Early Newborn Metabolic Patterning and Sudden Infant Death Syndrome.

IF 24.7 1区 医学 Q1 PEDIATRICS JAMA Pediatrics Pub Date : 2024-11-01 DOI:10.1001/jamapediatrics.2024.3033
Scott P Oltman, Elizabeth E Rogers, Rebecca J Baer, Ribka Amsalu, Gretchen Bandoli, Christina D Chambers, Hyunkeun Cho, John M Dagle, Kayla L Karvonen, Stephen F Kingsmore, Safyer McKenzie-Sampson, Allison Momany, Eric Ontiveros, Liana D Protopsaltis, Larry Rand, Erica Sanford Kobayashi, Martina A Steurer, Kelli K Ryckman, Laura L Jelliffe-Pawlowski
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Abstract

Importance: Sudden 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.

Objective: To evaluate and model the association between routinely measured newborn metabolic markers and SIDS in combination with established risk factors for SIDS.

Design, setting, and participants: This 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.

Exposures: Metabolites measured by NBS and established risk factors for SIDS.

Main outcomes and measures: The primary outcome was SIDS. Logistic regression was used to evaluate the association between metabolic markers combined with known risk factors and SIDS.

Results: Of 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 relevance: Results 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.

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新生儿早期代谢模式与婴儿猝死综合症
重要性:婴儿猝死综合症(SIDS)是美国婴儿死亡的主要原因。以前的研究表明,先天性代谢错误可能是导致婴儿猝死综合症的原因之一,但婴儿猝死综合症与代谢生物标志物之间的关系仍不清楚:评估常规测量的新生儿代谢标志物与婴儿猝死综合症既定风险因素之间的关系,并建立相关模型:这是一项病例对照研究,采用加州全州卫生规划与发展办公室和加州公共卫生部提供的数据进行回顾性队列嵌套。研究对象包括 2005 年至 2011 年期间在加利福尼亚州出生的婴儿,这些婴儿在常规新生儿筛查 (NBS) 中获得了完整的代谢数据。婴儿猝死症病例与对照组按胎龄和出生体重 z 评分 1:4 的比例进行匹配。配对数据分为训练子集(2/3)和测试子集(1/3)。数据分析时间为 2005 年 1 月至 2011 年 12 月:主要结果和测量指标:主要结果和测量指标:主要结果是婴儿猝死综合症。采用逻辑回归法评估代谢标志物与已知风险因素和婴儿猝死综合症之间的关系:在 2 276 578 名符合条件的婴儿中,发现了 354 例婴儿猝死综合症病例(0.016%)(平均[标码]胎龄为 38.3 [2.3] 周;220 名男性[62.1%])和 1416 例对照病例(平均[标码]胎龄为 38.3 [2.3] 周;723 名男性[51.1%])。在多变量分析中,14 种 NBS 代谢物在单变量分析中与婴儿猝死综合症显著相关:17-羟基孕酮、丙氨酸、蛋氨酸、脯氨酸、酪氨酸、缬氨酸、游离肉碱、乙酰-L-肉碱、丙二酰肉碱、戊二酰肉碱、月桂酰-L-肉碱、十二碳酰肉碱、3-羟基十四碳酰肉碱和亚油酰肉碱。包括 8 种代谢物的 14 标记婴儿猝死综合症模型在训练集中的接收操作特征曲线下面积为 0.75(95% CI,0.72-0.79),在测试集中的接收操作特征曲线下面积为 0.70(95% CI,0.65-0.76)。在模型预测概率大于 0.5 的 32 个测试集中,共有 20 个婴儿(62.5%)发生了婴儿猝死综合症。与模型预测概率小于 0.1 的婴儿相比,这些婴儿发生婴儿猝死综合症的几率是后者的 14.4 倍(95% CI,6.0-34.5):这项病例对照研究的结果表明,出生时代谢分析物异常与婴儿猝死综合症之间存在关联。这些研究结果表明,我们或许能够在婴儿出生后不久就识别出猝死症风险增加的婴儿,这将为进一步的机理研究和侧重于监测与预防的临床工作提供依据。
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来源期刊
JAMA Pediatrics
JAMA Pediatrics PEDIATRICS-
CiteScore
31.60
自引率
1.90%
发文量
357
期刊介绍: JAMA Pediatrics, the oldest continuously published pediatric journal in the US since 1911, is an international peer-reviewed publication and a part of the JAMA Network. Published weekly online and in 12 issues annually, it garners over 8.4 million article views and downloads yearly. All research articles become freely accessible online after 12 months without any author fees, and through the WHO's HINARI program, the online version is accessible to institutions in developing countries. With a focus on advancing the health of infants, children, and adolescents, JAMA Pediatrics serves as a platform for discussing crucial issues and policies in child and adolescent health care. Leveraging the latest technology, it ensures timely access to information for its readers worldwide.
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