Recently, a novel study exploring a possible link between an enzyme deficiency and increased risk of SIDS by Carmel Harrington and colleagues has been sending ripples through the sleep world. I’ve noticed a lot of excitement, and yet lots of people asking the inevitable question: ‘What does this mean for parents?’

It’s a good question. Whenever a new research study comes out with an important finding, we must ask ourselves what the implication is. Is it merely a scientific curiosity, or does it have real-world ramifications? Understandably, with a topic as emotive as SIDS

I will preface this by reminding people that I am not a sleep researcher, chemist, neuroscientist or a molecular scientist. I’m merely a responsive sleep advocate and public health nurse, who happens to have cared for many families who have suffered the loss of a child. My work will always have a person-first focus, and this means that I tend to zero in on what the meaning is for families.

But without further apologetics, this is my ‘real-world’ understanding of this study and its possible implication to those supporting families at the coal face.

This was a case- control study of 67 infants whose deaths were classified as a sudden unexpected death, whose blood spots taken from routine newborn blood screening were compared with gender and date of birth matched surviving control infants.

Briefly, they found that an enzyme called butyrylcholinesterase (BChE) was found in lower amounts in the blood of the infants who died.

What we already know about SIDS:

· We do not know what ‘causes’ SIDS. Although there are associations and risk factors, we cannot currently explain why some babies die, which is important, because if we knew why they had died, we would be better able to understand how to potentially prevent some of those deaths.

· The best or most widely accepted model we have to date remains the triple risk model, which explains a cluster of factors that are associated with higher prevalence of SIDS. These are; a vulnerable infant, a critical developmental period, and an environmental stressor.

· Some known infant vulnerabilities include male sex, prematurity and low birth weight, and some non-white ethnicities. Infants who have a respiratory condition and certain brain defects are also more vulnerable.

· Infants are most likely to die between 2-4 months.

· The environmental risk factors associated with SIDS include prone sleeping, cigarette smoke exposure, soft bedding, overheating and formula feeding.

· For some time, researchers have believed that there may be a factor involved in infant arousal levels that makes them more vulnerable to SIDS.

Probably the least well-understood part of the SIDS puzzle is what makes an infant more vulnerable. This is key, because many babies who sadly die do not have an obvious risk

factor or immediately apparent vulnerability. So, it has long been suspected that another mechanism may explain some of these so far unexplained deaths.

One proposed mechanism is that babies who die have altered arousal mechanisms – this means that they are less likely to stir and wake up if they are compromised. If, for example, an infant rolls onto their front, and the oxygen level drops due to reduced fresh air circulation, then the brain should trigger a wake up. This is thought to explain why infants are more at risk when we promote any strategy that decreases the arousal response – such as being overly warm, over-full, or on the stomach. Anything that promotes ‘longer, more undisturbed sleep’ should make us question safety, as we know that SIDS is associated with these decreased arousal responses. This is why products designed to reduce arousal aren’t such a great idea (think tight swaddling, the snoo, and so on).

But what might be causing some babies to have lower levels of arousal? Well, that’s what the study was looking at. The researchers were measuring levels of an enzyme that supports the functioning of the major neurotransmitter of the autonomic nervous system.

Sleep is a feature of the parasympathetic nervous system, while alertness and arousal responses are a feature of the sympathetic nervous system. Acetylcholine is a neurotransmitter involved in our autonomic nervous system – both in the sympathetic nervous system, but most of all in the parasympathetic nervous system. Acetylcholine affects both the central and peripheral nervous system by acting as a modulator of the autonomic nervous system. An important function is that it activates skeletal muscles – which are involved with voluntary movement and controlled by the brain and spinal cord. The effect on the parasympathetic nervous system is that acetylcholine causes muscles to contract or move. Acetylcholine also has an important role in memory, REM sleep promotion and seems to suppress inflammation.

Now, what has all this got to do with SIDS?

Well, acetylcholine is broken down by two enzymes – one of which is BChE. The other enzyme is Acetylcholinesterase (AchE), which the researchers were unable to measure in this study. These enzymes work on almost all body tissues, and it has been suggested that they may be markers of various diseases, including inflammatory disease and Alzheimer’s. Low levels of BChE may mean that less acetylcholine is available, and thus, this could explain one mechanism for decreased arousal response. The researchers point out that babies whose death is coded as SIDS also have decreased serotonin activity. Serotonin pathways and cholinergic pathways interact in a bidirectional way so the two systems may combine to lead to decreased arousal response and failed autoresuscitation.

Now, maybe if you’re like me, having read the study, you might have more questions than you did before. For a start, this study makes me wonder what the implication of this is for families, or if indeed this is something we need to sit on for a while and gather more data.

But here are my main musings from the study (and I reiterate my earlier caveat about not being a super clever molecular scientist here…)

· It would be useful to see a larger study exploring what the population level prevalence is of lower BChE.

· Does low BChE in and of itself cause some deaths to occur, or does it indirectly point to an altered arousal mechanism (i.e is it part of a more global deficiency)?

· The researchers were unable to measure AChE – it would be interesting to know to what extent a low level of one of the enzymes is representative of the level of the other, and whether one might compensate in some way if levels of one are low.

· It would also be useful to know whether there is a risk cut-off point for these low levels of BChE (and potentially AChE).

· It would be helpful to know whether there is a level at which pathologically low BChE means that SIDS is certain, or to what extent reducing other modifying risk factors is a significant enough buffer in those cases.

· How many SIDS deaths would this deficiency account for? We know that some SIDS deaths are re-classified as suffocation, subclinical infectious process, or due to a previously undiagnosed cardiac defect. Will we eventually be able to explain all SIDS cases by identifying more and more causes of death so that it is no longer an unexplained event?

· How many children in the population have survived these low levels of BChE and why did they survive? What was the protective mechanism? Or was it down to chance?

The biggest issue for me right now is the moral responsibility that comes from knowledge of something over which we currently have no control or cure. You may have already thought about this, but there is a major compassionate or ethical dilemma – this marker of lower BChE enzyme levels is present from birth. How do we handle that? Given that SIDS is a relatively rare event, and is likely to be multi-factorial, would we do more harm than good by informing parents of this low level of BChE? This is where understanding the relative risk of SIDS at different concentrations of BChE would be helpful to quantify the risk in some way. For example, if an outcome is rare, and a particular factor doubles the risk, it is still rare – but of course the take-home message to a parent is still likely to be one that might be fraught with doom and despair. Importantly, I must stress that there is no hint from the researchers that this would be their plan, and the lead author is well known to be the mother of a child who died of SIDS, so I very much doubt that lack of sensitivity to this issue is an immediate concern.

Essentially, I suppose I’m asking – would this information only be useful retrospectively, to explain an infant’s death, or would it be more useful to predict it? As a public health nurse with a family centred, compassionate focus, I do wonder whether it is right to inform a parent of a potentially life-threatening factor over which they have no control, and for which there is no preventative mechanism or cure.

But… if there was a way to treat this low level of BChE – wow. That really would be an incredible literal lifeline for families. I wait with some cautious and curious anticipation for the next steps…

Lyndsey Hookway is a paediatric nurse, health visitor, IBCLC, holistic sleep coach, PhD researcher, international speaker and author of 3 books. Lyndsey is also the Co-founder and Clinical Director of the Holistic Sleep Coaching Program, co-founder of the Thought Rebellion, and founder of the Breastfeeding the Brave project. Check Lyndsey’s speaker bio and talk brochure, as well as book her to speak at your event by visiting this page. All Lyndsey’s books, digital guides, courses and webinars can be purchased here, and you can also sign up for her free monthly newsletter here.