medwireNews: Multiple metabolic markers that are routinely measured during newborn screening (NBS) programs are linked to sudden infant death syndrome (SIDS) and may be useful for identifying children at risk soon after they are born, US researchers have found.
In a study of more than 2 million infants, the researchers found that 14 metabolites measured during NBS were associated with SIDS. These included: one hormone – 17-hydroxyprogesterone; five amino acids – alanine, methionine, proline, tyrosine, and valine; and eight acylcarnitines – free carnitine, acetyl-L-carnitine, malonyl carnitine (C-3DC), glutarylcarnitine (C-5DC), lauroyl-L-carnitine, dodecenoylcarnitine (C-12:1), 3-hydroxytetradecanoylcarnitine (C-14OH), and linoleoylcarnitine (C-18:2).
And, when they combined eight of these metabolites with demographic and clinical factors that were already known to be associated with SIDS, such as male sex, prematurity, and inadequate prenatal care, for example, the researchers were able to build a statistical model that predicted the likelihood of SIDS occurring.
“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,” Scott Oltman (University of California San Francisco School of Medicine, USA) and collaborators explain in JAMA Pediatrics.
The study population was formed from a cohort of 2,276,578 infants born between 2005 and 2011 who had complete metabolic data collected during NBS. Of these infants, 354 (0.016%) died as a result of SIDS, which the researchers say is defined as “a sudden and unexpected death of an infant younger than 1 year with a complete cause of death investigation that rules out suffocation or asphyxiation.”
Each of the SIDS cases were matched to four newborns of the same gestational age (mean 38.2 weeks) and birth weight Z score, giving a control cohort of 1416 newborns. In all, 62% of the SIDS cases and 51% of the matched control participants were male.
The final model included the following 14 variables: total parenteral nutrition administration and age at blood spot collection; infant sex; adequacy of prenatal care; race and ethnicity; maternal age; 17-hydroxyprogesterone; alanine; glycine; free carnitine; propionyl-L-carnitine (C-3); C-5DC; C-12:1; and C-14OH.
The researchers explain that the participants were divided into two groups; two thirds formed a cohort used to train the predictive model and the remainder formed a test cohort. The area under the receiver operating characteristic curve was 0.75 and 0.70 for the training and test cohorts, respectively.
Using the model, the investigators found that of 32 newborns in the test cohort with a predicted probability of greater than 0.5, 62.5% had SIDS. These infants were a significant 14.4 times more likely to have SIDS than those with a model-predicted probability less than 0.1. Oltman and team also report that 97.5% of infants predicted to be negative for SIDS at this cut point were true negatives.
“The most noteworthy metabolic pattern revealed by our study was the significance of acylcarnitines to identification of the likelihood of SIDS,” they observe, where elevated levels of free carnitine and C-14OH were associated with a higher risk for SIDS, whereas increased levels of C-3, C-5DC, and C-12:1 were linked to a lower risk.
The researchers acknowledge that while further validation and investigation is needed, “the present data provide possible actionable inroads for future mechanistic as well as basic science, clinical, and epidemiologic research.”
They conclude that these “novel inroads” will allow “scientists and clinicians to further investigate mechanisms of aberrant metabolites in SIDS in order to develop targeted therapeutics.”
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