Developmental trajectories of infants with multiplex family risk for Autism: a Baby Siblings Research Consortium Study

McDonald, N.M. and Senturk, D. and Scheffler, A. and Brian, J.A. and Carver, L.J. and Charman, T. and Chawarska, K. and Curtin, S. and Hertz-Piccioto, I. and Jones, Emily J.H. and Klin, A. and Landa, R. and Messinger, D.S. and Ozonoff, S. and Stone, W.L. and Tager-Flusberg, H. and Webb, S.J. and Young, G. and Zwaigenbaum, L. and Jeste, S.S. (2020) Developmental trajectories of infants with multiplex family risk for Autism: a Baby Siblings Research Consortium Study. JAMA Neurology 77 (1), pp. 73-81. ISSN 2168-6149.

Abstract

Importance: Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with different genetic etiologies. Prospective examination of familial-risk infants informs understanding of developmental trajectories preceding ASD diagnosis, potentially improving early detection. Objective: Compare outcomes and trajectories associated with varying familial risk for ASD across first 3 years of life. Design and Setting: Longitudinal, prospective observational study. Data from 11 sites in Baby Siblings Research Consortium (BSRC) database included. Data collected between 2003-2015. Infants followed for 3 years. Analyses conducted in 2018. Participants: Of initial 1,008 infants from BSRC database, 573 removed due to missing necessary data, diagnostic discrepancies, or only one older sibling. 435 younger siblings of children with ASD included; 355 from single-incidence families (1 sibling with ASD and 1+ sibling without ASD) and 80 from multiplex families (2+ siblings with ASD). No group differences in major demographics. Exposure: Number of ASD-siblings. Main Outcomes and Measures: Outcomes included ASD symptoms, cognitive abilities, and adaptive skills. Diagnosis (ASD/no-ASD) given at 36-month outcome. No-ASD group classified as atypical (developmental delays and/or social-communication concerns) or typical for some analyses. Generalized linear mixed models examined developmental trajectories by ASD outcome and familial-risk group. Results: In the 435 analyzed participants (age range at outcome: 32-43 months; 57% male), children from multiplex families were more likely than those from single-incidence families to 5 be classified as ASD (36% vs. 16%, p<.001) and less likely as typical (33% vs. 57%, p<.001), with similar rates of atypical classifications (31% vs. 27%, p=.49). No differences in ASD symptoms between multiplex and single-incidence groups, after controlling for ASD outcome (p=.18). During infancy, differences in cognitive and adaptive abilities observed based upon ASD outcome in single-incidence group only (ps<.001-.04). At 36 months, multiplex/no-ASD group had lower cognitive abilities than single-incidence/no-ASD group (p=.02), and multiplex had lower adaptive abilities than single-incidence, after controlling for ASD outcome (p=.02). Conclusions and Relevance: Infants with a multiplex family history of ASD should be monitored early and often and referred for early intervention at the first sign of concern. Direct examination of genetic contributions to neurodevelopmental phenotypes in infants with familial risk for ASD is needed.

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