Burrows Catherine A, Sung Sooyeon, Zheng Shuting, Young Greg S, Charman Tony, Klaiman Cheryl, Klin Ami, Marrus Natasha, Ozonoff Sally, Piven Joseph, Robins Diana L, Schmidt Rebecca J, Schwichtenberg A J, Webb Sara Jane, Zwaigenbaum Lonnie, Carver Leslie J, Chawarska Katarzyna, Curtin Suzanne, Jeste Shafali S, Iverson Jana M, Landa Rebecca J, Messinger Daniel S, Roberts Jane E, Stone Wendy L, Tager-Flusberg Helen, Esler Amy N, Miller Meghan, Bishop Somer L, Elison Jed T
Department of Pediatrics, University of Minnesota, Minneapolis.
Graduate School of Education, Kyung Hee University, Seoul, Korea.
JAMA Netw Open. 2025 Aug 1;8(8):e2525887. doi: 10.1001/jamanetworkopen.2025.25887.
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.
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.
Child sex and age and ASD diagnosis.
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.
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.
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).
与男性儿童相比，女性儿童在自闭症谱系障碍（ASD）的诊断年龄和患病率方面存在差异。纠正偏差来源对于改善公平的ASD识别至关重要。
确定在自闭症高家族患病风险（HFL）和低家族患病风险（LFL）的幼儿中，使用自闭症诊断观察量表（ADOS）测量ASD症状时是否存在性别差异。
设计、背景和参与者：这项队列研究收集了2003年1月1日至2021年12月31日期间来自婴儿兄弟姐妹研究联盟的纵向、前瞻性数据。参与者包括3106名有患ASD哥哥或姐姐的儿童（HFL组）和1444名没有患ASD哥哥或姐姐的儿童（LFL组）。纳入了参与者在20至40个月大时多达3次访视的数据。分析于2023年3月1日至2025年5月29日进行。
儿童性别、年龄和ASD诊断。
在ADOS项目级数据中检查性别和年龄的测量不变性。然后使用校正分数的混合效应模型检查诊断组和性别差异。
纳入了4550名参与者（2548名[56.0%]男性）的重复访视（n = 7557），其中1444名（31.7%）在LFL组，3016名（68.3%）在HFL组。验证性因素分析表明，社交沟通以及受限和重复行为模型在HFL组中与数据拟合良好，但在LFL组中拟合较差。在HFL组中，女性在眼神接触方面的受损程度被评定为较低（差异项目功能估计值[标准误] = 0.088 [0.033]；P = 0.01），与男性相比，她们对共同注意的反应（差异项目功能估计值[标准误] = 0.290 [0.105]；P = 0.01）以及社交主动行为的质量（差异项目功能估计值[标准误] = 0.053 [0.019]；P = 0.005）与潜在社交沟通困难较少相关。通过年龄和性别调整差异项目功能后，测量差异处于中等水平。女性表现出比男性更轻微的自闭症特征，尽管在被诊断为ASD的参与者中这种差距较小。
在一般人群中，许多社交沟通特征存在性别差异，但ASD诊断阈值并未考虑这些性别差异。未来的工具开发以及临床医生培训应认识到许多女性表现较轻微（眼神接触困难或社交障碍质量方面问题较少）。这可能有助于更早地识别发育差异并改善自闭症女性的结局（估计值[标准误] = -0.160 [0.061]；P = 0.009）。
