Research

Grant Applications

The Scottish Cot Death Trust funds research in a wide variety of disciplines relating to any aspect of sudden infant deaths. Since 1985 it has funded over £2,000,000 of research. Most of the work is carried out by university departments in the UK and very occasionally abroad.

Grant applications are reviewed twice yearly by a Scientific Advisory Committee.

There is a two-stage selection process.

Stage one requires applicants to submit a short outline of their intended proposal including hypothesis, methodology, outcome measures, availability of resource material, statistical procedures and estimate of yearly funding.

Outline proposals are submitted at the beginning of January and July in each year. The closing date for outline proposals this year is 18th July 2005. They are given an initial review and are shortlisted. Applicants whose proposals are shortlisted will be invited to submit a full application by mid-March or mid- September.

Outline proposal and full grant application forms can be downloaded, completed and mailed to:

The Scottish Cot Death Trust
Royal Hospital for Sick Children,
Yorkhill,

Download outline proposal form.

Download grant application form.

Current Research

The Scottish Cot Death Trust funds research in a wide variety of disciplines. Ongoing projects are:

Carbon monoxide: A possible risk factor for SIDS (University of Florence, Italy)

Research has shown that parental smoking, particularly maternal smoking during pregnancy, greatly increases the risk of SIDS for a baby. However, the reason for this has never been properly explained. In newborn babies there is a temporary change in the electro-physiology of the heart which reverts to normal in the vast majority of cases by 6 months of age. If there is a delay in reverting to normal, it may lead to abnormal rhythm of the heart pump and perhaps expose the infant to sudden death. This research group will examine the possibility that the babies exposed to carbon monoxide in the womb (that is, whose mothers smoke) may not make this important move back to normal at the same time as babies whose mothers do not smoke.

The distribution of ß-APP immunoreactivity in SIDS (University of Edinburgh)

Study of brain tissue has revealed a number of tiny abnormalities in SIDS babies. Researchers don’t understand what causes these and many are thought to be the result of lack of oxygen to the brain, an inevitable part of the death process. The research group will examine sections of the brain to identify a protein called ß-APP which is an early marker of damage to nerve cells in the grey matter and to the neuronal processes in the white matter. They will then to relate it to the APOE genotype(see above project) and hope to be able to get an insight into the early abnormalities in SIDS.

The use of ß-APP staining may also help demonstrate important differences between SIDS and cases of non-accidental injury.

Identification of Brainstem Sites Controlling Breathing in the Human Infant (Harvard University, USA)

In the medulla oblongata (part of the brain involved in regulation of automatic physiological functions) of animals a group of cells has been identified that are critical in the control of breathing. These cells are thought to be responsible for the generation of spontaneous rhythmic breathing, i.e., causing regular breathing to occur automatically, regardless of sleep or wake state. These cells have connections with other regions in the brain that control the mechanical muscles of breathing (i.e., diaphragm and muscles in the chest and ribs) and are thought to be able to detect changes in the need for oxygen and alter the rate of breathing accordingly.

Studies have shown that selectively destroying these cells causes an abnormal rhythm of breathing, frequently causing it to stop altogether before starting again (apnea), and an inability to alter breathing to respond to different normally occurring conditions. This group of cells is called the PreBötzinger Complex (preBötC). PreBötzinger Complex cells occupy a specific position in the medulla oblongata and contain the neurochemicals glutamate and somatostatin, specific criteria by which they may be identified.

As yet, a group of cells with the same functions as the preBötC in animals has not been identified in human brain. The aim of this project is therefore to identify a human version of the preBötC by looking for cells in the same position containing glutamate and somatostatin in normal human medulla oblongata. Given the critical involvement of the preBötC in control of breathing in animals, an abnormality in the preBötC in human infants may potentially cause sudden infant death syndrome (SIDS), as SIDS is postulated to involve abnormal central (brain) control of breathing during sleep. Furthermore, preBötC cells receive input from cells in the medulla containing the neurochemical serotonin (5-HT), which change breathing by altering the function of the preBötC. Given that studies in our laboratory have previously identified abnormalities in the 5-HT containing cells in the medulla in SIDS infants, abnormal 5-HT input to the preBötC may disrupt effective control of breathing and cause SIDS.

Successful identification of the preBötC in normal human brainstems will allow future comparison of this region in the medulla of infants dying from SIDS and enable us to examine the possibility that preBötC dysfunction may play a role in SIDS.

Recently completed research projects

Pathological defects in placentas from women whose newborn babies have suffered intra-uterine growth retardation and/or SIDS (Northwick Park Institute for Medical Research, London)

Sudden infant death syndrome (SIDS) is a silent killer, in as much as there are no previous signs, symptoms or warnings that it is going to happen. This research examined how SIDS babies develop before birth. The organ that plays the greatest role whilst a baby is developing is the placenta or the afterbirth. This organ is responsible for the transfer of all the nutrients and oxygen to the baby and removal of all waste products. Any abnormality within the placenta has the potential to affect adversely the way the baby develops.

The research team analysed different subcomponents of placentae from babies who died as a result of SIDS and compared them to normal healthy “control” placentae (that is, from babies who did not die), using highly sophisticated novel microscopical techniques. They found that placentae from SIDS infants develop differently from controls. Since placental features develop in an orderly fashion the team could get an idea at what time point a change was likely to have occurred. The feature showing the greatest difference was the intermediate villi in the SIDS placentae; this structure had a shape that was completely different to that of control placentae.

An intermediate villi with a different shape may impact on blood flow dynamics from the mother to the baby. The conclusion is that developmental changes in the placenta may have an effect on the development of the baby and may make him/her more susceptible to SIDS after birth.

