Epilepsies of early childhood are frequently resistant to therapy and often associated with cognitive and behavioural comorbidity. Aetiology focused precision medicine, notably gene-based therapies, may prevent seizures and comorbidities. Epidemiological data utilizing modern diagnostic techniques including whole genome sequencing and neuroimaging can inform diagnostic strategies and therapeutic trials. We present a 3-year, multicentre prospective cohort study, involving all children under 3 years of age in Scotland presenting with epilepsies. We used two independent sources for case identification: clinical reporting and EEG record review. Capture-recapture methodology was then used to improve the accuracy of incidence estimates. Socio-demographic and clinical details were obtained at presentation, and 24 months later. Children were extensively investigated for aetiology. Whole genome sequencing was offered for all patients with drug-resistant epilepsy for whom no aetiology could yet be identified. Multivariate logistic regression modelling was used to determine associations between clinical features, aetiology, and outcome. Three hundred and ninety children were recruited over 3 years. The adjusted incidence of epilepsies presenting in the first 3 years of life was 239 per 100 000 live births [95% confidence interval (CI) 216–263]. There was a socio-economic gradient to incidence, with a significantly higher incidence in the most deprived quintile (301 per 100 000 live births, 95% CI 251–357) compared with the least deprived quintile (182 per 100 000 live births, 95% CI 139–233), χ2 odds ratio = 1.7 (95% CI 1.3–2.2). The relationship between deprivation and incidence was only observed in the group without identified aetiology, suggesting that populations living in higher deprivation areas have greater multifactorial risk for epilepsy. Aetiology was determined in 54% of children, and epilepsy syndrome was classified in 54%. Thirty-one per cent had an identified genetic cause for their epilepsy. We present novel data on the aetiological spectrum of the most commonly presenting epilepsies of early childhood. Twenty-four months after presentation, 36% of children had drug-resistant epilepsy (DRE), and 49% had global developmental delay (GDD). Identification of an aetiology was the strongest determinant of both DRE and GDD. Aetiology was determined in 82% of those with DRE, and 75% of those with GDD. In young children with epilepsy, genetic testing should be prioritized as it has the highest yield of any investigation and is most likely to inform precision therapy and prognosis. Epilepsies in early childhood are 30% more common than previously reported. Epilepsies of undetermined aetiology present more frequently in deprived communities. This likely reflects increased multifactorial risk within these populations.

中文翻译：

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儿童早期癫痫：流行病学、分类、病因和社会经济决定因素

儿童早期癫痫经常对治疗产生抗药性，并且通常与认知和行为共病有关。以病因学为重点的精准医学，尤其是基于基因的疗法，可以预防癫痫发作和合并症。利用现代诊断技术（包括全基因组测序和神经成像）的流行病学数据可以为诊断策略和治疗试验提供信息。我们提出了一项为期 3 年的多中心前瞻性队列研究，涉及苏格兰所有 3 岁以下的癫痫患儿。我们使用两个独立的来源进行病例识别：临床报告和脑电图记录审查。然后使用捕获-再捕获方法来提高发病率估计的准确性。在就诊时和 24 个月后获得了社会人口学和临床详细信息。对儿童进行了广泛的病因学调查。为尚未确定病因的所有耐药性癫痫患者提供全基因组测序。多变量逻辑回归模型用于确定临床特征、病因和结果之间的关联。在 3 年内招募了 390 名儿童。出生后头 3 年出现癫痫的调整后发病率为每 10 万活产 239 例 [95% 置信区间 (CI) 216–263]。发病率存在社会经济梯度，与最贫困的五分之一人口（每 10 万活产婴儿 182 人，95 % CI 139–233)，χ2 优势比 = 1.7 (95% CI 1.3–2.2)。剥夺与发病率之间的关系仅在未确定病因的组中观察到，这表明生活在贫困程度较高地区的人群患癫痫的多因素风险更大。54% 的儿童确定了病因，54% 的儿童患有癫痫综合征。31% 的人有明确的癫痫遗传原因。我们提供了关于儿童早期最常见癫痫病原学谱的新数据。就诊 24 个月后，36% 的儿童患有耐药性癫痫 (DRE)，49% 的儿童患有全球发育迟缓 (GDD)。确定病因是 DRE 和 GDD 的最强决定因素。82% 的 DRE 患者和 75% 的 GDD 患者确定了病因。在患有癫痫症的幼儿中，应该优先考虑基因检测，因为它在任何研究中具有最高的产量，并且最有可能为精准治疗和预后提供信息。儿童早期癫痫的发生率比之前报道的高 30%。未确定病因的癫痫更常见于贫困社区。这可能反映了这些人群中多因素风险的增加。