Olfactory Testing in Perinatal Asphyxia: Enhancing Risk Assessment
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age6-72
SponsorUniversity of Parma
About this trial
Neonatal asphyxia remains a leading cause of neurodevelopmental disabilities despite advancements in perinatal care. Hypoxic-ischemic encephalopathy (HIE), a severe outcome of asphyxia, impacts 1-3 infants per 1,000 live births annually in industrialized nations, causing long-term neurological impairments such as cognitive dysfunction, motor deficits, and sensory impairments. Early identification of at-risk newborns is critical to initiate timely interventions and improve outcomes.
Olfactory perception, crucial for newborns' adaptation to extrauterine life, involves odor identification and memory. Odor perception is known to be impaired in adults with neurological disorders and in animal models of brain injury. However, no clinical studies have assessed olfactory function in newborns with signs of asphyxia. Olfactory memory, which can be evaluated through habituation to repeated odors, may provide insights into early brain function.
This study aims to evaluate whether olfactory memory can serve as an early marker of neurodevelopmental outcomes in newborns with signs of asphyxia. By assessing physiological, behavioral, and neurological responses to olfactory stimuli, the study seeks to explore the differences between infants with mild asphyxia and those with moderate-to-severe asphyxia.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Term newborns (37-41 weeks of gestational age) with signs of asphyxia at birth (cord pH < 7.10 and/or BE > -12).
Maternal age > 18 years.
No medication use during pregnancy (e.g., antipsychotics, antidepressants, sedatives, anticonvulsants, anxiolytics).
Absence of maternal infections.
Disqualifiers
Post-term infants (gestational age > 42 weeks).
Preterm infants (gestational age < 37 weeks).
Infants with genetic syndromes or congenital anomalies.
Infants from mothers using drugs of abuse.
Trial population
Newborns with signs of mild asphyxia and newborns with signs of moderate-severe asphyxia at high risk for hypoxic-ischemic encephalopathy and brain damage.
Trial design
Design model
Case-control
Time perspective
Prospective
Treatments tested in this trial
Olfactory Testing
Diagnostic testOlfactory Test: Odor stimuli will be administered using a custom-designed olfactometer, developed by engineers specifically for this study. The olfactometer will release different odorants (maternal breast milk, vanilla essential oil, rose essential oil, and water as a control) in a controlled way. Each odor will be presented between 6 and 72 hours of life for 10 seconds (On), followed by a 50-second pause (Off) for a total of 15 cycles (On-Off). A new odor will be presented 5 minutes after the previous one. The first olfactory test will be conducted during the Video-EEG recording, and the second one will take place during the fMRI acquisition.
Heart rate (HR), Heart Rate Variability (HRV), Respiratory Rate (RR), peripheral oxygen saturation (SpO2)
Diagnostic testSimultaneously with the presentation of odors, heart rate (HR), heart rate variability (HRV), respiratory rate (RR), and peripheral oxygen saturation (SpO2) will be monitored and recorded. The onset of the odor will be recorded using a manual timer.
Video-EEG
Diagnostic testThe infant's Video-EEG, as per guidelines following perinatal asphyxia, will be recorded for approximately 2 hours, including the period preceding odor administration (baseline).
fMRI
Diagnostic testNewborns will undergo an fMRI, as part of routine clinical practice, to identify any brain injury, its extent, and the structures involved. The use of a custom-built fMRI compatible olfactometer will facilitate these studies.
Neurodevelopment assessment
Diagnostic testBetween 12 and 18 months, the infants will undergo neurodevelopmental follow-up, during which the Bayley III assessment will be administered to evaluate any potential neurocognitive deficits.
Treatment groups
30 Participants
are divided into 2 treatment groupsGroup A: Mild Birth Asphyxia5 interventions
Group B: Moderate - Severe Birth Asphyxia5 interventions
Trial outcomes
Primary outcomes
1
Autonomic Responses to Olfactory Stimulation in Asphyxiated Newborns.
Heart Rate (HR) and Heart Rate Variability (HRV) will be continuously monitored via electrocardiography throughout the procedure and compared between the two groups. Data will be analyzed using software such as Kubios. For HRV, the following metrics will be extracted: SDNN (Standard Deviation of NN Intervals): Reflects overall HRV. RMSSD (Root Mean Square of Successive Differences): Reflects parasympathetic (vagal) activity. LF Power (Low-Frequency): Reflects both sympathetic and parasympathetic activity (0.04 - 0.15 Hz). HF Power (High-Frequency): Primarily reflects parasympathetic activity (0.15 - 0.4 Hz). LF/HF Ratio: Assesses the balance between sympathetic and parasympathetic activity, with a higher ratio indicating sympathetic dominance.
Time frame
during the Olfactory Testing2
Breathing patterns in Asphyxiated Newborns.
Variations in breathing patterns are assessed by the pulse oximeter that operates on the principle of light absorption, emitting red and infrared light through the skin. A photodetector measures the light absorbed by the blood, with oxygenated hemoglobin absorbing more infrared light and deoxygenated hemoglobin absorbing more red light. The ratio of light absorption at these wavelengths is used to estimate the percentage of oxygenated hemoglobin (Peripheral Oxygen Saturation - SpO2), displayed as a percentage on the device's screen. This metric provides insight into oxygenation levels in the bloodstream, which may improve due to enhanced respiratory efficiency triggered by olfactory exposure. The pulse oximeter also features a respiratory rate (RR) measurement, estimating RR by detecting changes in blood flow or pulse linked to breathing patterns.
Time frame
during the Olfactory Testing3
Cerebral functioning in Asphyxiated Newborns.
Amplitude EEG (aEEG) provides a continuous, real-time overview of cerebral function by measuring the brain's electrical activity. In the context of perinatal asphyxia, aEEG is used to detect abnormal brain patterns, such as reduced or absent brain activity. These patterns are reflected in the amplitude of the signal (measured in microvolts), which can indicate the severity of brain injury and help clinicians assess the extent of neurological damage.
Time frame
Within 6 to 72 hours of life4
Changes in olfactory evoked potentials (EOPs) in Asphyxiated Newborns.
The analysis of EOPs in response to olfactory stimuli, such as rose, vanilla, and breast milk, will be conducted using dedicated software like EEGLAB and ERPLAB (MATLAB). The analysis parameters for EOPs will include latency, amplitude, wave components, spatial distribution, duration, topography and localization, as well as habituation and adaptation. These parameters will be compared between the two groups.
Time frame
during the Olfactory TestingSecondary outcomes
1
Neurodevelopmental follow-up
The Bayley III assessment will be administered in both groups. It provides a comprehensive overview of a child's cognitive, motor, and socio-emotional abilities. The measures obtained from the Bayley-III include cognitive, motor, language, social-emotional and adaptive behavior scales. Scores from the different scales are converted into standard scores (mean of 100, standard deviation of 15), which help compare the child to the general population.
Time frame
Between 12 and 18 monthsSponsors and contacts
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University of Parma
Lead sponsor
Azienda Ospedaliero-Universitaria di Parma
Collaborator
Source ClinicalTrials.gov