From the Department of Health Research Methods, Evidence, and Impact (C.S.), McMaster University Hamilton, Ontario, Canada; University Medical Center of the Johannes Gutenberg University (A.C.M.), Mainz, Germany; Department of Family and Community Medicine (K.M.), University of Toronto, Ontario, Canada; Department of Health Sciences (D.B.), Brock University St. Catherines, Ontario, Canada; and Health Policy and Management (C.K.), Harvard T.H. Chan School of Public Health, Boston, MA.
Neurology. 2023 Nov 21;101(21):e2151-e2161. doi: 10.1212/WNL.0000000000207910. Epub 2023 Oct 25.
Headache disorders are among the leading causes of disability worldwide. While an association between adverse childhood experiences and primary headaches has been reported, the pooled magnitude across studies and pathways of the association are unknown. Our objectives were (1) to estimate the pooled effect of ≥1 adverse childhood experience (ACE) on primary headache disorders in adulthood and (2) to test the hypothesis that ACEs categorized as "threat" traumas or "deprivation" traumas have distinct effects on primary headaches based on a selected theory from our narrative review of how ACEs affect human development along the life course.
PubMed, EMBASE, MEDLINE, Web of Science, Google Scholar, Biological Psychiatry, and gray literature were searched up to March 16, 2023 (PROSPERO, CRD42020223403). Selected articles included (1) observational studies with a comparator group, (2) ACEs that occurred before 18 years of age, and (3) primary headaches occurring at or after 21 years of age. Pooled odds ratios (ORs) were calculated using multilevel linear random-effects modeling. The narrative review included theories that describe how ACEs affect human development and disease across the life course. We selected a theory from our narrative review and tested ACEs categorized according to this theory for any modification of point estimates.
Our search identified 32 studies, of which 28 were eligible for meta-analysis (n = 154,739 participants, 19 countries). The occurrence of ≥1 adverse childhood experience(s) was associated with primary headaches (pooled OR = 1.48 [95% CI 1.36-1.61]; high-quality evidence, 134,696 participants). As the number of ACEs increased, the odds of primary headaches increased (range: 1 ACE OR = 1.24 [95% CI 1.14-1.35] to ≥4 ACEs OR = 2.09 [95% CI 1.83-2.38], for trend <0.0001). From the narrative review, a neurodevelopmental theory that categorizes ACEs into threat or deprivation was tested, and both were independently associated with primary headaches (threat OR = 1.46 [95% CI 1.32-1.60] and deprivation OR = 1.35 [95% CI 1.23-1.49], respectively), accounting for heterogeneity ( = 0.021).
This systematic review and meta-analysis confirm that ACEs are important risk factors of primary headache disorders in adulthood. Our findings provide epidemiologic support that ACEs categorized as threat and deprivation may manifest as distinct pathways of early adversity.
头痛障碍是全球导致残疾的主要原因之一。虽然已有研究报告称儿童期不良经历与原发性头痛之间存在关联，但目前尚不清楚这些关联在研究间的综合程度和途径。我们的目的是：（1）评估≥1 项儿童期不良经历（ACE）对成年期原发性头痛障碍的综合影响；（2）根据我们对 ACE 如何影响人类生命历程中发展的叙述性综述中选择的理论，检验 ACE 被归类为“威胁”创伤或“剥夺”创伤对原发性头痛具有不同影响的假设。
截至 2023 年 3 月 16 日，我们在 PubMed、EMBASE、MEDLINE、Web of Science、Google Scholar、Biological Psychiatry 和灰色文献中进行了检索（PROSPERO、CRD42020223403）。入选的文章包括：（1）有对照组的观察性研究；（2）发生在 18 岁之前的 ACE；（3）21 岁及以上发生的原发性头痛。使用多水平线性随机效应模型计算合并优势比（OR）。叙述性综述包括描述 ACE 如何在生命过程中影响人类发展和疾病的理论。我们从叙述性综述中选择了一个理论，并根据该理论对 ACE 进行分类，以检验任何点估计的修正。
我们的检索共确定了 32 项研究，其中 28 项研究符合荟萃分析的纳入标准（n=154739 名参与者，来自 19 个国家）。≥1 项儿童期不良经历的发生与原发性头痛相关（合并 OR=1.48[95%CI 1.36-1.61]；高质量证据，134696 名参与者）。随着 ACE 数量的增加，原发性头痛的几率也随之增加（范围：1 项 ACE OR=1.24[95%CI 1.14-1.35]至≥4 项 ACE OR=2.09[95%CI 1.83-2.38]，趋势 P<0.0001）。从叙述性综述中，我们测试了一种将 ACE 分类为威胁或剥夺的神经发育理论，发现两者均与原发性头痛独立相关（威胁 OR=1.46[95%CI 1.32-1.60]和剥夺 OR=1.35[95%CI 1.23-1.49]），可解释异质性（=0.021）。
本系统评价和荟萃分析证实，ACE 是成年期原发性头痛障碍的重要危险因素。我们的研究结果提供了流行病学证据，表明 ACE 被归类为威胁和剥夺可能表现为早期逆境的不同途径。
