How does the development of infants with multiplex and single-incidence family risk for autism spectrum disorder (ASD) differ?
In this longitudinal cohort study of 445 children with multiplex or single-incidence family risk, 68% of children from multiplex families vs 43% of those from single-incidence families had ASD or atypical development at outcome. Children without ASD did not differ in ASD symptoms based on family risk status, but multiplex status was associated with lower cognitive abilities by age 3 years.
Infants with a multiplex family history of ASD should be monitored early and often and referred for early intervention services at the first sign of concern.
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.
To compare outcomes and trajectories associated with varying familial risk for ASD across the first 3 years of life.
Design, Setting, and Participants
This longitudinal, prospective cohort study used data from 11 sites in the Baby Siblings Research Consortium database. Data were collected between 2003 and 2015. Infants who were younger siblings of children with ASD were followed up for 3 years. Analyses were conducted in April 2018. Of the initial 1008 infants from the database, 573 were removed owing to missing necessary data, diagnostic discrepancies, or only having 1 older sibling.
Number of siblings with ASD.
Main Outcomes and Measures
Outcomes included ASD symptoms, cognitive abilities, and adaptive skills. Diagnosis (ASD or no ASD) was given at 36-month outcome. The no-ASD group was 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.
In the 435 analyzed participants (age range at outcome, 32-43 months; 246 male [57%]), 355 (82%) were from single-incidence families (1 sibling with ASD and ≥1 sibling without ASD) and 80 (18%) were from multiplex families (≥2 siblings with ASD). There were no significant group differences in major demographics. Children from multiplex families were more likely than those from single-incidence families to be classified as having ASD (29 of 80 [36%] vs 57 of 355 [16%]; 95% CI, 9%-31%; P < .001) and less likely as typical (26 of 80 [33%] vs 201 of 355 [57%]; 95% CI, −36% to −13%; P < .001), with similar rates of atypical classifications (25 of 80 [31%] vs 97 of 355 [27%]; 95% CI, −7% to 15%; P = .49). There were no differences in ASD symptoms between multiplex and single-incidence groups after controlling for ASD outcome (95% CI, −0.02 to 0.20; P = .18). During infancy, differences in cognitive and adaptive abilities were observed based on ASD outcome in the single-incidence group only. At 36 months, the multiplex/no-ASD group had lower cognitive abilities than the single-incidence/no-ASD group (95% CI, −11.89 to −2.20; P = .02), and the multiplex group had lower adaptive abilities than individuals in the single-incidence group after controlling for ASD outcome (95% CI, −9.01 to −1.48; 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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McDonald NM, Senturk D, Scheffler A, et al. Developmental Trajectories of Infants With Multiplex Family Risk for Autism: A Baby Siblings Research Consortium Study. JAMA Neurol. Published online October 07, 2019. doi:10.1001/jamaneurol.2019.3341
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