Supplementary Material for: Pediatric Acute Ischemic Stroke by Age-Group: A Systematic Review and Meta-Analysis of Published Studies and Hospitalization Records

Background: Although stroke is rare among the pediatric population, it is nevertheless associated with serious or life-threatening consequences. The etiologic factors of acute ischemic stroke (AIS) are likely to vary over the course of childhood development. The incidence rates of AIS, not previously systematically examined by pediatric age subgroup, could guide studies of its etiology. Objective: The aim of this study is to evaluate the incidence rate of AIS by age-group in the pediatric population (aged 0–17/18 years) and identify any common trends or sources of variability across different countries. Methods: Rates of pediatric AIS were collated from a systematic literature review of published studies globally (1983–2020) and hospitalization records from Europe and the USA (2015–2018). Records that were included in the analysis reported the code or description used for AIS diagnosis and age-specific data for children aged 0–17/18 years. AIS incidence rates were summarized by age-group, data source, country, and geographic region. A meta-analysis was conducted to assess the heterogeneity of AIS rates in neonates. Results: The pooled AIS incidence rate was 5.6 per 100,000 children across all records. When only records reporting the AIS incidence rates for children across the full age range (0–17/18 years) were analyzed, the pooled AIS incidence rate was 4.6 per 100,000 children and ranged from 7.0 per 100,000 (Germany) to 1.3 per 100,000 (Denmark). The highest pooled rates were observed in the 0–28-day age-group (24.6 per 100,000 live births), declining to the lowest rates in the 5–9-year age-group, and rising again in the 10–17/18-year age-group. AIS rates were the most heterogeneous in the 0–28-day age-group and across European countries. Significantly higher AIS rates in neonates were observed from hospital databases (35.9 per 100,000) than in the literature (19.4 per 100,000). AIS rates may be underestimated as pediatric AIS events are rare and challenging to diagnose, and limited age-specific data are available. Conclusions: Incidence rates of pediatric AIS by age-groups followed a consistent overall pattern of a reverse J-shaped curve, with the highest rates in neonates, across predominantly European and North American countries. Further research is warranted to examine if this pattern is observed in other geographic regions and to identify AIS risk factors specific to different phases of childhood development.背景：尽管卒中在儿科人群中较为罕见，但仍可引发严重乃至危及生命的不良结局。急性缺血性卒中（acute ischemic stroke, AIS）的病因学因素很可能随儿童发育进程发生变化。此前尚未有针对儿科年龄亚组系统分析AIS发病率的研究，而相关数据可为其病因学研究提供指导。 目的：本研究旨在评估0~17/18岁儿科人群中不同年龄组的AIS发病率，并明确不同国家间AIS发病率的共同趋势及差异来源。 方法：本研究的数据来源于两项渠道：一是1983年至2020年全球已发表研究的系统文献综述，二是2015年至2018年欧洲与美国的住院病历记录。纳入分析的研究均报告了AIS诊断所用的编码或描述信息，以及0~17/18岁儿童的年龄分层数据。本研究按年龄组、数据来源、国家及地理区域对AIS发病率进行汇总分析，并开展荟萃分析以评估新生儿AIS发病率的异质性。 结果：纳入所有记录的合并AIS发病率为5.6/10万儿童。仅分析报告全年龄段（0~17/18岁）儿童AIS发病率的记录时，合并发病率为4.6/10万儿童，范围为1.3/10万（丹麦）至7.0/10万（德国）。0~28天年龄组的合并发病率最高（24.6/10万活产儿），随后在5~9岁年龄组降至最低，至10~17/18岁年龄组时再次升高。0~28天年龄组及欧洲各国的AIS发病率异质性最高。医院数据库中新生儿AIS发病率（35.9/10万）显著高于文献报道的19.4/10万。由于儿科AIS事件罕见且诊断难度大，且可获取的年龄分层数据有限，AIS发病率可能存在低估情况。 结论：在以欧洲和北美为主的国家中，儿科AIS按年龄组划分的发病率整体呈现一致的倒J形曲线模式，新生儿期发病率最高。未来有必要开展进一步研究，以明确该模式是否在其他地理区域同样存在，并识别儿童发育不同阶段特有的AIS危险因素。