University of Montreal Hospital Research Centre, Montreal, Quebec, Canada; Institut national de santé publique du Québec, Montreal, Quebec, Canada; Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada; School of Public Health, University of Montreal, Montreal, Quebec, Canada.
Maternal and Infant Health Surveillance Section, Public Health Agency of Canada, Ottawa, Ontario, Canada.
J Pediatr. 2023 Jan;252:16-21.e2. doi: 10.1016/j.jpeds.2022.08.053. Epub 2022 Sep 6.
To determine the long-term risk of mortality among children with inborn errors of metabolism.
We conducted a retrospective cohort study of 1750 children with inborn errors of metabolism (excluding mitochondrial disorders) and 1 036 668 children without errors of metabolism who were born in Quebec, Canada, between 2006 and 2019. Main outcome measures included all-cause and cause-specific mortality between birth and 14 years of age. We used adjusted survival regression models to estimate HRs and 95% CIs for the association between inborn errors of metabolism and mortality over time.
Mortality rates were greater for children with errors of metabolism than for unaffected children (69.1 vs 3.2 deaths per 10 000 person-years). During 7 702 179 person-years of follow-up, inborn errors of metabolism were associated with 21.2 times the risk of mortality compared with no error of metabolism (95% CI 17.23-26.11). Disorders of mineral metabolism were associated with greater mortality the first 28 days of life (HR 60.62, 95% CI 10.04-365.98), and disorders of sphingolipid metabolism were associated with greater mortality by 1 year (HR 284.73, 95% CI 139.20-582.44) and 14 years (HR 1066.00, 95% CI 298.91-3801.63). Errors of metabolism were disproportionately associated with death from hepatic/digestive (HR 208.21, 95% CI 90.28-480.22), respiratory (HR 116.57, 95% CI 71.06-191.23), and infectious causes (HR 119.83, 95% CI 40.56-354.04).
Children with errors of metabolism have a considerably elevated risk of mortality before 14 years, including death from hepatic/digestive, respiratory, and infectious causes. Targeting these causes of death may help improve long-term survival.
确定先天性代谢错误患儿的长期死亡率。
我们对 1750 名患有先天性代谢错误（不包括线粒体疾病）的儿童和 1036680 名无代谢错误的儿童进行了回顾性队列研究，这些儿童均于 2006 年至 2019 年在加拿大魁北克出生。主要结局指标包括出生至 14 岁期间的全因死亡率和死因特异性死亡率。我们使用调整后的生存回归模型来估计随时间推移，先天性代谢错误与死亡率之间的关联的 HR 和 95%CI。
患有代谢错误的儿童死亡率高于未受影响的儿童（每 10000 人年 69.1 例死亡 vs 3.2 例死亡）。在 7702179 人年的随访期间，与无代谢错误相比，先天性代谢错误使死亡率增加了 21.2 倍（95%CI 17.23-26.11）。矿物质代谢紊乱与出生后 28 天内的死亡率升高相关（HR 60.62，95%CI 10.04-365.98），鞘脂代谢紊乱与 1 岁（HR 284.73，95%CI 139.20-582.44）和 14 岁（HR 1066.00，95%CI 298.91-3801.63）时的死亡率升高相关。代谢错误与肝脏/消化（HR 208.21，95%CI 90.28-480.22）、呼吸（HR 116.57，95%CI 71.06-191.23）和感染性病因（HR 119.83，95%CI 40.56-354.04）导致的死亡比例不成比例。
14 岁之前，患有代谢错误的儿童死亡率显著升高，包括肝脏/消化、呼吸和感染性病因导致的死亡。针对这些死因可能有助于提高长期生存率。
