Executive Dysfunction Early Postnatal Biomarkers among Children Born Extremely Preterm

OBJECTIVE: To see to what extent executive function limitations at age 10 years among children born extremely preterm (EP) are associated with blood levels of inflammatory and neurotrophic proteins during the first postnatal month. DESIGN: Longitudinal cohort SETTING: Children were enrolled shortly before or after birth. SUBJECTS: 692 children born before the 28(th) week of gestation who had an IQ ≥ 70 at age 10 years. EXPOSURES: Blood concentrations during the first four weeks of proteins with inflammatory and neurotrophic properties. MAIN OUTCOME MEASURES: 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 Zscore ≤ −1 on all three assessments (identified as the executive dysfunction composite (EDC) (N=104). RESULTS: Increased risks of the EDC associated with high concentrations of inflammatory proteins (IL-8, TNF-α, and ICAM-1) were modulated by high concentrations of neurotrophic proteins. This pattern 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. CONCLUSIONS: Among children born EP, risks of executive function limitations might be explained by perinatal systemic inflammation in the absence of adequate neurotrophic capability.