Objective To assess the role of nasal continuous positive airway pressure (CPAP) initiated at birth for prevention of death and bronchopulmonary dysplasia in very preterm infants. Design Systematic review. Data sources PubMed, Embase, the Cochrane Central Register of Controlled Trials, and online Pediatric Academic Society abstracts from the year of inception to June 2013. Eligibility criteria for selecting studies Randomised controlled trials evaluating the effect of nasal CPAP compared with intubation in preterm infants born at less than 32 weeks’ gestation and presenting the outcomes of either death or bronchopulmonary dysplasia, or both (defined as the need for oxygen support or mechanical ventilation at 36 weeks corrected gestation), during hospital stay. Results Four randomised controlled trials (2782 participants) met the inclusion criteria, with 1296 infants in the nasal CPAP group and 1486 in the intubation group. All the trials reported bronchopulmonary dysplasia independently at 36 weeks corrected gestation, with borderline significance in favour of the nasal CPAP group (relative risk 0.91, 95% confidence interval 0.82 to 1.01, risk difference −0.03, 95% confidence interval −0.07 to 0.01). No difference in death was observed (relative risk 0.88, 0.68 to 1.14, risk difference −0.02, −0.04 to 0.01, respectively). Pooled analysis showed a significant benefit for the combined outcome of death or bronchopulmonary dysplasia, or both, at 36 weeks corrected gestation for babies treated with nasal CPAP (relative risk 0.91, 0.84 to 0.99, risk difference −0.04, -0.07 to 0.00), number needed to treat of 25). Conclusion One additional infant could survive to 36 weeks without bronchopulmonary dysplasia for every 25 babies treated with nasal CPAP in the delivery room rather than being intubated.

Background —Matrix metalloproteinases (MMPs) contribute to collagen degradation and remodeling of the extracellular matrix after myocardial infarction; however, their role in myocardial dysfunction immediately after ischemia and reperfusion is unknown. Methods and Results —We measured the release of MMPs into the coronary effluent of isolated, perfused rat hearts during aerobic perfusion and reperfusion after ischemia. Aerobically perfused control hearts expressed pro-MMP-2 and MMP-2, as well as an unidentified 75-kDa gelatinase. These enzymes were also detected in the coronary effluent. After 20 minutes of global no-flow ischemia, there was a marked increase in pro-MMP-2 in the coronary effluent that peaked within the first minute of reperfusion. The release of pro-MMP-2 into the coronary effluent during reperfusion was enhanced with increasing duration of ischemia and correlated negatively with the recovery of mechanical function during reperfusion ( r ² =0.99). MMP-2 antibody (1.5 to 15 μg/mL) and the inhibitors of MMPs doxycycline (10 to 100 μmol/L) and o -phenanthroline (3 to 100 μmol/L) improved whereas MMP-2 worsened the recovery of mechanical function during reperfusion. Conclusions —These results show that acute release of MMP-2 during reperfusion after ischemia contributes to cardiac mechanical dysfunction. The inhibition of MMPs may be a novel pharmacological strategy for the treatment of ischemia-reperfusion injury.

Although bleeding associated with thrombocytopenia often complicates extracorporeal membrane oxygenation (ECMO), the mechanisms of platelet dysfunction during ECMO remain poorly understood. We investigated the role of matrix metalloproteinase (MMP)-2, which recently has been shown to mediate a novel pathway of platelet aggregation, in the platelet dysfunction induced by ECMO. Prospective longitudinal case study. Level III neonatal intensive care unit. Ten neonates treated with ECMO. ECMO procedure. Platelet counts and collagen-induced platelet aggregation ex vivo; plasma markers of platelet (soluble P-selectin) and endothelial (soluble E-selectin and total nitrite/nitrate) activation; plasma MMP-2 and MMP-9 activities; and concentrations of tissue inhibitors of MMPs. During ECMO, time-dependent platelet activation, as evidenced by thrombocytopenia, decreased platelet aggregation, and increased plasma soluble P-selectin concentrations were found in the absence of endothelial activation, as shown by normal plasma concentrations of soluble E-selectin and nitric oxide metabolites (nitrite/nitrate). There was a time-dependent increase in plasma MMP-2 but not MMP-9 activity; tissue inhibitors of MMPs were not detected. Plasma soluble P-selectin concentrations significantly correlated with simultaneous plasma MMP-2 (r2 = .37, p < .0001) but not with MMP-9 activities. Platelet dysfunction persisted despite repeated platelet transfusions to maintain platelet counts >100 × 109/L. ECMO resulted in the activation of platelets but not endothelial cells. During ECMO, platelet dysfunction persisted despite platelet transfusions. MMP-2 may play a role in the development of platelet dysfunction caused by ECMO.

An increasing body of evidence has revealed that interventions performed during resuscitation of extremely-low-gestational-age neonates (ELGANs) may have a direct influence on the immediate survival and also on long-term morbidity. It has been proposed that interventions in the delivery room and/or hypothermia could trigger changes constitutive of chronic lung disease. New approaches in the first minutes of life using more gentle parameters of intervention are being studied. Thus, titrating inspiratory fraction of oxygen, the use of non-invasive ventilation to reduce trauma to the lung, the use of polyethylene/polyurethane wrapping to avoid hypothermia and delaying cord clamping altogether constitute promising initiatives. The first minutes of life are a valuable window for intervention. However, whilst these practice changes make sense and there are emerging data to support them, further evidence including long-term follow up is needed to definitively change resuscitation procedures in ELGANs.

Background—: Guidelines on neonatal resuscitation recommend 90 chest compressions (CCs) and 30 manual inflations (3:1) per minute in newborns. The study aimed to determine whether CC s during sustained inflations (SIs) improves the recovery of asphyxiated newborn piglets in comparison with coordinated 3:1 resuscitation. Methods and Results—: Term newborn piglets (n=8/group) were anesthetized, intubated, instrumented, and exposed to 45-minute normocapnic hypoxia followed by asphyxia. Piglets were randomly assigned to receive either 3:1 resuscitation (3:1 group) or CCs during SIs (SI group) when the heart rate decreased to 25% of baseline. Piglets randomly assigned to the SI group received SIs with a pressure of 30 cm H ₂ O for 30 s. During the SI, CCs at a rate of 120/min were provided. SI was interrupted after 30 s for 1 s before a further 30-s SI was provided. CCs were continued throughout SIs. CCs and SI were continued until the return of spontaneous circulation. Continuous respiratory parameters, cardiac output, mean systemic and pulmonary artery pressures, and regional blood flows were measured. Mean (standard deviation) time for return of spontaneous circulation was significantly reduced in SI group versus 3:1 group (32 [11] s versus 205 [113] s, respectively). In the SI group, administration of oxygen and epinephrine was significantly lower, whereas minute ventilation and exhaled CO ₂ were significantly increased. The SI group had significantly higher mean systemic and pulmonary arterial pressures during resuscitation in comparison with the 3:1 group (51 [10] versus 31 [5] mm Hg; 41[7] versus 31 [7] mm Hg, respectively; all P <0.05), with improved cardiac output and carotid blood flow. Conclusions—: Combining CCs and SIs significantly improved the return of spontaneous circulation with better hemodynamic recovery in asphyxiated newborn piglets in comparison with standard coordinated 3:1 resuscitation.