Objective: To identify risk factors and generate hypotheses for pediatric post-concussion syndrome (PCS) using a phenome-wide association study (PheWAS). Methods: A PheWAS (case-control) was conducted following the development and validation of a novel electronic health record-based algorithm that identified PCS cases and controls from an institutional database of >2.8 million patients. Cases were patients ages 5-18 with PCS codes or keywords identified by natural language processing of clinical notes. Controls were patients with mild traumatic brain injury (mTBI) codes only. Patients with moderate or severe brain injury were excluded. All patients used our healthcare system at least three times 180 days before their injury. Exposures included all pre-injury medical diagnoses assigned at least 180 days prior. Results: The algorithm identified 274 pediatric PCS cases (156 females) and 1,096 controls that were age and sex matched to cases. Cases and controls both had a mean of >8 years of healthcare system use pre-injury. Of 202 pre-injury medical, four were associated with PCS after controlling for multiple testing: headache disorders (OR=5.3; 95%CI 2.8-10.1;P=3.8e-7), sleep disorders (OR=3.1; 95%CI 1.8-5.2; P=2.6e-5), gastritis/duodenitis (OR=3.6, 95%CI 1.8-7.0;P=2.1e-4), and chronic pharyngitis (OR=3.3; 95%CI 1.8-6.3;P=2.2e-4). Conclusions: These results confirm the strong association of pre-injury headache disorders with PCS and provides evidence for the association of pre-injury sleep disorders with PCS. An association of PCS with prior chronic gastritis/duodenitis and pharyngitis was seen that suggests a role for chronic inflammation in PCS pathophysiology and risk. These factors should be considered during the management of pediatric mTBI cases.

中文翻译：

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全基因组关联研究确定了小儿脑震荡综合征的危险因素

目的：使用全表型关联研究（PheWAS）识别儿童脑震荡后综合征（PCS）的危险因素并提出假设。方法：在开发和验证了一种新的基于电子病历的算法后，进行了PheWAS（病例对照），该算法从超过280万患者的机构数据库中识别出PCS病例和对照。病例为5-18岁的患者，其PCS代码或通过自然语言处理临床笔记确定的关键词。对照组仅是轻度创伤性脑损伤（mTBI）代码的患者。中度或重度脑损伤患者被排除在外。所有患者在受伤前至少180天使用了我们的医疗系统三次。暴露包括至少在180天之前分配的所有损伤前医学诊断。结果：该算法确定了274例小儿PCS病例（156例女性）和1,096例年龄和性别均与病例匹配的对照。病例和对照均在伤害前平均使用医疗系统超过8年。在202名受伤前医疗中，有4名在控制多项测试后与PCS相关：头痛疾病（OR = 5.3; 95％CI 2.8-10.1; P = 3.8e-7），睡眠障碍（OR = 3.1; 95％CI 1.8-5.2; P = 2.6e-5），胃炎/十二指肠炎（OR = 3.6，95％CI 1.8-7.0; P = 2.1e-4）和慢性咽炎（OR = 3.3; 95％CI 1.8-6.3; P ＝ 2.2e-4）。结论：这些结果证实了损伤前头痛症与PCS的强烈关联，并为损伤前睡眠障碍与PCS的关联提供了证据。观察到PCS与先前的慢性胃炎/十二指肠炎和咽炎相关，提示慢性炎症在PCS病理生理和风险中起作用。在小儿mTBI病例的治疗中应考虑这些因素。