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Mid-childhood outcomes of infant siblings at familial high-risk of autism spectrum disorder.

ABSTRACT: Almost 20% of infants with an older sibling with autism spectrum disorder (ASD) exhibit ASD themselves by age 3 years. The longer-term outcomes of high-risk infants are less clear. We examined symptoms of ASD, attention-deficit/hyperactivity disorder (ADHD) and anxiety, language, IQ, and adaptive behaviour at age 7 years in high- and low-risk children prospectively studied since the first year of life. Clinical outcomes were compared between high-risk children who met diagnostic criteria for ASD at age 7 (HR-ASD-7 group, n = 15), high-risk children without ASD (HR-Non-ASD-7 group, n = 24), and low-risk control children (LR group, n = 37). Diagnostic stability between age 3 and 7 years was moderate, with five children who did not meet diagnostic criteria for ASD at age 3 years being assigned the diagnosis at age 7, and three children showing the opposite pattern. The HR-ASD-7 group showed elevated ADHD and anxiety symptoms and had lower adaptive behaviour scores than LR controls. The HR-Non-ASD-7 group had higher repetitive behaviour, lower adaptive functioning and elevated scores on one anxiety subscale (Separation Anxiety) compared to LR controls, but evidence for subclinical ASD symptoms (the broader autism phenotype, BAP) was limited in the group as a whole, although we identified a subgroup with elevated ASD traits. The difficulties experienced by high-risk siblings at school-age extend beyond ASD symptoms. The pattern of difficulties exhibited by the HR-ASD-7 group may inform our understanding of developmental trajectories of co-occurring psychopathology in ASD. Autism Res 2017, 10: 546-557. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

SUBMITTER: Shephard E

PROVIDER: S-EPMC5408391 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Mid-childhood outcomes of infant siblings at familial high-risk of autism spectrum disorder.

Shephard Elizabeth E Milosavljevic Bosiljka B Pasco Greg G Jones Emily J H EJ Gliga Teodora T Happé Francesca F Johnson Mark H MH Charman Tony T

Autism research : official journal of the International Society for Autism Research 20161129 3

Almost 20% of infants with an older sibling with autism spectrum disorder (ASD) exhibit ASD themselves by age 3 years. The longer-term outcomes of high-risk infants are less clear. We examined symptoms of ASD, attention-deficit/hyperactivity disorder (ADHD) and anxiety, language, IQ, and adaptive behaviour at age 7 years in high- and low-risk children prospectively studied since the first year of life. Clinical outcomes were compared between high-risk children who met diagnostic criteria for ASD ...[more]

PMID: 27896942

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Project description:BACKGROUND:Language delay is extremely common in children with autism spectrum disorder (ASD), yet it is unclear whether measurable variation in early language is associated with genetic liability for ASD. Assessment of language development in unaffected siblings of children with ASD can inform whether decreased early language ability aggregates with inherited risk for ASD and serves as an ASD endophenotype. METHODS:We implemented two approaches: (1) a meta-analysis of studies comparing language delay, a categorical indicator of language function, and language scores, a continuous metric, in unaffected toddlers at high and low familial risk for ASD, and (2) a parallel analysis of 350 unaffected 24-month-olds in the Infant Brain Imaging Study (IBIS), a prospective study of infants at high and low familial risk for ASD. An advantage of the former was its detection of group differences from pooled data across unique samples; an advantage of the latter was its sensitivity in quantifying early manifestations of language delay while accounting for covariates within a single large sample. RESULTS:Meta-analysis showed that high-risk siblings without ASD (HR-noASD) were three to four times more likely to exhibit language delay versus low-risk siblings without ASD (LR-noASD) and had lower mean receptive and expressive language scores. Analyses of IBIS data corroborated that language delay, specifically receptive language delay, was more frequent in the HR-noASD (n?=?235) versus LR-noASD group (n?=?115). IBIS language scores were continuously and unimodally distributed, with a pathological shift towards decreased language function in HR-noASD siblings. The elevated inherited risk for ASD was associated with lower receptive and expressive language scores when controlling for sociodemographic factors. For receptive but not expressive language, the effect of risk group remained significant even when controlling for nonverbal cognition. CONCLUSIONS:Greater frequency of language delay and a lower distribution of language scores in high-risk, unaffected toddler-aged siblings support decreased early language ability as an endophenotype for ASD, with a more pronounced effect for receptive versus expressive language. Further characterization of language development is warranted to refine genetic investigations of ASD and to elucidate factors influencing the progression of core autistic traits and related symptoms.

Project description:ImportanceIn recent years, rates of vaccination have been declining. Whether this phenomenon disproportionately affects children with autism spectrum disorder (ASD) or their younger siblings is unknown.ObjectivesTo investigate if children after receiving an ASD diagnosis obtain their remaining scheduled vaccines according to the Advisory Committee on Immunization Practices (ACIP) recommendations and to compare the vaccination patterns of younger siblings of children with ASD with the vaccination patterns of younger siblings of children without ASD.Design, setting, and participantsThis investigation was a retrospective matched cohort study. The setting was 6 integrated health care delivery systems across the United States within the Vaccine Safety Datalink. Participants were children born between January 1, 1995, and September 30, 2010, and their younger siblings born between January 1, 1997, and September 30, 2014. The end of follow-up was September 30, 2015.ExposuresRecommended childhood vaccines between ages 1 month and 12 years.Main outcome and measureThe proportion of children who received all of their vaccine doses according to ACIP recommendations.ResultsThe study included 3729 children with ASD (676 [18.1%] female), 592?907 children without ASD, and their respective younger siblings. Among children without ASD, 250?193 (42.2%) were female. For vaccines recommended between ages 4 and 6 years, children with ASD were significantly less likely to be fully vaccinated compared with children without ASD (adjusted rate ratio, 0.87; 95% CI, 0.85-0.88). Within each age category, vaccination rates were significantly lower among younger siblings of children with ASD compared with younger siblings of children without ASD. The adjusted rate ratios varied from 0.86 for siblings younger than 1 year to 0.96 for those 11 to 12 years old. Parents who had a child with ASD were more likely to refuse at least 1 recommended vaccine for that child's younger sibling and to limit the number of vaccines administered during the younger sibling's first year of life.Conclusions and relevanceChildren with ASD and their younger siblings were undervaccinated compared with the general population. The results of this study suggest that children with ASD and their younger siblings are at increased risk of vaccine-preventable diseases.

Dataset Information

Mid-childhood outcomes of infant siblings at familial high-risk of autism spectrum disorder.

Publications

Mid-childhood outcomes of infant siblings at familial high-risk of autism spectrum disorder.

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