A biochemical marker in the brain may be the key to unlocking the mysterious cause behind sudden infant death syndrome (SIDS).

For years, parents whose infants died unexpectedly felt intense guilt because they believed they could have prevented it. Parents were advised that taking certain precautions, such as placing babies on their backs, preventing them from overheating and keeping cribs free of clutter, could reduce the chances of their babies suffering from SIDS.

The Centers for Disease Control and Prevention said there are about 3,400 sudden unexpected infant deaths in the U.S. each year, with some of those deaths attributed to SIDS, some due to accidental suffocation and others with unknown causes.

According to the Mayo Clinic, SIDS typically happens to babies less than a year old.

Some physical factors long thought to be associated with the condition include brain defects, low birth weight and respiratory infections, with other environmental factors thought to contribute, such as overheating or sleeping position.

But a study from Australia’s Sydney University found an enzyme called butyrylcholinesterase (BChE) was significantly lower in babies who died from SIDS when compared to living infants and those who died from other causes. The enzyme plays a key role in waking babies from sleep. Low levels can reduce their ability to awaken and alert parents to a problem.

“Babies have a very powerful mechanism to let us know when they are not happy,” lead researcher Dr. Carmel Harrington told The Sydney Children’s Hospitals 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.”

Harrington, who holds a PhD in sleep medicine, lost her 2-year-old son Damien to SIDS in 1991. She has spent decades trying to pinpoint the cause and believes BChE is the key.

“Does this shine light on what we can screen for in terms of looking for reasons why babies are vulnerable and what we can do in terms of treatment for that?” asked Riley Hospital for Children Pediatrician Dr. Melissa Klitzman. “We know it could be something with their heart or their breathing but is there something going on in terms of their nervous system that puts these babies really at increased risk for sudden infant death syndrome?”

Dr. Kiltzman said it’s still good advice to place sleeping infants on their backs and declutter their cribs to minimize the risk of suffocation, though the enzyme deficiency explanation may ease the guilt some parents feel after a child’s seemingly unexplainable death.

“It will offer some solace in terms of opening up a window for further research, she said.”

The study involved analyzing dried blood samples taken from newborns who died from SIDS and other known causes. When those samples were compared, the babies who died from SIDS had significantly lower activity from BChE than non-SIDS babies.

The discovery could lead to a test to identify at-risk newborns and find ways to address the enzyme deficiency.

Most important to Harrington, though, is the message to parents that they didn’t fail their child.

“These families can now live with the knowledge that this was not their fault,” she said.

Russ McQuaid contributed to this article.