The New York Times - Infants who die in their sleep of no apparent cause often have subtle defects in an area of the brain that regulates breathing, heart rate and arousal, doctors reported Wednesday.

The findings, appearing in The Journal of the American Medical Association, provide the strongest evidence yet that a physical abnormality, probably genetic in origin, can help explain what until recently was a matter of speculation for scientists and deep anxiety for new parents: sudden infant death syndrome, or SIDS.

More than 2,000 babies a year, about 7 of every 10,000 born in the United States, die of SIDS in the first months of their life. Researchers have found that many of the deaths occurred while the babies, most of them boys, were sleeping on their stomachs, often on soft bedding or in a bed with someone else.

A public education campaign teaching parents to place infants on their backs on a firm mattress has reduced the SIDS rate in recent years.
Suspicions of child abuse also cloud many sudden infant deaths, though recent research suggest abuse is responsible in less than 5 percent of such cases.

The new study confirms that a far more important cause is defects in how neurons process serotonin, a brain chemical associated with mood and arousal. Experts said the findings could help doctors develop a diagnostic test for SIDS risk and possibly preventive treatments.

"This is the most sophisticated, most impressive study so far looking at the serotonin system," said Dr. Debra Weese-Mayer, director of pediatric respiratory medicine at Rush University Medical Center in Chicago, "and it's going to drive genetic studies to find out what's behind this." Weese-Mayer wrote an editorial accompanying the Journal article.

The research team, led by doctors at Children's Hospital Boston, compared brain tissue from 31 infants who died of SIDS from 1997 to 2005 with samples from 10 babies who had died of other causes. They focused on an area of the brainstem called the medulla, which regulates breathing, sleep-and-wake cycles and other vital functions.

They found, among other oddities, that cells in this region of SIDS babies' brains were significantly less sensitive to serotonin than those in the other brains. The brainstem supports the autonomic nervous system, which helps rouse sleeping people if they are breathing too little oxygen, the authors said; and serotonin keeps the system responsive. The defects were particularly striking in male brains, which could account for boys' higher risk of SIDS, they said.

Previous studies had pointed to similar defects, but the new research pinpointed their location.

"I think this abnormality probably begins during gestation, in the womb, as the brainstem is developing," said Dr. Hannah Kinney, senior author of the study, which was financed by the National Institutes of Health and a coalition of SIDS advocacy groups, including the CJ Foundation for SIDS in New Jersey.

The study findings are based on tissue from white and Hispanic infants provided by the medical examiner's office in San Diego. They may not apply to other ethnic groups, Kinney said.

Evidence of a clear biological basis for SIDS deaths may comfort many parents who blame themselves, as well as give them reason to hope for treatments.

"For parents like us, I think we are looking forward to the next step, to get to the point where we'd have a screening test and a cure," said Robert Kossar, a father in New Jersey who with his wife, Michelle, started the Ryan Wolfe Kossar Foundation in honor of their infant son who died of SIDS in 2004.