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], p 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 (p = 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.

头痛疾病是全世界残疾的主要原因之一。虽然不良童年经历与原发性头痛之间存在关联，但各种研究的汇总程度以及这种关联的途径尚不清楚。我们的目标是 (1) 估计 ≥1 种不良童年经历 (ACE) 对成年后原发性头痛疾病的综合影响，以及 (2) 检验归类为“威胁”创伤或“剥夺”创伤的 ACE 具有不同影响的假设基于我们对 ACE 如何影响人类生命历程发展的叙述性回顾中选定的理论，对原发性头痛进行了研究。

检索截至 2023 年 3 月 16 日的 PubMed、EMBASE、MEDLINE、Web of Science、Google Scholar、Biological Psychiatry 和灰色文献（PROSPERO、CRD42020223403）。选定的文章包括 (1) 比较组的观察性研究，(2) 18 岁之前发生的 ACE，以及​​ (3) 21 岁或之后发生的原发性头痛。使用多级线性随机效应模型计算合并优势比 (OR)。叙述性回顾包括描述 ACE 如何影响人类整个生命过程中的发育和疾病的理论。我们从我们的叙述性评论中选择了一个理论，并测试了根据该理论分类的 ACE 对点估计的任何修改。

我们的检索确定了 32 项研究，其中 28 项符合荟萃分析条件（n = 154,739 名参与者，19 个国家）。≥1 次不良童年经历的发生与原发性头痛相关（汇总 OR = 1.48 [95% CI 1.36–1.61]；高质量证据，134,696 名参与者）。随着 ACE 数量的增加，原发性头痛的几率增加（范围：1 个 ACE OR = 1.24 [95% CI 1.14–1.35] 至 ≥4 个 ACE OR = 2.09 [95% CI 1.83–2.38]，趋势 p < 0.0001）。从叙述回顾中，测试了将 ACE 分类为威胁或剥夺的神经发育理论，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]，分别），解释异质性（p = 0.021）。

这项系统回顾和荟萃分析证实，ACE 是成年期原发性头痛的重要危险因素。我们的研究结果提供了流行病学支持，即被归类为威胁和剥夺的 ACE 可能表现为早期逆境的不同途径。