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Stephen Back, M.D., Ph.D., left, and Art Riddle, M.D., Ph.D., in the Back lab at Oregon Health & Science University.
Photo Credit: OHSU/Christine Torres Hicks
Scientific Frontline: Extended "At a Glance" Summary: Impact of Mild Intermittent Hypoxia on Preterm Brain Development
The Core Concept: Even a mild, temporary lack of oxygen (hypoxia) in premature infants can significantly alter long-term brain development. This early disruption can permanently hinder cognitive functions such as memory, learning, and emotional regulation well into adolescence and adulthood.
Key Distinction/Mechanism: While previous studies primarily focused on the devastating effects of severe or prolonged oxygen deprivation (which causes acute brain injury, inflammation, and seizures), this research identifies the profound impact of mild, intermittent hypoxia. The mechanism involves a disruption in neural communication between the hippocampus (responsible for memory and learning) and the cortex (responsible for reasoning and problem-solving), alongside abnormal maturation of hippocampal neurons that fail to recover by adulthood.
Major Frameworks/Components:
- Intermittent Hypoxia: Short, recurring episodes of low oxygen in tissues and cells, a common occurrence for preterm infants in the Neonatal Intensive Care Unit (NICU) due to immature respiratory control.
- Hippocampal-Cortical Disruption: The specific deterioration of neural communication pathways connecting the brain's memory center to its reasoning and problem-solving layer.
- Cellular Arrest: The abnormal maturation of neurons within the hippocampus, which fail to achieve normal developmental milestones as the organism reaches adulthood.
Branch of Science: Neuroscience, Neonatology, and Pediatrics.
Future Application: The findings provide a foundational rationale for enhanced early intervention therapies in the NICU, such as the extended use of nasal continuous positive airway pressure (CPAP) to minimize intermittent hypoxemia. Furthermore, it paves the way for new diagnostic protocols to identify at-risk infants early, allowing clinicians to initiate targeted cognitive, academic, and behavioral support before deficits present clinically.
Why It Matters: Because short hypoxic events are highly common in preterm infants, the revelation that these episodes are not benign fundamentally shifts neonatal care priorities. The discovery that "just one bad day in the NICU" can alter a patient's lifelong neurological trajectory highlights an urgent need for preventative respiratory treatments and early educational interventions to optimize quality of life.
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| A team of researchers evaluated the effects of mild hypoxia following premature birth, discovering it may have significant impacts on the developing brain. Photo Credit: OHSU/Christine Torres Hicks |
Researchers at Oregon Health & Science University have made a concerning discovery about preterm infant brain health: A mild, temporary lack of oxygen that many babies born prematurely may experience has a significant impact on long-term brain development, and may hinder memory and learning into adolescence and adulthood.
While receiving care in the Neonatal Intensive Care Unit, or NICU, preterm babies can experience low oxygen in their tissue and cells, known clinically as hypoxia. Because many complications of being born preterm can compromise the flow of oxygen, and preterm babies have immature respiratory control and lung function, short intermittent hypoxic events can be common.
Prior studies have focused on the effect of severe or prolonged hypoxic events associated with brain injury, inflammation and seizures in older children or adults; this is the first study to explore the brain’s susceptibility to mild intermittent hypoxia in the preterm period.
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| Stephen Back, M.D., Ph.D. Image Credit: OHSU |
“The sobering message of this research is that hypoxia, even when mild to moderate, is not benign and the consequences could be considerable,” said Stephen Back, M.D., Ph.D., professor of pediatrics in the OHSU School of Medicine and lead author of the study.
“These episodes of hypoxia are targeting very fundamental functions of the brain that are vital for long-term health. Essentially, just one bad day in the NICU could be all it takes to change the trajectory of brain development throughout life.”
The research team, led by Art Riddle, M.D., Ph.D., assistant professor of pediatrics in the OHSU School of Medicine, used a mouse model to evaluate the effects of mild hypoxia following premature birth. Researchers discovered a mechanism in the hippocampus — the part of the brain responsible for memory and learning — that may explain, at least in part, why these impacts occur.
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| Art Riddle, M.D., Ph.D. Photo Credit: OHSU |
When evaluating brain tissue in the mice after intermittent hypoxic events, researchers found that neural communication was impacted. Particularly, communication was hindered between the hippocampus region and the cortex — the brain’s outermost layer responsible for reasoning and problem-solving. Furthermore, neurons in the hippocampus matured abnormally and did not recover by adulthood.
Discovery could inform treatment
Neural communication is a critical function: It is the brain’s way of sending messages to and from different regions to relay critical information throughout the body. If neural communication is compromised, it can affect human function, including physical tasks like breathing and movement, and cognitive ones like emotional regulation, learning and memory.
Researchers warn of the implications for children’s overall health, well-being and life trajectory. Alterations in the development of these critical brain regions could impair attention, memory and emotional regulation, potentially leading to academic difficulties and behavioral concerns.
Future research should continue to examine the severity of these impacts and broader long-term consequences, the research team says, as well as investigate how other brain regions may also be susceptible to hypoxia.
Intermittent Hypoxia sometimes isn’t avoidable among preterm babies, Back notes. While the findings are concerning, neonatal providers say they provide the opportunity to advance treatments and early interventions for preterm infants to optimize health and quality of life.
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| Cindy McEvoy, M.D. Photo Credit: OHSU |
“Historically it is prolonged, significant hypoxic events that were the primary concern for long-term adverse outcomes, but this research tells us that mild intermittent episodes may also be a cause for concern,” said Cindy McEvoy, M.D., professor of pediatrics in the OHSU School of Medicine, who cares for critically ill preterm babies.
McEvoy says these results, if translated to humans, may prompt the use of additional interventions, including extending nasal continuous positive airway pressure, or CPAP, which has been proven to improve respiratory development in preterm babies and also to decrease episodes of short intermittent hypoxemia. These results may also be helpful in identifying early on which patients may need additional early interventions throughout childhood and adolescence.
“These impacts are not something we would see on standard tests or scans in the NICU; they are happening deep within the connections of the brain, and may present years later as the child develops,” she explained. “If we know these children are at risk for learning and memory challenges, we can intervene earlier and provide the support and resources they need to thrive.”
Funding: This study was supported by the National Institute of Neurological Disorders and Stroke, of the National Institutes of Health, under Award numbers R01NS138147, R01NS116674 and R01HL163517.
Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or other funders.
Published in journal: Journal of Neuroscience
Authors: Art Riddle, Taasin Srivastava, Kang Wang, Eduardo Tellez, Hanna O’Neill, Xi Gong, Abigail O’Niel, Jaden A Bell, Jacob Raber, Matthew Lattal, James Maylie, and Stephen A Back
Source/Credit: Oregon Health & Science University | Nicole Rideout
Reference Number: ns032326_01
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