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Background and Objectives: There is evidence that new methods of noninvasive ventilation (NIV) support have significantly changed respiratory distress syndrome (RDS) management in preterm infants. Further perspectives for neonatologists involve the assessment of different NIV strategies in terms of availability, effectiveness, and failure. This study evaluates the efficacy of 2 different NIV strategies for RDS treatment in very low birth weight (VLBW) infants: nasal synchronized intermittent positive pressure ventilation (NSIPPV), which is a modality of conventional ventilation with intermittent peak inspiratory pressure, and bilevel continuous positive airway pressure (BiPAP), not synchronized, with 2 alternate levels of continuous positive airway pressure., Methods: We conducted a 2-center randomized control study in 124 VLBW infants (<1500 g and <32 weeks of gestational age) with RDS who received NIV support (NSIPPV, n = 62; BiPAP, n = 62) within 2 hours of birth. We evaluated the performance of NIV strategies by selected primary outcomes (failure rate and duration of ventilation) and secondary outcomes., Results: The number of failures and duration of ventilation support did not differ between NSIPPV and BiPAP strategies (P > .05 for both). Moreover, no differences between groups were found regarding secondary outcomes (P > .05 for all)., Conclusions: The present data show no statistically significant differences between NSIPPV and BiPAP strategies in terms of duration of ventilation and failures, suggesting that both NIV techniques are effective in the early treatment of RDS in VLBW infants. Further randomized investigations on wider populations are needed to evaluate the effect of NIV techniques on long-term outcomes., (Copyright © 2015 by the American Academy of Pediatrics.)

Objective: Non-invasive ventilation (NIV) for RDS in extremely/very low birth-weight infants represents the new challenge for neonatologists. In this regard, data comparing the effectiveness of Bi-Level-NCPAP (BiPAP) versus nasal synchronized intermittent positive pressure ventilation (NSIPPV) as primary mode of treatment for RDS are lacking., Study Design: We conducted a retrospective study from December 2007 to December 2010 in seventy-eight infants, who received NIV (N-SIPPV: 33; BiPAP: 45). The primary outcomes were the length and failure of NIV. Secondary outcomes were adverse short-long term pulmonary outcomes, multiple doses of surfactant and others., Results: There were no significant differences (p > 0.05) between the two different NIV modes., Conclusion: The present findings suggest that N-SIPPV and BiPAP gives similar results in the RDS treatment. We did not find a benefit of one over the other ventilation mode and both could be constitute a valid option to conventional mechanical ventilation. The theoretical benefits of these two different methods of NIV are tidal volume enhancement, improvements of the functional residual capacity and of the mean airway pressure and reducing apnea episodes. Further randomized studies to assess the advantages and the efficacy of different methods of NIV for the treatment of the RDS are needed.

Objective: Data comparing the effectiveness of high-frequency oscillatory ventilation and of conventional mechanical ventilation in the treatment of respiratory distress syndrome of very low birth weight infants are, to date, still matter of debate. We investigated the effects of first intention high-frequency oscillatory ventilation or conventional mechanical ventilation support on selected primary and secondary outcomes in very low birth weight infants complicated by respiratory distress syndrome in which antenatal glucocorticoid prophylaxis was not performed., Design: Multicenter randomized control trial., Setting: Three tertiary centers of neonatal intensive care units from December 2004 to December 2007., Population: Eighty-eight very low birth weight infants complicated by respiratory distress syndrome, without antenatal glucocorticoids, supported by first intention high-frequency oscillatory ventilation (n = 44) or conventional mechanical ventilation (n = 44)., Interventions: All newborns were monitored by standard monitoring procedure, including routine laboratory variables, neurologic patterns, and ultrasound imaging. Primary outcomes were: the length of ventilatory support, the need of reintubation, and the length of nasal continuous positive airway pressure support in the postextubation period. Secondary outcomes were: the length of stay in neonatal intensive care unit and in hospital, death before discharge, adverse short- and long-term pulmonary and neonatal outcomes, and the need for a second dose of surfactant and of postnatal glucocorticoid treatment., Results: High-frequency oscillatory ventilation infants showed a significant lower duration (p < .001 for all) of ventilator dependency, lower need of reintubation and of duration of nasal continuous positive airway pressure support in the postextubation period. Among secondary outcomes in the high-frequency oscillatory ventilation infants, the need of a second dose of surfactant administration, and the length of stay in the neonatal intensive care unit and in hospital were significantly lower (p < .05 for all)., Conclusions: We found that high-frequency oscillatory ventilation in very low birth weight infants without antenatal glucocorticoid prophylaxis reduced the need of ventilatory support, surfactant therapy, and reintubation, and shortened neonatal intensive care unit and hospital stay, thus reducing unit and hospital costs. These data would support the usefulness of first intention high-frequency oscillatory ventilation strategy in managing in a selected population, such as very low birth weight newborns complicated by severe respiratory distress syndrome not antenatally treated with glucocorticoids.

