Perinatal asphyxia is considered to be one of the major causes of brain neurodegeneration in full-term newborns. The worst consequence of perinatal asphyxia is neurodegenerative brain damage, also known as hypoxic-ischemic encephalopathy. Hypoxic-ischemic encephalopathy is the leading cause of mortality in term newborns. To date, due to the complex mechanisms of brain damage, no effective or causal treatment has been developed that would ensure complete neuroprotection. Although hypothermia is the standard of care for hypoxic-ischemic encephalopathy, it does not affect all changes associated with encephalopathy. Therefore, there is a need to develop effective treatment strategies, namely research into new agents and therapies. In recent years, it has been pointed out that natural compounds with neuroprotective properties, such as melatonin, can be used in the treatment of hypoxic-ischemic encephalopathy. This natural substance with anti-inflammatory, antioxidant, anti-apoptotic and neurofunctional properties has been shown to have pleiotropic prophylactic or therapeutic effects, mainly against experimental brain neurodegeneration in hypoxic-ischemic neonates. Melatonin is a natural neuroprotective hormone, which makes it promising for the treatment of neurodegeneration after asphyxia. It is supposed that melatonin alone or in combination with hypothermia may improve neurological outcomes in infants with hypoxic-ischemic encephalopathy. Melatonin has been shown to be effective in the last 20 years of research, mainly in animals with perinatal asphyxia but, so far, no clinical trials have been performed on a sufficient number of newborns. In this review, we summarize the advantages and limitations of melatonin research in the treatment of experimental and clinical perinatal asphyxia.

Hyperinsulinaemic hypoglycaemia (HH) is the most common cause of persistent hypoglycaemia in infants and children with incidence estimated at 1 per 50,000 live births. Congenital hyperinsulinism (CHI) is symptomatic mostly in early infancy and the neonatal period. Symptoms range from ones that are unspecific, such as poor feeding, lethargy, irritability, apnoea and hypothermia, to more serious symptoms, such as seizures and coma. During clinical examination, newborns present cardiomyopathy and hepatomegaly. The diagnosis of CHI is based on plasma glucose levels <54 mg/dL with detectable serum insulin and C-peptide, accompanied by suppressed or low serum ketone bodies and free fatty acids. The gold standard in determining the form of HH is fluorine-18-dihydroxyphenyloalanine PET ((18)F-DOPA PET). The first-line treatment of CHI is diazoxide, although patients with homozygous or compound heterozygous recessive mutations responsible for diffuse forms of CHI remain resistant to this therapy. The second-line drug is the somatostatin analogue octreotide. Other therapeutic options include lanreotide, glucagon, acarbose, sirolimus and everolimus. Surgery is required in cases unresponsive to pharmacological treatment. Focal lesionectomy or near-total pancreatectomy is performed in focal and diffuse forms of CHI, respectively. To prove how difficult the diagnosis and management of CHI is, we present a case of a patient admitted to our hospital.

Heart diseases are a significant cause of morbidity and mortality in newborns. Diagnostic methods are often not sufficient or, in many cases, cannot be used. There is a great advance in medical knowledge concerning biomarkers in the diagnosis of circulatory system in adult patients. Among them, cardiac troponins play the main role. In current literature, there is not enough data concerning the possibility of using them in neonatal cardiac diagnostics.Aim of the Study. To evaluate diagnostic usefulness of cTnT in correlation with other markers of circulatory failure and myocardial damage in newborns with heart defects.Patients and Methods. The study involved 83 newborns up to 46 weeks of postmenstrual age. The exclusion criteria were severe perinatal asphyxia and presence of severe noncardiac diseases. Patients were divided into 2 main groups: group I—54 patients with congenital heart defects (CHDs), and group II (control)—29 healthy neonates. All patients underwent detailed examination of circulatory system. Cardiac troponin T (cTnT) concentrations were evaluated by Roche CARDIAC T Quantitive test.Results. Performed studies revealed that cTnT levels in newborns with heart pathology were significantly higher than in healthy ones. However, cTnT concentrations in patients with CHD did not correlate with clinical symptoms of heart failure, nor with echocardiographic markers of LV function. Type of heart defect did not influence cTnT levels as well. Only hemodynamic significance evaluated by echocardiography influenced the cTnT levels with statistical significance.Conclusions. (1) Statistically significant differences in cTnT levels between newborns with heart defects and healthy subjects were shown. (2) CTnT levels in newborns with heart defects refer only to hemodynamic significance of the defect.

