Marcus Autism Center, Children's Healthcare of Atlanta, Atlanta, Georgia.
Division of Autism and Related Disabilities, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia.
JAMA Netw Open. 2023 Sep 5;6(9):e2330145. doi: 10.1001/jamanetworkopen.2023.30145.
Autism spectrum disorder is a common and early-emerging neurodevelopmental condition. While 80% of parents report having had concerns for their child's development before age 2 years, many children are not diagnosed until ages 4 to 5 years or later.
To develop an objective performance-based tool to aid in early diagnosis and assessment of autism in children younger than 3 years.
DESIGN, SETTING, AND PARTICIPANTS: In 2 prospective, consecutively enrolled, broad-spectrum, double-blind studies, we developed an objective eye-tracking-based index test for children aged 16 to 30 months, compared its performance with best-practice reference standard diagnosis of autism (discovery study), and then replicated findings in an independent sample (replication study). Discovery and replication studies were conducted in specialty centers for autism diagnosis and treatment. Reference standard diagnoses were made using best-practice standardized protocols by specialists blind to eye-tracking results. Eye-tracking tests were administered by staff blind to clinical results. Children were enrolled from April 27, 2013, until September 26, 2017. Data were analyzed from March 28, 2018, to January 3, 2019.
Prespecified primary end points were the sensitivity and specificity of the eye-tracking-based index test compared with the reference standard. Prespecified secondary end points measured convergent validity between eye-tracking-based indices and reference standard assessments of social disability, verbal ability, and nonverbal ability.
Data were collected from 1089 children: 719 children (mean [SD] age, 22.4 [3.6] months) in the discovery study, and 370 children (mean [SD] age, 25.4 [6.0] months) in the replication study. In discovery, 224 (31.2%) were female and 495 (68.8%) male; in replication, 120 (32.4%) were female and 250 (67.6%) male. Based on reference standard expert clinical diagnosis, there were 386 participants (53.7%) with nonautism diagnoses and 333 (46.3%) with autism diagnoses in discovery, and 184 participants (49.7%) with nonautism diagnoses and 186 (50.3%) with autism diagnoses in replication. In the discovery study, the area under the receiver operating characteristic curve was 0.90 (95% CI, 0.88-0.92), sensitivity was 81.9% (95% CI, 77.3%-85.7%), and specificity was 89.9% (95% CI, 86.4%-92.5%). In the replication study, the area under the receiver operating characteristic curve was 0.89 (95% CI, 0.86-0.93), sensitivity was 80.6% (95% CI, 74.1%-85.7%), and specificity was 82.3% (95% CI, 76.1%-87.2%). Eye-tracking test results correlated with expert clinical assessments of children's individual levels of ability, explaining 68.6% (95% CI, 58.3%-78.6%), 63.4% (95% CI, 47.9%-79.2%), and 49.0% (95% CI, 33.8%-65.4%) of variance in reference standard assessments of social disability, verbal ability, and nonverbal cognitive ability, respectively.
In two diagnostic studies of children younger than 3 years, objective eye-tracking-based measurements of social visual engagement quantified diagnostic status as well as individual levels of social disability, verbal ability, and nonverbal ability in autism. These findings suggest that objective measurements of social visual engagement can be used to aid in autism diagnosis and assessment.
自闭症谱系障碍是一种常见的早期神经发育疾病。虽然 80%的父母报告说在孩子 2 岁之前就已经对孩子的发育有了担忧，但许多孩子直到 4 到 5 岁或更晚才被诊断出来。
开发一种客观的基于表现的工具，以帮助在 3 岁以下儿童中早期诊断和评估自闭症。
设计、设置和参与者：在两项前瞻性、连续纳入的广谱、双盲研究中，我们为 16 至 30 个月大的儿童开发了一种基于客观眼动追踪的指标测试，将其与自闭症的最佳实践参考标准诊断（发现研究）进行比较，并在独立样本（复制研究）中复制发现。发现和复制研究是在自闭症诊断和治疗的专业中心进行的。参考标准诊断是由对眼动追踪结果盲目的专家使用最佳实践标准化协议做出的。由对临床结果盲目的工作人员进行眼动追踪测试。研究对象于 2013 年 4 月 27 日至 2017 年 9 月 26 日招募。数据分析时间为 2018 年 3 月 28 日至 2019 年 1 月 3 日。
预设的主要终点是与参考标准相比，眼动追踪指标测试的敏感性和特异性。预设的次要终点衡量了眼动追踪指标与社会残疾、语言能力和非语言认知能力的参考标准评估之间的收敛有效性。
共收集了 1089 名儿童的数据：发现研究中 719 名儿童（平均[标准差]年龄，22.4[3.6]个月），复制研究中 370 名儿童（平均[标准差]年龄，25.4[6.0]个月）。在发现研究中，224 名（31.2%）为女性，495 名（68.8%）为男性；在复制研究中，120 名（32.4%）为女性，250 名（67.6%）为男性。根据参考标准专家临床诊断，发现研究中 386 名参与者（53.7%）非自闭症诊断，333 名（46.3%）自闭症诊断，复制研究中 184 名参与者（49.7%）非自闭症诊断，186 名（50.3%）自闭症诊断。在发现研究中，受试者工作特征曲线下面积为 0.90（95%置信区间，0.88-0.92），敏感性为 81.9%（95%置信区间，77.3%-85.7%），特异性为 89.9%（95%置信区间，86.4%-92.5%）。在复制研究中，受试者工作特征曲线下面积为 0.89（95%置信区间，0.86-0.93），敏感性为 80.6%（95%置信区间，74.1%-85.7%），特异性为 82.3%（95%置信区间，76.1%-87.2%）。眼动追踪测试结果与专家临床评估儿童个体能力水平相关，解释了参考标准评估的社会残疾、语言能力和非语言认知能力的 68.6%（95%置信区间，58.3%-78.6%）、63.4%（95%置信区间，47.9%-79.2%）和 49.0%（95%置信区间，33.8%-65.4%）的差异。
在两项针对 3 岁以下儿童的诊断研究中，基于客观眼动追踪的社会视觉参与度测量可以定量诊断自闭症状态以及自闭症儿童的社会残疾、语言能力和非语言认知能力的个体水平。这些发现表明，社会视觉参与度的客观测量可以用于辅助自闭症的诊断和评估。
