Sudden infant death syndrome - Research Paper Example

SUDDEN INFANT DEATH SYNDROME Sudden infant death syndrome or SIDS is a death of unknown etiology in children under the age of 1 year and is diagnosed by exclusion. In 1991 an expert panel convened by the National institute of child health and human development revised the definition of SIDS to "the sudden death of an infant under 1 year of age which remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene, and review of the clinical history." (2) (1) This new definition of SIDS differs from the older definition in two aspects. Firstly it eliminated the term that death was “unexplained by history” because it is now known that many risk factors predispose infants to SIDS and that most cases of SIDS have some underlying abnormality too. Secondly it warrants detailed examination of the scene of death and autopsy to diagnose SIDS, thus eliminating wrong diagnosis of instances of child abuse or inherited disorders as SIDS. Currently due to the misdiagnosis of deaths as SIDS a new term “sudden unexpected death in infancy” (SUDI) is used. Unexplained SUDI generally includes cases of SIDS and other deaths which cannot be explained due to incomplete information or uncertain situations. It is now known that a multitude of factors from genetics to modifiable environmental triggers influence the pathogenesis of SIDS and this knowledge has lead to the formulation of different recommendations for its prevention. EPIDEMIOLOGY SIDS is the most common cause of post-neonatal death in the USA. Epidemiological studies show that the risk of SIDS is greater than one in every thousand live births (Getahun D) with greater incidence in African and Native Americans. Although it is still the leading cause of death in infants less than 1 year of age, there has been considerable decline in its incidence since the 1980’s. This is due to the numerous studies that have been conducted which identified risk factors and underlying abnormalities which predispose infants towards SIDS and the guidelines for child care formulated from them. A large cross-sectional study carried out in Europe also showed that boys are at more risk of SIDS than girls (odds ratio of 1.49) (Carpenter RG). Interestingly SIDS is also seen to be 15-20 times more likely to occur in child-care settings. (Stable prevalence but changing risk factors of Sudden Infant Death Syndrome in child care setting in 2001)) SIDS rate and sleep position from 1988–2003 (deaths per 1,000 live births). As the graph shows rates of death by SIDS(bar graph) has decreased considerably as the rate of sleeping supine(line graph) in infants has increased since 1992. AAP_Academy of Paediatrics, BTS_Back to Sleep. Sleep position source: National Institute of Child Health and Human Development Household Survey. SIDS rate source: National Centre for Health Statistics, Centres for Disease Control and Prevention. PATHOLOGENESIS AND RISK FACTORS As mentioned above SIDS is diagnosed upon the basis of exclusion and hence it is confirmed only after investigations and autopsy according to protocol. During such autopsies of suspected SIDS cases certain definite changes and abnormalities were noted in respiratory and other organs. In a study to find evidence of antecedent hypoxia in SIDS cases it was noted that nearly 66% of cases had similar changes, with identifiable tissue markers, e.g. vascular endothelial growth factor (VEGF) in cerebrospinal fluid, to those of chronic persisting low-grade asphyxia. In deaths caused by SIDS the mean concentration of vascular endothelial growth factor in the CSF was found to be 308 pg/dL in contrast to non-SIDS deaths in which it was 85 pg/dL. (Jones KL) Other respiratory changes included thoracic petechiae and pulmonary congestion with edema. Certain brainstem and autonomic irregularities were also noted in other studies some of which were; continued rise in dendritic spines and slow formation of synapses in medulla indicative of slow neuronal development, decreases in serotonin 1A and 2A receptor immunoreactivity and a dysregulated autonomic system (Thompson MW). SIDS cases were also seen with hypoplasia of the arcuate nucleus. Based on such findings and other research data a triple risk hypothesis has been proposed to explain the pathophysiology of SIDS. In this hypothesis it is suggested that SIDS is caused by a combination of the following: an underlying abnormality in infants exposed to some risk factors at a vulnerable stage of development. (S. P. Guntheroth WG) Multiple genetic and environmental risks are proposed to work together to cause SIDS as shown in the figure. Source: CMJ Sudden Infant Death Syndrome Carl E. Hunt, Fern R. Hauk There are a multitude of irregularities that have been noted in SIDS cases ranging from neurological, cardiac and genetic. As mentioned above, there has been strong evidence suggesting that abnormalities in serotonin signaling play a role in the pathogenesis of SIDS. These abnormalities include decreased amounts of serotonin and its synthetic enzyme tyrosine hydroxylase and defective serotonin receptor binding in the medulla. Slow neuronal development in the arcuate nucleus also disposed these infants to poor