SUDDEN INFANT DEATH SYNDROME

Sudden infant death syndrome (SIDS) refers to the sudden unexpected death of an infant under the age of one year who prior to the event was considered to be completely healthy. The diagnosis also requires that a review of the clinical and environmental history, death scene investigation, and autopsy fail to reveal an alternative explanation of the death. In other words, the diagnosis of SIDS remains a diagnosis of exclusion.

Incidence

SIDS remains the primary cause of death for infants between one month and six months of age. Prior to 1991 the incidence rates of SIDS in the United States ranged between 1.2 and 2 per 1,000 live births. Of the developed countries of the world, some, including Sweden, Hong Kong, and Japan, reported rates as low as 0.3 to 0.5 per 1,000 live births. Others, such as Australia (especially Tasmania), New Zealand, and Northern Ireland reported rates as high as 3-7 per 1,000 live births. In 1995, three years after the Academy of Pediatrics issued guidelines recommending placing infants in the nonprone position (i.e., not lying on the stomach) for sleeping, Michael Malloy and his colleagues published a study noting a 33 percent drop in the incidence of SIDS within the United States. Other countries reported similar experiences after adopting infant sleep position changes. This lowered incidence was maintained for succeeding years, but it remains to be seen if additional decreases will occur with increasing compliance with the recommended sleep positioning guidelines.

Epidemiological Factors

While the cause of SIDS remains elusive, multiple studies have documented consistent epidemiological factors associated with higher SIDS risks in some groups of infants. Risk factor categories include maternal and prenatal, neonatal (newborn), postneonatal, geographic, and race/ethnicity groupings.

Maternal and prenatal risk factors constitute a lengthy list of biological and environmental conditions. These include shorter interpregnancy interval, increased placental weight, low socioeconomic status, nutritional deficiency, anemia, urinary tract infection, intrauterine hypoxia (oxygen deficiency), fetal growth retardation, smoking, drug exposure, poor prenatal care, young age, lower education, and increased number of pregnancies. Several studies have identified maternal smoking as a significant risk factor. The National Institute of Child Health and Human Development (NICHD) conducted a large study in the United States of 757 SIDS cases with two matched control groups. Seventy percent of the SIDS mothers in this study smoked. When compared with the control groups, the risk for infants of mothers who smoked is doubled and progressively increases as the number of cigarettes smoked per day increases. These infants also die at younger ages. Constriction of blood vessels leading to chronically diminished oxygen delivery to fetal tissues is thought to be the mechanism by which smoking increases the risk of SIDS.

Neonatal risk factors include poor growth, asphyxia (inadequate oxygen delivery to body tissues), prematurity, and low birthweight. As the gestational age decreases, the relative risk of SIDS increases. This is also true of birthweight. The incidence of SIDS in preterm infants whose birthweight is greater than 1,500 grams (3 pounds, 5 ounces) is about 8 per 1,000 live births, compared to preterm infants with birth-weights less than 1,500 grams, where the risk rises to 10 per 1,000 live births. Postnatally, male sex, age (two to four months), bottle feeding, overheating, smoking exposure, soft bedding materials, no pacifier use, and prone sleeping position have been identified as significant factors that independently increase the risk of SIDS.

Geographic and race/ethnicity factors play an additional role in increasing the relative risks. SIDS rates increase during cold weather months, in economically poor countries, and in infants of black race or Native-American ethnicity. Worldwide, groups such as Gypsy, Maori, Hawaiian, and Filipino also have increased SIDS rates.

Pathologic Findings

Extensive work has been done in an attempt to determine distinguishing pathological abnormalities that if present at autopsy would definitively identify SIDS as the cause of death. While there are findings that are commonly present at autopsy, no gross anatomical or microscopic abnormalities have been found that are distinct to SIDS. Nevertheless, a thorough postmortem (autopsy) examination demonstrating the absence of a causative abnormality is crucial to the diagnosis of SIDS. Especially important is not missing evidence of child abuse such as signs of (1) suffocation, (2) blunt trauma to the head, ribs, or extremities, and (3) retinal hemorrhages seen in shaken baby syndrome.

Commonly described findings in the central nervous system include: (1) increase in brain weight, presumably due to disordered development of the brain, (2) delayed myelination (maturation) of nerve cells, (3) gliosis (scarring) of brain-stem cells, (4) areas of leukomalacia (degeneration of brain tissue that occurred weeks to months earlier), and (5) abnormal dendritic spine density in selected areas of the brain stem. Evidence of chronic oxygen deprivation—such as persistence of brown fat around the adrenal glands, red blood cell production in the liver, and gliosis of the brain stem—add support to the theory that abnormal respiratory regulation may be the mechanism underlying SIDS.

Mechanism (Pathophysiology)

Current thinking regarding the mechanism of SIDS is focused on disordered regulation of the cardiorespiratory systems. The primary area of physiological regulation in humans is within the brain stem, which is located anatomically at the base of the brain. Abnormal findings on autopsy (as described in the above section), combined with clinical observations of abnormal regulatory control, support the view that delayed maturation or disruption of brain stem function results in the infant's lack of ability to respond when breathing and circulation patterns are insufficient to maintain life.