Transient neonatal hyperinsulinemic hypoglycemia (TNHI) is a form of neonatal-onset hyperinsulinism which usually resolves completely in a few days or months. It is secondary to conditions such as maternal diabetes mellitus or intra-uterine growth retardation. Other rare causes of TNHI are perinatal asphyxia and gestational diabetes. Hyperinsulinemic hypoglycemia (HI) is also observed in association with rare metabolic or genetic conditions. It can also occur in newborns without risk factors. TNHI is usually a transient phenomenon. However, some newborns can have prolonged HI that requires treatment with diazoxide, persists for several months and then resolves spontaneously. Neonatal hyperinsulinemic hypoglycemia must be promptly and correctly diagnosed and treated in order to avoid neurological consequences. We describe a case of transient neonatal hyperinsulinemic hypoglycemia in a full-term born without perinatal complications and appropriate for gestational age with an unfavourable neurological outcome.

There is a growing evidence on the use of biomarkers in daily practice both as of markers of brain/multiorgan damage and/or trophic factors. However, among different tools, Activin A, S100B protein, and Hemeoxygenase-1 (HO-1 or Heat Shock Protein 32, HSP32) assessment offer the possibility to investigate brain/multiorgan function and development. This could be especially useful in perinatal medicine that requires even more noninvasive techniques to fulfill the minimal handling diagnostic and therapeutic strategy. In this regard, among different biological fluids, human milk for its unique composition can constitute a wide source of knowledge useful both in clinical daily practice and in research.Therefore, this mini-review reports recent data on the presence and the usefulness of Activin A, S100B protein, and HO-1/HSP32 assessment in human milk as brain/multiorgan development markers. Results open up a new cue on the use of these markers in perinatal medicine as a key protein for investigations focusing on fetal/neonatal development.

Hypoxia-ischemia (H-I) constitutes the main phenomenon responsible for brain-blood barrier permeability modifications leading to cerebral vascular autoregulation loss in newborns. Hypotension, cerebral ischemia, and reperfusion are the main events involved in vascular auto-regulation loss leading to cell death and tissue damage. Reperfusion could be critical since organ damage, particularly of the brain, may be amplified during this period. An exaggerated activation of vasoactive agents, of calcium mediated effects could be responsible for reperfusion injury (R-I), which, in turns, leads to cerebral hemorrhage and damage. These phenomena represent a common repertoire in newborns complicated by perinatal acute or chronic hypoxia treated by risky procedures such as mechanical ventilation, nitric oxide supplementation, brain cooling, and extracorporeal membrane oxygenation (ECMO). Despite accurate monitoring, the post-insult period is crucial, as clinical symptoms and standard monitoring parameters may be silent at a time when brain damage is already occurring and the therapeutic window for pharmacological intervention is limited. Therefore, the measurement of circulating biochemical markers of brain damage, such as vasoactive agents and nervous tissue peptides is eagerly awaited in clinical practice to detect high risk newborns. The present article is aimed at investigating the role of dosage biochemical markers in non-invasive biological fluids such as S100B, a calcium binding protein, activin A, a protein expressed in Central nervous System (CNS).

