The brains of infants who die of sudden infant death syndrome (SIDS) produce low levels of serotonin, a brain chemical that conveys messages between cells and plays a vital role in regulating breathing, heart rate, and sleep, reported researchers funded by the National Institutes of Health.

SIDS is the death of an infant before his or her first birthday that cannot be explained after a complete autopsy, an investigation of the scene and circumstances of the death, and a review of the medical history of the infant and of his or her family. According to the National Center for Health Statistics, SIDS is the third leading cause of infant death (http://www.cdc.gov/NCHS/data/nvsr/nvsr57/nvsr57_14.pdf), claiming more than 2,300 lives in 2006.

The researchers theorize that this newly discovered serotonin abnormality may reduce infants’ capacity to respond to breathing challenges, such as low oxygen levels or high levels of carbon dioxide. These high levels may result from re-breathing exhaled carbon dioxide that accumulates in bedding while sleeping face down. The findings appear in the Feb. 3 issue of The Journal of the American Medical Association.

“We have known for many years that placing infants to sleep on their backs is the single most effective way to reduce the risk of SIDS,” said Alan E. Guttmacher, M.D., acting director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the NIH institute that funded the research. “The current findings provide important clues to the biological basis of SIDS and may ultimately lead to ways to identify infants most at risk as well as additional strategies for reducing the risk of SIDS for all infants.”

NICHD’s Back to Sleep (http://nichd.nih.gov/sids/) campaign urges parents and caregivers to place infants to sleep on their backs. Following the campaign’s launch in 1994, the rate of SIDS dropped by more than 50 percent. Widespread adoption of back sleeping appears to have reduced the occurrence of SIDS, but has not eliminated it.

For this study, senior author Hannah C. Kinney, M.D., of Harvard Medical School and Children’s Hospital Boston, and her colleagues examined small samples of tissue from the medulla, a region at the base of the brain that regulates basic functions such as body temperature, breathing, blood pressure, and heart rate. The researchers analyzed brain tissue from infants who died from SIDS and controls who died of other causes. Included in the analysis were 35 infants who died of SIDS, 5 infants who died unexpectedly of other causes, and 5 infants who were hospitalized and died for reasons associated with a lack of oxygen.

The researchers found that serotonin levels were 26 percent lower in tissue from infants who died of SIDS than in tissue from the group of infants who had otherwise died unexpectedly. Measurements of tryptophan hydroxylase, an enzyme needed to make serotonin, also were 22 percent lower.

In earlier work comparing SIDS cases with other infant deaths (http://www.nichd.nih.gov/news/releases/sids_serotonin.cfm), Kinney and her coauthors showed that the brains of infants who died of SIDS had higher concentrations of cells that use serotonin in the medulla oblongata, a region of the brain stem. For the current study, the researchers set out to see if this meant the SIDS infants’ brains in fact had altered levels of the brain chemical.

This abnormality appears to fit into the triple-risk model of SIDS, which holds that SIDS occurs only when three elements come together: an infant with an underlying vulnerability, a critical period of development, and an external stressor. The researchers speculate in this case that the low serotonin level would cause the underlying vulnerability. The first year of life is the critical period of development for stabilizing vital functions such as breathing. The final element of the model, sleeping face down, might provide the external stressor.

“Our research suggests that sleep unmasks the brain defect,” Dr. Kinney said. “When the infant is breathing in the face-down position, he or she may not get enough oxygen. An infant with a normal brainstem would turn his or her head and wake up in response. But a baby with an intrinsic abnormality is unable to respond to the stressor.”

“It’s no one single factor but a culmination of abnormalities that result in the death,” Dr. Kinney said. In fact, in 88 percent of the SIDS cases they examined, the researchers found two or more risk factors, such as the infant’s sleep position, an illness, or exposure to cigarette smoke.

Kinney hopes these findings will one day lead to a test that measures infants’ serotonin levels in the blood or other tissues that reflect brain serotonin levels. Such a test might make it possible to identify those at the highest risk for SIDS so that additional steps could be taken to protect them. In the near term, the findings will provide the basis for the development of animal models with serotonin deficiencies, to mimic what occurs in SIDS in human beings.

Researchers funded by the National Institutes of Health have identified three principal factors linked to whether caregivers place infants to sleep on their backs. Those three factors are: whether they received a physician’s recommendation to place infants only on their backs for sleep, fear that the infant might choke while sleeping on the back, and concerns for an infant’s comfort while sleeping on the back.

A large body of research has shown that placing infants on their backs to sleep reduces the risk of Sudden Infant Death Syndrome (SIDS), the leading cause of death during the first year of life in the United States.

“Placing infants on their backs for sleep remains the single most effective means we know to reduce the risk of sudden infant death syndrome,” said Marian Willinger, Ph.D., Special Assistant for SIDS research at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), which funded the analysis. “For the vast majority of infants, concerns about choking while back sleeping are unfounded.”

Dr. Willinger noted that certain conditions might prompt a physician to consider recommending against back placement. However, such recommendations are arrived at only after careful deliberation and after taking into account all the potential risks and benefits for the infant involved.

