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.

In perinatal medicine, there is an emerging interest on the potential usefulness of non-invasive brain biochemical monitoring in infants at risk for brain injury. To date, several biomarkers such as neuro-proteins, calcium binding proteins, oxidative stress markers, vasoactive agents, inflammatory mediators, have been investigated. Results showed that hypoxia insult, under different conditions, triggers a biochemical pathophysiological cascade of events leading to brain damage. In this setting, increased biomarkers concentrations in different biological fluids have been found to correlate with the occurrence of brain damage at short-long term both in preterm and term fetuses/newborns. However, before inclusion of any biomarker in guidelines, USA and European institutions have recently stated a panel of criteria that have to be fulfilled. Therefore, the present review offers an overview of the main biomarkers currently studied in perinatal medicine and their progresses according to institutions' criteria.

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.

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.

The present study shows that first intention N-SIPPV/BiPAP, as NIV support, augment the beneficial effects of N-CPAP contributing to a reduced risk of failure in VLBW infants complicated by RDS. Data open up to further RCTs on a wider population to evaluate NIV effectiveness on long-term outcomes.