RecruitingACTRN12623000672651

e-PINO: early Prediction of Infant Neurodevelopmental Outcomes using novel biomarkers

Sponsor

University of Queensland

Enrollment

660 participants

Start Date

Jun 7, 2023

Study Type

Observational

Conditions

Nature/mechanism of brain injury very early in the fetal or neonatal period Brain development in preterm infants Cerebral Palsy

Summary

SYNERGY -A synergistic research program, incorporating advanced neuroimaging, genetics and liquid biopsy, enabling fetal and newborn diagnosis, prognosis and prediction of treatment responses to prevent, treat and cure CP using precision-medicine interventions. Prevention in this context means a 40% reduction in the rate of CP, and treatment response means a reduction in the size and severity of brain injury, enabling increased function, participation in education, independent living and employment long-term. We propose to do this by bringing together this unique team to: • Accurately identifying the nature/mechanism of the brain injury very early in the fetal or neonatal period, to quantify the location, extent, mechanism and genomics of injury to determine the best prognosis and pathway to precision medicine interventions; • Integrating currently disparate measures of neural injury using cross-cutting research methods across 3 themes involving (1) neuroimaging and EEG, (2) genomics, and (3) liquid biopsy; • Synthesising and converging outputs from themes 1-3 using machine learning (ML) methods to inform theme 4: Translation to precision-medicine trials to prevent, treat and cure CP. • Developing systems to comprehensively monitor how these biomarkers, genomics and precision-medicine interventions impact both the incidence and severity of CP at a population level using our national CP population register (Australian Cerebral Palsy Register, largest country-wide register).

Eligibility

Sex: Both males and femalesMax Age: 24 Monthss

Plain Language Summary

Simplified for easier understanding

Cerebral palsy (CP) is a condition that affects movement and development, and it typically begins from brain injury around the time of birth. At the moment, it is very difficult to predict early on which babies will develop CP or how severe it will be. This study — called e-PINO — is using a combination of advanced brain imaging, genetic analysis, and blood-based markers (called liquid biopsy) to see if doctors can predict and better understand CP much earlier than currently possible, and to develop precision treatments. By combining these different measures using machine learning, the research team hopes to build a system that identifies the nature and extent of brain injury early, predicts outcomes with greater accuracy, and ultimately guides more targeted, personalised treatment for affected babies. The study recruits newborns admitted to neonatal intensive care units at three major Australian hospitals. Eligible infants include those born very preterm, moderately preterm, small for gestational age, or full-term with brain injury from reduced oxygen. Babies with known chromosomal abnormalities are not eligible. Families must live within 200 km of the hospital and speak English.

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Interventions

We will recruit 480 infants born very preterm (VPT), moderate-to-late preterm (MLPT), term but small for gestational age (SGA) or with hypoxic ischaemic encephalopathy (HIE) and 60 healthy term born infants (HT) (total n=540 infants), and collect advanced MRI (structural and multi-shell diffusion), EEG, blood, and a suite of motor/neurological assessment data, including Hammersmith Neonatal Neurological Examination (HNNE)/ Hammersmith Infant Neurological Assessment (HINE), General Movements Assessment (GMA), General Movements Optimality Score (GMOS), Motor Optimality Score (MOS) and visual assessment. These assessments will be conducted between birth, term equivalent age (TEA) and 3 months corrected age (CA). All assessments conducted are carried out at a hospital (Royal Brisbane Women’s Hospital, Monash Medical Centre or Westmead Hospital). Assessments at birth and TEA will be conducted across 2 sessions, while the 3-month assessments will be conducted in 1 session. Each session is estimated to take around 2 hours to complete. Assessments will be carried out by the appropriate health professionals, including radiologists (MRI), research nurses (MRI, EEG, sample collection, motor/neurological assessments), neonatologists (MRI, medical evaluation, primary outcomes) and physiotherapists (motor/neurological assessments). Primary outcomes will be Bayley-4 cognitive, motor, language and behaviour and executive function in addition to medical diagnosis of cerebral palsy (CP), developmental disability (DD), and symptomology of autism spectrum disorder (ASD), foetal alcohol spectrum disorder (FASD) at 2 years CA. We will use machine learning (ML) to predict Bayley-4 scores from neonatal MRI, EEG and motor/neurological/behavioural assessments to determine the strongest biomarkers for accurate prediction of neurodevelopment (i.e., assessment and time points). ML models will be trained using our previously recruited VPT infant cohort (PREBO; n=272), with transfer learning to improve predictions. Secondly, we will collect cord blood, infant blood and meconium at birth in participants enrolled in the study prior to birth, as well as infant blood, faecal samples and breast milk samples soon after birth in all participants. and at the same time points as neonatal assessments described above. This sample will be bio banked to provide a comprehensive resource for the characterisation of infants born preterm, small for gestational age (SGA), with Hypoxic-ischemic encephalopathy (HIE) or Stroke. In addition, we will collect and bank the birthing mother/both parent’s blood or saliva for this project’s analysis and for future analysis of HREC approved projects.