The survey also found that after increasing steadily, the proportion of infants placed to sleep on their backs leveled off in the years since 2001.

The study appears in the December issue of Archives of Pediatric and Adolescent Medicine. Its lead author is Eve R. Colson, M.D., of Yale University School of Medicine.

The NICHD launched the Back to Sleep campaign in 1994. The campaign urges parents and caregivers to place infants to sleep on their backs. Since the campaign began, the prevalence of babies being placed for sleep on their backs has increased from roughly 25 percent to roughly 70 percent. Corresponding with the increase in back sleeping, the SIDS rate has decreased by more than 50 percent.

To conduct the study, the scientists analyzed data from 1993 to 2007, obtained from the National Infant Sleep Position Study, an annual national phone survey. They found that the proportion of babies placed to sleep on their backs steadily increased between 1993 and 2001 but did not change after 2001.

The survey asked nighttime caregivers (mostly mothers): “Do you have a position you usually place your baby in?”

The researchers found that families who placed their infants on their backs were unlikely to say that they were concerned about their baby choking, or were unlikely to say that they were concerned that their baby would be uncomfortable on their back. These families also were likely to report that their doctor recommended back placement as the sole sleep position.

Conversely, caregivers who were concerned about infant choking, about infant comfort, and who had not received a recommendation for back-only placement from their physician were less likely to indicate that they had placed their infants to sleep on their backs.

The researchers also reported that African-American infants are placed to sleep on their backs less often than whites or Hispanics. The researchers showed that maternal attitudes about issues such as comfort and choking, and doctor recommendation for back sleeping contributed to much of the disparity in back placement between African-Americans and other groups.

A greater proportion of African-American infants than white or Hispanic infants die from SIDS each year.

The researchers concluded that reducing overall SIDS death rates depends on making sure families get back-sleeping advice from their physicians, and addressing concerns about choking and comfort.

Dr. Willinger noted that Back to Sleep Campaign materials address concerns about choking. She added that the campaign, which has a continuing education program for nurses, is in the final stages of preparation of a similar program for pharmacists, who often serve to reinforce health advice in many communities.

Similarly, the campaign will continue its work with practitioner groups to urge all health care professionals who come in contact with newborn infants to urge caregivers to place infants to sleep on their backs. In the study, the researchers reported that between 2003-2007, only 53.6 percent reported that their doctors had advised them to put their babies on their backs only.

Dr. Willinger explained that some caregivers may choose not to place infants on their backs for sleep because of concern that the infants might sleep less soundly. She added that if infants are consistently placed on their backs for sleep, they should become accustomed to sleeping in that position.

Recent studies have shown that infants placed on their sides were more likely to roll on to their stomachs and the current recommendation is for caregivers to place infants to sleep exclusively on their backs. Before this was discovered, however, the initial recommendation was that infants be placed on their backs or sides to sleep.

“Some health professionals may not be aware of the change,” Dr. Willinger said. “We’re continuing our efforts to make sure that they know — and know to tell their patients — that infants sleep safest on their backs.”

“We know that it is really important for health care providers to tell families that they should place their infants on the back to sleep,” said the study’s lead author, Dr. Colson. ” We can’t equivocate, or the message gets lost. And we need to serve as role models, placing infants to sleep on their backs, beginning the minute infants are born in our hospital nurseries and pediatric units.”

Information on reducing the risk of Sudden Infant Death Syndrome is available on the NICHD Web site. Steps parents and caregivers can take to reduce SIDS Risk are:

• Always place babies on their backs to sleep — Infants who sleep on their backs are less likely to die of SIDS than babies who sleep on their stomachs or sides. Placing your baby on his or her back to sleep is the number one way to reduce the risk of SIDS.
• Use the back sleep position every time — Infants who usually sleep on their backs but who are then placed on their stomachs, like for a nap, are at very high risk for SIDS. So it is important for babies to sleep on their backs every time, for naps and at night.
• Place your baby on a firm sleep surface, such as a safety-approved crib mattress covered with a fitted sheet — Never place an infant to sleep on a pillow, quilt, sheepskin, or other soft surface. Information on crib safety and regulatory requirements for infant cribs is available from the Consumer Product Safety Commission at http://www.cpsc.gov/info/cribs/index.html.
• Keep soft objects, toys, and loose bedding out of an infant’s sleep area – Don’t use pillows, blankets, quilts, sheepskins, or pillow-like bumpers in your baby’s sleep area. Keep all items away from the infant’s face.
• Avoid letting your baby overheat during sleep – Dress your infant in light sleep clothing and keep the room at a temperature that is comfortable for an adult.
• Think about using a clean, dry pacifier when placing your infant down to sleep, but don’t force the baby to take it. (If you’re breastfeeding, wait until your child is 1 month old, or is used to breastfeeding before using a pacifier.)

In addition to Dr. Colson, other authors of the study were Denis Rybin, Theodore Colton and Michael J. Corwin of Boston University; Lauren Smith, of the Massachusetts Department of Public Health; and George Lister, of University of Texas Southwestern Medical Center at Dallas.