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Background

The relationship between sudden infant death syndrome (SIDS) and biomarkers of metabolism remain unclear, according to new research published in JAMA Pediatrics. Investigators sought to evaluate routinely measured newborn metabolic markers and SIDS, in combination with established risk factors for the syndrome.

According to the investigative team, led by Scott P. Oltman, MS, of the California Preterm Birth Initiative at the University of California San Francisco, SIDS is defined as a sudden and unexpected death of an infant younger than 1 year of age with a completed cause of death investigation that rules out suffocation or asphyxiation.

As the primary cause of sudden unexplained infant death in the United States, SIDS accounted for 41% of all cases as a rate of 38.4 per 100,000 live births in 2020.

Study details and results

Nested within a retrospective cohort study, the case-control study used data from the California Office of Statewide Health Planning and Development and the California Department of Public Health. Included were California-born infants from 2005 to 2011 with full metabolic data collected as part of routine newborn screening (NBS).

"Our primary outcome was SIDS as the primary cause of death listed on the death certificate," stated the study authors.(ICD-10 code = R95). "Explanatory variables evaluated included infant and maternal characteristics from birth certificate and hospital discharge records as well as routine metabolites and clinical factors measured as part of the NBS."

After exclusions, the study included 354 infants with a mean gestational age of 38.3 weeks. Of these infants, 37.9% were female. Each of the 354 infants were matched to 4 surviving controls by gestational age and birth weight z score. The total controls number was 1416 with a mean gestational age of 38.3 weeks, of which 48.9% were female.

"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 study authors reported.

For a 14-marker SIDS model, which included 8 metabolites, the area under the receiver operating characteristic curve 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 the 32 infants in the test set with a model-predicted probability greater than 0.5, 20 infants had SIDS (62.5%). Results demonstrated that these infants had 14.4-times the odds of having SIDS (95% CI, 6.0-34.5) compared to those with a model-predicted probability less than 0.1.

"Many well-established risk factors for SIDS were important variables in our predictive models," stated the authors. "Young maternal age (<18 years), male sex, and less adequate prenatal care were all associated with increased risk of having an infant with SIDS in our model. Many previous studies have found all 3 factors to be associated with increased risk."

Conclusion

Based on the model constructed in the study, which revealed that infants who experienced SIDS had distinct metabolic patterns at birth compared to those who did not, findings of this case-control study suggested that, "metabolic profiles at birth may have utility for individualized, targeted counseling aimed at identifying infants with an increased vulnerability to SIDS," the investigative team wrote.

"Further, these patterns point to novel inroads for scientists and clinicians to further investigate mechanisms of aberrant metabolites in SIDS in order to develop targeted therapeutics," they concluded.

Reference:

Oltman SP, Rogers EE, Baer RJ, et al. Early Newborn Metabolic Patterning and Sudden Infant Death Syndrome. JAMA Pediatr. Published online September 09, 2024. doi:10.1001/jamapediatrics.2024.3033