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Published on: January 12, 2018
Executive Dysfunction Early Postnatal Biomarkers among Children Born Extremely Preterm.
Alan Leviton1, Robert M Joseph2, Raina N Fichorova3
1Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115-5724, USA. alan.leviton@childrens.harvard.edu.
Perinatal inflammation increases executive function risks in extremely preterm children, but neurotrophic proteins may offer protection. This suggests inflammation, without sufficient neurotrophic support, underlies executive dysfunction in this vulnerable population.
Area of Science:
- Neuroscience
- Developmental Biology
- Pediatrics
Background:
- Extremely preterm birth (before 28 weeks gestation) poses significant risks for neurodevelopmental outcomes.
- Executive function limitations are common in survivors of extreme preterm birth.
- The interplay between perinatal inflammation and neurotrophic factors in shaping long-term executive function is not fully understood.
Purpose of the Study:
- To investigate the association between early-life inflammatory and neurotrophic protein levels and executive function at age 10 in extremely preterm children.
- To explore whether neurotrophic proteins modulate the risk of executive dysfunction associated with inflammation.
Main Methods:
- Longitudinal study of 692 children born before 28 weeks gestation.
- Blood samples analyzed for inflammatory (IL-8, TNF-α, ICAM-1) and neurotrophic proteins in the first postnatal month.
- Executive functions (working memory, inhibition, switching) assessed at age 10 using standardized neuropsychological tests (Differential Ability Scales-II, NEPSY-II).
- Analysis of executive dysfunction composite and specific limitations (working memory, inhibition-switching).
Main Results:
- High concentrations of inflammatory proteins (IL-8, TNF-α, ICAM-1) were associated with an increased risk of the executive dysfunction composite.
- High concentrations of neurotrophic proteins modulated this increased risk.
- This protective modulation by neurotrophins was observed for working memory limitations (with IL-8, TNF-α) and switching limitations (with ICAM-1).
Conclusions:
- Perinatal systemic inflammation may explain executive function limitations in extremely preterm children, particularly when neurotrophic capacity is insufficient.
- Neurotrophic proteins play a crucial role in mitigating the negative impact of inflammation on developing executive functions.
- Early-life inflammatory and neurotrophic profiles are critical determinants of neurodevelopmental trajectories in extremely preterm infants.
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