ventilatory and blood pressure responses to hypoxia. Researches also indicate that many cases of SIDS have some underlying cardiac dysfunction. Some studies report long QT intervals and tachycardia in infants who later succumbed to SIDS (Ackerman MJ). Although there might be a correlation between cardiac abnormalities and the probability of SIDS, small sample sizes of such studies limit the possibility of forming a definite relationship and larger studies need to be carried out in this area. Certain gene polymorphisms, in combination with environmental triggers, have also been suggested to contribute to the occurrence of SIDS. Among these are; genes encoding for heat shock proteins, cardiac ion channels, 5-HT transporter gene and deletions in gene for complement C4 but as is the case with cardiac irregularities this correlation is not completely clear. (Thompson MW) In the last twenty years numerous risk factors have been identified in SIDS victims, among which most are modifiable risk factors. Modifiable factors are those which can be controlled by life-style modifications so that they play a decreased role in a disease’s pathogenesis. Modifiable risk factors for SIDS include maternal risk factors, sleeping posture, sleep environment and overheating. Exposure to maternal risk factors greatly increases the likelihood of SIDS. There is a strong relationship of SIDS occurrence with maternal smoking. Infants born to mothers who smoked are generally at a 3-5 times higher risk of succumbing to SIDS than those born to non-smoking mothers (MacDorman MF). It is not very clear whether pre-natal or post-natal smoking exposure is more correlated as most infants of smoking mothers are exposed to both forms. The relationship between smoking in mothers and SIDS is also found to be dosage dependent i.e. risk increases with the increase in the quantity of exposure. Thus the probability of SIDS increases with increase in the number of cigarettes smoked, increase in the number of smokers in a house and smoking in the presence of an infant in a room. Exposure to cigarette some in specific moments during an infant’s development can also enhance the chances of SIDS. Although it is difficult to quantify the amount of smoke a child is exposed too, data does suggest that keeping a child in a smoke-free environment significantly reduces the chances of SIDS. Studies also show that children born to mothers who smoke develop abnormal compensatory mechanisms to injurious stimuli e.g. hypoxia which suggests a possible mechanism for the pathogenesis of SIDS and this field certainly needs to be explored further. Apart from smoking other drugs abused by mothers are also implicated to increase risk of SIDS in their children. These drugs include opiates, alcohol and abusing other forms of tobacco besides cigarettes but evidence supporting the possible role of these substances to the occurrence of SIDS has been circumstantial and requires further investigations. Maternal age is also a very important risk factor. It is seen that children born to teenage mothers are at a much higher risk of dying of SIDS in contrast to children of non-teenage mothers. Although it is an independent variable in itself, greater risk of SIDS occurrence in children of teenage mothers can partly be attributed to poor or no prenatal care and poor care later in pregnancy. Poor prenatal and third trimester care predisposes the child to SIDS too and it is seen that generally teenage mothers are deficient in their knowledge and practice of child care as compared to adult pregnant females. There has been increasing evidence implicating the position of a child during sleep to be an important contributor to the probability of SIDS. Prone sleeping increases the risk many fold as compared to other positions. The recommended posture during sleep is supine as it greatly reduces SIDS probability. As falsely believed previously, making an infant sleep on their side does not reduce the chances of SIDS death. In fact recent studies have revealed that children sleeping on their sides are at higher risk than those sleeping supine (Fleming PJ). Another important point to note here is that when children sleep on their sides it is very likely that they might switch to a prone position during sleep. Such children are at a much higher risk (odds ratio of 8.7) than those who sleep in one posture mostly (Li DK). A number of cases of SIDS have also been reported to have occurred when children were sleeping ‘unaccustomed prone’ i.e. children who normally sleep supine or on their side but were found sleeping prone when death occurred. This highlights the theory that changing sleep positions put children at more risk. Besides the posture of sleep the environment during sleep has also been seen to put children at risk or SIDS. Infants sharing beds with parents or other family members have been noted to be at more risk. This correlation is more pronounced with increased durations of sleep with bed sharing. On the other hand sharing rooms instead of beds has noted to have a protective effect against SIDS death. Sharing rooms with infants at risk is thus recommended as it also leads to better inspection and care of the child. Sharing