Research review 2007 

The epidemiological profile of SIDS has changed in recent years, following the widespread adoption of the recommendation to sleep babies on their backs and other key messages proven to reduce the cot death risk.

Deprived families
This was highlighted by the Avon research group, led by Professor Peter Fleming, who found that over the last 20 years, the proportion of SIDS deaths occurring in socio economically deprived families has risen from 47% to 74% and the proportion affecting prematurely born infants has risen from 12% to 34%.(1 )

Rising proportion of bedsharing deaths
In addition, the proportion of deaths occurring in infants who were bedsharing with their parents has risen from 12% to 39% (and 11% while sofa sharing), although it is important to recognise that the absolute number of deaths occurring in these circumstances has fallen, although to a lesser extent than the fall in the death rate among non-bedsharing infants.

Education
Similar demographic changes have also been observed in other countries, for example in Norway, where the risk of SIDS fell among infants born to well educated men between the 1970s and the 1990s, while it actually rose during the same period among infants born to poorly educated women.(2)

Smoking
The importance of smoking as a risk factor has been emphasised in a number of publications. In one of these,(3) the Avon group showed that the proportion of SIDS cases occurring in babies of smoking mothers had risen from 50% to 80% while the proportion of mothers in the population as a whole had fallen from 30% to 20%.

The risk is dose related: a baby born to a mother who smoked 20 or more cigarettes during pregnancy is more than 8 times more likely to die of SIDS than one born to a non-smoking mother. Studies from Leicester(4) and Germany(5) confirm that nicotine and cotinine (a metabolite of nicotine) levels in body fluids and hair of babies are higher, unsurprisingly, in babies of smoking mothers but also that these chemicals were detected in some babies whose mothers denied smoking during or after pregnancy, suggesting that these accounts are not always reliable or that passive smoking from sources other than the mother may be important. Also, the German study found cotinine levels were not significantly higher in breast fed infants whose mothers smoked than in bottle fed ones, indicating that transfer of nicotine and cotinine in breast milk was not a significant factor and that passive smoking was the major cause of the observed high levels.

Brain stem function
The reason that smoking is such an important risk factor is not well understood, but animal studies have previously suggested that nicotine may adversely affect the part of the brain (the brain stem) that is responsible for basic life support functions such as control of breathing and heart function and the ability to arouse from sleep if breathing is compromised.(6) The group led by Dr Hannah Kinney at Harvard Medical School has been studying neurotransmitter function in the brain stem for some time, particularly the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). In one recent study marked differences were found in the distribution of both neurons (brain cells) that synthesize 5-HT and of the receptors for 5-HT in the medulla when babies who had died of SIDS were compared with those who had died of other causes.(7) Work in this area is continuing, and a another recent study from the same group has defined the normal developmental pattern of the 5-HT system in the human medulla as a basis for further studies of abnormal development and function.(8)

Infection and bacterial toxins
Research is continuing in a number of laboratories on the role of altered inflammatory responses to infection and exposure to bacterial toxins, which may be an important contributory factor in many cases of SIDS. Inflammation is largely mediated by chemicals called cytokines, some of which increase the magnitude of the inflammatory response (e.g. a chemical called interleukin-6, IL-6) while others (e.g. IL-10) reduce it. Scientists in Newcastle, Australia(9) and Oslo (10) have recently found genetic differences (polymorphisms) in the chemical structure of IL-6 between babies who died of SIDS and normal controls. Another group in Manchester has also found polymorphisms for a chemical called vascular endothelial growth factor (VEGF) that are commoner in SIDS babies than others,(11) as well as confirming the differences in IL-6 structure. VEGF is important in the development of many vital organs including the lungs, and it is hypothesised that the polymorphism found in SIDS infants may predispose to abnormal respiratory responses during stress.

