Clinical trial NCT04816331: Follow-up of Inflammatory Responses and Multiorgan Outcomes FoLlowing Neonatal Brain injurY
Official title: Follow-up of Inflammatory Responses and Multiorgan Outcomes FoLlowing Neonatal Brain injurY
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Neonatal Encephalopathy
Keywords: Brain Injuries
Multiple Organ Failure
Infant
Inflammation
Neutrophils
Lead sponsor: University of Dublin, Trinity College
Sponsor class: OTHER
Collaborators: name: Health Research Board, Ireland
First posted: 2021-03-25
Enrollment: 200
Sex: ALL
Minimum age (years): 2
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children at 2-3 years of age who were enrolled in the HRB-funded Neonatal Inflammation and Multiorgan dysfunction and Brain injUry reSearch group (NIMBUS) project. These babies had Neonatal Encephalopathy and required Therapeutic Hypothermia and are matched with controls.

Patients recruited as part of the NIMBUS study in 3 Dublin Maternity Hospitals: the National Maternity hospital (NMH), the Rotunda hospital \& the Coombe Women's and Infant's University Hospital (CWIUH) with an average of 120 infants with Neonatal encephalopathy (NE) Grade I-III deliveries per annum. This study will enrol 100 infants with NE and 100 controls (recruited in Tallaght University Hospital). The controls include age-matched normal children born at term with a normal delivery and postnatal course.

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.

Eligibility criteria: Inclusion Criteria:

* Children at 2-3 years
* With diagnosis of Neonatal Encephalopathy
* Required Therapeutic Hypothermia

Exclusion Criteria:

-

Primary outcomes:
measure: Number of participants with cardiovascular dysfunction in childhood
timeFrame: Children at 2-3 years of age
measure: Number of participants with renal dysfunction in childhood
timeFrame: Children at 2-3 years of age
measure: Number of participants with haematological anomalies persisting in childhood
timeFrame: Children at 2-3 years of age
measure: Number of participants with neurological outcomes
timeFrame: Children at 2-3 years of age
Secondary outcomes:
measure: Number and identity of miRNAs upregulated or downregulated in blood of participants.
timeFrame: Children at 2-3 years of age
measure: Fold change of inflammasome components (NLRP3 and ASC) in RNA isolated from blood of participants.
timeFrame: Children at 2-3 years of age
measure: Concentration level in pg/mL of multicytokines in serum of participants.
timeFrame: Children at 2-3 years of age
measure: Bayley Scales of Infant and Toddler development (BSID III) scores of participants.
timeFrame: Children at 2-3 years of age
Other outcomes:
Locations:
city: Dublin
country: Ireland
facility: The Coombe Women & Infants University Hospital
city: Dublin
country: Ireland
facility: The National Maternity Hospital, or Holles Street Hospital
city: Dublin
country: Ireland
facility: The Rotunda Hospital
city: Dublin
country: Ireland
facility: The Tallaght University Hospital
city: Dublin
country: Ireland
facility: Trinity College Dublin, The University of Dublin
Study officials:
affiliation: Professor of Paediatrics & Child Health, Paediatrics
name: Eleanor Molloy, Prof.
role: PRINCIPAL_INVESTIGATOR
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