beds on uneven surfaces e.g. couches etc. are much more harmful than on even surfaces. Another aspect of sleep environment which puts children at greater risk is the type of surface on which the child sleeps. Research shows that very soft bedding e.g. comforters, quilts, soft and old mattresses and polystyrene pillows put children at two to three times more risk of sudden death. (Mitchell EA) A sleeping environment that promotes overheating e.g. more than one layer of clothing, heavy quilts or comforters, warm room temperature and sweating during sleep further increase the probability of SIDS. It s important to understand that the above mentioned risks are much more hazardous when in combination instead of isolated exposure for e.g. a research conducted in Scandinavian countries showed that children sleeping prone on soft bedding were at fifteen to twenty times more risk than those sleeping prone. Thus it is important to reduce exposure to a combination of risks as it has a multiplicative effect. Moving away from the modifiable risk factors of sudden infant death, numerous other non modifiable risks are suspected to contribute to its pathogenesis. Amongst these risks the important ones are socio-demographic factors, infections, pre-term babies, apnea and a history of prior instances of sudden death in the family. Infants born in families with a poor socio-economic status are more predisposed towards dying suddenly as in SIDS because generally it is seen that poor and uneducated families are less likely to take the precautions recommended to prevent the incidence of SIDS. Other socio-demographic factors include uneducated mothers and single marital status. As mentioned initially it is also noted that certain ethnicities are at a higher risk for dying unexpectedly than other. African and Native Americans and Native Alaskans are the races at highest risk. This pattern can be for genetic reasons or due to the poor economic and living condition that many people from these races live in. Infections are an important reason for many explained deaths in infancy but it is also implicated to trigger events of SIDS. During autopsies of infants who succumbed to SIDS it was noted that SIDS cases harbor more pathogenic stains of microorganisms e.g. staphylococcus aureus and E.coli. Most autopsies also yield positive cultures for other bacterias too but the inference that infections could be the cause sudden infant death cannot be made from these findings. It is more generally implicated that infections contribute to its pathogenesis and trigger death. Apnea, just like infections, is also suspected to contribute to the pathway that leads to SIDS. Premature babies are also at a higher risk for SIDS as compared to full term babies. In premature babies there is more likelihood of hypoxic injury which is thought to contribute to SIDS pathogenesis. Along with this infants with low birth weight (low birth weight is also common in pre term infants) are also at a higher risk. The association of low birth weight and pre term delivery with sudden infant death is low but still very strong. This is because many other known risk factors of SIDS are also known causes of low birth weight and premature deliveries for e.g. cigarette smoking is known to cause both as well as poor care of fetus during pregnancy. A positive family history for previous instances of SIDS is also thought to increase the probability of another such episode. Brothers and sisters of SIDS victims are at a six times higher risk of dying the same way (L. R. Guntheroth WG). Twins are also more at risk than singletons. Despite these correlations the actual possibility of two SIDS related deaths in one family is very rare since the incidence of sudden infant death is low too (less than two per thousand live births in the United States). As proposed in the triple risk model, exposure to these risk factors at a vulnerable stage of development is thought to lead to SIDS. Evidence supporting this model can be seen in the fact that most cases of sudden infant death are reported in infants between the ages of two to four months, a stage during which vital organs of the cardiovascular, neurological and respiratory systems are forming. PREVENTION Since many of the major risk factors associated with sudden infant death syndrome are modifiable the American Association of Pediatrics (*) and other such organizations have come up with a list of recommendations for child care so that this sort of death can be prevented. Prevention of SIDS lies predominantly on changing lifestyles and focusing on proper maintenance of a child environment to minimizing the identified risks. Term and pre term infants should both be made to sleep supine. Sleeping supine is believed to increase incidents of asphyxiation due to choking but such incidents are not evidenced in literature on sleep. Sleeping supine is actually less harmful than sleeping prone as the latter position puts stress on the thoracic cavity. Apart from sleeping supine guidelines for child care also recommend that children should sleep on their on cots or cribs preferably in the same room where the parents sleep so that they can monitor the baby. Children should also not