Babies who have brain injury also frequently have involvement of their kidneys, lung and heart. Although clinical care in the neonatal period is well defined there are few guidelines and evidence for developmental, heart and kidney followup in childhood. The investigators aim to develop and implement guidelines for health care workers and families on Followup after Neonatal Brain Injury. Inflammation is an important factor in brain injury of newborns and also affects their heart lungs and other parts of their body. The investigators will use tests from the newborn period to predict outcome and help parents with planning health needs for their baby rather than waiting until any issues arise later on. By understanding inflammation the investigators can find methods to decrease the negative effects and improve outcomes in the future for babies and families.
Neonatal brain injury is an important cause of neonatal death and disability such as cerebral palsy. Perinatal global hypoxic ischemic associated with Neonatal Encephalopathy (NE) results in multi-organ dysfunction which may persist in later childhood. In addition perinatal inflammation has been associated with neonatal brain injury and implicated in adult neuropsychiatric conditions. The investigators aim to examine multi-organ dysfunction in early childhood in children who had NE by examining detailed cardiac, renal, neurological, haematological and neurodevelopmental outcomes. The investigators have previously defined detailed multi organ dysfunction (MOD) in this cohort in the neonatal period in infants with NE including organ outcomes as well as serum, urine and cerebrospinal fluid (CSF) biomarkers. They are now age-appropriate for detailed neurocognitive assessment and correlation with these biomarkers and the investigators plan to compare with age- matched controls. Immunological markers such as the inflammasome and microRNAs are altered in the neonatal period and may persist in early childhood. The investigators will modify negative inflammatory responses in vitro with specific antagonists as well as correlating these immune biomarkers with outcomes. Quantifying multiorgan dysfunction in the neonatal period to ensure appropriate follow-up of all organs is merited. This would help in advanced clinical planning and long term follow up. In addition, understanding, the immune response in these children with NE and exploring systemic inflammation holds promise for future development of immunomodulatory adjunctive therapies and biomarkers to predict outcomes.
Study Type
OBSERVATIONAL
Enrollment
200
Medical records and clinical measurements: Detailed antenatal, birth, resuscitation, oxygen requirements throughout inpatient stay and detailed neonatal intensive care management will be collected. Therapeutic Hypothermia treatment including initiation, duration and clinical examination, and investigations such as scans. In addition, clinical data will include medication, neurological (paediatric developmental psychologist assessment and Bayley Scales of Infant and Toddler Development) and multiorgan examination. Questionnaires for caregivers to assess social-emotional and adaptive domains. Tissue samples analysis and processing: Samples of blood, urine and saliva will be used for laboratory testing. Biomarker correlation with Multiorgan outcomes using statistical analysis: Data collected from medical records, clinical measurements, questionnaires, and tissue processing will be analysed using SPSS software for statistical analysis and modelling.
The Coombe Women & Infants University Hospital
Dublin, Ireland
The National Maternity Hospital, or Holles Street Hospital
Dublin, Ireland
The Rotunda Hospital
Dublin, Ireland
The Tallaght University Hospital
Dublin, Ireland
Trinity College Dublin, The University of Dublin
Dublin, Ireland
Number of participants with cardiovascular dysfunction in childhood
It will be determined by normal or abnormal echocardiography using Tissue doppler and functional imaging.
Time frame: Children at 2-3 years of age
Number of participants with renal dysfunction in childhood
It will be assessed using renal scoring systems such as the Kidney disease Improving Global Outcomes (KDIGO) Acute Kidney injury score (scores 1 to 3, being 3 worse outcome) and measuring the concentration of urinary biomarkers (in mg/L) such as albumin, B2 microglobulin, Cystatin c, EGF, NGAL, OPN and UMOD. Deviations of the reference range values for the scores and urinary biomarkers will indicate renal dysfunction. Results will be reported as number of patients with renal dysfunction in childhood.
Time frame: Children at 2-3 years of age
Number of participants with haematological anomalies persisting in childhood
Number of patients with signs of coagulopathy will be defined using three indicators: APTT/PT (units per seconds), fibrinogen (mg/dL) and Leukocyte/neutrophil (percentage and units per Liter). Deviations of the reference range values for the three indicators will point to haematological anomalies. Results will be reported as number of patients with signs of coagulopathy.
Time frame: Children at 2-3 years of age
Number of participants with neurological outcomes
Presence or absence of seizures, motor and sensory dysfunction will be evaluated using Serial Cranial ultrasounds.
Time frame: Children at 2-3 years of age
Number and identity of miRNAs upregulated or downregulated in blood of participants.
Between 350 and 800 miRNAs will be assessed in serum from patients and controls.
Time frame: Children at 2-3 years of age
Fold change of inflammasome components (NLRP3 and ASC) in RNA isolated from blood of participants.
Using RNA extracted from whole blood of patients and controls, the fold change RNA expression of inflammasome components (NLRP3 and ASC) will be evaluated.
Time frame: Children at 2-3 years of age
Concentration level in pg/mL of multicytokines in serum of participants.
Multiplex cytokine analysis will be performed and reported in pg/mL in serum. Cytokines to be included: Interleukin-1 alpha (IL-1α), Interleukin-1 beta (IL- 1β), Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-10 (IL-10), Tumour Necrosis Factor-alpha (TNF-α), Interferon-gamma (IFN-δ), Vascular Endothelial Growth Factor (VEGF), Granulocyte Colony Stimulating Factor (G-CSF) and Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF), Erythropoietin, Neuronal glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase L1 and S100B.
Time frame: Children at 2-3 years of age
Bayley Scales of Infant and Toddler development (BSID III) scores of participants.
Bayley Scales of Infant and Toddler development (BSID III) score is an assessment instrument designed to measure motor, cognitive, language, social-emotional, and adaptive behavior development in babies and young children. Composite scores are derived for cognitive, language, and motor development and scaled to a metric, with a mean of 100, standard deviation of 15, and range of 40 to 160. Scores lower than 85 indicating mild impairment, and lower than 70 indicating moderate or severe impairment. Scores equal or higher than 85 indicate normal development.
Time frame: Children at 2-3 years of age
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.