Sudden infant death syndrome (SIDS) accounts for the greatest share of deaths in children between the ages of 1 and 12 months. What if a blood test could explain a third of SIDS deaths – and in the future, help prevent them? New findings by a Boston Children’s Hospital team show that an increased level of serotonin in blood serum may underpin some SIDS deaths and suggests the possibility that this biological vulnerability may one day be detected in the blood of living infants.

While there are known risk factors for SIDS – such as sleeping face–down or on soft surfaces – how and why such seemingly minor threats kill some children, and not others, remains a mystery.

“Research on the underlying pathology of SIDS is critical to further our understanding of the biological mechanisms contributing to a SIDS death,” says Robin Haynes, PhD, a researcher in the Department of Pathology at Boston Children’s Hospital.

Haynes works in the laboratory of neuropathologist Hannah Kinney, MD, and with Richard Goldstein, MD, program director of Robert’s Program on Sudden Unexpected Death in Pediatrics.

“We’re looking at SIDS like it’s a group of diseases that have yet to be discovered — all of which currently result in sudden death without explanation,” says Goldstein.

In previous work spanning more than a decade, the team has linked SIDS with abnormally–decreased serotonin levels in the brainstem, which controls many basic functions necessary for life. However, brainstem serotonin cannot be assessed in living patients and can only be assessed at autopsy with specialized techniques that are not readily available.

Haynes and colleagues studied 61 infants who had died from SIDS and found that 31 percent – nearly a third – had substantially increased levels of serotonin in their blood serum.

The findings were reported in the Proceedings for the National Academy of Sciences journal.

“We have been seeking accessible methods to identify vulnerable infants. Brainstem serotonin cannot be measured using simple clinical methods,” says Goldstein. “The wonderful thing about blood serum is how easy it is to test.”

Blood serum, the clear component of blood that contains electrolytes, hormones and any circulating drugs, is readily collected from both living and deceased infants.

“This raises the possibility of a forensic diagnostic biomarker – and, in the future, a screening test that could detect which babies are at higher risk of SIDS,” says Alan Michelson, MD, senior author of the paper and the director of the Center for Platelet Research Studies at Dana–Farber/Boston Children’s Cancer and Blood Disorders Center. The team’s findings suggest that biological vulnerability might put an infant at risk for SIDS when faced with environmental challenges such as sleeping in the face–down position. SIDS is a type of SUDP (sudden unexplained death in pediatrics), which is a “catch–all” term for sudden deaths in children that cannot be explained by standard post–mortem investigation. SUDP accounts for more deaths than cardiac disease or cancer in children under 19 years of age. In partnership with the Massachusetts Office of the Chief Medical Examiner, Robert’s Program is systematically researching the biological bases for SUDP.

Moving forward, the team will work to further understand the association between increased serotonin in the blood serum and decreased serotonin in the brainstem.

“The problem of SIDS is that the diagnosis comes after death, with no apparent cause. That’s a challenge to us,” says Goldstein. “We’re throwing everything we have at this with the ultimate goal of attributing specific, biological causes to all SIDS deaths.”