ImportanceSudden infant death syndrome (SIDS) is a major cause of infant death in the US. Previous research suggests that inborn errors of metabolism may contribute to SIDS, yet the relationship between SIDS and biomarkers of metabolism remains unclear.ObjectiveTo evaluate and model the association between routinely measured newborn metabolic markers and SIDS in combination with established risk factors for SIDS.Design, Setting, and ParticipantsThis was a case-control study nested within a retrospective cohort using data from the California Office of Statewide Health Planning and Development and the California Department of Public Health. The study population included infants born in California between 2005 and 2011 with full metabolic data collected as part of routine newborn screening (NBS). SIDS cases were matched to controls at a ratio of 1:4 by gestational age and birth weight z score. Matched data were split into training (2/3) and testing (1/3) subsets. Data were analyzed from January 2005 to December 2011.ExposuresMetabolites measured by NBS and established risk factors for SIDS.Main Outcomes and MeasuresThe primary outcome was SIDS. Logistic regression was used to evaluate the association between metabolic markers combined with known risk factors and SIDS.ResultsOf 2 276 578 eligible infants, 354 SIDS (0.016%) cases (mean [SD] gestational age, 38.3 [2.3] weeks; 220 male [62.1%]) and 1416 controls (mean [SD] gestational age, 38.3 [2.3] weeks; 723 male [51.1%]) were identified. In multivariable analysis, 14 NBS metabolites were significantly associated with SIDS in a univariate analysis: 17-hydroxyprogesterone, alanine, methionine, proline, tyrosine, valine, free carnitine, acetyl-L-carnitine, malonyl carnitine, glutarylcarnitine, lauroyl-L-carnitine, dodecenoylcarnitine, 3-hydroxytetradecanoylcarnitine, and linoleoylcarnitine. The area under the receiver operating characteristic curve for a 14-marker SIDS model, which included 8 metabolites, was 0.75 (95% CI, 0.72-0.79) in the training set and was 0.70 (95% CI, 0.65-0.76) in the test set. Of 32 infants in the test set with model-predicted probability greater than 0.5, a total of 20 (62.5%) had SIDS. These infants had 14.4 times the odds (95% CI, 6.0-34.5) of having SIDS compared with those with a model-predicted probability less than 0.1.Conclusions and RelevanceResults from this case-control study showed an association between aberrant metabolic analytes at birth and SIDS. These findings suggest that we may be able to identify infants at increased risk for SIDS soon after birth, which could inform further mechanistic research and clinical efforts focused on monitoring and prevention.

中文翻译：

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早期新生儿代谢模式和婴儿猝死综合征


重要性婴儿猝死综合症 （SIDS） 是美国婴儿死亡的主要原因。先前的研究表明，先天性代谢缺陷可能导致 SIDS，但 SIDS 与代谢生物标志物之间的关系仍不清楚。目的评估和建模常规测量的新生儿代谢标志物与 SIDS 之间的关联，并结合已确定的 SIDS.Design、环境和参与者风险因素这是一项病例对照研究，使用来自加州全州卫生规划与发展办公室和加州公共卫生部的数据嵌套在回顾性队列中。研究人群包括 2005 年至 2011 年间在加利福尼亚出生的婴儿，作为常规新生儿筛查 （NBS） 的一部分收集了完整的代谢数据。通过胎龄和出生体重 z 评分以 1：4 的比例将 SIDS 病例与对照组相匹配。匹配数据分为训练 （2/3） 和测试 （1/3） 子集。分析了 2005 年 1 月至 2011 年 12 月的数据。主要结局和测量主要结局是 SIDS。采用 Logistic 回归评估代谢标志物结合已知危险因素与 SIDS 之间的相关性。结果在 2 276 578 名符合条件的婴儿中，确定了 354 例 SIDS （0.016%） 病例 （平均 [SD] 胎龄，38.3 [2.3] 周;220 名男性 [62.1%]）和 1416 名对照 （平均 [SD] 胎龄，38.3 [2.3] 周;723 名男性 [51.1%]）。 在多变量分析中，在单变量分析中，14 种 NBS 代谢物与 SIDS 显著相关：17-羟孕酮、丙氨酸、蛋氨酸、脯氨酸、酪氨酸、缬氨酸、游离肉碱、乙酰左旋肉碱、丙二酰肉碱、戊二酰肉碱、月桂酰-L-肉碱、十二烯酰肉碱、3-羟基十四烷酰肉碱和亚油酰肉碱。包括 8 种代谢物的 14 个标志物 SIDS 模型的受试者工作特征曲线下面积在训练集中为 0.75 （95% CI，0.72-0.79），在测试集中为 0.70 （95% CI，0.65-0.76）。在测试集中模型预测概率大于 0.5 的 32 名婴儿中，共有 20 名 （62.5%） 患有 SIDS。与模型预测概率小于 0.1 的婴儿相比，这些婴儿患 SIDS 的几率 （95% CI， 6.0-34.5） 是 14.4 倍。这些发现表明，我们可能能够在出生后不久识别出 SIDS 风险增加的婴儿，这可以为进一步的机制研究和专注于监测和预防的临床工作提供信息。