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New research on sudden infant death syndrome (SIDS) – a devastating illness that has long been deemed a medical mystery – went viral recently, after a group of researchers in Australia claimed they uncovered a potential cause of the illness.

The study found that babies with lower levels of butyrylcholinesterase (BChE) activity, which plays a role in autonomic function, had greater odds of dying from SIDS, reported Carmel Harrington, PhD, of The Children's Hospital at Westmead in Sydney, and colleagues, writing in .

"This discovery has opened up the possibility for intervention and finally gives answers to parents who have lost their children so tragically," Harrington said in a press release. "These families can now live with the knowledge that this was not their fault."

The study, which was published in early May, made headlines for its "breakthrough" findings. In a , Harrington said, "I know that in 3 to 5 years' time, SIDS will be a thing of the past," adding that more funding is needed for future research.

Biological factors can likely predispose a baby to SIDS, which is further evidenced by this study. However, experts say these findings represent incremental progress, as opposed to a "breakthrough" set of findings that could change the game for SIDS prevention and detection.

Richard Goldstein, MD, a pediatric palliative care doctor at Boston Children's who has conducted SIDS research, said that because so little research is done in this area, studies like this are important. However, sensationalizing those findings is not beneficial for the field.

While "quite happy" to see research progress, he told 番茄社区, "They didn't have to go any farther than saying 'We're looking for a peripheral marker for arousal, here's some preliminary findings. Isn't that exciting?'"

New Findings

In the case-control study by Harrington and colleagues, the researchers aimed to determine levels of BChE activity in babies who died from SIDS. They measured BChE in dried blood spot samples taken routinely via a heel prick at birth, collecting samples over a 5-year period between 2016 and 2020.

Harrington's group measured BChE in a group of babies who died from SIDS as well as a group who died from other causes, and matched each case with 10 surviving infants who had the same birth date and were of the same gender.

The researchers matched 26 babies who died from SIDS and 41 who died from other causes to 655 control cases. Ultimately, they found that the cohort of babies who died from SIDS had lower levels of BChE than those who died of other causes (OR 0.73 per U/mg, 95% CI 0.60-0.89, P=0.0014).

But Goldstein noted the wide range in those levels in both SIDS and non-SIDS cases, with substantial overlap between the groups for BChE specific activity, saying future studies are needed to confirm that the levels of BChE are significantly lower in infants who die from SIDS.

Rachel Moon, MD, chair of the American Academy of Pediatrics' Task Force on SIDS, agreed.

"While the differences in blood levels of this enzyme were statistically different -- even if this is confirmed by larger, additional studies -- there is enough overlap in the blood levels between cases and controls that it could not be used as a blood test at this point with any reasonable predictive value," she said in a statement.

She added that the sample size of this study was too small and that these findings are not definitive.

A Medical Mystery

SIDS, which refers to the unexplained deaths of children under a year old, has long been a medical mystery that is devastating to families.

Harrington had a personal connection to this research, as her own son died from SIDS almost 30 years ago. A few years after her child's death, she watched a friend's baby succumb to it as well. Following these tragedies, Harrington, who was trained in biochemistry but working as a lawyer, left her law job to around the causes of SIDS.

While public health interventions to date have focused on sleep guidance, many researchers who study the condition believe that there are biological mechanisms involved.

In a recent perspective article in the authored by Goldstein and two others, the group wrote that "few experts would argue with the current focus on prevention, which is based on associations between infant-sleep practices and SIDS rates in multiple countries."

The Back to Sleep campaign, which was introduced in the U.S. in the 1990s, encouraged parents to place their babies on their backs to sleep to avoid accidental deaths. After the campaign started, SIDS rates were slashed in half. But since 1996, SIDS prevalence has remained relatively stagnant (currently 90.1 per 100,000 live births), Goldstein's group wrote, making the case for biological factors that contribute to the illness.

Other Hypotheses

Researchers in this field hypothesize that there is something biologically different about babies who die from SIDS, Goldstein said. Previous studies have identified chemicals in the brainstem that may disrupt a baby's arousal capability during sleep – a disruption that would keep them from waking or struggling if they couldn't breathe.

For example, babies with elevated levels of serotonin, which plays a key role in sleep, were found to have a higher risk of dying from SIDS, according to a that was co-authored by Goldstein.

That study analyzed 61 babies who died from SIDS, and found that one-third of those babies had elevated serotonin levels. These findings on elevated serotonin as a potential risk factor contradicted an earlier study that determined that lower serotonin levels could be a risk factor for SIDS.

Researchers are also studying gene variations that may make an infant vulnerable to SIDS. A recent study in the added further evidence that brain aquaporins, which regulate brain water and cerebrospinal fluid movement, may have a role in the predisposition to SIDS. Other studies (some of which ) have identified a wide array of genetic variations that could be linked to SIDS.

There is a huge need for research to provide answers for families affected by SIDS, who are left in the dark about the tragedy that takes the life of their children, Goldstein said. In addition to a history of criminalization against parents of babies who die from SIDS, the lack of information available for them is a "terrible situation," he added.

"The fact that we don't bring our best diagnostic resources to it and there's no accountability to answering parents is an astounding phenomenon in modern life," Goldstein said.

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