Despite tremendous success at reducing SIDS rates since inception of the Back to Sleep campaign in 1994, SIDS remains the leading cause of death for infants one month to one year of age. In the United States, it strikes one infant every four hours. In Orange County, one out of every 2000 +/- babies dies of SIDS. The Back to Sleep campaign warns parents about the dangers of tummy sleeping, soft bedding, bed sharing and tobacco exposure both during pregnancy and after birth as leading risk factors. SIDS recognizes no boundaries, makes no distinctions to race, ethnic origin, income or background. SIDS could strike any one of our families or friends without warning. It causes loving families intense grief.
Department of Pathology, Children's Hospital Boston and Harvard Medical School, Boston, MA 02115, USA. Hannah.Kinney@childrens.harvard.edu
The sudden infant death syndrome (SIDS) is the sudden death of an infant under one year of age that is typically associated with sleep and that remains unexplained after a complete autopsy and death scene investigation. A leading hypothesis about its pathogenesis is that many cases result from defects in brainstem-mediated protective responses to homeostatic stressors occurring during sleep in a critical developmental period. Here we review the evidence for the brainstem hypothesis in SIDS with a focus upon abnormalities related to the neurotransmitter serotonin in the medulla oblongata, as these are the most robust pathologic findings to date. In this context, we synthesize the human autopsy data with genetic, whole-animal, and cellular data concerning the function and development of the medullary serotonergic system. These emerging data suggest an important underlying mechanism in SIDS that may help lead to identification of infants at risk and specific interventions to prevent death.
PMID: 19400695 [PubMed - indexed for MEDLINE]Publication Types, MeSH Terms, Substances, Grant Support
Ritchie Centre for Baby Health Research, Monash Institute of Medical Research, Monash University, Melbourne, Victoria, Australia.
OBJECTIVE: Impairment of the arousal process from sleep is thought to be involved in the pathogenesis of sudden infant death syndrome (SIDS). We hypothesized that a greater propensity for cortical arousal in the prone position may, in a normal infant, be a protective mechanism to promote complete arousal in a vulnerable sleeping position, a protection that is absent in SIDS victims. We aimed to examine the arousal process in a group of infants exposed to maternal smoking, who are thus at higher risk for SIDS. DESIGN: Twelve healthy, full-term infants born to smoking mothers were studied using daytime polysomnography at 2 to 4 weeks, 2 to 3 months and 5 to 6 months postnatal age. Data were compared with 13 healthy infants born to nonsmoking mothers. Arousal was induced by pulsatile air-jet stimulation to the nostrils during active and quiet sleep, in both supine and prone positions. For each stimulus, physiologic and electroencephalogram changes were visually assessed and arousal responses were classified as sub-cortical activation or cortical arousal. RESULTS: In smoke-exposed infants, the progression from sub-cortical activation to cortical arousal was depressed at 2 to 4 weeks and 5 to 6 months. There was no effect of maternal smoking observed at 2 to 3 months; however, a significant dose-dependent relationship between cortical activation proportions and urinary cotinine levels was present in both supine and prone positions. CONCLUSION: We have shown that maternal smoking is associated with impaired arousal processes to trigeminal stimulation that may increase the risk for SIDS. This further highlights the importance of public education of the risks of maternal smoking.
PMID: 19413145 [PubMed - indexed for MEDLINE]
Use of a Fan During Sleep and the Risk of Sudden Infant Death Syndrome
Kimberly Coleman-Phox, MPH; Roxana Odouli, MSPH; De-Kun Li, MD, PhD
Arch Pediatr Adolesc Med. 2008;162(10):963-968.
Objective To examine the relation between room ventilationduring sleep and risk of sudden infant death syndrome (SIDS).
Design Population-based case-control study.
Setting Eleven California counties.
Participants Mothers of 185 infants with a confirmed SIDSdiagnosis and 312 randomly selected infants matched on countyof residence, maternal race/ethnicity, and age.
Intervention Fan use and open window during sleep.
Main Outcome Measure Risk of SIDS.
