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Signa Vitae

Journal of Intensive Care and Emergency Medicine

Early instrumental predictors of long term neurodevelopmental impairment in newborns with perinatal asphyxia treated with therapeutic hypothermia


Background. Hypoxic-ischemic encephalopathy (HIE) is a leading cause of disability in full-term newborns. Long-term consequences of HIE, even when treated by hypothermia, are not easily predictable.

Aims. To assess the potential role of electroencephalography and neuroimaging parameters as early predictors of neurodevelopmental outcome in HIE newborns treated with hypothermia.

Methods. We retrospectively evaluated 13 HIE patients treated with hypothermia in January 2012-September 2014. We reviewed their amplitude-integrated electroencephalography (a-EEG) at 6, 12 and 24 hours (h), cranial ultrasonography (US) at 12, 72 h and >7 days of life (DOL) and brain magnetic resonance (MRI) performed at 7-28 DOL, according to validated scores. aEEG, US and MRI patterns were correlated to neurodevelopmental outcome at 18-24 months, considered as negative if one of the following was present: Mental Development Index (MDI)<85, motor, visual or hearing impairment.

Results. The severity of a-EEG, US and MRI alterations at each time point was not different according to the outcome. MDI was negatively correlated with aEEG score at 12h (R= -0.571, p=0.04) and with US score at 72h (R= -0.630, p=0.02). A positive correlation was found between aEEG score at 6h and US score at >7DOL (R=0.690, p=0.013). US alterations of the cortical matter at 72h were directly correlated with a-EEG score at 12h (R = 0.606, p=0.028) and 24h (R=0.605, p=0.029).

Conclusions. Early instrumental evaluations, in particular aEEG and US, seem to predict neurodevelopmental outcome at 18-24 months in HIE newborns treated with hypothermia.

Key words: asphyxia, hypoxic-ischemic encephalopathy, hypothermia, newborn

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Respiratory disorders and neonatal outcomes of triplet pregnancies – our ten year experience


Objective. To compare respiratory disorders (respiratory distress syndrome, requirement for respiratory support, development of chronic lung disease), duration of hospitalization and other neonatal outcomes between newborns born from triplet pregnancies over a ten year period.

Methods. A retrospective analysis of 34 triplet pregnancies delivered between 2006 and 2015 in one perinatal tertiary centre. Ninety-nine newborns from these pregnancies were divided into 2 groups: one consisted of 56 neonates (19 sets of triplets) born between 2006 and 2011 and the second contained 43 neonates delivered from 15 triplet pregnancies between 2012 and 2015.

Results. There were no differences in the incidence of respiratory distress syndrome and chronic lung disease between group I and group II. In both groups, a similar amount of patients required respiratory support. We did not notice any significant differences in the type of ventilation (mechanical ventilation or nasal continuous positive airway pressure -nCPAP), duration of ventilation, length of hospitalization or the incidence of complications of prematurity, such as 3rd or 4th grade intraventricular hemorrhage (IVH) and retinopathy of prematurity (ROP) stage > 2, between both groups.

Conclusion. Despite important progress in perinatal care and wide use of advanced technologies in neonatal intensive care there has been no significant improvement in neonatal outcomes of triplets during the past 10 years. Multiple pregnancies still remain a risk factor for respiratory disorders and other neonatal complications in prematurely delivered newborns.

Key words: triplets, newborn, respiratory disorders, outcome

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Proinflammatory cytokines in a newborn: a literature review


Inflammation is a protective response to infection or injury. The inflammatory response is controlled primarily by cytokines, which are endogenous mediators of the immune system. Cytokines are produced by various different cell types in response to multiple types of stimuli and have overlapping biologic activity. Cytokines also are directly involved in the activation of cells at the inflammatory site. Movement of leukocytes to the inflammatory site is directed along a chemotactic gradient, where the strongest concentration of chemoattractants is at the site of inflammation. Cytokines are involved at each step of this process and act both locally and systemically to initiate, maintain, and finally resolve the inflammatory response. The interplay among these proinflammatory cytokines, antiinflammatory cytokines, and naturally occurring cytokine inhibitors determines the inflammatory response and its effectiveness. Because of the immaturity of the immune system of newborn cytokine is specific. Tumor necrosis factor- (TNF-) and interleukin-6 (IL-6) amplify the immune response through activation of the cytokine cascade and the production of other proinflammatory cytokines and chemokines. In a group of proinflammatory cytokines TNF- and IL-6 have undoubtedly significant role in the cytokine cascades of physiological and pathophysiological responses.

Key words: interleukin-6, tumor necrosis factor-alpha, newborn

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Coagulation disorders in premature infants – case report


Hemorrhagic disease of the newborn, with incidence 1% to 2% of newborn babies is often a serious problem and urgent condition in pediatric intensive care unit. Article describes a case of coagulation disorder in premature infant and the management of that case.

Key words: newborn, hemorrhagic disease, coagulation disorder

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The role of nitric oxide in apoptosis modulation in newborns with pneumonia


Introduction. Nitric oxide (NO) is an important diagnostic marker and mediator in the inflammatory process, which plays a key role in the mechanism of programmed cell death, thus, forming the basis of many pathological diseases.

Methods. The study involved 73 newborns with pneumonia (moderate severity in 44 neonates (group 1), severe pneumonia in 29 (group 2)). The intensity of neutrophil apoptosis and necrosis was determined by flow cytometry, whereas nitric oxide metabolites were measured by spectrophotometry.

Results. The level of nitric oxide metabolites (NO2+NO3) in newborns with pneumonia was higher than in healthy children (16.93 (15.82; 17.79) μmol/ml) and correlated with disease severity (in group 1 – 22.65 (21.42; 23.40) μmol/ml in group 2 – 26.82 (25.81; 27.91) μmol/ml). The level of NO3 increased moderately, while NO2 generation was more intense, exceeding control indexes in both groups (рc1<0.001; рc2<0.001; р12<0.001).

The occurrence of intensive neutrophil apoptosis was revealed in newborns with pneumonia of moderate severity (рc1<0.001), while necrosis prevailed in severe pneumonia (рc2<0.001).

Inverse correlation (R=-0.63; р<0.05) was found between the level of nitric oxide metabolites and neutrophil apoptosis; and direct correlation (R=0.68; р<0.05) was revealed between NO metabolites and neutrophil necrosis indices.

Conclusions. Increased generation of nitric oxide metabolites, that directly correlated with disease severity in newborns with pneumonia, was found. NO2 has multidirectional effects on neutrophil apoptosis and necrosis, leading to toxic accumulation of neutrophils in the organism, thus enhancing the inflammatory and intoxication process that impact disease severity.

Key words: nitric oxide, apoptosis, necrosis, neutrophils, pneumonia, newborn

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