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A Data-Driven Approach in an Unbiased Sample Reveals Equivalent Sex Ratio of Autism Spectrum Disorder–Associated Impairment in Early Childhood

      Abstract

      Background

      Sex differences in the prevalence of neurodevelopmental disorders are particularly evident in autism spectrum disorder (ASD). Heterogeneous symptom presentation and the potential of measurement bias hinder early ASD detection in females and may contribute to discrepant prevalence estimates. We examined trajectories of social communication (SC) and restricted and repetitive behaviors (RRBs) in a sample of infant siblings of children with ASD, adjusting for age- and sex-based measurement bias. We hypothesized that leveraging a prospective elevated familial likelihood sample, deriving data-driven behavioral constructs, and accounting for measurement bias would reveal less discrepant sex ratios than are typically seen in ASD.

      Methods

      We conducted direct assessments of ASD symptoms at 6 to 9, 12 to 15, 24, and 36 to 60 months of age (total nobservations = 1254) with infant siblings of children with ASD (n = 377) and a lower ASD-familial-likelihood comparison group (n = 168; nobservations = 527). We established measurement invariance across age and sex for separate models of SC and RRB. We then conducted latent class growth mixture modeling with the longitudinal data and evaluated for sex differences in trajectory membership.

      Results

      We identified 2 latent classes in the SC and RRB models with equal sex ratios in the high-concern cluster for both SC and RRB. Sex differences were also observed in the SC high-concern cluster, indicating that girls classified as having elevated social concerns demonstrated milder symptoms than boys in this group.

      Conclusions

      This novel approach for characterizing ASD symptom progression highlights the utility of assessing and adjusting for sex-related measurement bias and identifying sex-specific patterns of symptom emergence.

      Keywords

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      Linked Article

      • Balanced Sex Ratios and the Autism Continuum
        Biological PsychiatryVol. 92Issue 8
        • Preview
          Autism is a heterogeneous neurodevelopmental condition that is diagnosed more frequently in males than females (note that in this commentary, the use of “female” and “male” refers to sex assigned at birth). The ratio of male to female diagnosis is about 3.25 to 1 when evaluated using ascertainment methods that actively screen a population-based sample, compared with the 4.56 to 1 ratio in individuals who have already had a diagnosis of autism (1). In many cases, females tend to not receive a diagnosis of autism until later in life when they have increased difficulties navigating a more complex social environment, or they tend to receive co-occurring diagnoses early in life that overshadow their autism.
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