Perinatal asphyxia is mainly a brain disease leading to the development of neurodegeneration, in which a number of peripheral lesions have been identified; however, little is known about the expression of key genes involved in amyloid production by peripheral cells, such as lymphocytes, during the development of hypoxic-ischemic encephalopathy. We analyzed the gene expression of the amyloid protein precursor, β-secretase, presenilin 1 and 2 and hypoxia-inducible factor 1-α by RT-PCR in the lymphocytes of post-asphyxia and control neonates. In all examined periods after asphyxia, decreased expression of the genes of the amyloid protein precursor, β-secretase and hypoxia-inducible factor 1-α was noted in lymphocytes. Conversely, expression of presenilin 1 and 2 genes decreased on days 1–7 and 8–14 but increased after survival for more than 15 days. We believe that the expression of presenilin genes in lymphocytes could be a potential biomarker to determine the severity of the post-asphyxia neurodegeneration or to identify the underlying factors for brain neurodegeneration and get information about the time they occurred. This appears to be the first worldwide data on the role of the presenilin 1 and 2 genes associated with Alzheimer’s disease in the dysregulation of neonatal lymphocytes after perinatal asphyxia.

Perinatal asphyxia is a complex disease involving massive death of brain cells in full-term newborns. The most impressive consequence of perinatal asphyxia is a neurodegenerative brain injury called hypoxic–ischemic encephalopathy. Management of newborns after perinatal asphyxia is very difficult due to the lack of measurable biomarkers that would be able to assess the severity of the brain injury in the future, help in the selection of therapy, assess the results of treatment and determine the prognosis for the future. Thus, these limitations make long-term neurodevelopmental outcomes unpredictable during life. Quantifying biomarkers that can detect subclinical changes at a stage where routine brain monitoring or imaging is still mute would be a major advance in the care of neonates with brain neurodegeneration after asphyxia. Understanding the effect of perinatal asphyxia on changes in blood neurodegenerative biomarkers over time, which would be commonly used to assess the severity of postpartum encephalopathy, would be an important step in developing precision in predicting the consequences of brain injuries. We urgently need more accurate early predictive markers to guide clinicians when to use neuroprotective therapy. The needed neurodegenerative biomarkers may represent neuronal pathological changes that can be recognized by new technologies such as genomic and proteomic. Nevertheless, the simultaneous blood tau protein and various amyloid changes with the addition of an autophagy marker beclin 1 after perinatal asphyxia have not been studied. We decided to evaluate serum biomarkers of neuronal injury characteristic for Alzheimer’s disease such as amyloid peptides (1-38, 1-40 and 1-42), tau protein and beclin 1, which can predict the progression of brain neurodegeneration in future. In this paper, we report for the first time the significant changes in the above molecules in the blood after asphyxia compared to healthy controls during the 1–7, 8–14 and 15+ days ELISA test.

Heart diseases are currently a significant cause of morbidity and mortality in newborns. The existing diagnostic methods are often not sufficient or, in many cases, cannot be used. Great advances have been achieved in medical knowledge concerning biomarkers for the diagnosis of circulatory system disorders in adult patients. Among these biomarkers, N-terminal pro-brain type natriuretic peptide (NT-proBNP) plays a main role. However, in the existing literature, there is not enough data concerning the physiological features of this biomarker in newborns and its potential use in neonatal cardiac diagnostics. To evaluate the diagnostic usefulness of NT-proBNP measurements in correlation with other markers of circulatory failure and myocardial damage in newborns with heart defects. This study involved 126 newborns. Patients were divided into 2 main groups: group I included infants with congenital heart defects (CHD) and group II (control) included healthy neonates. Newborns with CHD were further divided into 2 subgroups: group Ia with simple shunts and group Ib with combined heart defects. Patients in group I were further divided according to the hemodynamic significance of CHD. The NT-proBNP level was evaluated using the CARDIAC proBNP immunologic test (Cobas h232; Roche Diagnostics, Basel, Switzerland). The NT-proBNP concentrations were significantly higher in newborns with CHD compared to healthy ones. Newborns with combined heart defects had higher levels of NT-proBNP than newborns with simple shunts. The NT-proBNP concentrations in newborns with CHD correlated with echocardiographic parameters of hemodynamic significance and with left ventricular ejection fraction (LVEF). Additionally, NT-proBNP correlated with clinical symptoms of heart failure (HF; Ross classification, Reithmann's score). Statistically significant differences in NT-proBNP level between newborns with heart defects and healthy controls were shown. In newborns with heart diseases, significant correlations were found between NT-proBNP level and the type of heart defect (simple shunt or combined defects), the hemodynamic significance of the defect, LVEF, and the clinical intensity of HF.