Sudden infant death syndrome (SIDS) was not recognized as an entity until the early 1960s. Recent definitions of SIDS have stressed the importance of conducting a complete necropsy examination that includes death scene investigation and case history review.1 However, the diagnosis of SIDS remains one of exclusion. Using standard necropsy protocols to define SIDS as a cause of death, it is now possible to obtain good agreement between pathologists independently assessing a case.
The most striking recent development in the epidemiology of SIDS has been the approximately 50% decline2 in the incidence of SIDS in various countries following intervention to reduce the prevalence of the prone sleeping position during infancy (Figure 1). The number of deaths attributed to SIDS has fallen dramatically in the United Kingdom, New Zealand, Australia, the Netherlands, Norway, Denmark, and Ireland.3 This article examines the significanee of this sequence of events and discusses the possible contribution of other factors to SIDS.
Sudden infant death syndrome occurs with a peak incidence at 2 to 4 months of age with the rate decreasing thereafter. It has been proposed that this age at death curve reflects a physiological vulnerability at the relevant postnatal development phase of the infant. Sudden infant death syndrome has a male case predominance and is more common among infants of high birth order. An association between lower socioeconomic status and SIDS has been documented in many studies. The independent contribution of poverty after adjustment for factors such as maternal age, parity, bottle feeding, and smoking remains to be fully assessed. Differences in SIDS rates have been observed between ethnic groups. Some of the rate difference between ethnic groups can be explained by differences in socioeconomic status, and in fact, a National Institute for Child Health and Human Development study showed that the higher SIDS rates for black Americans was entirely explained by this factor.4 The SIDS incidence among ethnic groups in New Zealand and Asians and non 'Asian families in Birmingham do not appear to be explained by socioeconomic class. This suggests that culturally related infant care practices may be an important determinant of SIDS.
Figure 1. Mortality due to cot death for 100 000 live births in selected countries from 1987 through 1991. Data from reference 32. ("Concerns data about sudden unexpected death; this is a somewhat wider definition than cot death or sudden infant death syndrome. + Concerns data about the wider topic signs, symptoms, and ill-defined conditions. #Data available until 1989 only. ##Until and including 1990; concerns data from West Germany.)
Another clear demographic relationship is that between maternal age and risk of SIDS. The vast majority of studies have found that young mothers are considerably more likely to have an infant die of SIDS than older mothers. Adjustment for parity increases this risk. While some of this association between SIDS and young maternal age can be explained by socioeconomic status, it cannot entirely be explained by this. Two large-scale population studies have found the overall recurrence rate of SIDS in subsequent siblings to be four to five times the rate in the general population.5,6 However, when counseling parents at an individual level, the risk factor profile of the family must be taken into account.
Several antenatal factors have been associated with a higher risk of SIDS. Low birthweight is consistently associated with a risk grathent for SIDS. A large study on 1233 SIDS infants found this relationship to be exponential.7 Low gestational age also is associated with increased risk. After adjustment for gestational age, low birthweight infants remain at increased risk of SIDS.8 Intrauterine growth retardation also has been found to be associated with SIDS in other studies. The impaired growth in utero appears to be symmetrical in type, ie, SIDS infants have a reduction in length as well as weight. It has been suggested that this type of growth retardation reflects mechanisms that operate in early pregnancy, before peak growth velocity is reached.9 Unlike control infants, SIDS infants have been found to weigh less than their prior siblings.4 The incidence of SIDS is higher among infants born from multiple pregnancies, particularly among the growth-retarded cotwin set. Low birthweight appears to account for some, but not all, of the association of twinning with SIDS.
Previously reported associations between SIDS and maternal anemia, placenta previa, abnormal uterine bleeding during pregnancy, and hypertension during the third trimester have not been consistently replicated. A short interpregnancy interval has been associated with SIDS in several studies. Maternal opiate drug taking during pregnancy has been consistently related to a higher SIDS risk. Maternal cocaine drug taking during pregnancy has been associated with SIDS in some reports but not others. Symptomatic apnea has been more commonly reported among the infants of substance-abusing mothers than nonsubstance-abusing mothers.10 The increase in risk present in the infants of drug-taking mothers is likely to be, at least partially, due to confounding factors that have not yet been assessed adequately.
