63: Inflammation pathway gene polymorphisms are associated with neurodevelopmental delay at age 2

Abstract

ObjectiveTo determine if infants with neurodevelopmental delay at age 2 years are more likely to have single nucleotide polymorphisms (SNPs) in inflammation and coagulation pathway genes. Previous studies suggest that SNPs in these pathways contribute to susceptibility to cerebral palsy (CP). Whether these SNPs contribute to other forms of neurodevelopmental delay is unknown.Study DesignCase-control secondary analysis of a randomized trial of single versus multiple course corticosteroids. A custom multiplex SNP assay evaluated 48 polymorphisms in inflammation and coagulation pathways. Cases were children with mental developmental and/or psychomotor delay (Bayley MDI and/or PDI <85) at age 2. CP cases were excluded. Controls had normal neurodevelopment (MDI and PDI 85). DNA from placenta and/or fetal cord serum was required for inclusion (available for 125/218 cases). Univariate (Chi-Square) analyses compared allele and genotype frequencies. Because this was an exploratory study, no multiple comparison correction was made.Results125 cases and 147 controls were analyzed. Genotype frequencies for IL-1β and IL-6 were significantly different between cases and controls, as were allele frequencies for IL-1β, IL-4 receptor (IL-4R), and IL-6 (Table).Tabled 1ConclusionFetal inflammation pathway SNPs are associated with neurodevelopmental delay at age 2. These SNPs may contribute to cerebral injury in motor and non-motor pathways, and therefore confer susceptibility to both CP and other forms of neurodevelopmental delay. Better understanding of risk factors associated with fetal cerebral injury may provide a basis for future prevention/intervention trials. ObjectiveTo determine if infants with neurodevelopmental delay at age 2 years are more likely to have single nucleotide polymorphisms (SNPs) in inflammation and coagulation pathway genes. Previous studies suggest that SNPs in these pathways contribute to susceptibility to cerebral palsy (CP). Whether these SNPs contribute to other forms of neurodevelopmental delay is unknown. To determine if infants with neurodevelopmental delay at age 2 years are more likely to have single nucleotide polymorphisms (SNPs) in inflammation and coagulation pathway genes. Previous studies suggest that SNPs in these pathways contribute to susceptibility to cerebral palsy (CP). Whether these SNPs contribute to other forms of neurodevelopmental delay is unknown. Study DesignCase-control secondary analysis of a randomized trial of single versus multiple course corticosteroids. A custom multiplex SNP assay evaluated 48 polymorphisms in inflammation and coagulation pathways. Cases were children with mental developmental and/or psychomotor delay (Bayley MDI and/or PDI <85) at age 2. CP cases were excluded. Controls had normal neurodevelopment (MDI and PDI 85). DNA from placenta and/or fetal cord serum was required for inclusion (available for 125/218 cases). Univariate (Chi-Square) analyses compared allele and genotype frequencies. Because this was an exploratory study, no multiple comparison correction was made. Case-control secondary analysis of a randomized trial of single versus multiple course corticosteroids. A custom multiplex SNP assay evaluated 48 polymorphisms in inflammation and coagulation pathways. Cases were children with mental developmental and/or psychomotor delay (Bayley MDI and/or PDI <85) at age 2. CP cases were excluded. Controls had normal neurodevelopment (MDI and PDI 85). DNA from placenta and/or fetal cord serum was required for inclusion (available for 125/218 cases). Univariate (Chi-Square) analyses compared allele and genotype frequencies. Because this was an exploratory study, no multiple comparison correction was made. Results125 cases and 147 controls were analyzed. Genotype frequencies for IL-1β and IL-6 were significantly different between cases and controls, as were allele frequencies for IL-1β, IL-4 receptor (IL-4R), and IL-6 (Table).Tabled 1 125 cases and 147 controls were analyzed. Genotype frequencies for IL-1β and IL-6 were significantly different between cases and controls, as were allele frequencies for IL-1β, IL-4 receptor (IL-4R), and IL-6 (Table). ConclusionFetal inflammation pathway SNPs are associated with neurodevelopmental delay at age 2. These SNPs may contribute to cerebral injury in motor and non-motor pathways, and therefore confer susceptibility to both CP and other forms of neurodevelopmental delay. Better understanding of risk factors associated with fetal cerebral injury may provide a basis for future prevention/intervention trials. Fetal inflammation pathway SNPs are associated with neurodevelopmental delay at age 2. These SNPs may contribute to cerebral injury in motor and non-motor pathways, and therefore confer susceptibility to both CP and other forms of neurodevelopmental delay. Better understanding of risk factors associated with fetal cerebral injury may provide a basis for future prevention/intervention trials.