Infants with Down syndrome and congenital heart disease have altered peri-operative immune responses

Pediatr Res. 2022 Dec;92(6):1716-1723. doi: 10.1038/s41390-022-02000-3. Epub 2022 Mar 29.

Abstract

Background: Infants with Down syndrome (DS) have an altered immune response. We aimed to characterise the inflammatory response in infants with DS and congenital heart disease (CHD) peri-operatively in comparison to infants with CHD and a normal chromosomal complement, and to healthy infants pre-operatively.

Methods: Infants with DS/CHD, infants without DS but with CHD (CHD only) and healthy infants were prospectively recruited and serial serum cytokines evaluated peri-operatively using multiplex ELISA: tumour necrosis factor (TNF)-α and TNF-β; interferon (IFN)-γ, interleukin (IL)-1α, IL-2, IL-6, IL-8, IL-18, IL-1β, IL-10, and IL-1ra; vascular endothelial growth factor (VEGF); granulocyte macrophage colony-stimulating factor (GM-CSF); and erythropoietin (EPO).

Results: Ninety-four infants were recruited including age-matched controls (n = 10), DS/CHD (n = 55), and CHD only (n = 29). Children with DS/CHD had significantly lower concentrations of several cytokines (IL-10, IL-6, IL-8, IL-1β, VEGF) in the pre- and post-operatively vs CHD only and controls. EPO and GM-CSF were significantly higher in DS/CHD (p value <0.05).

Conclusions: Children with DS/CHD had significantly lower concentrations of several cytokines compared to controls or children with CHD only. EPO and GM-CSF were significantly higher in children with DS/CHD. The assessment of the immune response may be suitable for the predictable clinical outcomes in these children.

Impact: This study demonstrated that children with Down syndrome (DS) and congenital heart disease (CHD) have significant alterations in pro-inflammatory and anti-inflammatory immune responses peri-operatively. These changes may contribute to adverse clinical outcomes, including sepsis, chylothorax, and autoimmunity. They may impact the pathogenesis and outcome post-operatively and long term in this population. Children with DS and CHD have significantly lower cytokine concentrations, increased EPO and GM-CSF, and decreased VEGF pre- and post-operatively. Assessing their inflammatory state peri-operatively may facilitate the development of a predictive model that can inform tailored management of these infants using novel therapies including immunomodulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Cytokines / metabolism
  • Down Syndrome*
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Heart Defects, Congenital* / surgery
  • Humans
  • Immunity
  • Infant
  • Interleukin-10
  • Interleukin-6
  • Interleukin-8
  • Vascular Endothelial Growth Factor A

Substances

  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Interleukin-10
  • Vascular Endothelial Growth Factor A
  • Interleukin-6
  • Interleukin-8
  • Cytokines