In a world-first breakthrough, researchers in Australia have identified a biomarker that could help detect babies more at risk of sudden infant death syndrome (SIDS) while they are alive.
SIDS is the unexplained death of an apparently healthy infant less than one year of age during a period of sleep. And while the incidence of SIDS has been more than halved in recent years due to research and recommendations on sleeping position, smoking while pregnant and other risk factors, the rate of SIDS remains high, contributing to almost 50 percent of all post-neonatal deaths in Western countries.
In fact, Carmel Harrington, study lead and Honorary Research Fellow at The Children's Hospital at Westmead, lost her own son to SIDS 29 years ago. Since then, she has dedicated her career to finding answers for the condition, supporting much of her research through her crowd-funding campaign named after her deceased son Damien.
Harrington’s new paper, published in The Lancet’s eBioMedicine, is a huge step forward in that mission, one that could change the lives of many going forward.
Harrington and team analyzed 722 dried blood spots taken at birth as part of the standard Newborn Screening Program, including 67 from sudden unexpected death in infants (SUDI)—26 SIDS cases and 41 non-SIDS. All dried blood spots were analyzed for Butyrylcholinesterase biomarker activity. Butyrylcholinesterase (BChE) is an enzyme of the cholinergic system, a major branch of the autonomic system. Once analyzed, the research team compared the results of the 67 SUDI cases with 10 date of birth- and gender-matched controls.
According to the results, the researchers found that BChE levels were significantly lower in babies who subsequently died of SIDS compared with both living controls and other infant deaths with known causes. There was no evidence of an association between BChE levels—or gender—and age at death. Additionally, since decreased BChE activity was noted at birth, the researchers believe the vulnerability likely originates during the gestational period.
Numerous previous studies have described an arousal deficit in infants who eventually succumb to SIDS, and BChE is known to play a major role in the brain’s arousal pathway. There are two distinct arousal types defined in infants: sub-cortical activation and full cortical arousal. Any impairment of these protective responses could render an infant vulnerable to respiratory and cardiovascular uncertainties that their little bodies cannot overcome.
Additionally, previous literature has suggested that BChE may be involved in maintaining acetylcholine (ACh) levels in the arousal systems of the central nervous system.
“It may be that a decrease in BChEsa implies a decrease in available ACh and thus a resultant impaired arousal response to a given environmental challenge, whether it be infection, apnoea or CO2 rebreathing as a result of prone sleeping,” the researchers hypothesize in their paper. “It will be important to identify whether the decreased BChEsa we observed in the peripheral blood of our SIDS cases is also evident in the brain because of the possible role BChE plays in maintaining ACh levels.”
Overall, the research findings identify, for the first time, a measurable vulnerability of infants at risk of SIDS and provide a specific target for future research into interventions prior to death. The researchers say the next step is to begin looking at introducing the BChE biomarker into newborn screening and develop specific interventions to address the enzyme deficiency. They expect this research to take about five years to complete.
“This discovery changes the narrative around SIDS and is the start of a very exciting journey ahead,” said Harrington. “We are going to be able to work with babies while they are living and make sure they keep living. The discovery [also] finally gives answers to parents who have lost their children so tragically. These families can now live with the knowledge that this was not their fault.”