Summary: Researchers have developed a blood test that analyzes gene activity to identify newborns who, after oxygen deprivation at birth, are at heightened risk of neurodevelopmental disorders.
Source: Imperial College London
New early blood test may predict which infants affected by birth oxygen deprivation will develop serious neurodisabilities such as cerebral palsy and epilepsy.
A prototype diagnostic examines patterns of gene expression—genes being switched on or off—in a baby’s blood shortly after birth. The test aims to distinguish which neonates who experienced oxygen deprivation (birth asphyxia) are likely to develop long-term neurological problems. By pinpointing the most relevant genes and pathways, researchers hope to reveal targets for interventions that could prevent or reduce permanent brain injury.
This work was led by researchers at Imperial College London in collaboration with teams in India, Italy and the United States, and the findings are published in the journal Scientific Reports.
The clinical research took place in Indian hospitals where birth asphyxia affects an estimated 0.5–1.0 million infants each year. Oxygen deprivation at birth can arise for several reasons, including reduced maternal oxygenation, infection, or complications involving the umbilical cord. Brain injury after such events can develop over hours to months and may involve different brain regions, producing a range of outcomes from cerebral palsy and epilepsy to sensory impairments such as deafness or blindness.
Because symptoms and injury progression vary, clinicians currently face difficulty identifying which babies will go on to experience adverse neurodevelopmental outcomes and which early interventions will be most effective. The new blood-based approach seeks to improve that early risk stratification.
In this preliminary study of 45 infants who suffered oxygen deprivation at birth, researchers collected blood within six hours after delivery and followed the children until 18 months of age to determine neurodevelopmental status. Using next-generation sequencing, the team compared whole-blood transcriptomic profiles—the pattern of genes being expressed—between infants who later developed neurodisabilities and those who did not.
Analysis revealed 855 genes with statistically significant differences in expression between the two outcome groups, with two genes showing the strongest associations. Further investigation of these genes and the cellular pathways they influence could clarify mechanisms that lead to neurodisability after neonatal encephalopathy and suggest opportunities to interrupt those processes therapeutically.
Lead author Dr Paolo Montaldo, from the Centre for Perinatal Neuroscience at Imperial, commented that while early intervention is crucial to improving outcomes after birth-related oxygen deprivation, identifying which infants require intensive treatment and determining the best approaches remain major challenges.
Senior author Professor Sudhin Thayyil, also from the Centre for Perinatal Neuroscience at Imperial, noted that blood-based molecular signatures can deepen understanding of the disease mechanisms that drive brain injury and help develop or refine neuroprotective therapies.
The infants in the study were enrolled in the Hypothermia for Encephalopathy in Low and middle-income countries (HELIX) trial, which evaluates therapeutic hypothermia (cooling) as a neuroprotective strategy after neonatal encephalopathy. While cooling has been shown to reduce the risk of adverse outcomes in higher-income settings, it may be impractical in some lower-resource environments and still leaves about 30 percent of cooled infants with poor outcomes—highlighting the need for additional or alternative treatments.
The research team plans to expand the transcriptomic study to a larger cohort and to focus on the most promising genes and pathways identified in this pilot work. Their goal is to refine a rapid, reliable test that can be applied soon after birth to guide early interventions and accelerate development of targeted neuroprotective therapies.
Funding: The study received support from a Neonatal Medicine Endowment Chair funded by the Weston Garfield Foundation.
About this neurology and neuroscience research
Source: Imperial College London
Media Contacts: Hayley Dunning – Imperial College London
Image Source: Image is in the public domain.
Original Research: Open access — “Transcriptomic profile of adverse neurodevelopmental outcomes after neonatal encephalopathy” by Paolo Montaldo et al., Scientific Reports.
Abstract
Transcriptomic profile of adverse neurodevelopmental outcomes after neonatal encephalopathy
A rapid, early diagnostic capable of identifying encephalopathic newborns at risk of poor outcomes would accelerate the development and targeting of neuroprotective treatments. This study tested whether whole-blood transcriptomic signatures measured within six hours of birth could predict neurodevelopmental outcomes at 18 months after neonatal encephalopathy. Next-generation sequencing was performed on whole-blood RNA from the first 47 infants recruited to the HELIX trial; two infants with culture-positive sepsis were excluded, leaving 45 for analysis. We identified 855 genes that were differentially expressed between infants with good versus adverse outcomes, with RGS1 and SMC4 the most significant. Pathway analysis—adjusted for sex, trial randomisation (cooling versus usual care) and estimated leukocyte proportions—showed over-representation of genes involved in melatonin signaling and polo-like kinase pathways among infants with adverse outcomes. These preliminary findings indicate that early transcriptomic profiling could serve as a promising tool for rapid risk stratification in neonatal encephalopathy, offering insights into biological mechanisms and potential therapeutic targets for neuroprotection.