. 2025 Aug 1;8(8):e2525887.

doi: 10.1001/jamanetworkopen.2025.25887.

Sex-Related Measurement Bias in Autism Spectrum Disorder Symptoms in the Baby Siblings Research Consortium

Catherine A Burrows¹, Sooyeon Sung², Shuting Zheng³, Greg S Young⁴, Tony Charman⁵, Cheryl Klaiman⁶, Ami Klin⁶, Natasha Marrus⁷, Sally Ozonoff⁴, Joseph Piven⁸, Diana L Robins⁹, Rebecca J Schmidt¹⁰, A J Schwichtenberg¹¹, Sara Jane Webb¹², Lonnie Zwaigenbaum¹³, Leslie J Carver¹⁴, Katarzyna Chawarska¹⁴, Suzanne Curtin¹⁵, Shafali S Jeste¹⁶, Jana M Iverson¹⁷, Rebecca J Landa^{18

19}, Daniel S Messinger²⁰, Jane E Roberts²¹, Wendy L Stone²², Helen Tager-Flusberg²³, Amy N Esler¹, Meghan Miller⁴, Somer L Bishop²⁴, Jed T Elison^{1

25}

Affiliations

¹ Department of Pediatrics, University of Minnesota, Minneapolis.
² Graduate School of Education, Kyung Hee University, Seoul, Korea.
³ Department of Psychiatry and Behavioral Sciences, University of Texas at Austin, Austin.
⁴ Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis.
⁵ Department of Psychology, King's College London, London, UK, on behalf of the BASIS Network.
⁶ Marcus Autism Center, Children's Healthcare of Atlanta and Emory University School of Medicine, Emory University, Atlanta, Georgia.
⁷ Department of Psychiatry, Washington University in St Louis, St Louis, Missouri.
⁸ Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, on behalf of the IBIS network.
⁹ A. J. Drexel Autism Institute, Drexel University, Philadelphia, Pennsylvania.
¹⁰ School of Medicine, Public Health Sciences, University of California, Davis, Davis.
¹¹ Department of Human Development and Family Science, Purdue University, West Lafayette, Indiana.
¹² Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle.
¹³ Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
¹⁴ Department of Psychology, University of California, San Diego, San Diego.
¹⁵ Department of Child and Youth Studies, Brock University, St Catharines, Ontario, Canada.
¹⁶ Departments of Neurology and Pediatrics, Children's Hospital Los Angeles, Los Angeles, California.
¹⁷ Department of Physical Therapy, Sargent College of Health and Rehabilitation Sciences, Boston University, Boston, Massachusetts.
¹⁸ Center for Autism Services, Science and Innovation, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
¹⁹ Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
²⁰ Department of Psychology, University of Miami, Miami, Florida.
²¹ Department of Psychology, University of South Carolina, Columbia.
²² Department of Psychology, University of Washington, Seattle.
²³ Department of Psychological and Brain Sciences, Boston University, Boston, Massachusetts.
²⁴ Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco.
²⁵ Institute of Child Development, University of Minnesota, Minneapolis.

PMID: 40779266
PMCID: PMC12334962
DOI: 10.1001/jamanetworkopen.2025.25887

Sex-Related Measurement Bias in Autism Spectrum Disorder Symptoms in the Baby Siblings Research Consortium

Catherine A Burrows et al. JAMA Netw Open. 2025.

. 2025 Aug 1;8(8):e2525887.

doi: 10.1001/jamanetworkopen.2025.25887.

Authors

Affiliations

¹ Department of Pediatrics, University of Minnesota, Minneapolis.
² Graduate School of Education, Kyung Hee University, Seoul, Korea.
³ Department of Psychiatry and Behavioral Sciences, University of Texas at Austin, Austin.
⁴ Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis.
⁵ Department of Psychology, King's College London, London, UK, on behalf of the BASIS Network.
⁶ Marcus Autism Center, Children's Healthcare of Atlanta and Emory University School of Medicine, Emory University, Atlanta, Georgia.
⁷ Department of Psychiatry, Washington University in St Louis, St Louis, Missouri.
⁸ Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, on behalf of the IBIS network.
⁹ A. J. Drexel Autism Institute, Drexel University, Philadelphia, Pennsylvania.
¹⁰ School of Medicine, Public Health Sciences, University of California, Davis, Davis.
¹¹ Department of Human Development and Family Science, Purdue University, West Lafayette, Indiana.
¹² Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle.
¹³ Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
¹⁴ Department of Psychology, University of California, San Diego, San Diego.
¹⁵ Department of Child and Youth Studies, Brock University, St Catharines, Ontario, Canada.
¹⁶ Departments of Neurology and Pediatrics, Children's Hospital Los Angeles, Los Angeles, California.
¹⁷ Department of Physical Therapy, Sargent College of Health and Rehabilitation Sciences, Boston University, Boston, Massachusetts.
¹⁸ Center for Autism Services, Science and Innovation, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
¹⁹ Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
²⁰ Department of Psychology, University of Miami, Miami, Florida.
²¹ Department of Psychology, University of South Carolina, Columbia.
²² Department of Psychology, University of Washington, Seattle.
²³ Department of Psychological and Brain Sciences, Boston University, Boston, Massachusetts.
²⁴ Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco.
²⁵ Institute of Child Development, University of Minnesota, Minneapolis.