Maternal smoking during pregnancy is associated with SIDS.11 A dose response relationship for maternal smoking and SIDS risk has been demonstrated. It is thought that part of maternal smoking's effect on SIDS may be operating through intrauterine growth retardation of the infant. However, a residual association of maternal smoking with SIDS remains after adjustment for birthweight, suggesting that other pathways such as passive inhalation of smoke postnatally also may be involved. Maternal smoking modifies the relation between maternal anemia and SIDS. Low hematocrit was not a risk factor for SIDS among nonsmokers but became an important predictor among heavy smokers, suggesting that the two factors may interact through the mechanism of chronic fetal hypoxia.12 An analysis of digital and palmar dermatoglyphic patterns identified four dermatoglyphia regions with pattern frequencies differing from controls.13 These findings indicate a genetic or early intrauterine environmental influence in SIDS infants. An increased incidence of dysmorphism and congenital anomalies among SIDS infants also supports this contention. The prenatal factors discussed above may act to increase the infant's vulnerability to sudden death during the postnatal period.
The association between prenatal smoking and SIDS has been mentioned previously. Consistent evidence for an association between postnatal maternal smoking and SIDS also has been obtained from studies of both retrospective and prospective design. The odds ratios observed have generally been high, exceeding three in some studies. In those studies where concurrent measurement of other known risk factors has been undertaken, smoking has appeared to be second only in importance to prone sleeping position. In addition, the association is biologically plausible. Infants of parents who smoke have higher hospital admission rates for lower respiratory infection, and respiratory virus infection frequently is found in SIDS infants. Nonetheless, there are still questions about the causal role of postnatal smoking. Most importantly, it has been difficult to separate its effect from that of prenatal smoking as in the studies reported only a small percentage of mothers smoked exclusively either pre- or postnatally.
A large NMIHS study14 was able to estimate the risk associated with postnatal smoking only. The odds ratio for postnatal smoking alone was 2.2 while for the combined effects of prenatal and postnatal smoking it was 4.1. This study had a major deficiency in that the data on smoking was collected on case mothers after the death of the infant, thereby increasing the likelihood of recall bias. Furthermore, most mothers who were classified as not having smoked prenatally had smoked in the first 6 weeks of pregnancy while unaware of their conception. In a New Zealand case-control study, a dose response grathent was identified between the numbers of smokers in the household and SIDS risk.15 Smoking by the father increased the risk of SIDS if the mother smoked, but had no effect if she did not smoke.15 Without further evidence, it is still not possible to determine how important smoking by other family members is to SIDS. At this stage, postnatal smoking does appear to increase an infant's risk of SIDS even after adjustment for confounding factors such as socioeconomic status, and parents should be instructed not to smoke near their baby or better still, not to smoke at all.
Prone Sleeping Position
Since the first formal epidemiological study that made measurements that allowed an estimation of the association between sleeping position and SIDS in 1965, there have been more than 12 case-control studies. In every one of these studies, a positive association between prone sleeping position and SIDS was demonstrated. One prospective study published in 1991 also found a strong positive association confirming that the previously demonstrated link was not due to recall bias among parents.16
One puzzling aspect of the studies was that although they all provided evidence for an association between prone position and SIDS, the size of the effect estimated differed between studies and locations. Subsequent work has suggested that this may be due to the fact that some other factors modify or enhance the effect of prone position. For example, when an infant has a history of recent illness or when it is swaddled or on a soft natural-fiber mattress or in a heated room, the risk for the prone position is greatly in excess of what it would be if none of these factors were present.17 The differing distribution of such factors between countries may explain the apparent difference in risk for SIDS conferred by sleeping position in various countries. However, it is apparent that the prone position is associated with increased risk for all infants and that some of its potentiators (eg, recent illness) are not readily avoidable.
Figure 2. Effect modification: the risk of the prone position is increased by recent illness. (Reprinted with permission from Ponsonby AL, Dwyer T, Gibbons LE, et al. Factors potentiating the risk of sudden infant death syndrome associated with the prone position. W Engl J Med. 1993;329:377-382. Copyright® 1993, Massachusetts Medical Society.)
