The Severity of Neurological Dysfunction in Preschool Children, Secondary to Damage Generated During the Perinatal Period, is Associated With a Pro-Inflammatory Pattern of Serum Molecules

Abstract

Disorders in the child's neurological development caused by perinatal risks can lead to long-term altered neurological signs that begin at an early age and involve persistent functional disorders. Recent data suggest that tissue dysfunction, not just acute damage, may initiate or perpetuate an inflammatory response. The aim of this study was to find out if any neurological dysfunction in preschool children secondary to damage generated during the perinatal period is associated with the magnitude of perinatal risks and long-term modifications in the serum concentrations of inflammatory molecules. The participants, aged 1-4 years, were on neurodevelopmental follow-up and rehabilitation therapy from the first three months of life and had no acute disease data. We classified the children into three groups according to the importance of their perinatal risks: low, medium, and high. The results show that 1) the magnitude of perinatal risks correlated with the severity of neurological dysfunction; 2) the greatest changes in the concentrations of the molecules of the inflammatory process were associated with the most altered neurological signs. This suggests that persistent nervous system dysfunction keeps inflammatory responses active even in the absence of an acute process of infection or damage.

Keywords: inflammation; neurodevelopment; neurological signs; perinatal risks; sequelae.

Figure 1

Molecules of the Inflammatory Process and Perinatal Risks. Children at low perinatal risk had positive Z-scores for mean concentrations of IP-10, MCP-1, MIP-1A, and TNF; and negative Z-scores for IL-8, LTB4, and RvD1. Medium perinatal risks group had negative Z-scores for all these molecules, except RvD1. The Z-scores of the children with high perinatal risk had the opposite sign to that of the low risk group, except for RvD1. The table expresses the complete numerical data and the significances across the groups and the paired comparisons. *p < 0.01 vs low-risk group; **p < 0.05 vs medium-risk group.

Figure 2

Molecules of the Inflammatory Process and Tone Alterations. (A) Hypotonia vs hypertonia. The Z-scores of the means of GM-CSF, IL-6, IL-17A, IL-10, IL-8, IFN-α, and IFN-γ were all positive in hypertonia and negative in hypotonia. (B) Degrees of tone alterations. In the mild degree group, Z-scores were all negative for GM-CSF, IL-6, IL-17A, and RvD1; in the moderate degree they were all positive. In the severe degree group, IL-6 and IL-17A were positive and GM-CSF and RvD1 were negative. The table expresses the complete numerical data and the significances across the groups and the paired comparisons. *p < 0.05 vs mild degree group.

Figure 3

Molecules of the Inflammatory Process and Pathological Reflex Activity. Children with pathological reflex activity had positive Z-scores for the means of IFN-α, IL-1α, MIP-1B, IL-4, and IL-13. The Z-scores of all these mediators were negative in the children without pathological reflex activity. The only child with moderate degree pathological reflex activity had much higher concentrations of all these molecules than the mild degree. The table expresses the complete numerical data and the significances across the groups and the paired comparisons.