Follow-up of Inflammatory Responses and Multiorgan Outcomes FoLlowing Neonatal Brain injurY
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Neonatal Encephalopathy
- Sponsor
- University of Dublin, Trinity College
- Enrollment
- 200
- Locations
- 5
- Primary Endpoint
- Number of participants with cardiovascular dysfunction in childhood
- Last Updated
- 5 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Prof. Eleanor Molloy
Professor of Paediatrics & Child Health, Paediatrics
University of Dublin, Trinity College
Eligibility Criteria
Inclusion Criteria
- •Children at 2-3 years
- •With diagnosis of Neonatal Encephalopathy
- •Required Therapeutic Hypothermia
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Number of participants with cardiovascular dysfunction in childhood
Time Frame: Children at 2-3 years of age
It will be determined by normal or abnormal echocardiography using Tissue doppler and functional imaging.
Number of participants with renal dysfunction in childhood
Time Frame: Children at 2-3 years of age
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.
Number of participants with haematological anomalies persisting in childhood
Time Frame: Children at 2-3 years of age
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.
Number of participants with neurological outcomes
Time Frame: Children at 2-3 years of age
Presence or absence of seizures, motor and sensory dysfunction will be evaluated using Serial Cranial ultrasounds.
Secondary Outcomes
- Concentration level in pg/mL of multicytokines in serum of participants.(Children at 2-3 years of age)
- Number and identity of miRNAs upregulated or downregulated in blood of participants.(Children at 2-3 years of age)
- Fold change of inflammasome components (NLRP3 and ASC) in RNA isolated from blood of participants.(Children at 2-3 years of age)
- Bayley Scales of Infant and Toddler development (BSID III) scores of participants.(Children at 2-3 years of age)