The sum of the evidence on sleeping position led policy-making bodies in a number of countries in the 1990s to advise parents to avoid placing their infants prone. In a number of locations, parents responded very strongly to this advice. In Tasmania, Australia, for example, the prevalence with which parents usually placed their newborn infants prone fell from 31% in 1990 to 4% in early 1992. Similar responses were seen elsewhere. A substantial fall in rates rapidly occurred. In Tasmania, the rate fell from 3.8 per 1000 live births in 1975-1990 to 1.6 in 1991. In England and Wales, the number of SIDS deaths has declined by 70% from 1988 to 1992.3 In Australia, the rate fell from 1.9 per 1000 live births in 1990 to 1.4 per 1000 in 1991, to 1.1 per 1000 in 1992, and to 0.98 per 1000 in 1993.18 In New Zealand, the rate for 1991, 2.5 per 1000 live births, was 33% lower than in 1988-1990.
In Tasmania, an analysis of the particular contribution of changes in prone position prevalence to the fall has been undertaken using data obtained from a cohort study that has been ongoing since 1988.19 This analysis has estimated that the change in prevalence of sleeping position has accounted for 70% of the SIDS rate decline. No other factor studied including breast-feeding, smoking, or thermal balance accounted for more than 6.3% of the decline. This evidence leaves little doubt that the prone sleeping position is a major contributor to SIDS.
Despite the changes elsewhere, the incidence of SIDS in the United States has not changed substantially over time with incidence rates in 1980, 1988, and 1989 of 1.53, 1.40, and 1.39 per 1000 live births, respectively.20 WiUinger et al2 report the US rates remained stable in 1991, declining less than 2% per year. In May 1994, the American Academy of Pediatrics, with selected agencies of the federal government, reported that the proportion of infants sleeping prone had only declined slightly in the past 2 years.21 So it is possible that the change in prevalence of prone position has been insufficient to achieve the reduction in SIDS rate observed elsewhere.
A concern that has been raised is that the prone position might not be an important risk factor in the United States. However, the data from an NICHD case control study indicate that the SIDS incidence in the United States would fall by at least 22% if healthy infants no longer slept prone.22 Furthermore, a Washington study23 reported that 8 months after an article about the risk of prone sleeping appeared in the Seattle Times, SIDS deaths were reduced by 52% in King County and 20% in an adjacent county where the paper was received but had increased by 3.4% in the rest of the State.
A protective association between breast-feeding and SIDS has been found in some case-control studies of SIDS but not others. Some of the studies did not take into account confounding by socioeconomic status, and as breast-feeding is linked to socioeconomic status, this is a serious deficiency. Kraus et al24 found that the association of breast-feeding with SIDS was much reduced in the US Collaborative Perinatal Project after adjustment for maternal education and birthweight.
However, in a New Zealand case-control study, the reduced risk for SIDS in breast-fed infants (ie, risk for SIDS in breast-fed infants during the first 6 months) persisted after controlling for demographic, maternal, and infant factors. Infants exclusively breast-fed for the last 2 days before death or interview were at lower risk of SIDS (odds ratio [OR] = 0.65 [0.46, 0.911).25
Overall, the data fall short of providing strong evidence for a causal role for breast-feeding in the prevention of SIDS. More well-designed observational epidemiological studies are needed before it will be possible to determine whether breastfeeding itself is important or whether it is merely closely linked to other preventive activities or environments.
The incidence of SIDS has been more frequent in winter than summer in most locations where studies have been conducted. However, the winter peak of SIDS incidence recently has declined in Australia, New Zealand, England, and Wales,2 suggesting that seasonal influences are less important in these communities now that infants are no longer sleeping prone. The other piece of evidence that suggests the effect of climate is not absolute is that the relationship between low climatic temperature and SIDS incidence differs substantially among communities.26 Possible explanations for the link between low climatic temperature and SIDS include respiratory viral infection and paradoxical hyperthermia of the infant by an overcompensatory increase in infant clothing or bedroom heating.
The case series reports of overheating among cot death victims, postmortem pathological changes consistent with heatstroke, and signs of perspiration provide some support for a role for thermal stress in some SIDS cases. In an Avon case-control study, SIDS infants were more likely to have been heavily wrapped (OR= 1.14 per tog of thermal insulation above 8 tog of thermal insulation) and to have had heating on all night (OR = 2.7) than populationbased controls.27 In a Tasmanian case-control study, SIDS infants were more likely to have excess clothing and bedding than control infants for a given room temperature.28 The effect of room heating, warm bedroom temperature, or recent illness on SIDS is greater in prone than side or back sleeping infants (Figure 2), suggesting that the mechanisms of hyperthermia or carbon dioxide rebreathing deserve further investigation.
