Elevated protein concentrations in newborn blood and the risks of autism spectrum disorder, and of social impairment, at age 10 years among infants born before the 28th week of gestation

Among the 1 of 10 children who are born preterm annually in the United States, 6% are born before the third trimester. Among children who survive birth before the 28th week of gestation, the risks of autism spectrum disorder (ASD) and non-autistic social impairment are severalfold higher than in the general population. We examined the relationship between top quartile inflammation-related protein concentrations among children born extremely preterm and ASD or, separately, a high score on the Social Responsiveness Scale (SRS total score ≥65) among those who did not meet ASD criteria, using information only from the subset of children whose DAS-II verbal or non-verbal IQ was ≥70, who were assessed for ASD, and who had proteins measured in blood collected on ≥2 days (N = 763). ASD (N = 36) assessed at age 10 years is associated with recurrent top quartile concentrations of inflammation-related proteins during the first post-natal month (e.g., SAA odds ratio (OR); 95% confidence interval (CI): 2.5; 1.2-5.3) and IL-6 (OR; 95% CI: 2.6; 1.03-6.4)). Top quartile concentrations of neurotrophic proteins appear to moderate the increased risk of ASD associated with repeated top quartile concentrations of inflammation-related proteins. High (top quartile) concentrations of SAA are associated with elevated risk of ASD (2.8; 1.2-6.7) when Ang-1 concentrations are below the top quartile, but not when Ang-1 concentrations are high (1.3; 0.3-5.8). Similarly, high concentrations of TNF-α are associated with heightened risk of SRS-defined social impairment (N = 130) (2.0; 1.1-3.8) when ANG-1 concentrations are not high, but not when ANG-1 concentrations are elevated (0.5; 0.1-4.2).