30029870

PMC6684153

Objectives

To test the hypothesis that higher blood levels of neurotrophic proteins (proteins that support neuronal survival and function) in the first 2 weeks of life are associated with a lower risk of cognitive impairment at 10 years.

Study design

We evaluated 812 10-year-old children with neonatal blood specimens enrolled in the multicenter prospective Extremely Low Gestational Age Newborn Study, assessing 22 blood proteins collected on 3 days over the first 2 weeks of life. Using latent profile analysis, we derived a cognitive function level based on standardized cognitive and executive function tests. We defined high exposure as the top quartile neurotrophic protein blood level on ≥2 days either for ≥4 proteins or for a specific cluster of neurotrophic proteins (defined by latent class analysis). Multinomial logistic regression analyzed associations between high exposures and cognitive impairment.

Results

Controlling for the effects of inflammatory proteins, persistently elevated blood levels of ≥4 neurotrophic proteins were associated with reduced risk of moderate (OR, 0.35; 95% CI, 0.18–0.67) and severe cognitive impairment (OR, 0.22; 95% CI, 0.09–0.53). Children with a cluster of elevated proteins including angiopoietin 1, brain-derived neurotrophic factor, and regulated upon activation, normal T-cell expressed, and secreted had a reduced risk of adverse cognitive outcomes (OR range, 0.31–0.6). The risk for moderate to severe cognitive impairment was least with 0–1 inflammatory and >4 neurotrophic proteins.

Conclusions

Persisting elevations of circulating neurotrophic proteins during the first 2 weeks of life are associated with lowered risk of impaired cognition at 10 years of age, controlling for increases in inflammatory proteins.

CDC Public Access

R01 HD092374/NICHD NIH HHS/National Institute of Child Health & Human Development/United States
U01 NS040069/NINDS NIH HHS/National Institute of Neurological Disorders and Stroke/United States
UG3 OD023348/ODCDC CDC HHS/Office of the Director/United States
UH3 OD023348/ODCDC CDC HHS/Office of the Director/United States