Follow-up of Inflammatory Responses and Multiorgan Outcomes FoLlowing Neonatal Brain injurY

NCT04816331 | Unknown

• 1 other identifier: ILP-POR-2019-086
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 5

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.

Conditions

Neonatal Encephalopathy

Keywords

Brain Injuries; Multiple Organ Failure; Infant; Inflammation; Neutrophils

Outcome Measures

Primary Outcomes (4)

• Number of participants with cardiovascular dysfunction in childhood

  It will be determined by normal or abnormal echocardiography using Tissue doppler and functional imaging.

  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.

  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.

  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.

  Children at 2-3 years of age

Secondary Outcomes (4)

• 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

• Concentration level in pg/mL of multicytokines in serum 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

Study Arms (2)

Neonatal Encephalopathy (NE)

This study is a follow up of 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. Detailed antenatal, birth, resuscitation, oxygen requirements throughout inpatient stay and detailed neonatal intensive care management were collected. In addition, details of Therapeutic Hypothermia treatment including initiation, duration and clinical examination, investigations including cranial USS, MRI, EEG and placental histology analysis performed as were recorded.

Other: Medical records and clinical measurements

Controls

The controls include age-matched normal children born at term with a normal delivery and postnatal course.

Other: Medical records and clinical measurements

Interventions

Medical records and clinical measurements OTHER

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.

Also known as: Questionnaires for caregivers to assess social-emotional and adaptive domains, Tissue samples analysis and processing: blood, saliva and urine

Controls; Neonatal Encephalopathy (NE)

Eligibility Criteria

• Age: 2 Years - 3 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• 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.

You may qualify if:

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

Sponsors & Collaborators

• University of Dublin, Trinity College: lead
• Health Research Board, Ireland: collaborator

Study Sites (5)

The Coombe Women & Infants University Hospital

Dublin, Ireland

Location

The National Maternity Hospital, or Holles Street Hospital

Dublin, Ireland

Location

The Rotunda Hospital

Dublin, Ireland

Location

The Tallaght University Hospital

Dublin, Ireland

Location

Trinity College Dublin, The University of Dublin

Dublin, Ireland

Location

Related Publications (25)

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• O'Hare FM, Watson RW, O'Neill A, Segurado R, Sweetman D, Downey P, Mooney E, Murphy J, Donoghue V, Molloy EJ. Serial cytokine alterations and abnormal neuroimaging in newborn infants with encephalopathy. Acta Paediatr. 2017 Apr;106(4):561-567. doi: 10.1111/apa.13745. Epub 2017 Feb 16.

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Biospecimen

Retention: SAMPLES WITH DNA

Peripheral venous samples Urine Saliva

MeSH Terms

Conditions

Brain Injuries; Multiple Organ Failure; Inflammation

Interventions

Medical Records; Surveys and Questionnaires; Urination

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Shock; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Records; Data Collection; Epidemiologic Methods; Investigative Techniques; Organization and Administration; Health Services Administration; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health; Urinary Tract Physiological Phenomena; Reproductive and Urinary Physiological Phenomena

Study Officials

• Eleanor Molloy, Prof.

  Professor of Paediatrics & Child Health, Paediatrics

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Target Duration: 1 Month
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Paediatrics & Child Health, Paediatrics

Study Record Dates

• First Submitted: March 2, 2021
• First Posted: March 25, 2021
• Study Start: August 4, 2020
• Primary Completion: June 30, 2022
• Study Completion: September 30, 2022
• Last Updated: March 25, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

IE (5)