Objective: Although early brain overgrowth is frequently reported in autism spectrum disorder (ASD), the relationship between ASD and head circumference (HC) is less clear, with inconsistent findings from longitudinal studies that include community controls. Our aim was to examine whether head growth in the first 3 years differed between children with ASD from a high-risk (HR) sample of infant siblings of children with ASD (by definition, multiplex), HR siblings not diagnosed with ASD, and low-risk (LR) controls. Method: Participants included 442 HR and 253 LR infants from 12 sites of the international Baby Siblings Research Consortium. Longitudinal HC data were obtained prospectively, supplemented by growth records. Random effects nonlinear growth models were used to compare HC in HR infants and LR infants. Additional comparisons were conducted with the HR group stratified by diagnostic status at age 3: ASD (n= 77), developmental delay (DD; n= 32), and typical development (TD; n= 333). Nonlinear growth models were also developed for height to assess general overgrowth associated with ASD. Results: There was no overall difference in head circumference growth over the first 3 years between HR and LR infants, although secondary analyses suggested possible increased total growth in HR infants, reflected by the model asymptote. Analyses stratifying the HR group by 3-year outcomes did not detect differences in head growth or height between HR infants who developed ASD and those who did not, nor between infants with ASD and LR controls. Conclusion: Head growth was uninformative as an ASD risk marker within this HR cohort. © 2014 American Academy of Child and Adolescent Psychiatry.

Identification of genetic biomarkers associated with autism spectrum disorders (ASDs) could improve recurrence prediction for families with a child with ASD. Here, we describe clinical microarray findings for 253 longitudinally phenotyped ASD families from the Baby Siblings Research Consortium (BSRC), encompassing 288 infant siblings. By age 3, 103 siblings (35.8%) were diagnosed with ASD and 54 (18.8%) were developing atypically. Thirteen siblings have copy number variants (CNVs) involving ASD-relevant genes: 6 with ASD, 5 atypically developing, and 2 typically developing. Within these families, an ASD-related CNV in a sibling has a positive predictive value (PPV) for ASD or atypical development of 0.83; the Simons Simplex Collection of ASD families shows similar PPVs. Polygenic risk analyses suggest that common genetic variants may also contribute to ASD. CNV findings would have been pre-symptomatically predictive of ASD or atypical development in 11 (7%) of the 157 BSRC siblings who were eventually diagnosed clinically.

BACKGROUND: We previously reported that infants who developed autism spectrum disorder (ASD) had increased cerebrospinal fluid (CSF) in the subarachnoid space (i.e., extra-axial CSF) from 6 to 24 months of age. We attempted to confirm and extend this finding in a larger independent sample. METHODS: A longitudinal magnetic resonance imaging study of infants at risk for ASD was carried out on 343 infants, who underwent neuroimaging at 6, 12, and 24 months. Of these infants, 221 were at high risk for ASD because of an older sibling with ASD, and 122 were at low risk with no family history of ASD. A total of 47 infants were diagnosed with ASD at 24 months and were compared with 174 high-risk and 122 low-risk infants without ASD. RESULTS: Infants who developed ASD had significantly greater extra-axial CSF volume at 6 months compared with both comparison groups without ASD (18% greater than high-risk infants without ASD; Cohens d = 0.54). Extra-axial CSF volume remained elevated through 24 months (d = 0.46). Infants with more severe autism symptoms had an even greater volume of extra-axial CSF from 6 to 24 months (24% greater at 6 months, d = 0.70; 15% greater at 24 months, d = 0.70). Extra-axial CSF volume at 6 months predicted which high-risk infants would be diagnosed with ASD at 24 months with an overall accuracy of 69% and corresponding 66% sensitivity and 68% specificity, which was fully cross-validated in a separate sample. CONCLUSIONS: This study confirms and extends previous findings that increased extra-axial CSF is detectable at 6 months in high-risk infants who develop ASD. Future studies will address whether this anomaly is a contributing factor to the etiology of ASD or an early risk marker for ASD.