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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.
Insights
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.
Abstract:
We evaluated the relationship between blood levels of inflammatory and neurotrophic proteins during the first postnatal month in 692 children born before the 28th week of gestation and executive function limitations among those 10-year olds who had an IQ ≥ 70. The measures of dysfunction were Z-scores ≤ -1 on the Differential Ability Scales-II working memory (WM) assessment) (N = 164), the NEPSY-II (A Developmental NEuroPSYchological Assessment-II) Inhibition-Inhibition assessment) (N = 350), the NEPSY-II Inhibition-Switching assessment) (N = 345), as well as a Z-score ≤ -1 on all three assessments (identified as the executive dysfunction composite (N = 104). Increased risks of the executive dysfunction composite associated with high concentrations of inflammatory proteins (IL-8, TNF-α, and ICAM-1) were modulated by high concentrations of neurotrophic proteins. This pattern of modulation by neurotrophins of increased risk associated with inflammation was also seen for the working memory limitation, but only with high concentrations of IL-8 and TNF-α, and the switching limitation, but only with high concentrations of ICAM-1. We infer that among children born extremely preterm, risks of executive function limitations might be explained by perinatal systemic inflammation in the absence of adequate neurotrophic capability.
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