An Evaluation of Cot Mattresses and their Covers as Reservoirs of Toxigenic Bacteria (De Montfort University, Leicester)

The purpose of this research was to investigate the possibility that potentially harmful bacteria become established in cot mattress foams and/or their covers, giving rise to sources of possible infection that may invade the upper respiratory tract of infants. The methodology involved bacteriological testing of currently used polyurethane foam cot mattresses donated by the public; information on the history of use of the cot mattresses was obtained via a mattress donor questionnaire.

The bacteria in cot mattresses was influenced by the sleeping position of the infant and movement on a cot mattress promoted aerial release of bacteria from polyurethane foam. Use of a non-integral (not completely covered in plastic) cot mattress was associated with increased levels of bacterial contamination within the exposed polyurethane foam. Previous use by another child of a non-integral mattress was associated with significantly increased levels of Staphylococcus aureus within cot mattress polyurethane foams. This is a bacterium which is found more frequently in infants who have died suddenly and unexpectedly than in infants who have died from known causes.

The findings could provide a plausible explanation for recently identified possible risk factors for SIDS, i.e. sleeping at night on mattresses used previously by another child and use of mattresses not entirely covered with a waterproof cover. Data obtained on soluble protein and dust-mite allergen levels within polyurethane foams corroborate these findings. The fact that bacterial growth/survival is encouraged by organic matter contamination, such as urine, breast or formula milk, or by high relative humidity indicates that maintenance of a clean and dry cot environment would help to minimise development of reservoirs of bacteria within cot mattress materials. Staphylococcus aureus was shown to have good survival capability on polyurethane foam even at low relative humidity and to be capable of breakdown of polyurethane.

The molecular basis of intrauterine growth retardation in cases of sudden and unexpected death in infancy (University of Dundee)

Glucose is the primary source of energy for the brain. The brain cannot make sufficient glucose for its own needs so it must obtain glucose from the blood. It is therefore vital that blood glucose concentrations are maintained within a restricted range – neither too high or too low.

Episodes of low blood glucose can lead to brain damage and in extreme cases even to death. Low birth weight infants are particularly vulnerable to low blood glucose levels, and low birth weight is also a risk factor for sudden and unexpected death in infancy. Research has previously shown that some infants dying suddenly and unexpectedly have defects in liver glucose production, which could lead to low blood glucose at times of stress or reduced milk intake.

The researchers in Dundee believe that many of these defects in liver glucose production are as a result of failures to regulate this system at birth. They have investigated the molecular nature of this regulation, and have shown that subtle alteration in the structure of regulatory regions of genes that control glucose levels occur in some infants. The next phase of this work is to identify these changes in genes at the time of birth to determine which infants are at greatest risk at times of stress. Once we have the knowledge of which infants are at risk then simple preventative measures such as changes in feeding patterns combined with emergency action plans to deal with the normal minor ailments of infancy will lower the risks.

Smokechange: Smoking Cessation during Pregnancy
A Randomised Controlled Trial of Home-based Motivational Interviewing (University of Glasgow)

This study aimed to establish whether the use of motivational counselling during pregnancy would help pregnant women to stop smoking. All self-reported smokers in two Glasgow maternity hospitals were given routine information about smoking and pregnancy by the study midwives. Half of them were, in addition, offered an extra 2-5 home-based motivational interviewing sessions lasting about 30 minutes each. Their quit and reduction rate was compared with those offered information only, and self reporting was corroborated by measuring routine blood or saliva cotinine at late pregnancy follow-up compared with booking.
The researchers concluded that, even with dedicated, well-trained midwives, the offer of motivational counselling on its own did not decrease the habits of pregnant smokers.

Apolipoprotein E Genotype: A comparison and SIDS and known causes of death in infancy (University of Edinburgh)

Some theories about the causes of SIDS have centred on poor control of breathing, subtle heart abnormalities, or an unusual susceptibility for the baby's defences to be overwhelmed by minor infections or other environmental problems which normal babies are well able to survive. This variation between babies may be controlled by the baby's genes.

For a number of years the work of this research team has focussed on brain damage in babies who die in infancy and the investigation of the possible causes. They identified the apolipoprotein E (ApoE) gene as possibly relevant to SIDS for a number of reasons. This gene is concerned with transport and maintenance of fatty substances in the body. It also has a role in controlling the response to infection. The brain has a high content of fat combined with protein which it uses for the insulation of nerve fibres. The gene exists naturally in three different forms ApoE e2, ApoE e3 and ApoE e4 which vary in their ability to maintain normal fats and proteins. Variations in the gene have also been clearly linked to the response of the brain to ageing (ApoE 4 is more common in Alzheimer's disease) and to other harmful circumstances such as stroke and head injury. The researchers wished to establish whether the unusual forms of the ApoE gene (ApoE 4 and ApoE 2) were more common in babies who died of SIDS compared with other babies who died of known disorders at the same age.

They investigated 296 babies, made up of 170 babies who died of SIDS and 126 babies who died of other causes. They compared these findings with the knowledge they had already gained about healthy babies who were still alive as well as what is known about adults. They found a small increase in the number of SIDS babies who possessed the ApoE e4 gene compared with non-SIDS babies. However the difference was not sufficiently large to convince them that the ApoE gene was a major influence in causing SIDS. They are undertaking further work to see if there are differences between the babies who have different ApoE genes. These differences are likely to be subtle. Meanwhile there are other likely genes which influence a baby's ability to survive and future research will certainly move in this direction.