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
Authors: Korzeniewski Steven J. , Allred Elizabeth N. , O’Shea T. Michael , Leviton Alan , Kuban Karl C. K. ,   for the ELGAN study investigators, Lee Kathleen , McGovern Anne , Gambardella Jill , Ursprung Susan , Ecklund Ruth Blomquist Kristen , Bassan Haim , Butler Samantha , Duplessis Adré , Hahn Cecil , Limperopoulos Catherine , Khwaja Omar , Soul Janet S. , Shah Bhavesh , Christianson Karen , Hampf Frederick , Gilmore Herbert , McQuiston Susan , Martin Camilia R. , Hallisey Colleen , Hurley Caitlin , Creixell Miren , Share Jane , Van Marter Linda J. , Durfee Sara , Insoft Robert M. , Wilson Jennifer G. , Pimental Maureen , Westra Sjirk J. , Krishnamoorthy Kalpathy , Cole Cynthia , Fiascone John M. , Madden Janet , Nylen Ellen , McCauley Anne Furey Roy , Church Paige T. , Keller Cecelia , Miller Karen J. , Bednarek Francis , Naples Mary , Powers Beth , Wellman Jacqueline , Adair Robin , Bream Richard , Miller Alice , Scheiner Albert , Stine Christy , Ehrenkranz Richard , Williams Joanne , Romano Elaine , Miller Cindy , Close Nancy , Romano Elaine , Williams Joanne , O’Shea T. Michael , Gordon Debbie , Harold Teresa , Specter Barbara , Allred Deborah , Dillard Robert , Goldstein Don , Hiatt Deborah , Hounshell Gail , Waldrep Ellen , Washburn Lisa , Welch Cherrie D. , Engelke Stephen C. , Moseley Sherry , Pare Linda , Smart Donna , Wilson Joan , Adler Ira , Buckwald Sharon , Helms Rebecca , Kerkering Kathyrn , MacGilvray Scott S. , Resnik Peter , Bose Carl , Bose Gennie , Fordham Lynn A. , Bostic Lisa , Marshall Diane , Milowic Kristi , Wereszczak Janice , Poortenga Mariel , Sutton Dinah , Betz Bradford W. , Bezinque Steven L. , Junewick Joseph , Burdo-Hartman Wendy , Fagerman Lynn , Lohr Kim , Pastyrnak Steve , Sutton Dinah , Solomon Carolyn , Cavenagh Ellen , Caine Victoria J. , Olomu Nicholas , Price Joan , Paneth Nigel , Karna Padmani , Lenski Madeleine , Schreiber Michael D. , Yoon Grace , Feinstein Kate , Caldarelli Leslie , O’Connor Sunila E. , Msall Michael , Plesha-Troyke Susan , Batton Daniel , Kring Beth , Brooklier Karen , Kring Beth , Oca Melisa J. , Solomon Katherine M. 
Published: June 2018

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).