Comprehensive analytical epidemiological data on the risks of cosleeping in relation to SIDS are not available. In a recent analytical study published to date, Scragg et al29 reported that bed sharing during last sleep was associated with SIDS in mothers who smoked, but not in mothers who did not smoke. Alcohol consumption on the night of death was not documented specifically. This report contrasts with ecological observations that ethnic groups that traditionally have low SIDS rates are more likely to keep the baby in the same bed or bedroom as the parents. McKenna et al30 assert that from the evolutionary perspective, it is more natural for infants to sleep with their parents. However, we would agree with Byard31 that the context of cosleeping must be taken into account. Cosleeping several feet above the floor on a soft mattress with pillows and layers of synthetic material is a different entity to the form of cosleeping conducted by tribal or other cultures. Further analytical work is required in this area, and as a starting point, the term cosleeping needs to be carefully defined and described.
Other Aspects of the Infant's Sleeping Environment
In May 1994, the American Academy of Pediatrics and representatives of the federal government recommended that soft surfaces and gas-trapping objects be avoided in an infant's sleeping environment.21 This recommendation is consistent with the epidemiological evidence. Thus, the infant's sleeping environment should be designed for good air circulation near the infant's face and special care should be taken to ensure that the infant's face and most of his or her head remains clear from the mattress, blankets, or any other object at all times. Infants should not sleep on adult free-flow waterbeds.
The large fall in SIDS incidence following the interventions to lower the prevalence of prone position have confirmed the fact that prone position is part of the principal causal pathway to SIDS in many communities, being responsible for more than half of the deaths in a number of locations. The recognition of this fact should lead to some change in the balance of current research. The imperative now is to obtain more information on the pathophysiological mechanism that explains the effect of prone position.33 Already there is some evidence that rebreathing of carbon dioxide-rich air, overheating, or airway obstruction could lead to death, and that prone position would make each of these mechanisms more likely to occur. However the evidence is insufficient to confirm any of these as all or part of the explanation. Pathophysiological work in laboratory settings is required to advance knowledge further.
There is also a need to explain those deaths that are due to causes quite separate from prone position. It is likely that parental smoking will account for a substantial proportion of the remaining deaths. Some of the others will be due to less common factors impacting on vulnerable infants who have demonstrated other signs of poor general development and of ill health. If action were taken to reduce the prevalence of readily preventable causes, it is likely that an annual rate of 0.5 SIDS deaths per 1000 live births could be achieved in many societies, including the United States.
1. Zyllce JW. Sudden infant death syndrome: resurgent research offers hope. JAMA. 1989:262:1565-1566.
2. Willinger M, Hoffman HJ, Hartford RB. Infant sleep position and risk for sudden infant death syndrome: report of meeting held January 13 and 14, 1994, National Institutes of Health, Bethesda, MD. Ratones. 1994:93:814-819.
3. Gilbert R. The changing epidemiology of SIDS. Arch Dis Child. 1994;70:445-449.
4. Harper RM, Hoffman JF, ed*. Sudden Infant Death Syndrome. Risk Factors and Basic Mechanisms, New York: NY: PMA Publishing Corp; 1988.
5. Guntheroth WG, Lohmann R, Spiers PS. Risk of sudden infant death syndrome in subsequent siblings. ; ftdtarr. 1990;116:520-524.
6. Irgens LM, Skjaerven R, Peterson DR. Prospective assessment of recurrence risk in sudden infant death syndrome siblings. J Rafia. 1984;104:349-351.
7. Black L, David RJ, Brouillette RT1 Hunt CE. Effects of birthweight and ethnicity on sudden infant death syndrome. J Pedtotr. 1986;108:209-214.
8. Golding J, Limerick S. Macfarlane A. Sudden infant Death, Rittems, Puzzles and Problems. Shepton Malien, England. Open Books Publishing Ltd; 1985.
9. Buck GM, Cookfair DL, Michalek AM, et al. Intrauterine growth retardation and risk of sudden infant death syndrome (SIDS). Am J Epidemiol. 1989;129:874-884.
10. Ward SL. Bautista D, Chan L. et al. Sudden infant death syndrome in infants of substance abusing mothers. J Pediocr. 1990;1 17:876-881.
