Researchers have discovered that some infants who have died of sudden infant death syndrome (SIDS) show abnormalities in not just one -- but two -- receptors located in an area of the brainstem thought to be involved in the control of breathing, carbon dioxide sensitivity, and blood pressure responses. This discovery confirms earlier evidence of a similar brain abnormality in another receptor and provides additional support for the theory that malfunctions in the brain region known as the arcuate nucleus may be a strong factor in SIDS.
SIDS, the sudden, unexplained death of an infant under one year of age, strikes nearly 3,000 infants each year and is the leading cause of death among infants one month to one year of age.
The study, partially funded by the National Institute of Child Health and Human Development (NICHD), appears in the November issue of the Journal of Neuropathology and Experimental Neurology.
Specifically, researchers found a significant decrease in kainate binding to kainate neurotransmitter receptors in the arcuate nucleus of the brainstem in a group of SIDS infants. "Brain and nerve cells communicate by means of molecules called neurotransmitters," explained Dr. Hannah Kinney, study author, NICHD grantee, and researcher at Children's Hospital and Harvard Medical School in Boston.
Neurotransmitters produced in one brain cell bind to special receptor molecules on neighboring brain cells, in much the same way the key fits into a lock. In the case of SIDS victims, it appears that the decreased binding to the kainate receptor results in faulty communication among nerve cells and may prevent infants from responding to life-threatening cardiorespiratory events during sleep.
Earlier reported findings suggested that a significant decrease in binding of another receptor, the muscarinic cholinergic receptor (mAChR) in the arcuate nucleus, could prevent SIDS victims from responding to potentially life-threatening, but frequent events, that occur during sleep. These events include responding to the rising levels of carbon dioxide or decreasing levels of oxygen that might occur when infants, lying face down in heavy bedding or blankets, rebreathe trapped air.
"This finding is exciting in that it confirms our earlier discovery of the mAChR receptor, and strengthens the argument that a deficit in the arcuate nucleus -- specifically in two receptors involved in signaling neurons -- may be partially responsible for some SIDS deaths," explained Dr. Kinney.
The kainate and muscarinic cholinergic receptors, located in the arcuate nucleus on the ventral or front surface of the brainstem, are thought to be directly involved in the body's ability to respond to rising levels of carbon dioxide, according to experimental animal studies.
Dr. Kinney and a scientific team studied the brainstems of 79 infants who had succumbed to SIDS and other causes. The scientific team included Dr. J. Filiano of Children's Hospital at Dartmouth; Dr. L. Sleeper of the New England Research Institutes; Dr. M. Valdes-Dapena of the University of Miami; Dr. W. White of Pfizer Central Research; Dr. H. Krous of San Diego Children's Hospital; and Dr. F. Mandell, L. Rava, and A. Panigraphy of Children's Hospital and Harvard Medical School.
In this study, the average receptor binding in the arcuate nucleus was significantly different between SIDS and the control groups. In addition, the average decrease in receptor binding for SIDS, relative to the control group of infants who had died suddenly from other causes, is greater for the kainate receptor (52%) than the mAChR receptor (27%).
"We now have a clue about the region of the brain that is involved -- and that there may be a more global, neural cell defect in the arcuate nucleus. We know two of the neurotransmitters involved. Our next step is to find out how and why this occurs," said Kinney.
One of the goals of this research is to eventually develop a screening test to identify infants at risk or a standard of measurement of kainate receptor binding that could be used for diagnosis at autopsy.
"This finding is also extremely important for the back sleeping recommendation," said Kinney. "We think this new finding fits in with the rebreathing theory -- that infants sleeping in the prone (stomach) position are rebreathing trapped air and, unable to sense and respond to the excess carbon dioxide, die suddenly."
In 1992, the American Academy of Pediatrics (AAP), after reviewing studies that had linked infant prone (stomach) sleeping with an increased risk of SIDS, recommended that infants be placed on their back or side to reduce the risk of SIDS. In 1994, the NICHD joined the AAP and initiated the "Back to Sleep" campaign, which recommended placing healthy infants on their backs or sides to sleep to reduce the risk of SIDS.
Prior to the "Back to Sleep" campaign, nearly 70% of babies were stomach sleeping.
"Now, only about 21% of babies are stomach sleeping -- and the SIDS death rate has dropped 38% between 1992 and 1996," reported NICHD Director Duane Alexander, M.D., at the AAP annual meeting in New Orleans on November 4, 1997.
The NICHD is joined by several federal agencies, including the Maternal and Child Health Bureau, the AAP, the SIDS Alliance, and the Association of SIDS and Infant Mortality Programs in spreading the word about the importance of back sleeping. To order "Back to Sleep" materials, write to NICHD/Back to Sleep, 31 Center Drive, Room 2A32, Bethesda, MD 20892-2425, or call toll-free, 1-800-505-CRIB. An Internet site providing the latest campaign information is also available at http://www.nih.gov/nichd.
The NICHD is part of the National Institutes of Health, the biomedical research arm of the Federal government.