Genomic Imaging Version 1
Research type
Research Study
Full title
Genomic Imaging in Neonatal Encephalopathy (GENIE) study
IRAS ID
233406
Contact name
Sudhin Thayyil
Contact email
Sponsor organisation
Imperial College London
Duration of Study in the UK
5 years, 0 months, 0 days
Research summary
Research Summary:
Babies who experience a lack of oxygen around the time of birth can develop a condition called neonatal encephalopathy, which may lead to long‑term disabilities. Cooling treatment (therapeutic hypothermia) is now widely used and helps many babies, but up to half of survivors still develop developmental problems. Researchers are therefore looking for additional treatments that could work alongside cooling. To develop these personalised treatments, doctors need a quick and reliable way to understand why each baby became unwell and how their body is responding in the first hours after birth.
One promising approach is to study gene activity in the baby’s blood. Gene expression shows which biological processes are switched on or off in response to injury, infection, or lack of oxygen.
What the study aimed to do
The study investigated whether patterns of gene activity in a baby’s blood sample taken shortly after birth could predict which babies would go on to develop disabilities by two years of age.How the study was done
The research team followed newborn babies who received cooling treatment for neonatal encephalopathy across several hospitals. Blood samples were collected before cooling began, frozen, and later analysed using advanced sequencing technology to measure gene activity. The children’s development was assessed again at 18–24 months.What the researchers found
The study identified 1,793 genes whose activity was linked to poorer developmental outcomes. Three genes—CD163L1, RCVRN, and LZTS2—showed the strongest differences between babies who did well and those who developed disabilities. Many of the affected genes were part of pathways controlled by HIF‑1α, a key regulator of the body’s response to low oxygen.What this means
The findings suggest that, in high‑income countries, the biological processes driving neonatal encephalopathy are mainly related to acute oxygen deprivation around the time of birth. The gene activity patterns seen within the first six hours of life could help identify babies at highest risk of disability, opening the door to more personalised treatments in the future.Despite cooling therapy, half of the babies with neonatal encephalopathy still have adverse outcomes. Rapid identification of the babies who will not respond to cooling therapy, and understanding why they do not, is fundamental for the development of future personalised neuroprotective therapies. In this work, we will examine the feasibility of three different methods (host gene expression profile, epigenetics, and copy number variants) for classifying (disease stratification) babies with neonatal encephalopathy. \n\nAIMS\t\n1.\tTo compare the activity of specific genes in blood (host gene expression) at birth with brain injury on magnetic resonance imaging and neurodisability at 2 years in babies with neonatal encephalopathy\n2.\tTo examine the relation of epigenetic changes and neurodisability after neonatal encephalopathy\n3.\tTo examine the association of copy number variants and neurodisability after neonatal encephalopathy\n\nMETHODS\nA total of 300 term encephalopathic babies will be recruited from participating NHS hospitals over a 3 year period. Small amount of blood will be collected soon after birth and will be send to Imperial College London for genomic analysis. All babies will have magnetic resonance imaging during neonatal period and detailed neurodevelopmental assessment between 18 to 24 months, as a part of routine clinical care. Next generation sequencing and bioinformatic analysis will be used to identify a minimal set of activated or deactivated genes (gene signature) that are associated with brain injury patterns and long-term disability. \n\nBENEFITS\nOur goal is to develop a point of care test for disease stratification in neonatal encephalopathy. If successful, this will lead to a paradigm shift in the way we identify and treat babies with perinatal asphyxia, and will open up a new avenue for developing individualised neuroprotective therapies.\n
REC name
South West - Cornwall & Plymouth Research Ethics Committee
REC reference
17/SW/0212
Date of REC Opinion
29 Sep 2017
REC opinion
Further Information Favourable Opinion