Results Fan use during sleep was associated with a 72%reduction in SIDS risk (adjusted odds ratio [AOR], 0.28; 95%confidence interval [CI], 0.10-0.77). The reduction in SIDSrisk seemed more pronounced in adverse sleep environments. Forexample, fan use in warmer room temperatures was associatedwith a greater reduction in SIDS risk (AOR, 0.06; 95% CI, 0.01-0.52)compared with cooler room temperatures (0.77; 0.22-2.73). Similarly,the reduction associated with fan use was greater in infantsplaced in the prone or side sleep position (AOR, 0.14; 95% CI,0.03-0.55) vs supine (0.84; 0.21-3.39). Fan use was associatedwith a greater reduction in SIDS risk in infants who shareda bed with an individual other than their parents (AOR, 0.15;95% CI, 0.01-1.85) vs with a parent (0.40; 0.03-4.68). Finally,fan use was associated with reduced SIDS risk in infants notusing pacifiers (AOR, 0.22; 95% CI, 0.07-0.69) but not in pacifierusers (1.99; 0.16-24.4). Some differences in the effect of fanuse on SIDS risk did not reach statistical significance.
Conclusion Fan use may be an effective intervention forfurther decreasing SIDS risk in infants in adverse sleep environments.
SIDS Linked to Low Levels of Serotonin
NIH-Funded Study Finds Abnormalities in Brain Region That Regulates Breathing, Sleep
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.
Information on reducing the risk of Sudden Infant Death Syndrome is available on the NICHD Web site (http://www.nichd.nih.gov/health/topics/Sudden_Infant_Death_Syndrome.cfm).
The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the Institute’s Web site at http://www.nichd.nih.gov/.
The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
HTR2A variation and sudden infant death syndrome: a case-control analysis.
Department of Pediatrics, Rush Children's Hospital at Rush University Medical Center, Chicago, IL, USA.
AIM: The serotonergic (5-HT) system functions in central autonomic regulation with homeostatic roles in cardiorespiratory control, thermoregulation, arousal and sleep-wake cycling. Altered function and development of this system in cases of sudden infant death syndrome (SIDS) have been established, but the aetiology of these disturbances remains unclear. The serotonin receptor, HTR2A, functions within this system with roles in the homeostatic response to hypoxia including excitatory effects on respiration, gasping and rhythm generation, all functions potentially compromised in SIDS. The objective of this study was to examine the relationship between SIDS risk and HTR2A variation. METHODS: All coding regions, intron-exon boundaries and the promoter region of HTR2A were PCR amplified and analysed by standard sequencing in 96 SIDS cases and 96 matched controls. RESULTS: Twenty-one HTR2A variations were identified in this case-control cohort, including four novel variations (c.C-1185A, c.T-923C, c.T-17C and c.C50T). None of the variations identified showed a significant association with SIDS. CONCLUSION: This report provides evidence that despite known alterations of the 5-HT system in SIDS, and the logical role for the HTR2A receptor, genetic variation of HTR2A as studied in our cohort is not responsible for these alterations. These results represent a further step in the investigation of the aetiology of the altered serotonin system in SIDS cases.
Centers for Disease Control and Prevention, Maternal and Infant Health Branch, Division of Reproductive Health, Mail Stop K-23, 4770 Buford Hwy NE, Atlanta, GA 30341-3717, USA. firstname.lastname@example.org
OBJECTIVE: Accidental suffocation and strangulation in bed, a subgroup of sudden, unexpected infant deaths, is a leading mechanism of injury-related infant deaths. We explored trends and characteristics of these potentially preventable deaths. METHODS: In this descriptive study, we analyzed US infant mortality data from 1984 through 2004. To explore trends in accidental suffocation and strangulation in bed and other sudden, unexpected infant deaths, we calculated cause-specific infant mortality rates and estimated proportionate mortality. Sudden, unexpected infant death was defined as a combination of all deaths attributed to accidental suffocation and strangulation in bed, sudden infant death syndrome, and unknown causes. Finally, we examined factors that were reported as contributing to these accidental suffocation and strangulation in bed deaths. RESULTS: Between 1984 and 2004, infant mortality rates attributed to accidental suffocation and strangulation in bed increased from 2.8 to 12.5 deaths per 100000 live births. These rates remained relatively stagnant between 1984 and 1992 and increased between 1992 and 2004; the most dramatic increase occurred between 1996 and 2004 (14% average annual increase). In contrast, total sudden, unexpected infant death rates remained stagnant between 1996 and 2004, whereas the proportion of deaths attributed to sudden infant death syndrome declined and to unknown cause increased. Black male infants <4 months of age were disproportionately affected by accidental suffocation and strangulation in bed. Beds, cribs, and couches were reported as places where deaths attributed to accidental suffocation and strangulation in bed occurred. CONCLUSIONS: Infant mortality rates attributable to accidental suffocation and strangulation in bed have quadrupled since 1984. The reason for this increase is unknown. Prevention efforts should target those at highest risk and focus on helping parents and caregivers provide safer sleep environments.
PMID: 19171619 [PubMed - indexed for MEDLINE]