None listed
Conditions
Brief summary
Broad aim of this prospective Observational study is to learn which tests (clinical, MRI and EEG) can be used in the neonatal period, to accurately identify which babies may have problems later in life, so that those babies and their families can be provided with the help they need as early as possible. We aim to determine the risk of adverse neurodevelopment earlier and more accurately than currently possible in a cohort of up to 80 term babies born with HIE and a healthy term reference group between Royal Brisbane and Women's Hospital and Mater Mothers Hospital.. To do this we will use: i) advanced brain MRI to determine the structural wiring diagram of the brain ('brain connectome'), ii) dense array EEG to establish the functional activity or electrical 'traffic' being carried on the main branch of the connectome and iii) structured clinical neurodevelopmental assessments to provide a cutting edge view of the state of brain development. We aim to achieve this in a prospective longitudinal cohort study of up to 80 term infants born >35 weeks GA with HIE, and a reference group of 20 healthy term born infants. Infants greater than 35+ weeks GA will undergo either a clinical MRI at 1.5T or a research brain MRI at 3T at day 1-10 post-delivery (day 5-7 optimal) to develop our understanding of the brain structure and maturation at this time point. A combination of neurological and neuromotor assessments will be performed at less than 7 days post MRI to understand the relationship between brain structure and function. These data will be compared to clinical neurodevelopmental assessments at 3 and 24 months corrected age. HYPOTHESIS 1 In a prospective cohort of infants born at term at risk of CP, we will assess the following aims: Aim 1: Determine the sensitivity and specificity of (i) Structural MRI (sMRI) and Diffusion MRI (dMRI), and (ii) General Movements assessment (GMA) at 41 weeks and at 3 months for CP diagnosis at 24 months corrected age (CA). Hypothesis 1: (i) Absent myelination of the posterior limb of the internal capsule (PLIC) on T1-weighted MRI, and (ii) absent fidgety movements at 3 months will be sensitive and specific for CP at 24 months. SECONDARY HYPOTHESES Aim 2: Determine whether Diffusion MRI (dMRI) and EEG, Functional Connectivity (FC) are associated with severity of CP at age 24 months. Hypothesis 2: (i) Lower fractional anisotropy (FA) of the corticospinal tracts, and (ii) reduced connectivity in the neonatal Connectome will be associated with a higher Gross Motor Function Classification System (GMFCS) classification and poorer function on Neurosensory Motor Developmental Assessment (NSMDA) and Bayley III scales of cognitive and motor development. Aim 3: Determine whether structural MRI can predict the pattern of CP at age 24 months. Hypothesis 3: Location, extent and symmetry of brain injury will be associated with pattern and severity of CP.
Interventions
Infants greater than 35+ weeks GA will undergo either a clinical MRI at 1.5T or a research brain MRI at 3T (at Day 1-10 post-delivery; day 5-7 optimal) to develop our understanding of the brain structure and maturation at this time point. They will have a concurrent neurological assessment (Hammersmith Neonatal Neurological Examination), visual assessment and General Movements Assessment (GMA). At 3 months of age infants will have a neurological assessment (Hammersmith Infant Neurological Examin
Infants greater than 35+ weeks GA will undergo either a clinical MRI at 1.5T or a research brain MRI at 3T (at Day 1-10 post-delivery; day 5-7 optimal) to develop our understanding of the brain structure and maturation at this time point. They will have a concurrent neurological assessment (Hammersmith Neonatal Neurological Examination), visual assessment and General Movements Assessment (GMA). At 3 months of age infants will have a neurological assessment (Hammersmith Infant Neurological Examination), visual assessment and General Movements Assessment (GMA). At 24 months corrected age infants will be assessed for Cerebral Palsy (CP) and Motor and Cognitive outcomes. The results from these assessments will be compared to the results from the Gross Motor Function Classification System for Cerebral Palsy (GMFCS).
Sponsors
Prof Roslyn Boyd
Eligibility
Sex/Gender
All
Age
35 Weeks to 42 Weeks
Healthy volunteers
Yes
Inclusion criteria
HIE Group: (a) All babies who enter the Paean Trial, are eligible for the NEBO follow-up trial. (b) Moderate to severe encephalopathy in the first 7 days after term delivery (greater than 35 plus weeks PMA) using the modified Sarnat classification; (c) Male or female infants born at 35 plus 0 weeks gestation with HIE (perinatal depression). (d) One or more of the following indications of perinatal depression: • Apgar of 5 at 10 minutes after birth OR • receiving ongoing resuscitation e.g. assisted ventilation (positive pressure ventilation or CPAP) or chest compressions at 10 minutes after birth OR • on cord blood or arterial or venous blood obtained at less than 60 minutes after birth, • pH less than 7.00 OR • base deficit of 12.0 mmol/L. e) Moderate to severe encephalopathy, defined between one and six hours after birth by one or both of the following: • 3 out of 6 modified Sarnat criteria indicating moderate/severe encephalopathy; • OR • 2 out of 6 modified Sarnat criteria between one and six hours after birth, plus seizure(s) requiring anticonvulsant treatment (diagnosed either clinically or using EEG monitoring) at any time of study entry; f) Hypothermia treatment initiated by 6 hours of age; i.e. controlled whole-body cooling planned to continue for 72 hours, to a target temperature (adjusted manually or with a device) and subsequent controlled re-warming g) Informed consent; h) Ability to receive 3T MRI at 1-10 days post-delivery (day 5-7 optimal) at 35+ weeks PMA (no metal inserts; i.e. no VP shunts) In ADDITION the following babies not entered into the PAEAN intervention trial would be eligible for the NEBO observational trial: i. Babies cooled too late ii. Postnatal arrest with subsequent HIE iii. Parents not approached (e.g. mother in ICU/too ill on 1st day) iv. Babies whose parents declined PAEAN (not happy about an intervention trial but would agree to an observational study). v. Babies who met all other criteria for PAEAN but had a contraindication to cooling – e.g. uncontrolled pulmonary hypertension or coagulopathy/bleeding – so didn’t get cooled. Healthy term reference group: Infants a) born between 35 and 42 weeks gestation following an uncomplicated pregnancy and delivery, b) have a birth weight above the 10th percentile c) not admitted to neonatal intensive or special care units following their birth.
Exclusion criteria
(a) Unable to return for follow-up; (b) Children with major congenital anomalies (c) Where cessation of life support is under active discussion
Outcome results
None listed