Olfactory testing in infants with perinatal asphyxia: Enhancing encephalopathy risk stratification for future health outcomes

Perinatal asphyxia (PA) is a leading cause of neonatal morbidity and mortality, often resulting in long-term neurodevelopmental challenges. Despite advancements in perinatal care, predicting long-term outcomes remains difficult. Early diagnosis is essential for timely interventions to reduce brain injury, with tools such as Magnetic Resonance Imaging, brain ultrasound, and emerging biomarkers playing a possible key role. Olfaction, one of the earliest senses to develop, may provide valuable insights into long-term neurodevelopmental outcomes following PA due to its intricate neural connections with regions responsible for memory, emotion, and homeostasis. Newborns demonstrate early olfactory abilities, such as recognizing maternal odors, which are vital for bonding, feeding, and emotional regulation. These responses are processed by a network of brain regions, including the olfactory bulb (OB), piriform cortex, amygdala, and orbitofrontal cortex. Hypoxic injury to these regions, particularly the OB, may disrupt olfactory processing in infants with PA, potentially affecting their cognitive and social development. Investigating the relationship between olfactory system development and perinatal brain injury could lead to innovative diagnostic and therapeutic approaches. Further research, including clinical and animal studies, is necessary to fully explore the potential of olfactory assessments in predicting outcomes after PA. This educational review explores and discusses the potential of olfaction as a predictor of long-term outcomes and a tool for risk stratification following PA, opening new pathways for interventions and improved care.