11. Malloy MH, KIeinman JC, Land GH, Schramm WF. The association of maternai smoking with age and cause of infant death. AmJ Epidemiol. 1988;128:46-55.
12. Bulterys MG, Greenland S, Kraus JF. Chronic fetal hypoxia and sudden infant death syndrome: interaction between maternal smoking and low hematocrit during pregnancy. Pediatrics. 1990;86:535-540.
13. Kosakewich H, Fox K, Plato CC, et al. Dermatoglyphics in sudden infant death syndrome, Rsdwrr Perno!. 1992;12:637-651.
14. Schoendorf KC, Kiely JL. Relationship of sudden infant death syndrome to maternal smoking during and after pregnancy. Pediatrics. 1992;12:905-908.
15. Mitchell EA, Ford RPK1 Stewart AW, et al. Smoking and sudden infant death syndrome, ftawnfa. 1993;91:893-896.
16. Dwyer T, Ponsonby AL, Newman NM, Gibbons LE. Prospective cohort study of prone sleeping position and sudden infant death syndrome. Lancet. 1991:337:1244-1247.
17. Ponsonby AL, Dwyer T, Gibbons LE, et al. Factors potentiating the risk of sudden infant death syndrome associated with the prone position. N Engl J Med. 1993;329;377-382.
18. Fetal and Infant Deaths 1988-1992, Wellington, New Zealand: New Zealand Health Information Service, Ministry of Health: 1993.
19. Dwyer T, Ponsonby A-L, Blizzard L, Newman NM. Cochrane JA. The contribution of changes in the prevalence of prone sleeping position to the decline in SIDS in Tasmania. MMA. 1995;273:783-789.
20. Variations in the incidence of sudden infant death syndrome (SIDS), United States, 1980-1988. Stat Bull Metrop Insur Co. 1993;74:10-18.
21. Katrwinke! J, Brocks ], Keertan ME. Malloy M. Infant sleep position and sudden infant death syndrome (SIDS) in the United States: Joint commentary from the American Academy of Pediatrics and selected agencies of the federal government. Pediatrics. 1994;93:820.
22. Ponsonby A-L, LVyer T, Gibbons LE. The risk of sudden infant death. N Engl J Med, 1994;330:64.
23. Spiers PS, Guntheroth WG. Recommendations to avoid the prone sleeping position and recent statistics for sudden infant death syndrome in the United States. Archives of Pediatrics and Adolescent Medicine. 1994;148:141-146.
24. Kraus JF, Greenland S, Bulterys M. Risk factors for sudden infant death syndrome in the US collaborative perinatal project. Int J Epidemiol. 1989;18:113-120.
25. Ford RPK, Taylor BJ, Mitchell EA, et al. Breastfeeding and the risk of sudden infant death syndrome. Int J Epidemiol. 1993;22:885-890.
26. Jones ME, Ponsonby A-L, Dwyet T, Gilbert N. The relation between climate, temperature and SIDS differs amongst communities: results from an ecological analysis. Epidemiologo. 1994;5:332-336.
27. Fleming PJ, Gilbert R, Aza: Y, et al. Interaction between bedding and sleeping position in the sudden infant death syndrome: a population based case-control study. BMI- 1990:301:85-89.
28. Ponsonby AL, Dwyer T, Gibbons LE, Cochrane J, Jones ME, McCaIl MJ. Thermal environment and sudden infant death syndrome: case control study. BM J 1992:304:277-304.
29. Scragg R, Mitchell EA, Taylot BJ, et al. Bedsharing, smoking, and alcohol in the sudden infant death syndrome. New Zealand Cot Death Study Group. BMJ-1993;307:1312-1318.
30. McKenna JJ, Mosko S, Dungy C, et al. Sleep and arousal patterns of co-sleeping human mother/infant pain: a preliminary physiological study with implications fot the study of sudden infant death syndrome (SIDS). AmJ Phys Anthropo!. 1990;83:331-347.
31. Byard RW. Is co-sleeping in infancy a desirable or dangerous practice? J Poediacr Child HeM. 1994;30:198?99.
32. De Jonge GA,Hoogenboetem J. Wiegedood in Nederland in de periode 1980-193. Ned Tijdschr Geneeskd. 1994;138:2133-2137.
33. Dwyer T, Ponsonby A-L Sudden infant death syndrome - insights from epidemiological research. J Epidemiol Community Health. 1992;46:98-102.