Sudden Infant Death Syndrome is not common, exactly, but it isn’t rare either. And despite a considerable decline in SIDS over the past 20 years, it remains the leading cause of death among babies between 1 month old and 1 year old, according to the Centers for Disease Control and Prevention.

At the same time, the underlying reasons for SIDS have remained a mystery, even after decades of study. That’s beginning to change. The latest research has dramatic implications for scientists’ understanding of SIDS, and hints at the distant possibility of a blood test that might be used to screen newborns for the syndrome.

A study published Monday in the Proceedings of the National Academy of Sciences finds a substantial number of SIDS deaths appear to be linked to elevated serotonin, a chemical that helps regulate breathing and other functions. Researchers tested the blood of 61 babies whose deaths were characterized as SIDS and found that nearly one-third of them had increased levels of the neurotransmitter in their blood.

“This is a very exciting finding,” says Rosemary Higgins, a neonatologist at the National Institute of Child Health and Human Development, which oversaw the study. “More research would need to be done, but it could possibly lead to a forensic test to distinguish SIDS deaths from other causes of death among infants.”

SIDS deaths are notoriously difficult to track, in part because some infant deaths—like accidental suffocation by bedding in an unsafe sleep environment—are counted as SIDS deaths even though they aren’t truly inexplicable. About 3,700 babies died suddenly and unexpectedly in 2015, the most recent year for which the CDC has data. The agency counts 1,600 of those 3,700 total deaths as SIDS.

So the possibility of a forensic test that could determine which deaths are truly attributable to SIDS could further doctors’ understanding of the syndrome in key ways. For example, such a test would be a necessary step toward eventually developing a screening for at-risk newborns before they die. Though the possibility of such a screening is still a long way off, Higgins says.

The latest PNAS study builds on a growing body of evidence that suggests brain abnormalities—some of which entail elevated serotonin levels—may be linked to SIDS. One previous study, published in the Journal of the American Medical Association in 2010, found a link between SIDS and lower levels of serotonin in the brain, whereas the latest PNAS study, which looked at elevated serotonin, focused on serotonin levels in the blood.

These earlier findings, coupled with the latest research, suggest that an abnormality in serotonin metabolism—leading to lower or higher levels in different parts of the body—could indicate an underlying vulnerability that increases a baby’s SIDS risk. Researchers are still working to understand a causal link, however.

Many questions remain. Because the researchers were specifically testing serotonin levels, they don’t know whether the 19 babies with elevated serotonin in their blood had any other abnormalities in common. It’s also unclear whether the same groups that suffer higher rates of SIDS deaths are also more likely to have elevated serotonin serum. For instance, black babies and Native American babies are more than twice as likely as white babies, Asian babies, or Hispanic babies to die of SIDS. Premature babies and boys are also disproportionately represented among SIDS deaths compared with full-term babies and girls. “The cost of testing and the rarity of the event are prohibitive to screening at the moment,” said Peter Blair, an epidemiologist who focuses on SIDS at the University of Bristol in England. “If we can improve identification of a small group at high risk, then maybe.”

One of the biggest questions posed by the latest study is: Just how big of a risk factor is increased serotonin in the blood? In other words, among babies who have higher levels of serotonin in their blood, how much more likely are they to be victims of SIDS? After all, most of the babies in the study group had normal blood serotonin levels.

(NIH)

Most researchers view the syndrome as part of a “triple-risk model,” meaning SIDS results from three interacting factors that affect the baby all at once. The three factors in the triple-risk model include the underlying vulnerability, the stressful environment, and the critical phase of development that the infant is in. Under this model, an infant with an underlying vulnerability would also have to be in a bad situation—like being placed on his or her stomach when put to sleep, which is unsafe for newborns—to trigger SIDS.

Although SIDS deaths are sudden, a latent vulnerability may be present for days or months prior to death, the researchers of the PNAS study wrote, and may even originate during gestation.

For the time being, the best advice for parents and other caregivers who are worried about SIDS is still to follow the “safe to sleep” guidelines: That means a baby should always be put to bed in an empty crib with a firm mattress. The crib should be free of any toys, bedding, blankets, or pillows. And the baby should be placed flat on his or her back.

But it will be hard to completely eliminate the risk for SIDS until scientists understand just where it comes from.

“Just as important with these findings," says Blair, who did not work on the study, "is that we are getting closer to identifying causal mechanisms for SIDS. The welcome fall in [SIDS-death] rates is due to good risk-reduction advice rather than an increased understanding of why these infants die.”