Brainstem abnormalities 

31 October 2006

Comment on the JAMA paper by David Paterson et al on multiple serotonergic brainstem abnormalities in SIDS

Many previous papers have found apparent differences in brainstem function between SIDS and non-SIDS deaths in infancy. In addition to previous studies by Dr Kinney and collaborators (the authors of the new study), referred to in the paper,1-3 there are reports from another group in Chicago4, 5 also implicating the serotoninergic system. There is also a considerable amount of work from the laboratory of Dr Hugo Lagercrantz in Stockholm, among others, demonstrating abnormalities in neurotransmitter systems in SIDS babies and animal models, including the interesting observation that nicotine adversely affects the development of these systems6 (smoking in pregnancy is a well established risk factor for SIDS). This new paper is therefore an interesting extension of previous work.

Dr Kinney is the originator of the triple risk hypothesis of SIDS, which holds that SIDS is likely when three separate categories of risk coincide. The first is some genetic or inborn susceptibility (which the new work comes within), the second is a particular stage of development (which is necessary to explain the age range distribution of SIDS) and the third is the effect of one or more ‘exogenous stressors’ such as infection, hypoxia or overheating. It is clear from the paper that the differences that were found between SIDS and non-SIDS medullae were large in magnitude and most unlikely to be due to chance or sampling error. The authors therefore interpret their new findings as support for the triple risk hypothesis.

The authors’ interpretation of the significance of their findings in relation to the causation of SIDS may be correct but this does not rule out a contribution of other genetic differences between cases and controls such as variation in mediators of inflammation. Although the authors focus on the possible role of hypoxia and carbon dioxide retention as exogenous triggers, infection or exposure to bacterial toxins might also exert their deleterious effects partly through the disordered serotoninergic system documented in this and previous papers. Furthermore, the clinical information available was insufficient to allow for an assessment of the effect of smoking on the findings, as mentioned by the authors in the last paragraph of the Study Limitations section of the Comment part of the paper.

In addition, the comment that ‘normal babies will wake up, turn over and start breathing faster when carbon dioxide levels rise’ (attributed to Dr Kinney in the press release) is unlikely to be correct, since the peak incidence of SIDS is in the age range 2-4 months, at which developmental stage babies cannot turn over anyway.

That said, the findings in the new paper are important, taken with the previous reports referred to above, but are unlikely to be the only inherited or non-modifiable risk factor, considering for example the work of the various scientists (e.g. Drucker, Blackwell, Opdal) who have also found convincing evidence that minor genetic differences between babies may cause some of them to be more vulnerable than others to common infections, especially those caused by certain types of bacteria.

Professor George Haycock, FSID’s Scientific advisor, says: “Although the causes of sudden death in infancy remain unknown, it is generally agreed they are multi-factorial, and the present paper adds useful information. But much more research is needed in order to understand and, ultimately, prevent these tragedies, which claim about 300 babies’ lives each year in the UK.”


References

1. Kinney HC, Filiano JJ, White WF: Medullary serotonergic network deficiency in the sudden infant death syndrome: review of a 15-year study of a single dataset. J Neuropathol Exp Neurol 60:228-247, 2001.
2. Kinney HC, Randall LL, Sleeper LA, et al.: Serotonergic brainstem abnormalities in Northern Plains Indians with the sudden infant death syndrome. J Neuropathol Exp Neurol 62:1178-1191, 2003.
3. Panigrahy A, Filiano J, Sleeper LA, et al.: Decreased serotonergic receptor binding in rhombic lip-derived regions of the medulla oblongata in the sudden infant death syndrome. J Neuropathol Exp Neurol 59:377-384, 2000.
4. Weese-Mayer DE, Zhou L, Berry-Kravis EM, et al.: Association of the serotonin transporter gene with sudden infant death syndrome: a haplotype analysis. Am J Med Genet A 122:238-245, 2003.
5. Weese-Mayer DE, Berry-Kravis EM, Maher BS, et al.: Sudden infant death syndrome: association with a promoter polymorphism of the serotonin transporter gene. Am J Med Genet A 117:268-274, 2003.
6. Holgert H, Hokfelt T, Hertzberg T, Lagercrantz H: Functional and developmental studies of the peripheral arterial chemoreceptors in rat: effects of nicotine and possible relation to sudden infant death syndrome. Proc Natl Acad Sci U S A 92:7575-7579, 1995.

– ENDS –

For more information call Nicola Peckett, Communications Manager, on 020 7227 5212 or Stacey Kerr, Communications Officer, on 020 7227 5210. Out of hours 07904 198 552.


Notes to editors:

The Foundation for the Study of Infant Deaths is the UK’s leading baby charity working to prevent sudden deaths and promote health. FSID funds research (nearly £9 million to date), supports bereaved families and promotes safe baby care advice.

FSID runs a Helpline (020 7233 2090) for parents and professionals seeking advice on safe baby care. The Helpline also supports bereaved families.

 

More Press releases »