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expert reaction to study attempting to identify cause of and biomarker for Sudden Infant Death Syndrome (SIDS)

A study published in eBioMedicine identifies a possible biomarker for Sudden Infant Death Syndrome (SIDS).


Prof Peter Fleming, Professor of Infant Health, University of Bristol, said:

“The authors in the paper have been very correctly reticent about this study being overinterpreted.

“The study shows a small difference in the activity level of butyrylcholinesterase, taken just after birth, between those babies who died of SIDS and those who died of something else or didn’t die.  But the difference is very small.  It is significant at the population level but not at the individual level.

“It is a small study but is well done – it is excellent science but the number of babies in it who died of SIDS is small.  It is a preliminary study and we must not overinterpret it.

“At the individual baby level, 50% of the babies in this study who died of SIDS had butyrylcholinesterase levels in the same range as healthy babies.  So this is not a biomarker at an individual level.

“In the study the authors had little information about the individual babies (for correct information governance reasons).  They didn’t know for example whether mothers smoked or babies had growth problems in utero.

“It is possible that what this study is showing is that infants of mothers who smoke during pregnancy have lower levels of butyrylcholinesterase.  Smoking in pregnancy is a known risk factor and babies of mothers who smoked in pregnancy are about four times more likely to die from SIDS.  So it could be that the result is showing a biological reason behind a risk factor we already know about – the authors don’t know whether mothers smoked, so we can’t rule this out as a possibility.

“Also babies who have growth problems in utero are at greater risk of SIDS – the authors didn’t have data on that, so we don’t know whether that could be an explanation too.

“This is still an important study, but it might be pointing towards a biological reason why some babies are at higher risk of SIDS from the risk factors we already know about, rather than identifying a ‘new’ risk factor.

“The odds ratios in the paper for healthy babies compared to babies who died from SIDS are between 0.6 and 0.89 – this means that for babies with low levels of butyrylcholinesterase the risk of SIDS was up to 66% higher than normal.  By contrast, we know that smoking in pregnancy increases the risk by 400% – so this is a small risk by comparison.

“We cannot take from this study that we can do a test on individual babies to work out their risk of SIDS, but it will be important to replicate the findings in a larger study and investigate how this finding relates to the other known risk factors for SIDS.”


Prof Alastair Sutcliffe, Professor of General Paediatrics, UCL, said:

“This study is attempting to have some proxy measure of increased risk of SIDS.  It was controlled study, which is a strength.

“It has long been recognised that SIDS is not a single entity.  The most dramatic intervention has been the ‘back to sleep’ campaign.  Other recognised risks are co-sleeping if a carer is drunk or on drugs.

“The balance of SIDS deaths outstanding to date (the back to sleep campaign having caused a 50% reduction of the condition) are a mixed range of causes with some never determined.

“The researchers have taken data from existing blood spots and compared the assay of an enzyme which moderates the actions of a neurotransmitter.  They could not assay one of the two neurotransmitters, acetyl cholinesterase, so the one they did measure was butyrylcholinesterase.  This only represents part of what is going on at the neurotransmitter end plate (literally where two nerves at a junction communicate with each other) as one enzyme could not be measured.  Notwithstanding this, the findings suggest different levels of the measured enzyme in children who have died versus controls.

“So where might this lead?  First it might be that other researchers do not corroborate this finding and it was a random positive result (I hope not for SIDS sake).  Second, it might be that further research corroborates the same finding, in which case there is then an indication to do a full national study.  The third question to answer is when butarylcholiesterase goes up, what is the effect on acetylcholinesterase?, does that interplay and if so on which direction?

“It is way too early to start talking about at-risk SIDS screening being brought in, those blood samples are precious.  However the initiative led by these researchers may lead to great insights.

“The key and established facts around SIDS – ‘back to sleep’, don’t over heat, no smoking, no drinking if co-sleeping – remain some way to be universally applied.  It remains a sad and salient fact that you are most likely to die as a human being the day of your birth – this is before SIDS, and is an area (the care of pregnant women) where resources need to be continued to focussed and increased.”



‘Butyrylcholinesterase is a potential biomarker for Sudden Infant Death Syndrome’ by Carmel Therese Harrington et al. was published in eBioMedicine.

DOI: 10.1016/j.ebiom.2022.104041



Declared interests

None received.

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