Glucose metabolism
Professor Ann Burchell and her colleagues in Dundee have been studying glucose metabolism in infancy and in particular in premature infants and SIDS victims for some years now. The latest finding to emerge from this work is that polymorphisms for an important protein in glucose metabolism, the glucose-6-phosphate transporter, differ among various groups of infants, in particular between SIDS infants and non-SIDS infants born at term.(12) Thus abnormalities of glucose metabolism, in addition to the other genetic variations previously discussed, may also contribute to mortality from SIDS, perhaps because affected infants are unable to raise their blood glucose levels in the normal manner in response to stress.

Immunisation reduces SIDS risk
Some people (in the absence of any scientific evidence) have suggested in the past that immunisations routinely given in infancy may increase the risk of SIDS. The recent publication of an important meta-analysis by the German SIDS research group is therefore to be welcomed, because it shows clearly that immunisation reduces, rather than increases, the risk of SIDS significantly.(13) The effect is substantial, the risk to immunised babies being approximately half that to non-immunised ones. The recommendation that all infants should receive the normal programme of immunisations in infancy and beyond is strongly reinforced by these findings, and is explicitly endorsed by the Epidemiology Working Group of the International Society for the Prevention of Infant Death (ISPID).

An overview of the current state of SIDS research, written in (as far as possible) non-technical language, was recently published in the Journal of Family Health Care.(14)

References:
1 Blair PS, Sidebotham P, Berry PJ, et al. Major epidemiological changes in sudden infant death syndrome: a 20-year population-based study in the UK. Lancet 2006;367(9507):314-9.
2 Arntzen A, Samuelsen SO, Daltveit AK, et al. Post-neonatal mortality in Norway 1969-95: a cause-specific analysis. Int J Epidemiol 2006;35(4):1083-9.
3 Fleming P, Blair PS. Sudden Infant Death Syndrome and parental smoking. Early Hum Dev 2007;83(11):721-5.
4 Joseph DV, Jackson JA, Westaway JA, et al. Effect of parental smoking on cotinine levels in newborns. Arch Dis Child Fetal Neonatal Ed 2007.
5 Bajanowski T, Brinkmann B, Mitchell EA, et al. Nicotine and cotinine in infants dying from sudden infant death syndrome. Int J Legal Med 2008;122(1):23-8.
6 Cohen G, Roux JC, Grailhe R, et al. Perinatal exposure to nicotine causes deficits associated with a loss of nicotinic receptor function. Proc Natl Acad Sci U S A 2005;102(10):3817-21.
7 Paterson DS, Trachtenberg FL, Thompson EG, et al. Multiple serotonergic brainstem abnormalities in sudden infant death syndrome. Jama 2006;296(17):2124-32.
8 Kinney HC, Belliveau RA, Trachtenberg FL, et al. The development of the medullary serotonergic system in early human life. Autonomic Neuroscience: Basic and Clinical 2007;132:81-102.
9 Moscovis SM, Gordon AE, Al Madani OM, et al. IL6 G-174C associated with sudden infant death syndrome in a Caucasian Australian cohort. Hum Immunol 2006;67(10):819-25.
10 Opdal SH, Rognum TO. The IL6 -174G/C polymorphism and sudden infant death syndrome. Hum Immunol 2007;68(6):541-3.
11 Dashash M, Pravica V, Hutchinson IV, et al. Association of sudden infant death syndrome with VEGF and IL-6 gene polymorphisms. Hum Immunol 2006;67(8):627-33.
12 Forsyth L, Scott HM, Howatson A, et al. Genetic variation in hepatic glucose-6-phosphatase system genes in cases of sudden infant death syndrome. J Pathol 2007;212(1):112-20.
13 Vennemann MM, Hoffgen M, Bajanowski T, et al. Do immunisations reduce the risk for SIDS? A meta-analysis. Vaccine 2007;25(26):4875-9.
14 Haycock G. Recent research in sudden infant death syndrome. J Fam Health Care 2007;17(5):149-51.

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