Hypoxia-ischemia (H-I) constitutes the main phenomenon responsible for brain-blood barrier permeability modifications leading to cerebral vascular auto-regulation loss in newborns. Hypotension, cerebral ischemia, and reperfusion are the main events involved in vascular auto-regulation loss leading to cell death and tissue damage. Reperfusion could be critical since organ damage, particularly of the brain, may be amplified during this period. An exaggerated activation of vasoactive agents, of calcium mediated effects could be responsible for reperfusion injury (R-I), which, in turns, leads to cerebral hemorrhage and damage. These phenomena represent a common repertoire in newborns complicated by perinatal acute or chronic hypoxia treated by risky procedures such as mechanical ventilation, nitric oxide supplementation, brain cooling, and extracorporeal membrane oxygenation (ECMO). Despite accurate monitoring, the post-insult period is crucial, as clinical symptoms and standard monitoring parameters may be silent at a time when brain damage is already occurring and the therapeutic window for pharmacological intervention is limited. Therefore, the measurement of circulating biochemical markers of brain damage, such as vasoactive agents and nervous tissue peptides is eagerly awaited in clinical practice to detect high risk newborns. The present review is aimed at investigating the role of biochemical markers such as adrenomedullin, a vasoactive peptide; S100B, a calcium binding protein, activin A, a glycoprotein, in the cascade of events leading to I-R injury in newborns complicated by perinatal asphyxia.

Objective: To investigate the rate of radiographic progression and identify prognostic factors of radiographic progression, radiographic damage, and physical disability in juvenile idiopathic arthritis (JIA)., Methods: Ninety-four JIA patients with a median disease duration of 1.1 years were followed up prospectively for a median of 4.5 years. Bilateral wrist radiographs were obtained at baseline, at 1 year, and at the last followup visit. Radiographic damage was assessed by the carpal length (Poznanski score), and physical disability by the Childhood Health Assessment Questionnaire (C-HAQ). Yearly radiographic progression, the Poznanski score at the final visit, and the C-HAQ score at the final visit were used as outcome measures. Baseline parameters included demographic, clinical, laboratory, and radiographic data., Results: The mean +/- SD Poznanski score was -1.2 +/- 1.3 at baseline, -1.7 +/- 1.8 at the 1-year visit, and -1.9 +/- 2.2 at the final visit (P < 0.0001). Radiographic progression was greater during the first year (mean +/- SD -0.5 +/- 1.1) than between the 1-year visit and the final visit (-0.2 +/- 1.3). The mean yearly radiographic progression during the entire study period was -0.1 +/- 0.4. Logistic regression analysis revealed that radiographic progression during the first year was the only baseline parameter that was predictive of all 3 study outcomes. The final Poznanski score was also predicted by the baseline Poznanski score, whereas female sex was protective against radiographic progression., Conclusion: We identified the prognostic factors for poorer outcome in polyarticular-course JIA. The changes in the early Poznanski score can be used to predict long-term joint damage and physical disability.

Objective: To investigate the efficacy and safety of a combination therapy with methotrexate (MTX) and cyclosporine A (CyA) in patients with juvenile idiopathic arthritis (JIA) who were refractory to MTX as a single second-line agent., Methods: Seventeen consecutive patients with JIA who had refractory polyarthritis despite a minimum of 6 months of MTX as a single second-line agent at the dose of 15 to 25 mg/m2/week were continued with MTX with the addition of CyA (4 mg/kg/day) for 6 to 30 months (median 10 months) were analyzed. The clinical response to therapy was assessed through the preliminary definition of improvement in JIA., Results: At the end of the treatment, as compared to the time when CyA was added to MTX, 8 patients (47%) met the 30% definition of improvement; among them 5 (29%) met the 70% definition of improvement, and 2 (12%) achieved complete disease control. Seven patients (41%) experienced side effects: 4 gastrointestinal discomfort, 1 liver transaminase elevation, and 2 increase > or = 30% in the serum creatinine concentration. No patients was discontinued from combination therapy due to adverse events., Conclusion: In our JIA patients who were refractory to MTX as a single second-line agent, the addition of CyA was associated with a significant clinical improvement in roughly half of the patients.

Macrophage activation syndrome (MAS) is a potentially life threatening complication of chronic rheumatic diseases, particularly systemic juvenile idiopathic arthritis (JIA). A number of triggers have been related to the development of MAS, including viral infections, nonsteroidal antiinflammatory drug therapy, and gold salt injections. We describe a patient with systemic JIA who developed MAS shortly after receiving methotrexate, suggesting that this drug can be regarded as a potential trigger of MAS in children with JIA.