lower fractional excretion of sodium (3 +/- 3 versus 4 +/- 2%, P = 0.08); moreover, 12/81 (15%) INDO patients versus 1/94 (1%) IBU patients became oliguric (< 1 ml/kg per h) during treatment (P = 0.017)., Conclusion: Our findings confirm that, by comparison with indomethacin, ibuprofen has fewer effects on renal function in terms of urine output and fluid retention, with much the same efficacy and safety in closing patent ductus arteriosus in preterm infants with respiratory distress syndrome. In particular, no increased incidence of intracranial haemorrhage was observed after ibuprofen treatment.

Plasma nitrite (NO2-) and nitrate (NO3-) are the stable end-products of endogenous nitric oxide (NO) metabolism. NO is present in the exhaled air of humans, but it is not clear if exhaled NO may be an indicator of the systemic endogenous NO production. The aims of the study were to determine the levels of exhaled NO and plasma NO2-/NO3- in healthy term and preterm newborns, and to assess if exhaled NO correlates with plasma NO2-/NO3- at birth. After the stabilization of the newborn, we measured by chemiluminescence the concentration of NO in the mixed expired breath of 133 healthy newborns. Measurement of exhaled NO was repeated after 24 and 48 hours. Plasma NO2-/NO3- levels at birth were measured by the Griess reaction. NO concentrations were 8.9 (CI 8.1-9.8) parts per billion (ppb), 7.7 (CI 7.2-8.3) ppb and 9.0 (CI 8.4-9.6) ppb at birth, 24 and 48 hours, respectively. At birth, exhaled NO was inversely correlated with gestational age (p=0.008) and birth weight (p<0.001). Plasma NO2-/NO3- level was 27.30 (CI 24.26-30.34) micromol/L. There was no correlation between exhaled NO and plasma NO2-/NO3- levels at birth (p=0.88). We speculate that the inverse correlation between exhaled NO and gestational age and birth weight may reflect a role of NO in the postnatal adaptation of pulmonary circulation. At birth, exhaled NO does not correlate with plasma NO2-/NO3- and does not seem to be an index of the systemic endogenous NO production.

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 Delta[HbO2], Delta[Hb] and Deltaoxidized-reduced cytochrome aa(3) were recorded every 5 s. Changes in cerebral blood volume were calculated from the changes in total Hb x 0.89/large vessel Hb concentration. Increased oxyhemoglobin, Delta[HbO2], total Hb, Delta[Hb (sum)], and cerebral blood volume, DeltaCBV, were found in 13/19 neonates, with the exception of a neonate who only had increased in Delta[Hb], Delta[Hb (sum)] and DeltaCBV. During the stimulation phase there was a significant increase in DeltaCBV (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 DeltaCBV decreased to 0.04 (+/-0.07) mL/100 g (t test, p = 0.01), so did Delta[Hb (sum)] (p = 0.02). Hemodynamic responses of the subjects who showed increases in Delta[Hb (sum)] and Delta[HbO(2)] were analyzed to study the Delta[Hb]. The responder subjects could be classified into two groups according to Delta[Hb] changes: 8/13 (61.5%) showed an increase of Delta[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 Delta[HbO(2)] and Delta[Hb (sum)]. The DeltaCBV 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.

The study aimed to assess how well the severity of clinical conditions in extremely low birth weight infants in the first 12 h of life, as measured by the CRIB (clinical risk index for babies), relates to hospital outcome and subsequent disability at 18 months of age. The CRIB was confirmed as a valid index of initial neonatal risk, even in extremely low birth weight infants, predicting hospital outcome (death or major brain lesions) more accurately than birth weight or gestational age. However, an adjustment of the CRIB score for gestational age might enhance its positive predictive value in relation to short-term developmental outcome in this particular population.

Advance in the science and technology of neonatal and pediatric critical care have resulted in improved outcome for high risk newborn and children. Effective interhospital transport programmes are necessary for the appropriate use of resources and has become an integral component of regionalized perinatal care. It is now well established that use of an organized neonatal and pediatric transport team results in a fall in mortality and morbidity of infant. The American College of Obstetrician and Gynecologist and, recently, American Academy of Pediatrics published guidelines and recommendations for safe interhospital transfer of neonates, infants and children. Training of personnel, selection of equipment, organization and communication between hospitals are critical elements of a successful transport system. We present an overview of the role, principles and operating procedures of such neonatal-pediatric transport team and the basis of clinical stabilization before and during transfer. We also discuss data of the first 17 month experience of the Neonatal-Pediatric Transport Service of the Department of Pediatrics, University of Padua.

Pediatric intensive care units (PICUs) have been developed to provide intensive care for children between post-neonatal age and adolescence. These units have largely been developed in North America, mainly in tertiary hospitals. In Italy, critically ill children are still often nursed on adult ICU's, where medical and nursing staff often lack pediatric training. Here we report the first 5-year experience of the multidisciplinary PICU developed at the Department of Pediatrics, University of Padua, focusing on PICU and patients characteristics, as well as on the evaluation of outcome by means of the Pediatric Risk of Mortality (PRISM) score.

Extracorporeal membrane oxygenation (ECMO) has become a nearly standard treatment for neonates with refractory hypoxemic respiratory failure due to various disease. Even though in the non-neonatal age the experience is less extensive, an increased widespread interest on the possible applications in children with severe life-threatening respiratory or cardiovascular insufficiency is well documented in the literature. General contraindications include presence of active bleeding, underlying lethal disease, congenital malformations, or severe brain damage. Whilst in the neonatal population common entry criteria have been widely accepted, the identification of precise parameters capable to predict mortality and thus indicating an ECMO support in older patients are still lacking. At present, nonetheless, more than 10.000 newborns and 1.000 children with severe respiratory insufficiency at high mortality risk have received an ECMO treatment, with a survival rate of more than 80% and 50%, respectively. The initial results of our ECMO program for both neonatal and pediatric patients with refractory respiratory failure are encouraging, both in terms of mortality and morbidity, and they will be briefly discussed.