Author Of 1 Presentation
ASSOCIATION BETWEEN NEURODEVELOPMENTAL OUTCOMES IN CHILDREN BORN VERY PREMATURELY AND GENETIC VARIANTS AFFECTING GLUTAMATE TRANSPORT AND INFLAMMATION
Abstract
Background
Children born ≤32 weeks have higher risk of motor and cognitive disabilities compared to peers born at term. Inflammation and glutamate excitotoxicity potentiate each other in preterm brain injuries. Genetic variants in these pathways may modify this risk.
Objectives
To test whether risk variants in the glutamate transporter (EAAT2-200/-181) and pro-inflammatory cytokines (TNFα-308, IL1ß-511, IL6-174) interact, predisposing preterm survivors with functional variants in both pathways to higher risk of impairment.
Methods
In the APIP cohort (n=309), we defined exposure as TNFα-308 (GG/GA/AA), IL1ß-511 (CC/CT/TT), IL6-174 (CC/CG/GG) and EAAT2-200 (CC/CA/AA)/-181 (AA/AC/CC); primary outcome as cerebral palsy (CP) at 2y; secondary outcomes as cystic periventricular leukomalacia (cPVL); movement and cognition assessments at 2y (Griffiths Scales) and 5y (Movement ABC; British Ability Scales, BAS). 202 children had data for CP, both EAAT2 variants and at least one cytokine variant.
Results
TNFα-308 was associated with both CP (p=0.04) and cPVL (p=0.05), with 3/10 children with AA risk genotype having these outcomes compared to 6/100 with GG. BAS score was 9 points lower with IL1ß-511 CC reference genotype (n=53) compared to CT (n=46) (p=0.02). BAS was weakly associated with EAAT2-200 (p=0.09), specifically the verbal ability subscale (p=0.03). IL1ß-511 was associated with the non-verbal reasoning subscale (p=0.003). There were no associations with the Griffiths and M-ABC scores, or with IL6-174. Our study was underpowered to assess interaction, due to rarity of both risk genotype combinations and CP.
Conclusion
This exploratory study suggests an association between neurodevelopmental outcomes in children born ≤32 weeks and pro-inflammatory/glutamatergic variants.