Table_2_Premature Mortality, Risk Factors, and Causes of Death Following Childhood-Onset Neurological Impairments: A Systematic Review.docx

Background: Neurological impairment (NI) and disability are associated with reduced life expectancy, but the risk and magnitude of premature mortality in children vary considerably across study settings. We conducted a systematic review to estimate the magnitude of premature mortality following childhood-onset NI worldwide and to summarize known risk factors and causes of death.
Methods: We searched various databases for published studies from their inception up to 31st October 2020. We included all cohort studies that assessed the overall risk of mortality in individuals with childhood-onset epilepsy, intellectual disability (ID), and deficits in hearing, vision and motor functions. Comparative measures of mortality such as the standardized mortality ratio (SMR), risk factors and causes were synthesized quantitatively under each domain of impairment. This review is registered on the PROSPERO database (registration number CRD42019119239).
Results: The search identified 2,159 studies, of which 24 studies were included in the final synthesis. Twenty-two (91.7%) studies originated from high-income countries (HICs). The median SMR was higher for epilepsy compared with ID (7.1 [range 3.1–22.4] vs. 2.9 [range 2.0–11.6]). In epilepsy, mortality was highest among younger age groups, comorbid neurological disorders, generalized seizures (at univariable levels), untreatable epilepsy, soon after diagnosis and among cases with structural/metabolic types, but there were no differences by sex. Most deaths (87.5%) were caused by non-epilepsy-related causes. For ID, mortality was highest in younger age groups and girls had a higher risk compared to the general population. Important risk factors for premature mortality were severe-to-profound severity, congenital disorders e.g., Down Syndrome, comorbid neurological disorders and adverse pregnancy and perinatal events. Respiratory infections and comorbid neurological disorders were the leading causes of death in ID. Mortality is infrequently examined in impairments of vision, hearing and motor functions.
Summary: The risk of premature mortality is elevated in individuals with childhood-onset NI, particularly in epilepsy and lower in ID, with a need for more studies for vision, hearing, and motor impairments. Survival in NI could be improved through interventions targeting modifiable risk factors and underlying causes.

背景：神经系统损害（Neurological impairment, NI）与残疾均与预期寿命缩短相关，但儿童期早死的风险与严重程度在不同研究场景中差异显著。本研究开展了一项系统综述，旨在估算全球范围内儿童起病NI患者的早死严重程度，并总结已知的死亡危险因素与死因。
方法：我们检索了多个数据库自建库至2020年10月31日的已发表研究。纳入所有评估儿童起病癫痫、智力障碍（intellectual disability, ID）、以及听觉、视觉与运动功能缺损人群总体死亡风险的队列研究。针对各损害维度，我们对标准化死亡率比（standardized mortality ratio, SMR）等死亡比较指标、危险因素与死因开展了定量综合分析。本综述已在PROSPERO数据库注册（注册编号：CRD42019119239）。
结果：本次检索共识别出2159项研究，最终纳入24项研究进行综合分析。其中22项（91.7%）研究来自高收入国家（high-income countries, HICs）。癫痫患者的中位SMR高于ID患者（7.1，范围3.1~22.4 vs 2.9，范围2.0~11.6）。在癫痫患者中，年轻群体、合并神经系统共病者、全面性发作（单变量分析层面）、难治性癫痫患者、确诊后短期内患者以及结构性/代谢性病因类型的患者死亡率最高，但性别未显示出差异。绝大多数死亡（87.5%）与癫痫无关。在ID患者中，年轻群体死亡率最高，且女性较普通人群死亡风险更高。早死的重要危险因素包括重度至极重度功能损害、先天性疾病（如唐氏综合征）、合并神经系统共病以及不良妊娠与围生期事件。ID患者的主要死因为呼吸道感染与神经系统共病。目前针对视觉、听觉与运动功能损害的死亡率研究较为少见。
总结：儿童起病NI患者的早死风险升高，其中癫痫患者风险尤为显著，ID患者风险相对较低；针对视觉、听觉与运动功能损害的相关研究仍有待加强。通过针对可干预危险因素与潜在病因开展干预，可改善NI患者的生存状况。