PMID: 40779266
PMCID: PMC12334962
DOI: 10.1001/jamanetworkopen.2025.25887

Abstract

Importance: Disparities exist in age of diagnosis and prevalence of autism spectrum disorder (ASD) for female compared with male children. Correcting for sources of bias is critical for improving equitable ASD identification.

Objective: To determine whether sex differences exist in measurement of ASD symptoms using the Autism Diagnostic Observation Schedule (ADOS) among young children at high familial likelihood (HFL) and low familial likelihood (LFL) of ASD.

Design, setting, and participants: This cohort study collected longitudinal, prospective data from the Baby Siblings Research Consortium between January 1, 2003, and December 31, 2021. Participants included 3106 children who had an older sibling with ASD (HFL group) and 1444 without (LFL group). Data from as many as 3 visits when participants were aged 20 to 40 months were included. Analysis occurred between March 1, 2023, and May 29, 2025.

Exposures: Child sex and age and ASD diagnosis.

Main outcomes and measures: Measurement invariance by sex and age was examined across item-level ADOS data. Diagnostic group and sex differences were then examined using mixed-effect models on corrected scores.

Results: Repeated visits (n = 7557) from 4550 participants (2548 [56.0%] male) were included, of whom 1444 (31.7%) were in the LFL and 3016 (68.3%) in the HFL groups. Confirmatory factor analysis indicated social communication and restricted and repetitive behaviors models fit the data well in the HFL group but poorly in the LFL group. In the HFL group, females were rated as less impaired in eye contact (differential item functioning estimate [SE] = 0.088 [0.033]; P = .01), and their response to joint attention (differential item functioning estimate [SE] = 0.290 [0.105]; P = .01) and quality of social overtures (differential item functioning estimate [SE] = 0.053 [0.019]; P = .005) was associated with less underlying social communication difficulties compared with males. Adjusting for differential item functioning by age and sex resulted in moderate levels of measurement differences. Females showed milder autistic traits than males, although this gap was smaller in the participants diagnosed with ASD.

Conclusions and relevance: Sex differences exist in the general population in many social communication traits, yet ASD diagnostic thresholds do not account for these sex differences. Future instrument development, as well as clinician training, should acknowledge milder presentation (fewer difficulties with eye contact or quality of social impairments) in many females. This may help identify developmental differences earlier and improve outcomes for autistic females (estimate [SE] = -0.160 [0.061]; P = .009).

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Burrows reported receiving funding toward travel to the Baby Siblings Research Consortium (BSRC) Annual Meeting from Autism Science Foundation during the conduct of the study. Dr Charman reported receiving personal fees from F. Hoffmann–La Roche Ltd and royalties from Guildford Press and Sage Publishing outside the submitted work. Dr Klaiman reported receiving personal fees from EarliTec, Wiley, and J&K Seminars outside the submitted work. Dr Marrus reported receiving grant support from Washington University in St Louis during the conduct of the study. Dr Robins reported being the co-owner of M-CHAT LLC, which licenses use of intellectual property, the Modified Checklist for Autism in Toddlers (M-CHAT) and the M-CHAT Revised, with Follow-Up (M-CHAT-R/F), for use in commercial products. Dr Schmidt reported receiving grant support from Simons Foundation during the conduct of the study and personal fees for consulting from Linus Technology outside the submitted work. Dr Zwaigenbaum reported receiving grant support from Kids Brain Health Foundation, Autism Science Foundation, and Stollery Children’s Hospital Foundation during the conduct of the study. Dr Carver reported receiving grant support from Autism Speaks and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) during the conduct of the study. Dr Landa reported grants from the National Institute of Mental Health during the conduct of the study. Dr Bishop reported sales from the ADOS-2 from Western Psychological Services outside the submitted work. No other disclosures were reported.

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doi: 10.1001/jamanetworkopen.2025.25893

References

1. Messinger DS, Young GS, Webb SJ, et al. Early sex differences are not autism-specific: a Baby Siblings Research Consortium (BSRC) study. Mol Autism. 2015;6(1):32. doi: 10.1186/s13229-015-0027-y - DOI - PMC - PubMed
1. Shattuck PT, Durkin M, Maenner M, et al. Timing of identification among children with an autism spectrum disorder: findings from a population-based surveillance study. J Am Acad Child Adolesc Psychiatry. 2009;48(5):474-483. doi: 10.1097/CHI.0b013e31819b3848 - DOI - PMC - PubMed
1. McDonnell CG, DeLucia EA, Hayden EP, et al. Sex differences in age of diagnosis and first concern among children with autism spectrum disorder. J Clin Child Adolesc Psychol. 2021;50(5):645-655. doi: 10.1080/15374416.2020.1823850 - DOI - PubMed
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Sex-Related Measurement Bias in Autism Spectrum Disorder Symptoms in the Baby Siblings Research Consortium

Affiliations

Sex-Related Measurement Bias in Autism Spectrum Disorder Symptoms in the Baby Siblings Research Consortium

Authors

Affiliations

Abstract

Conflict of interest statement

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Comment in

References

MeSH terms

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