Description

Neonatal asphyxia is the leading cause of neurodevelopmental disability. Despite recent advances in perinatal medicine, which have improved associated mortality, the neurological outcomes of hypoxic-ischemic events in newborns remain significant. The incidence of neonatal asphyxia is estimated to be 1.5 per 100 live births per year in industrialized countries with advanced obstetric-neonatal care. Between 1 and 3 infants per 1,000 live births suffer from severe neurological impairment due to perinatal asphyxia, developing hypoxic-ischemic encephalopathy.

Early identification of newborns with signs of asphyxia who are at high risk for hypoxic-ischemic encephalopathy and brain damage can improve outcomes by enabling the early initiation of rehabilitative interventions. Hypoxic-ischemic injury often results in impairments in audiovisual perception, cerebral palsy, cognitive dysfunction, memory difficulties, and other neurological sequelae.

Olfactory perception (the sense of smell) is one of the most important sensory functions in humans. In newborns, the sense of smell plays a crucial role, allowing them to perceive maternal odors and breast milk, guiding them in adapting to their environment and completing the physiological transition from intrauterine to extrauterine life. Olfactory neurosensory function involves several abilities, particularly odor identification and memory. Olfactory perception is also linked to olfactory memory, which can be tested as a habituation response. Olfactory memory is defined as the recollection of odorants. In recent studies, exposure to pleasant odors, such as breast milk or vanilla, has been shown to reduce perceived pain during invasive procedures in healthy full-term newborns. Olfactory stimuli can generate various physiological changes, regulating heart and respiratory rates, as well as triggering motor responses that guide head movements and initiate orofacial responses.

Some studies have shown that brain injury impairs odor perception: smell is altered in several neurological conditions, including both neurodevelopmental and neurodegenerative disorders. In Alzheimer (AD), Parkinson disease (PD) and in stroke, several cortical and subcortical areas directly involved in olfactory function are damaged or show signs of atrophy, including the olfactory bulb (OB), primary olfactory cortex (POC), hippocampus, orbitofrontal cortex (OFC), amygdala, and olfactory tract. Moreover, reduced odor detection early in life, along with anatomical and functional alterations in olfactory and higher-order cortical networks, has been reported in neurodevelopmental disorders such as Autistic Spectrum Disorder (ASD) and Attention Deficit / Hyperactivity Disorder (ADHD).

Olfactory dysfunction has also been studied and demonstrated in animal models through the induction of brain damage in rabbits. So far, no study has evaluated olfactory function in the clinical setting of brain injury due to neonatal asphyxia.

In cases of perinatal asphyxia, early identification of hypoxic-ischemic encephalopathy is achieved through continuous video-electroencephalographic monitoring, which is currently considered the gold standard for evaluating brain functions and detecting subclinical seizures. Although EEG does not directly assess olfactory function, certain electroencephalographic alterations may suggest impairment in brain regions involved in olfactory perception (piriform cortex, insular cortex, and amygdala).There are numerous studies in the literature that adopt various methods of olfactory testing in healthy newborns, but no validated tool or test exists to evaluate olfactory memory in newborns.

This study aims to assess olfactory function in newborns exhibiting signs of asphyxia at birth and to investigate whether infants with mild asphyxia differ from those with moderate to severe asphyxia.

The hypotheses of this study is that olfactory stimulation with odors such as rose, vanilla, and breast milk induces changes in heart rate, respiratory rate, peripheral oxygen saturation, EEG activity, and neuroimaging measures in asphyxiated newborns. These changes also occur following repeated olfactory stimuli. Olfactory memory, or habituation to odors, is delayed or absent in newborns with moderate-severe asphyxia.