Potential Biomarker Found for Sudden Infant Death Syndrome

The term Sudden Unexpected Death in Infancy (SUDI) covers both explained and unexplained deaths. The unexplained deaths are termed Sudden Infant Death Syndrome (SIDS). Despite intensive studies over the past decades, the mechanisms which lead to SIDS remain elusive.

It is currently believed that SIDS is not due to a single factor, but is multi-factorial in origin. Acetylcholine (ACh) is a major neurotransmitter of the autonomic nervous system and the principal neurotransmitter of the parasympathetic nervous system. It is hydrolyzed at cholinergic synapses by two enzymes, Acetylcholinesterase (AChE), and Butyrlycholinesterase (BChE) (also known as pseudocholinesterase).

Clinical Scientists at the Children's Hospital at Westmead (Westmead, Australia) analyzed 722 dried blood samples (DBS) including 67 DBS (58% male) from SUDI infants (26 SIDS and 41 Non-SIDS), and 655 date of birth- and gender-matched controls: SIDS cases, mean age-at death 15.7 (± 8·1) weeks, (4-35 weeks), 54% male and Non-SIDS cases, mean age at death 31.7 (± 30) weeks, (1-103 weeks), 64% male.

Total BChE for each sample was quantified using the DetectX Butyrylcholinesterase Fluorescent Activity Kit (Arbor Assays, Ann Arbor, MI, USA) and the signal was read at 510nm with excitation at 390nm. Total protein in each sample was quantified using the BCA (Bicinchoninic acid) Dual Range Protein Detection Kit (Arbor Assays). The specific activity of BChE (BChEsa) was calculated by dividing BChE activity (mU/mL) by the total protein content (µg/ml) giving BChEsa in mU/µg. Results were reported in U/mg.

The investigators reported that conditional logistic regression showed that in groups where cases were reported as “SIDS death” there was strong evidence that lower BChE specific activity (BChEsa) was associated with death (OR=0.73 per U/mg, 95% CI 0.60-0.89), whereas in groups with a “Non-SIDS death” as the case there was no evidence of a linear association between BChEsa and death (OR=1.001 per U/mg, 95% CI 0.89-1.13).

The authors concluded that BChEsa, measured in dried blood spots taken 2-3 days after birth, was lower in babies who subsequently died of SIDS compared to surviving controls and other Non-SIDS deaths. They concluded that a previously unidentified cholinergic deficit, identifiable by abnormal-BChEsa, is present at birth in SIDS babies and represents a measurable, specific vulnerability prior to their death. The study was published on May 06, 2022 in the journal EBioMedicine.

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