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Circulating biomarkers in extremely preterm infants associated with ultrasound indicators of brain damage
Alan Leviton1, Elizabeth N Allred1, Raina N Fichorova2
1Boston Children's Hospital, and Harvard Medical School, Boston, MA, USA.
Insights
Blood protein levels in the first month of life can indicate brain damage risk in very preterm infants. High inflammation markers increase risk, while some proteins may offer protection or aid repair.
Area of Science:
- Neonatal neurology
- Biomarker discovery
- Neuroprotection research
Background:
- Very preterm infants are at high risk for brain damage.
- Early detection and understanding of brain injury are crucial for intervention.
- Endogenous proteins may play a role in brain protection and repair.
Purpose of the Study:
- To evaluate if blood protein concentrations in the first postnatal month predict brain damage in very preterm newborns.
- To investigate the association between specific protein levels and sonographically identified brain injuries.
Main Methods:
- Analysis of blood samples from 1219 very preterm infants.
- Measurement of protein concentrations using electrochemiluminescence and multiplex immunobead assays.
- Correlation of top-quartile protein concentrations with cranial ultrasound findings.
Main Results:
- Elevated inflammation-related proteins (IL-6, IL-8, ICAM-1) in early postnatal weeks correlated with increased risk of ventriculomegaly and echolucent lesions.
- Interleukin-6 receptor (IL6R) and basic fibroblast growth factor (bFGF) showed potential to modulate these risks.
- Proteins thought to protect or repair brain tissue did not consistently reduce the identified risks.
Conclusions:
- Blood protein profiles in early infancy offer insights into brain injury risk in very preterm infants.
- Findings support the role of endogenous proteins in modulating brain injury and promoting repair.
- Further research into these biomarkers could inform neuroprotective strategies.
Aim:
To assess to what extent the blood concentrations of proteins with neurotrophic and angiogenic properties measured during the first postnatal month convey information about the risk of sonographically-identified brain damage among very preterm newborns.
Methods:
Study participants were 1219 children who had a cranial ultrasound scan during their stay in the intensive care nursery and blood specimens collected on 2 separate days at least a week apart during the first postnatal month. Concentrations of selected proteins in blood spots were measured with electrochemiluminescence or with a multiplex immunobead assay and the risks of cranial ultrasound images associated with top-quartile concentrations were assessed.
Results:
High concentrations of multiple inflammation-related proteins during the first 2 postnatal weeks were associated with increased risk of ventriculomegaly, while high concentrations of just 3 inflammation-related proteins were associated with increased risk of an echolucent/hypoechoic lesion (IL-6, IL-8, ICAM-1), especially on day 7. Concomitant high concentrations of IL6R and bFGF appeared to modulate the increased risks of ventriculomegaly and an echolucent lesion associated with inflammation. More commonly high concentrations of putative protectors/repair-enhancers did not appear to diminish these increased risks.
Conclusion:
Our findings provide support for the hypothesis that endogenous proteins are capable of either protecting the brain against damage and/or enhancing repair of damage.
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