For decades, scientists have struggled to explain why some infants die from sudden infant death syndrome (SIDS) and others seem less susceptible. While there are many factors that play a role in the etiology of SIDS, both environmental and developmental, 2022 research published in The Lancet’s eBioMedicine highlights a potential biomarker that may provide a clue to an underlying cause.

What is SIDS?

SIDS is the unexplained death of a seemingly healthy infant under 1 year of age, typically occurring while the child is sleeping. Education through safe sleep campaigns has reduced the number of SIDS deaths in recent years, though the syndrome is still responsible for about 3,400 infant deaths every year, according to the Centers for Disease Control and Prevention. 

SIDS is an incredibly heartbreaking phenomenon without a clear cause, and can leave families of SIDS victims wracked with guilt and confusion. 

What causes vulnerability to SIDS?

A team of researchers from The Children’s Hospital Westmead in Sydney, led by Dr. Carmel Harrington, a mother who had lost her infant son to SIDS 29 years ago, set out to assess if levels of a specific biomarker, the enzyme butyrylcholinesterase (BChE), differed in infants who are more susceptible to SIDS. 

SIDS is a complex syndrome due to multiple factors, some of which may be related to environment. But it has been suspected that SIDS may be associated with a defect or an underdevelopment in the part of a baby’s brain controlling breathing and arousal from sleep. If an infant stops breathing while sleeping, the brain should function to startle the baby awake—but in some cases, the brain doesn’t function properly to sufficiently wake the child, leading to the infant’s death.

Related: Breastfeeding cuts SIDS risk in half

The enzyme BChE is thought to play a role in the brain’s arousal pathways, and may provide a clue to the functioning of the infant’s autonomic system—offering insight as to why some babies may not wake up if they have difficulty breathing while sleeping.

SIDS is thought to occur when three factors occur simultaneously: a vulnerable infant, a critical developmental period for homeostatic control, and an external stressor (such as soft bedding), note the study authors, who set out to determine what might make an infant vulnerable. 

Related: Does bed-sharing increase the risk of SIDS?

A measurable SIDS biomarker may provide a clue

By analyzing the dried blood spots from heel pricks taken after birth from 722 infants, study authors were able to compare the dried blood samples of 67 babies who died from SIDS with the blood samples of surviving babies who had the same birth date and gender. 

“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,” write the researchers. 

The findings show that abnormal levels of BChE may hint at a defect and represent “a measurable, specific vulnerability” of a SIDS infant. Though environmental factors like not using safe sleep practices and secondhand smoke exposure and smoking during pregnancy can also be major risk factors for SIDS, as well as issues affecting cardiovascular development, this is the first study to pinpoint a measurable biomarker in infants who die from SIDS.

“Thus, the finding presents the possibility of identifying infants at future risk for SIDS and it provides a specific avenue for future research into interventions prior to death,” the authors note.

“Babies have a very powerful mechanism to let us know when they are not happy,” Harrington told The Sydney Children’s Hospital Network. “Usually, if a baby is confronted with a life-threatening situation, such as difficulty breathing during sleep because they are on their tummies, they will arouse and cry out. What this research shows is that some babies don’t have this same robust arousal response.”

More research is needed to confirm the findings in a study with a much larger sample size and controls for additional factors, but the results are promising. 

The authors hope that this will lead to the development of screening tests that can give parents more information about whether their child may be more susceptible to SIDS, and how to take extra precautions if so.

A version of this story was originally published on May 13, 2022. It has been updated.