Several areas of respiratory regulation have been studied. Abnormalities of breathing patterns—such as recurrent brief apneic episodes, prolonged apneic event, and periodic breathing—have been observed in infants who later died of SIDS. The ability to electronically monitor and record breathing patterns in infants sparked enthusiasm for screening and monitoring of infants felt to be at high risk for SIDS.

However, experience has proven this intervention is not reliable in detecting which infants with abnormal breathing patterns will actually subsequently die of SIDS. In addition, multiple false alarms from the monitoring equipment resulted in high noncompliance rates in the home setting.

Diminished respiratory responsiveness to excessive buildup of carbon dioxide (hypercarbia) or to excessively low levels of oxygen (hypoxia) has also been found in infants at risk for SIDS. Nevertheless, the ability to discriminate between these infants and those not at risk who may have similar diminished responsiveness is lacking as of 2001.

A third respiratory regulation control mechanism is the arousal response. When experiencing hypocarbia or hypoxia, a normal sleeping infant will arouse and increase respiratory efforts in response to this life-threatening situation. Infants lacking sufficient arousal responsiveness will continue sleeping, becoming progressively more hypoxic, resulting in cardiorespiratory failure and sudden death.

Other mechanisms that are thought to be associated with the occurrence of SIDS include abnormal cardiac rhythms and increased body and/or environmental temperatures. It is likely that the pathophysiology of SIDS involves complex interactions between abnormal regulatory control systems and epidemiological risk factors such as poor intrauterine growth, exposure to smoking, prone sleep positioning, and prematurity.

Management

When a previously healthy infant is found unexpectedly dead, it is intensely emotionally traumatic. Caregivers blame themselves and each other. Families can be torn apart as a result of such an experience. For these reasons, proper management by experienced professionals is essential. A thorough investigation to determine the true cause of death is required. Other causes of sudden unexpected deaths of infants that have been mistakenly labeled as SIDS include congenital abnormalities of the heart and brain, metabolic disorders, occult infection (an infection that had escaped discovery), and accidental and non-accidental trauma. Nonaccidental trauma or child abuse mistaken for SIDS has been highlighted by several high-profile cases in both the United States and Europe. The recommended approach when an infant is found unexpectedly dead consists of a thorough investigation at the scene to detail the environmental circumstances. This should be followed by a careful review of the infant's medical, social, and family histories, followed by a complete postmortem examination by an experienced forensic pathologist. In some cases, laboratory studies on family members may be indicated. Counseling of parents is essential so that they have accurate information as to the cause of their infant's death and the implications for future children, as well as for emotional support. Community resources should be provided for ongoing support.

Prevention

Although a definitive cause of SIDS remains unknown and there are no methods to predict which infants will die from SIDS, parents should be educated about strategies that will lessen the likelihood of a SIDS event. Parents should be advised to place infants on their backs for sleeping, provide a firm mattress, avoid loose clothing and blankets in the crib, avoid overheating their infant, breast-feed, and take their infant for regular medical care.

See also: INFANCY; INFANT MORTALITY

Bibliography

American Academy of Pediatrics. "Changing Concepts of Sudden Infant Death Syndrome: Implications for Infant Sleeping Environment and Sleep Position." Pediatrics 105 (2000):650-656.

American Academy of Pediatrics. "Distinguishing Sudden Infant Death Syndrome from Child Abuse Fatalities." Pediatrics 107 (2001):437-441.

Back to Sleep Campaign. "Reduce the Risk of Sudden Infant Death Syndrome (SIDS)" (brochure). Washington, DC: Back to Sleep Campaign, 1994.

Butlerys, Marc G., Sander Greenland, and Jess Kraus. "Chronic Fetal Hypoxia and Sudden Infant Death Syndrome: Interaction between Maternal Smoking and Low Hematocrit during Pregnancy." Pediatrics 86 (1990):535-540.

Hunt, Carl E., guest ed. "Apnea and SIDS" (special issue). Clinics in Perinatology 19, no. 4 (1992).

Hunt, Carl E. "Sudden Infant Death Syndrome." In Waldo E. Nelson ed., Nelson Textbook of Pediatrics. Philadelphia: Saunders, 1996.

Jeffery, Heather, Angelique Megevand, and Megan Page. "Why the Prone Position Is a Risk Factor for Sudden Infant Death Syndrome." Pediatrics 104 (1999):263-269.

Klonoff-Cohen, Hillary S., Sharon L. Edelstein, Ellen Lefkowitz, Indu P. Srinivasan, and David Kaegi. "The Effect of Passive Smoking and Tobacco Exposure through Breast Milk on Sudden Infant Death Syndrome." Journal of the American Medical Association 273 (1995):795-798.

Malloy, Michael H., and Daniel H. Freeman. "Birth Weight and Gestational Age-Specific Sudden Infant Death Syndrome Mortality: United States, 1991 versus 1995." Pediatrics 105 (2000):1227-1231.

Carol A. Miller