Study points to brain abnormality that may explain sudden infant death syndrome

A new study using radioactive psychedelics suggests that infants who die of SIDS have abnormal serotonin receptors

By Nicole Karlis

Senior Writer

Published May 25, 2023 1:30PM (EDT)

Upset mother and empty crib (Photo illustration by Salon/Getty Images)
Upset mother and empty crib (Photo illustration by Salon/Getty Images)

It's a new parent's worst nightmare: sudden infant death syndrome (SIDS), a mysterious, fatal affliction in newborns with an unknown cause. Last year, a study published in the Lancet journal eBioMedicine offered compelling evidence that a cholinergic enzyme in living infants could be a biomarker, and indicate a newborn's risk of SIDS.

Despite three decades of public health efforts, SIDS remains the leading cause of death for infants in the U.S. An estimated 1,389 babies died from SIDS in 2020. At the time when the study was published, parents on social media understandably expressed a collective sigh of relief and jubilation. Some went as far to say "they found the cure for SIDS." As The Scientist reported after the buzz faded, the report was in some ways taken out of context. One year later, a cure has yet to materialize.

But hope isn't lost. This week, another piece has been added to the global search for a cause, and eventual cure or treatment for the syndrome. A separate group of scientists published a paper on May 25 in the Journal of Neuropathology & Experimental Neurology adding to other evidence that SIDS could be the cause of abnormalities in the serotonergic system, which relates to the neurotransmitter serotonin. It is implicated in a wide range of physiological and psychological processes, including mood, sleep and circadian rhythms.

In the study, the researchers collected brain tissue from the San Diego Medical Examiner's Office of infants who died from SIDS between 2004 and 2011. Through examining their brain stem tissue, they found that the serotonin 2AC receptor was altered, which indicates irregularities in this system could make these infants vulnerable to death under certain conditions.

To discover this, the researchers used a radioactive psychedelic compound called 125I-DOI. The drug DOI binds readily to serotonin receptors, including 2AC, and is commonly used in serotonin research. When humans take it, it's similar to a trippy kind of amphetamine. But in this study, the researchers employed a version of DOI tagged with an iodine radioisotope, which makes it radioactive (and therefore unsafe for human consumption) but allowed researchers to monitor its interactions with serotonin receptors. They found that in babies that died from SIDS, this radioactive psychedelic had a different behavior compared to controls.

In an interview with Salon, the paper's lead researcher Robin Haynes, Principal Associate in Pathology at Boston Children's Hospital, explained that as a neurotransmitter, serotonin in the lower brainstem is also critical for breathing and autonomic function. Haynes provided an example of how one of the major functions of serotonin is the "live protective reflexes."

"The bottom line is that SIDS babies do have abnormalities"

"Let's say an infant is lying face down in a pillow in the prone position. They start rebreathing air, and so their oxygen levels become low, and there are protective processes that babies have that will arouse them," Haynes said. "They go through a process called autoresuscitation, which kickstarts breathing. It leads to a gasp and that kickstarts breathing and those are normal processes and serotonin is important for these processes."

What Haynes and her colleagues found is that the 2AC receptor — which previous animal studies had shown is an important receptor in the autoresuscitation process — were at abnormal levels. Haynes said that the serotonin receptors interplay with the acetylcholine system, which is what the researchers focused on in the eBioMedicine study in 2022. Acetylcholine is a neurotransmitter involved in many functions, including muscle movement, and heart rate. However, how serotonin and acetylcholine are connected to SIDS remains unclear.

"I think the bottom line is that SIDS babies do have abnormalities. We always talk about SIDS being heterogeneous in nature, meaning that there are different pathologies that contribute," Haynes said. "So neurotransmitters are one potential pathology, serotonin being one of them, that we're focusing just on, genetics is another aspect."

Haynes said she thinks of the search for the cause of SIDS as a piece of pie. "Hopefully we can identify more and more of these pieces of the pie to get the full picture of the heterogeneous nature of SIDS," she said.

Meanwhile, Haynes and her colleagues advise that safe sleep practices — such as placing an infant on their back to sleep, in a crib without pillows, blankets or loose clothing — should be implemented to protect babies from SIDS. As previously mentioned, over the last 30 years the American Academy of Pediatrics (AAP) has said that infants sleeping on their backs is the safest way for them to sleep. Since the start of the 1994 Back-to-Sleep campaign, the rate of SIDS has declined more than 50 percent. But it's also plateaued.

With only a few short weeks or months for new mothers to figure out infant sleep before any sort of parental leave expires, an unregulated industry of infant sleep experts has emerged selling false promises of improving infant sleep.

"Everyone's taught, put them on their back, breastfeed, don't smoke cigarettes, keep them in your room, things like that, which have all been shown to be beneficial, and yet, over the last 22 years, there's been no progress in reducing the deaths," Dr. Harvey Karp, pediatrician and Founder & CEO of Happiest Baby, told Salon in an interview in January. The CDC estimates that there are 3,500 sleep-related deaths among babies each year, including SIDS.

"3,500 babies every year, which is just, a rough comparison, that's the number of innocent Americans who died in 9/11, which was a national catastrophe. And it's happening every single year," Karp said. In April, the Snoo, a rocking bassinet that keeps babies on their backs which Karp created, received approval from the Food and Drug Administration (FDA) as a medical device, the first step to getting it covered by insurance.

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"The big deal here is that this is the first time the FDA says Snoo has been proven to be safe and effective for keeping babies on the back," Karp told Salon. "Now we have a way of doing that."

However, without a Snoo, many sleep-deprived parents turn to co-sleeping with their babies when they're extremely sleep deprived, as Salon previously reported. With only a few short weeks or months for new mothers to figure out infant sleep before any sort of parental leave expires, an unregulated industry of infant sleep experts has emerged selling false promises of improving infant sleep. When that doesn't happen, it can lead to an opportunity for parents to participate in unsafe sleep practices.  

Haynes said that the fact that SIDS cases have leveled off despite an increase in infants sleeping on their backs tells researchers that there is more to learn about the cause of SIDS.

"The more that we learn, the more we can piece together and ask the right questions. But in terms of safe sleep, where we are now is that SIDS infants have a biological abnormality that makes them vulnerable to death whenever they're in an unsafe sleep position," Haynes said. "Because we have no way of identifying as such, parents always have to follow safe sleep practices. It's so important."

Haynes added that while the biological components are out of the parents' control, the sleeping environment is in their control.

"I think we all recognize how difficult it is to be a new parent," Haynes said. "What is in the parent control is how you bed share and how you choose to do it. I am not an expert on the bed sharing aspect of it, but epidemiological evidence shows alcohol consumption, smoking — those can increase the risk."

While this research is compelling, the study authors note that abnormalities in other parts of the brain unrelated to serotonin have also been implicated in SIDS, which emphasizes the need for further research. "At this point, however, the most robust and reproducible findings in SIDS have been in components of the [serotonon] system," they write, adding recommendations to use other radioactive drugs like 125I-DOI to illuminate the source of this terrifying syndrome.

By Nicole Karlis

Nicole Karlis is a senior writer at Salon, specializing in health and science. Tweet her @nicolekarlis.

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Babies Parenting Reporting Sids Sleep Sudden Infant Death Syndrome