Birth asphyxia as the major complication in newborns: moving towards improved individual outcomes by prediction, targeted prevention and tailored medical care

Abstract

Perinatal Asphyxia-oxygen deficit at delivery-can lead to severe hypoxic ischaemic organ damage in newborns followed by a fatal outcome or severe life-long pathologies. The severe insults often cause neurodegenerative diseases, mental retardation and epilepsies. The mild insults lead to so-called "minimal brain-damage disorders" such as attention deficits and hyperactivity, but can also be associated with the development of schizophrenia and life-long functional psychotic syndromes. Asphyxia followed by re-oxygenation can potentially lead to development of several neurodegenerative pathologies, diabetes type 2 and cancer. The task of individual prediction, targeted prevention and personalised treatments before a manifestation of the life-long chronic pathologies usually developed by newborns with asphyxic deficits, should be given the extraordinary priority in neonatology and paediatrics. Socio-economical impacts of educational measures and advanced strategies in development of robust diagnostic approaches targeted at effected molecular pathways, biomarker-candidates and potential drug-targets for tailored treatments are reviewed in the paper.

Fig. 1

Newborn with asphyxic deficits. For timely protection against severe outcomes, a predictive diagnostics should be performed to detect individual pathology predisposition followed by targeted preventive measures and creation of personalised treatment algorithms. Data taken from [1]

Fig. 2

Frequent complications leading to neonatal deaths with the highest contributions by birth asphyxia as monitored Tamil Nadu, India. Data taken from [1, 6]

Fig. 3

Prevalence of neonatal mortality represented in percentages with respect to a delivery area as monitored in South Africa [7]

Fig. 4

The prevalence of birth asphyxia as documented by a series of population studies: a corresponding number of cases has been calculated per 1,000 life births. Data taken from [–21]

Fig. 5

Significant regional preferences in PA-related mortality depending on the density of healthcare units (maximal and minimal density in metropolitan and rural area, respectively) as documented for South Africa. Data taken from [1, 7]

Fig. 6

Ratio of newborns with asphyxic deficits born to uneducated versus educated mothers. Data taken from [22]

Fig. 7

Influence of maternal and paternal professional activity on prevalence of birth asphyxia in sub-grouped families as monitored in Nepal [16, 23]

Fig. 8

A brief description of the APGAR system for the severity grading of perinatal asphyxia (PA) in newborns: PA severity ranges between 0 and 10, whereby 10 (healthy) corresponds to the best score 2 for all five parameters evaluated; *acrocyanosis occurs due to altered parameters of blood flow resulting in a gradually changing skin colour. Data taken from [1, 24]

Fig. 9

Advanced strategies in the development of a robust diagnostic platform and novel drug targets with high potential for their clinical implementation

Fig. 10

The sequence of steps resulting in a set-up of clinically relevant perinatal asphyxia conditions and well reproducible asphyxiated newborn rats [25]. The uterus horns containing foetuses are placed in a water-bath at 37°C for 20 min to simulate severe birth asphyxia. Without re-oxygenation, the asphyxiated pups die after 22 min. By using this model, mild insults can be observed by 5–10 min simulation of perinatal asphyxia followed by immediate re-oxygenation

Fig. 11

Metabolic particularities, impairments and individual outcomes by perinatal asphyxia. Abbreviations: mtDNA = mitochondrial DNA; chrDNA = chromosomal DNA; ATP = adenosine three-phosphate; PPPM = predictive, preventive and personalised medicine

Fig. 12

Transcription levels of the TAU-protein as measured in experimental rats exposed to birth asphyxia versus control animals (normoxia). The transcriptome-profies are specific for the brain-regions – Mesencephalon, Hypothalamus and Telencephalon. The brain-region/time specific peaks correlate with the appearance of TAU-transcripts in full blood of all asphyxiated animals tested. Data taken from [96]

Fig. 13

Transcription levels of the HER-2 protein as measured in experimental rats exposed to birth asphyxia versus control animals (normoxia). The transcriptome-profies are specific for the brain-regions – Mesencephalon, Hypothalamus and Telencephalon. The brain-region specific up-regulation (1 month after asphyxia) and down-regulation (48 h) correlates well with the respective appearance/disappearance of HER-transcripts in full blood asphyxiated animals. Data taken from [96]