made to sleep on soft uneven structures e.g. sofas or cushions. Soft materials such as quilts, stuffed toys, comforters, pillows and sheep skins should not be placed in a child’s sleeping area. The child’s head should be uncovered during sleep. It is important to avoid overheating and insulation in an infant, thus children should not be made to wear unnecessary layers of clothing and the ideally the room temperature, if controllable, should be adjusted accordingly. Soft materials as mentioned above also cause over heating as parents or guardians tend to set these structures around or below the child to comfort them. Infants should be made to sleep on a firm flat mattress and placement of devices to maintain the sleeping posture is not recommended. The use of pacifiers is recommended in the guidelines of the American Association of Pediatrics. Pacifier use should be initiated after a month of breast feeding and placed when laying down an infant to make him/her sleep but should not be inserted again once the child is asleep. One of the most important recommendations, not only for prevention of SIDS but to maintain good health of the child, is that a child’s exposure to cigarette smoke be minimalized. Mothers should not smoke during pregnancy and it should be made sure that the child is not exposed to any second hand smoke. AAP guidelines also stress on the fact that educational strategies should be formed so that better compliance in high risk populations can be achieved. It also focuses on the need for expansion of the National back to sleep campaign so that more people are aware of the risks associated with prone and side sleeping. Summary of the guidelines recommended by the American Association of Pediatrics*. (Task Force on Sudden Infant Death Syndrome. The changing concept of sudden infant death syndrome: diagnostic coding shifts, controversies regarding the sleeping environment, and new variables to consider in reducing risk.Source:Carl E Hunf, Fern R Hauck, Review sudden infant death syndrome CMAJ vol.174/no.13) Results of a meta-analysis showing the odds ratio for pacifier use. Source: American Association of Paediatrics website (AAP website: reproduced with permission from Hauck FR, Omojokun OO, Siadaty MS. Do pacifiers reduce the risk of sudden infant death syndrome? A meta-analysis. Pediatrics. 2005;116:e716.) DIFFERENTIAL DIAGNOSIS AND SUMMARY Since the diagnosis of sudden infant death syndrome is based upon the criteria of exclusion it is important to rule out other overt causes of death which are sometimes misdiagnosed as SIDS. In children with previous known episodes of hypoxia or asphyxiation it is important to rule out the possibility of child abuse. This can be difficult to judge as in such cases the offender is normally close to the child but certain key points e.g. previous recurrent cases of cyanosis in child, previous unexplained deaths in family or death at age greater than months, can indicate towards foul play. Apart from fatal incidents of child abuse deaths resulting from certain metabolic causes (which are over looked) e.g. defects in fat metabolism are also misdiagnosed as SIDS. As seen in the above discussion, SIDS has a complex cause dependant on the simultaneous occurrence of multiple factors. Although the precise mechanism of SIDS death is far from known current literature provides adequate measures to rule out other causes of death and also to reduce its occurrence. Although the incidence of SIDS has decreased tremendously there are still a lot of challenges that need to be addressed which include vigorous spreading of the recommended guidelines to child care providers and parents and close examination of the trends in SIDS occurrence. At the same time adequate support programs with proper counseling should be set up for the families of the deceased as this unexpected form of death in infants can be very traumatizing for them. BIBLIOGRAPHY: 1, Centres for Disease Control. "Sudden Infant Death Syndrome-- United States, 1983-1994." 1996. Sudden infant death syndrome (SIDS) is "the sudden death of an infant under 1 year of age which remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene, and review of the clinical history." Although SIDS is a diagnosis of exclusion and of unknown etiology, it is the leading cause of postneonatal mortality in the United States, accounting for approximately one-third of all such deaths. This report analyzes age-, race-, and region-specific trends for SIDS in the United States during 1983-1994 (the latest year for which final data are available) and indicates that annual rates of SIDS declined more than three times faster during 1990-1994 than during 1983-1989. Ackerman MJ, Siu BL, Sturner WQ, Tester DJ, Valdivia CR, Makielski JC, Towbin JA. "Postmortem molecular analysis of SCN5A defects in sudden infant death syndrome." PubMed (2001): 286(18):2264. Carpenter RG, Irgens LM, Blair PS, England PD, Fleming P, Huber J, Jorch G, Schreuder P. "Sudden unexplained infant death in 20 regions in Europe: case control study." PubMed (2004): 363(9404):185. CE, Hunt. "Gene-environment interactions: implications for sudden unexpected deaths in infancy." Arch Dis Child (2005): 90(1):48. Control, Centres for Disease. "Sudden Infant Death Syndrome--United States, 1983-1994." 