Boston scientists reported yesterday the most extensive signs yet that Sudden Infant Death Syndrome, a mysterious killer of some 3,000 American babies a year, stems from abnormalities in a part of the brain that controls basic functions like breathing.
The findings, by researchers at Children's Hospital Boston, fit into an emerging biological theory of SIDS -- one that backs up the practical advice to prevent crib death by putting all babies to sleep on their backs.
Scientists believe that SIDS babies are born with a genetic defect that keeps them from responding properly to a "stressor " such as lacking adequate oxygen while lying face-down. Babies who die of SIDS apparently have not developed a sort of "alarm system" that would make them respond to rising carbon dioxide levels by turning their heads and breathing harder, said Dr. Hannah Kinney of Children's Hospital, who is senior author of the study, published in today's issue of the Journal of the American Medical Association.
The study was based on autopsies of 31 SIDS victims, about three-quarters of whom had widespread serotonin abnormalities in the brain stem. Serotonin, best known for its role in lifting depression, serves many functions in the brain; in the brain stem, it helps regulate breathing and other automatic bodily functions.
The advances in understanding the biology of SIDS could eventually translate into screening babies to determine whether they are at genetic risk and then giving them drugs to correct their brain abnormalities, researchers say.
But for now, Kinney said, "the most important thing about this work is that it gives biological plausibility to the 'Back to Sleep' campaign."
The campaign encourages parents to put babies to sleep on their backs and is widely credited with reducing the SIDS death rate by more than 50 percent since the early 1990s.
Serotonin abnormalities have been suspected as the possible villain in SIDS for several years, but the new research finds that they are more widespread and serious than previously believed.
"This is a fabulous clue," said Dr. Gene Nattie, a Dartmouth College physiology professor who researches SIDS but was not involved in Kinney's work.
"To have these kinds of clues," he said, "gives investigators who want to find ways that biology could go awry, and cause death, a much better handle on where to start."
The serotonin work also raises the prospect of new tools for forensic investigators trying to determine whether an infant died of SIDS or abuse.
The serotonin abnormalities were found in about 75 percent of the SIDS victims in the study , Kinney said. In theory, if an autopsy of a dead infant found such abnormalities, it could be considered strong evidence that the cause of death was SIDS.
The tests are "not ready for prime time in the sense that they're not ready for routine clinical use," said Dr. Carl Hunt, a federal researcher who studies SIDS. But "it's important that the pediatric community know" that such postmortem tests are on their way.
Despite recent progress on the serotonin link, many SIDS cases remain unexplained, including one-quarter of the ones in the Kinney study. Until more is understood, pediatricians recommend that all babies be put to sleep on their backs. Among the 31 victims in Kinney's study, 65 percent apparently died while sleeping on their side or stomach.
Experiments are underway on mice that have been engineered to have a serotonin defect much like the one suspected in SIDS, treating them with Prozac-like drugs to see to see if their condition improves, Kinney said. Prozac works by beefing up the brain's supply of serotonin.
But a drug solution may not prove simple, warned Andrew Tryba, an assistant physiology professor and SIDS researcher at Medical College of Wisconsin. The serotonin system in the brain is so complex, that it's unclear whether a Prozac-like drug would work as hoped, he said.
Until much more research is done, he said, it would not be prudent to give a baby, whose brain is still developing, a Prozac-like drug.
Researchers are also still a long way from being able to detect serotonin abnormalities in a living baby. The serotonin defects are not detectable on brain scans, either. Until recent work by Kinney and others, pathologists had examined the brains of SIDS victims for decades and always thought they looked normal.
Some researchers are trying to develop tests of infants' automatic functions such as breathing patterns and heart-rate variability to screen for possible risk of SIDS, Kinney said.
It is not yet clear, Kinney and other researchers said, whether the serotonin defects in SIDS are connected to sleep apnea in later life, or known serotonin-related problems -- such as depression.
The new work by the Boston scientists, who are part of a national network of SIDS researchers, would have been impossible without brain samples provided by colleagues in San Diego, Kinney said. There, she said, parents of SIDS babies hoping to raise the caliber of research pressured the Legislature into passing a law allowing researchers to obtain fresh brain tissue from SIDS victims without individual parental consent.
"They have done more, in my opinion, to revolutionize SIDS research than almost anything else," Kinney said.
If current progress continues, she added, one result may be that the very name of SIDS could change. It could eventually be renamed "serotonin brainstem defect," she said.
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