New clue to SIDS: Metabolic signatures identified

A group of researchers has discovered distinct metabolic signatures that may be linked to sudden infant death syndrome (SIDS), raising the possibility of developing biomarkers to aid prediction and diagnosis of the condition.

In a metabolomics research, 35 out of 828 metabolites isolated from postmortem serum samples showed a significant association with SIDS. The strongest associations were observed for ornithine (odds ratio [OR], 21.98; p=6.44×10^-7), 5-hydroxylysine (OR 19.49; p=6.78×10^-7), 1-stearoyl-2-linoleoyl-GPC (18:0/18:2) (OR, 16.80; p=3.4×10^-7), ribitol (OR, 8.19; p=4.2×10^-8), and arabitol/xylitol (OR, 7.70; p=9.6×10^-6). [EBioMedicine 2025:111:105484]

In addition to individual metabolite associations, Weighted Gene Co-expression Network Analysis (WGCNA) led to the identification of several metabolite clusters associated with SIDS. The strongest correlation was seen for two clusters enriched for metabolites in the tyrosine metabolism and lipid (sphingomyelins) pathways.

Tyrosine is an amino acid that the body uses to create hormones and neurotransmitters like dopamine and epinephrine, which are crucial for stress response, nerve communication, and hormone regulation. Problems with arousal, which tyrosine can influence, have been linked to SIDS. [Adv Pharmacol 2013;68:399-404; Trends Pharmacol Sci 2007;28:93-102; Early Hum Dev 2003;75:S147-S166]

Meanwhile, sphingomyelins are a type of sphingolipid, which is essential for brain development, and are a key component of myelin, the protective sheath around nerve fibres. Myelination issues have long been suspected to be a factor in SIDS. Sphingomyelins are also important for lung function as part of surfactant, a biomarker of ongoing interest in SIDS research. [J Neuropathol Exp Neurol 1991;50:29-48; Pediatr Pulmonol 2008;43:160-168; J Biol Chem 2014;289:10668-10679]

For the analyses, postmortem serum samples were obtained from 266 infants from the Chicago Infant Mortality Study (CIMS) and 34 infants from the NIH NeuroBioBank (NBB). Compared with non-SIDS controls, SIDS cases were younger (median age 81 vs 112 days; p<0.001) and had a greater prevalence of bed sharing (48 percent vs 32 percent).

Potential for prediction, diagnosis

“This research significantly contributes to our understanding of SIDS by employing a comprehensive metabolomic analysis, leveraging advanced liquid chromatography-mass spectrometry to analyse postmortem serum samples from infants diagnosed with SIDS and other causes of sudden death (non-SIDS),” said the researchers from the University of Virginia, Charlottesville, Virginia, US.

Metabolite biomarkers linked to SIDS are identified, and their roles in key biological pathways, including lipid and fatty acid metabolism, stress response, and oxidative stress, are clarified, they added.

“The findings from this study, combined with existing research, underscore the potential of metabolomics as a powerful tool in unravelling the complex aetiology of SIDS. By identifying specific metabolites and pathways, this research provides foundational knowledge to develop predictive biomarkers and preventive strategies,” the researchers noted.

They called for further validation studies to pave the way for clinical application.

“We are getting closer to explaining the pathways leading to a SIDS death,” commented senior researcher Dr Fern Hauck. “Our hope is that this research lays the groundwork to help identify, through simple blood tests, infants who are at higher risk for SIDS and to save these precious lives.”