Developmental Trajectories of Infants with Multiplex Family Risk for Autism: A Baby Siblings Research Consortium Study

Nicole M. McDonald, Damla Senturk, Aaron Scheffler, Jessica A. Brian, Leslie J. Carver, Tony Charman, Katarzyna Chawarska, Suzanne Curtin, Irva Hertz-Piccioto, Emily J.H. Jones, Ami Klin, Rebecca Landa, Daniel S. Messinger, Sally Ozonoff, Wendy L. Stone, Helen Tager-Flusberg, Sara Jane Webb, Gregory Young, Lonnie Zwaigenbaum, Shafali S. Jeste

Research output: Contribution to journalArticle

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: 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. Exposures: 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. Results: 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.

Original languageEnglish (US)
JournalJAMA Neurology
DOIs
StateAccepted/In press - Jan 1 2019

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Autistic Disorder
Siblings
Research
Aptitude
Incidence
Autism Spectrum Disorder
Databases
Neurobehavioral Manifestations

ASJC Scopus subject areas

  • Clinical Neurology

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McDonald, N. M., Senturk, D., Scheffler, A., Brian, J. A., Carver, L. J., Charman, T., ... Jeste, S. S. (Accepted/In press). Developmental Trajectories of Infants with Multiplex Family Risk for Autism: A Baby Siblings Research Consortium Study. JAMA Neurology. https://doi.org/10.1001/jamaneurol.2019.3341

Developmental Trajectories of Infants with Multiplex Family Risk for Autism : A Baby Siblings Research Consortium Study. / McDonald, Nicole M.; Senturk, Damla; Scheffler, Aaron; Brian, Jessica A.; Carver, Leslie J.; Charman, Tony; Chawarska, Katarzyna; Curtin, Suzanne; Hertz-Piccioto, Irva; Jones, Emily J.H.; Klin, Ami; Landa, Rebecca; Messinger, Daniel S.; Ozonoff, Sally; Stone, Wendy L.; Tager-Flusberg, Helen; Webb, Sara Jane; Young, Gregory; Zwaigenbaum, Lonnie; Jeste, Shafali S.

In: JAMA Neurology, 01.01.2019.

Research output: Contribution to journalArticle

McDonald, NM, Senturk, D, Scheffler, A, Brian, JA, Carver, LJ, Charman, T, Chawarska, K, Curtin, S, Hertz-Piccioto, I, Jones, EJH, Klin, A, Landa, R, Messinger, DS, Ozonoff, S, Stone, WL, Tager-Flusberg, H, Webb, SJ, Young, G, Zwaigenbaum, L & Jeste, SS 2019, 'Developmental Trajectories of Infants with Multiplex Family Risk for Autism: A Baby Siblings Research Consortium Study', JAMA Neurology. https://doi.org/10.1001/jamaneurol.2019.3341
McDonald, Nicole M. ; Senturk, Damla ; Scheffler, Aaron ; Brian, Jessica A. ; Carver, Leslie J. ; Charman, Tony ; Chawarska, Katarzyna ; Curtin, Suzanne ; Hertz-Piccioto, Irva ; Jones, Emily J.H. ; Klin, Ami ; Landa, Rebecca ; Messinger, Daniel S. ; Ozonoff, Sally ; Stone, Wendy L. ; Tager-Flusberg, Helen ; Webb, Sara Jane ; Young, Gregory ; Zwaigenbaum, Lonnie ; Jeste, Shafali S. / Developmental Trajectories of Infants with Multiplex Family Risk for Autism : A Baby Siblings Research Consortium Study. In: JAMA Neurology. 2019.
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title = "Developmental Trajectories of Infants with Multiplex Family Risk for Autism: A Baby Siblings Research Consortium Study",
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: 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. Exposures: 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. Results: 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.",
author = "McDonald, {Nicole M.} and Damla Senturk and Aaron Scheffler and Brian, {Jessica A.} and Carver, {Leslie J.} and Tony Charman and Katarzyna Chawarska and Suzanne Curtin and Irva Hertz-Piccioto and Jones, {Emily J.H.} and Ami Klin and Rebecca Landa and Messinger, {Daniel S.} and Sally Ozonoff and Stone, {Wendy L.} and Helen Tager-Flusberg and Webb, {Sara Jane} and Gregory Young and Lonnie Zwaigenbaum and Jeste, {Shafali S.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1001/jamaneurol.2019.3341",
language = "English (US)",
journal = "JAMA Neurology",
issn = "2168-6149",
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TY - JOUR

T1 - Developmental Trajectories of Infants with Multiplex Family Risk for Autism

T2 - A Baby Siblings Research Consortium Study

AU - McDonald, Nicole M.

AU - Senturk, Damla

AU - Scheffler, Aaron

AU - Brian, Jessica A.

AU - Carver, Leslie J.

AU - Charman, Tony

AU - Chawarska, Katarzyna

AU - Curtin, Suzanne

AU - Hertz-Piccioto, Irva

AU - Jones, Emily J.H.

AU - Klin, Ami

AU - Landa, Rebecca

AU - Messinger, Daniel S.

AU - Ozonoff, Sally

AU - Stone, Wendy L.

AU - Tager-Flusberg, Helen

AU - Webb, Sara Jane

AU - Young, Gregory

AU - Zwaigenbaum, Lonnie

AU - Jeste, Shafali S.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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: 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. Exposures: 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. Results: 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.

AB - 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: 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. Exposures: 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. Results: 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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