Researchers from Imperial College London have discovered that a simple blood test could potentially determine the underlying cause of brain injury in newborn babies. The study focused on infants with brain injuries caused by hypoxia, a lack of oxygen. By analyzing patterns of gene expression in the blood, doctors can identify the cause of the injury and determine if the newborn is likely to respond to cooling treatment, a common method for treating brain injury in infants. The findings, published in the journal JAMA Network Open, have the potential to lead to a quick and effective diagnostic test for brain injury in newborns, greatly aiding in treatment decisions.
The study included infants from both low and middle-income countries (LMICs) and high-income countries (HICs). There was a stark contrast in gene expression between the two groups, suggesting different underlying causes of brain injury. Lead investigator Professor Sudhin Thayyil explains that babies from LMICs exhibited gene expression patterns similar to those seen in individuals with sleep apnea, indicating intermittent hypoxia during pregnancy and birth. This is likely caused by various chronic stressors, such as malnutrition and infection, as well as the normal labor process, leading to hypoxia and subsequent brain injury. On the other hand, babies from HICs showed gene expression patterns indicative of a single, acute cause of brain injury, such as maternal bleeding during birth resulting in a sudden drop in blood oxygen levels in the fetus.
Hypoxic-ischemic encephalopathy (HIE), also known as birth asphyxia, is a type of brain injury that occurs when a baby’s brain does not receive enough oxygen before or shortly after birth. HIE is a leading cause of death and disability among full-term newborns worldwide, with approximately 3 million babies affected each year. The burden of HIE is especially high in South Asia, particularly in India, which accounts for 60% of all HIE-related deaths globally.
Previous studies conducted in HICs have shown that whole-body cooling treatment can improve outcomes for babies with HIE, leading to its widespread adoption in many HICs and some hospitals in South Asia. However, a significant study encompassing LMICs found that whole-body cooling actually worsened outcomes for infants with HIE and may have increased the risk of mortality.
The current research sheds light on the difference in treatment response between the two groups of babies and could potentially pave the way for a simple test to determine which infants would benefit from cooling treatment. The study involved 35 babies with HIE from Italy (HIC) and 99 babies from LMICs in South Asia (India, Sri Lanka, and Bangladesh). Blood samples were taken shortly after birth, and the babies were assessed at 18 months of age. The South Asian cohort experienced significantly higher rates of death and severe disabilities compared to the Italian cohort.
The researchers identified correlations between gene expression at birth and outcomes at 18 months in both cohorts. In the HIC cohort, they found 1,793 significant genes associated with adverse outcomes, while in the South Asian cohort, they found 99 significant genes associated with adverse outcomes. Surprisingly, only 11 genes were significant in both cohorts, but they were expressed in opposite directions, either switched on or off. This dramatic divergence in gene expression highlights the distinct underlying causes of brain injury between the two groups and explains why some babies respond positively to cooling treatment while others do not.
The researchers emphasize that the differences between the cohorts are not related to ethnicity; instead, socioeconomic factors play a significant role. The type of chronic brain injury commonly observed in LMICs could also exist in deprived areas of HICs. Similarly, among wealthier populations in LMICs, acute brain injury akin to that seen in HICs may be more prevalent.
The ultimate goal for clinicians worldwide is to quickly identify the type of brain injury present in newborns, facilitating prompt and targeted treatment. Professor Thayyil and his team are actively working towards this goal. The discovery of a blood test to pinpoint the cause of brain injury in newborns represents a significant advancement in the field, offering hope for improved diagnoses and treatment decisions for infants worldwide.
