Circulating Inflammatory-Associated Proteins in the First Month of Life and Cognitive Impairment at Age 10 Years in Children Born Extremely Preterm

Karl C K Kuban, Robert M Joseph, Thomas M O’Shea, Timothy Heeren, Raina N Fichorova, Laurie Douglass, Hernan Jara, Jean A Frazier, Deborah Hirtz, Julie Vanier Rollins, Nigel Paneth, Extremely Low Gestational Age Newborn (ELGAN) Study Investigators

J Pediatr. 2016 Oct 24. pii: S0022-3476(16)31038-1.

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Early CRP, TNF-a, IL-8, ICAM-1, and epo associated with IQ values >2 SD below expected mean (ORs: 2.0-2.3) and with mod to severe cognitive impairment on a composite measure of IQ and EF (ORs: 2.1-3.6). Additionally, severe cognitive impairment was associated with late protein elevations of C-reactive protein (OR: 4.0), IL-8 (OR: 5.0), ICAM-1 (OR: 6.5), vascular endothelial growth factor-receptor 2 (OR: 3.2), and thyroid-stimulating hormone (OR: 3.1). Mod cognitive impairment most strongly associated with elevations of IL-8, ICAM-1, and VEGF-R 2. When 4 or more inflammatory proteins elevated early, risk of IQ <70 and overall impaired cognitive ability was more than doubled (ORs: 2.1-2.4); presence of 4 or more inflammatory protein elevated late strongly linked to adverse cognitive outcomes (ORs: 2.9-4.8).