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Brainstem Abnormality Linked to SIDS

October 31, 2006

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Preliminary research suggests that brainstem abnormalities involving certain serotonin pathways in the brain may play a more important role in SIDS than previously thought, according to an article in the current issue of JAMA.

Sudden infant death syndrome (SIDS) is the leading cause of postneonatal infant death in the United States. Despite intensive research, the causes of SIDS remain unknown, according to background information in the article.

Previous research has suggested that abnormalities in the receptor binding of the serotonergic neurons in the medulla, the section of the brainstem that regulates breathing, may play a role in SIDS.

David S. Paterson, Ph.D., of Children's Hospital Boston and Harvard Medical School, Boston, and colleagues examined the relationship between SIDS cases and cellular defects associated with altered 5-HT receptor binding in the 5-HT pathways in the medulla of the brain.

The researchers analyzed frozen samples of the medulla from 31 infants who died from SIDS and from 10 infants who died from causes other than SIDS.

"We found that the medullary 5-HT abnormalities in SIDS are more extensive than previously suggested," the authors wrote. "This study strengthens the hypothesis that medullary 5-HT dysfunction is associated with SIDS and may lead to death by a failure of respiratory and autonomic responses ... during sleep," they added.

The study also found, in an explanatory analysis, reduced receptor binding density in male compared with female SIDS cases, an observation that may help explain why males are more vulnerable to SIDS.

The abnormalities were documented during the era of stringent public messages on risk reduction, including that for supine sleep position. The majority (65 percent) of the SIDS cases in this data set, however, were sleeping prone or on their side at the time of death, indicating the need for continued public health messages on safe sleeping practices.

The researchers speculate that the increased risk of SIDS in the prone or face-down position may reflect the infants' inability to respond to the challenge to breathe in the face-down position, due to the abnormalities in the medullary 5-HT system that compromise protective reflexes, including arousal and head turning.

"This study provides biological plausibility for certain risk reduction strategies in SIDS …," the authors wrote. "Moreover, it generates new hypotheses for testing about 5-HT-related brainstem pathology underlying sudden death in early life in future SIDS autopsies and in experimental mechanistic models."

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