Olfactory Testing in Perinatal Asphyxia: Enhancing Risk Assessment

NCT06744244 | Recruiting

• 1 other identifier: 27408
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mild Birth Asphyxia; Moderate Birth Asphyxia

Keywords

Perinatal Asphyxia; Hypoxic-Ischemic Encephalopathy; Biomarkers; Olfactory Function

Outcome Measures

Primary Outcomes (7)

• 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.

  during the Olfactory Testing

• 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.

  during the Olfactory Testing

• 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.

  Within 6 to 72 hours of life

• 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.

  during the Olfactory Testing

• Spectral analysis of brain oscillatory rhythms to monitor changes in global brain activity.

  Brain activity will be continuously monitored with electroencephalography (EEG) throughout the procedure using a 12-channel system and oscillatory activity across brain rhythm bands (Delta: 0.5 - 4 Hz, Theta: 4 - 8 Hz, Alpha: 8 - 12 Hz, Beta: 12 - 30 Hz, Gamma: 30 - 100 Hz) will be analyzed with dedicated software such as EEGLAB (MATLAB) in both groups.

  Within 6 to 72 hours of life

• Changes in behavioral responsens to Olfactory Stimulation in Asphyxiated Newborns.

  Facial expressions obtained from video-recordings will be assessed by two neonatologists, who will be blinded to the odor used to obtain insight into changes in behavioral responsens. A score will be assigned on a scale of 0 to 100 (0 = extremely disgusted; 100 = extremely pleased). The neonatologists will view the video as many times as necessary to ensure the highest accuracy inscoring. The videos will be destroyed after 5 years.

  Within 6 to 72 hours of life

• Highlight a different activation within brain areas involved in olfactory perception, memory, and learning through fMRI.

  Data from functional magnetic resonance imaging (fMRI) will be analyzed to compare the activation of regions of interest (ROIs), especially in regions such as the olfactory bulb, entorhinal cortex, hippocampus, and amygdala, between the two groups of patients during the execution of olfactory test. The parameters that will be evalueted and compared between the two groups will be: BOLD Signal (Blood Oxygenation Level Dependent), Activation Intensity (Signal Strength), Peak Activation, Time Course of Activation, Functional Connectivity and Effect Size.

  Within 6 to 72 hours of life

Secondary Outcomes (1)

• Neurodevelopmental follow-up

  Between 12 and 18 months

Study Arms (2)

Mild Birth Asphyxia

Term newborns (37-41 weeks of gestational age) with signs of moderate asphyxia at birth (cord pH \< 7.10 and/or BE \> -12), with mild asphyxia at birth.

Diagnostic Test: Olfactory Testing; Diagnostic Test: Heart rate (HR), Heart Rate Variability (HRV), Respiratory Rate (RR), peripheral oxygen saturation (SpO2); Diagnostic Test: Video-EEG; Diagnostic Test: fMRI; Diagnostic Test: Neurodevelopment assessment

Moderate - Severe Birth Asphyxia

Term newborns (37-41 weeks of gestational age) with signs of moderate asphyxia at birth (cord pH \< 7.10 and/or BE \> -12) with moderate asphyxia at birth, at risk of developing hypoxic-ischemic encephalopathy, who don't need hypothermia treatment and with severe asphyxia at birth, at risk of developing hypoxic-ischemic encephalopathy who don't need hypothermia treatment.

Diagnostic Test: Olfactory Testing; Diagnostic Test: Heart rate (HR), Heart Rate Variability (HRV), Respiratory Rate (RR), peripheral oxygen saturation (SpO2); Diagnostic Test: Video-EEG; Diagnostic Test: fMRI; Diagnostic Test: Neurodevelopment assessment

Interventions

Olfactory Testing DIAGNOSTIC_TEST

Olfactory 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.

Mild Birth Asphyxia; Moderate - Severe Birth Asphyxia

Heart rate (HR), Heart Rate Variability (HRV), Respiratory Rate (RR), peripheral oxygen saturation (SpO2) DIAGNOSTIC_TEST

Simultaneously 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.

Mild Birth Asphyxia; Moderate - Severe Birth Asphyxia

Video-EEG DIAGNOSTIC_TEST

The infant's Video-EEG, as per guidelines following perinatal asphyxia, will be recorded for approximately 2 hours, including the period preceding odor administration (baseline).

Mild Birth Asphyxia; Moderate - Severe Birth Asphyxia

fMRI DIAGNOSTIC_TEST

Newborns 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.

Mild Birth Asphyxia; Moderate - Severe Birth Asphyxia

Neurodevelopment assessment DIAGNOSTIC_TEST

Between 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.

Mild Birth Asphyxia; Moderate - Severe Birth Asphyxia

Eligibility Criteria

• Age: 6 Hours - 72 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study 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.

You may qualify if:

• 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.
• Apgar score \< 5 at 10 minutes of life.
• Newborns with mild asphyxia at birth.
• Newborns with moderate asphyxia at birth, at risk of developing hypoxic-ischemic encephalopathy, who don't need hypothermia treatment.
• Newborns with severe asphyxia at birth, at risk of developing hypoxic-ischemic encephalopathy who don't need hypothermia treatment.

You may not qualify if:

• 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.
• Infants with scalp injuries or lesions.
• Infants with microcephaly.
• Infants who underwent therapeutic hypothermia.

Sponsors & Collaborators

• University of Parma: lead
• Azienda Ospedaliero-Universitaria di Parma: collaborator

Study Sites (1)

Azienda Ospedaliero-Universitaria di Parma

Parma, 43126, Italy

RECRUITING

Related Publications (26)

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  BACKGROUND

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  BACKGROUND

MeSH Terms

Conditions

Hypoxia-Ischemia, Brain

Interventions

Heart Rate; Respiratory Rate; Oxygen Saturation; Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Vital Signs; Physical Examination; Diagnostic Techniques and Procedures; Diagnosis; Hemodynamics; Cardiovascular Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Respiration; Respiratory Physiological Phenomena; Metabolism; Tomography; Diagnostic Imaging

Study Officials

• Serafina Perrone, MD, PhD

  Università di Parma

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Serafina Perrone, MD, PhD

CONTACT

3388704211; serafina.perrone@unipr.it

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 6, 2024
• First Posted: December 20, 2024
• Study Start: September 10, 2024
• Primary Completion: January 1, 2025
• Study Completion (Estimated): September 10, 2026
• Last Updated: December 31, 2024

Record last verified: 2024-12

Locations

IT (1)