adrenomedullin and Asphyxia-Neonatorum

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.

Topics: Adrenomedullin; Asphyxia Neonatorum; Biomarkers; Brain Ischemia; Glial Fibrillary Acidic Protein; Heme Oxygenase-1; Humans; Infant, Newborn; Oxidative Stress; Phosphopyruvate Hydratase; S100 Calcium Binding Protein beta Subunit

Hypoxia-ischemia constitutes a risk in infants by altering cerebral blood flow regulatory mechanisms and causing loss of cerebral vascular auto-regulation. Hypotension, cerebral ischemia, and reperfusion are the main events involved in vascular auto-regulation leading to cell death and tissue damage. These dramatic phenomena represent a common repertoire in infants complicated by perinatal acute or chronic hypoxia. To date, despite accurate perinatal and intra-operative monitoring, the post-insult period is crucial, since clinical symptoms and monitoring parameters may be of no avail and therapeutic window for pharmacological intervention (6-12 hours) may be limited, at a time when brain damage is already occurring. 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 infants. The present review is aimed at investigating the role as circulating biochemical markers such as adrenomedullin, S100B, activin A, neuronal specific enolase (NSE), glial fibrillary acid protein (GFAP), in the cascade of events leading to ischemia reperfusion injury in infants complicated by perinatal asphyxia.

Topics: Activins; Adrenomedullin; Asphyxia Neonatorum; Biomarkers; Brain; Carrier Proteins; Humans; Hypoxia, Brain; Infant, Newborn; Milk, Human; Nerve Growth Factors; Oxygen; Reperfusion Injury; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Spectroscopy, Near-Infrared

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.

Topics: Activins; Adrenomedullin; Asphyxia Neonatorum; Biomarkers; Brain Injuries; Humans; Hypoxia-Ischemia, Brain; Infant, Newborn; Nerve Growth Factors; S100 Calcium Binding Protein beta Subunit; S100 Proteins

Adrenomedullin (AM) is a newly discovered vasodilator peptide that participates in the regulation of cerebral blood flow. The aim of this study was to investigate whether circulating AM was increased in infants with prenatal asphyxia who developed intraventricular hemorrhage (IVH).. : A case-control study was performed on 40 full-term asphyxiated newborns: 20 developed IVH (group A) and 20 did not (group B). Forty term healthy newborns represented the control group. Biochemical laboratory parameters, neurological patterns, cerebral ultrasound scanning, and Doppler velocimetry were assessed at 12 and 72 h from birth. Plasma AM concentration was measured at 12 h from birth by means of a specific RIA.. AM levels were significantly higher in group A (20.2 +/- 5.2 fmol/ml) than in group B (8.4 +/- 2.1 fmol/ml) or controls (9.3 +/- 2.6 fmol/ml). In asphyxiated newborns, AM concentration was correlated with middle cerebral artery PI value only in group B.. Increased concentration of AM at 12 h from birth in asphyxiated newborns who later developed IVH suggests that this peptide may participate in the loss of cerebral vascular autoregulation in response to hypoxia and could be useful to discriminate, among newborns at risk, those with an adverse neurological outcome.

Topics: Adrenomedullin; Asphyxia Neonatorum; Case-Control Studies; Cerebral Hemorrhage; Cerebral Ventricles; Humans; Infant, Newborn; Nerve Growth Factors; Peptides; Risk Factors; Vasodilator Agents

The aim of the present study was to investigate the role of adrenomedullin (ADM) as a hypoxia-inducible marker of clinically relevant tIssue hypoxia in acute birth asphyxia of term newborn infants.. For this purpose, ADM mRNA was determined in human placental tIssue of 20 term pregnancies complicated by birth asphyxia (pH and base deficit values, clinical score). In addition, ADM mRNA was measured in leukocytes of the asphyxiated newborn infants during the first 12 h of life (n=12). Controls were available from ten healthy term pregnancies. In vitro, hypoxia-inducible expression of ADM mRNA was evaluated in human choriocarcinoma cells (BeWo) and human leukocytes exposed to hypoxia (1% O(2)) for 1-24 h. mRNA levels were measured by TaqMan real-time PCR.. In vitro, ADM mRNA related to porphobilinogen deaminase (PBGD) mRNA levels significantly increased in response to hypoxia within a period of 4 h in leukocytes and 12 h in BeWo cells. In human placental tIssue, significantly higher levels of ADM/PBGD mRNA were present in asphyxiated newborn infants with severe hypoxic-ischemic encephalopathy (HIE) (n=5) compared with patients with mild or no HIE (n=15). Increased levels of ADM/PBGD mRNA levels were found during the first hours of life in leukocytes of neonates with severe HIE compared with controls.. Our results indicate an upregulation of ADM gene expression in human placenta and leukocytes in clinically relevant hypoxic-ischemic birth complications and suggest ADM gene expression as a promising marker for severe complications due to perinatal asphyxia such as HIE.

Topics: Adrenomedullin; Asphyxia Neonatorum; Biomarkers; Cell Hypoxia; Female; Gene Expression; Humans; Hydroxymethylbilane Synthase; Hypoxia-Ischemia, Brain; Infant, Newborn; Leukocytes; Peptides; Placenta; Pregnancy; Reference Values; RNA, Messenger; Tumor Cells, Cultured