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Evaluation of neurovascular coupling during neuroprotective therapies: A single site HEAL ancillary study
Lina F Chalak1, Shu Kang2, Srinivas Kota1
1Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, United States of America.
Insights
Erythropoietin did not improve neurovascular coupling in infants with birth asphyxia. This study highlights the need for physiological biomarkers to assess treatment effectiveness in real-time for future infant neuroprotection trials.
Area of Science:
- Neonatal medicine
- Neuroscience
- Biomarker research
Background:
- Birth asphyxia poses a critical need for physiological biomarkers to monitor infant treatment responses in real-time.
- This study investigated neurovascular coupling (NVC) non-invasively as a potential biomarker.
- It was an ancillary study to the High-Dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial.
Purpose of the Study:
- To measure neurovascular coupling (NVC) non-invasively in infants with birth asphyxia.
- To determine if erythropoietin (Epo) administration impacts NVC.
- To correlate NVC changes with neurodevelopmental outcomes.
Main Methods:
- Recruited 27 neonates from a single-center Level III Neonatal Intensive Care Unit between 2017-2019.
- Measured NVC non-invasively during a blinded, randomized trial.
- Defined neurodevelopmental impairment using BSID-III cognitive scores and GMFCS, with outcomes blinded.
Main Results:
- No significant difference in NVC was observed between the erythropoietin (Epo) and placebo groups.
- Rank-based analysis of covariance models supported the lack of difference in NVC.
- These findings align with the trial's overall negative results on neurodevelopmental outcomes.
Conclusions:
- Erythropoietin administration did not alter neurovascular coupling in infants with birth asphyxia.
- The study's results are consistent with the overall negative findings of the HEAL trial.
- Physiological biomarkers like NVC are crucial for elucidating mechanisms and guiding future neuroprotective therapy trials.
Background:
There is a critical need for development of physiological biomarkers in infants with birth asphyxia to identify the physiologic response to therapies in real time. This is an ancillary single site study of the High-Dose Erythropoietin for Asphyxia and Encephalopathy (Wu et al., 2022 [1]) to measure neurovascular coupling (NVC) non-invasively during an ongoing blinded randomized trial.
Methods:
Neonates who randomized in the HEAL enrolled at a single-center Level III Neonatal Intensive Care Unit were recruited between 2017 and 2019. Neurodevelopmental impairment was blinded and defined as any of the following: cognitive score <90 on Bayley Scales of Infant Toddler Development, third edition (BSID-III), Gross Motor Function Classification Score (GMFCS) ≥1.
Results:
All twenty-seven neonates enrolled in HEAL were recruited and 3 died before complete recording. The rank-based analysis of covariance models demonstrated lack of difference in NVC between the two groups (Epo versus Placebo) that was consistent with the observed lack of effect on neurodevelopmental outcomes.
Conclusion:
We demonstrate no difference in neurovascular coupling after Epo administration. These findings are consistent with overall negative trial results. Physiological biomarkers can help elucidate mechanisms of neuroprotective therapies in real time in future trials.