1996. Fleming PJ, Blair PS, Bacon C, Bensley D, Smith I, Taylor E, Berry J, Golding J, Tripp J. "Environment of infants during sleep and risk of the sudden infant death syndrome: results of 1993-5 case-control study for confidential inquiry into stillbirths and deaths in infancy. Confidential Enquiry into Stillbirths and Deaths Regional Coordinators ." BMJ (1996): 313(7051):191. Getahun D, Amre D, Rhoads GG, Demissie K 3. "Maternal and Obtetrics risk factors for Sudden Infant Death Syndrome in the United States." PubMed (2004): 103(4):646. Guntheroth WG, Lohmann R, Spiers PS. "Risk of sudden infant death syndrome in subsequent siblings." J Pediatr (1990): 116(4):520. Guntheroth WG, Spiers PS. "The triple risk hypothese in sudden infant death syndrome." Pubmed: paedatrics (2002): 110(5):e64. Jones KL, Krous HF, Nadeau J et al. "Vascular endothelial growth factor in the cerebrospinal fluid of infants who died of sudden infant death syndrome: evidence for antecedent hypoxia. ." Medline: Paedatrics (2003): 111:358-63. Carl E Hunf, Fern R Hauck, Review sudden infant death syndrome CMAJ vol.174/no.13) Li DK, Petitti DB, Willinger M, McMahon R, Odouli R, Vu H, Hoffman HJ. "Infant sleeping position and the risk of sudden infant death syndrome in California, 1997-2000." AMJ Epidemiology (2003): 157(5):446. MacDorman MF, Cnattingius S, Hoffman HJ, Kramer MS, Haglund B. "Sudden infant death syndrome and smoking in the United States and Sweden." AMJ Epidemiology (1997): 146(3):249. The association between sudden infant death syndrome (SIDS) and maternal smoking was compared between the United States and Sweden-two countries with different health care and social support programs and degrees of sociocultural heterogeneity. For 1990-1991 among the five US race/ethnic groups studied, SIDS rates ranged from a high of 3.0 infant deaths per 1,000 live births for American Indians to a low of 0.8 for Hispanics and Asian and Pacific Islanders. The SIDS rate for Sweden (using 1983-1992 data) was 0.9. The strong association between maternal smoking and SIDS persisted after controlling for maternal age and live birth order. Adjusted odds ratios ranged from 1.6 to 2.5 for mothers who smoked 1-9 cigarettes per day during pregnancy (compared with nonsmokers) and from 2.3 to 3.8 for mothers who smoked 10 or more cigarettes per day during pregnancy. Although birth weight had a strong independent effect on SIDS, the addition of birth weight to the models lowered the odds ratios for maternal smoking only slightly, suggesting that the effect of smoking on SIDS is not mediated through birth weight. SIDS rates increased with the amount smoked for all US race/ethnic groups and for Sweden. Smoking is one of the most important preventable risk factors for SIDS, and smoking prevention/intervention programs have the potential to substantially lower SIDS rates in the United States and Sweden and presumably elsewhere as well. Mitchell EA, Scragg L, Clements L. "Soft cot mattresses and the sudden infant death syndrome." NZMJ (1996): 109(1023):206. "Stable prevalence but changing risk factors of Sudden Infant Death Syndrome in child care setting in 2001." PubMed (2005): 116(4):972. *"Task Force on Sudden Infant Death Syndrome. The changing concept of sudden infant death syndrome: diagnostic coding shifts, controversies regarding the sleeping environment, and new variables to consider in reducing risk." PEDIATRICS (2005): 116:1245-55. There has been a major decrease in the incidence of sudden infant death syndrome (SIDS) since the American Academy of Pediatrics (AAP) released its recommendation in 1992 that infants be placed down for sleep in a nonprone position. Although the SIDS rate continues to fall, some of the recent decrease of the last several years may be a result of coding shifts to other causes of unexpected infant deaths. Since the AAP published its last statement on SIDS in 2000, several issues have become relevant, including the significant risk of side sleeping position; the AAP no longer recognizes side sleeping as a reasonable alternative to fully supine sleeping. The AAP also stresses the need to avoid redundant soft bedding and soft objects in the infant's sleeping environment, the hazards of adults sleeping with an infant in the same bed, the SIDS risk reduction associated with having infants sleep in the same room as adults and with using pacifiers at the time of sleep, the importance of educating secondary caregivers and neonatology practitioners on the importance of “back to sleep,” and strategies to reduce the incidence of positional plagiocephaly associated with supine positioning. This statement reviews the evidence associated with these and other SIDS-related issues and proposes new recommendations for further reducing SIDS risk. Thompson MW, Hunt CE. Avery's neonatology: pathophysiology and management of the newborn. Philadelphia: Lippincott Williams & Wilkins, 2005. Willinger M, James LS, Catz C 2. "Defining the sudden infant death syndrome (SIDS): deliberations of an expert panel convened by the National Institute of Child Health and Human Development." 1991. 11:667. Read More