Sudden Infant Death Syndrome (SIDS) and Seratonin: The Genetic Segue
Professor Debra E. Weese-Mayer, Children's Memorial Hospital, Chicago
£85,500 over 2 years

To identify variations in genes that may contribute to the risk of SIDS. Identification of these genes may further define the genetic profile of infants at risk of SIDS, explain underlying mechanisms for SIDS and ideally allow for the implementation of mechanism specific treatment of the "at risk" infant.

Safe Sleeping: Does swaddling improve infant sleep without decreasing arousability?
Professor Rosemary Horne, Melbourne, Australia
£12,900 over 1 year

Swaddling is a method of improving infant sleep in the supine position. However, swaddling may reduce infant arousability. This study will examine the effects of swaddling on infant sleep and arousal and aims to identify if swaddling can be safely recommended to reduce SIDS.

Disruptions in the balance between Placental Villous Trophoblast Proliferation and Apoptosis in Intra Uterine Growth Restriction (IUGR) and Sudden Infant Death Syndrome (SIDS) and the consequences for foetal growth
- Dr Tahera Ansari, NPIMR (£80,194.80 over 3 years)

There has been a considerable reduction in the number of infants dying from Sudden Infant Death Syndrome (SIDS) or cot death over the past decade. World wide scientific research on SIDS has highlighted a number of specific risk factors, e.g. maternal smoking and sleep position and has also pointed towards an infant born with hidden developmental vulnerability. Our research has centred on events prior to birth whilst the baby is still growing and developing inside the mother. The organ that plays the greatest role whilst a baby is developing is the placenta or after-birth. This organ is responsible for the transfer of the nutrients and oxygen to the baby and removal of waste products. Any abnormality within the placenta has the potential to adversely affect the way the baby develops.

The placenta has a unique group of cells which make up a membrane responsible for the transfer of oxygen and nutrients to the baby from the mother. The way this placental membrane develops is crucial for healthy growth of both the placenta and the baby. Our investigation will look at how this membrane renews itself by analysing the balance between cells dying and reproducing in placentae from healthy infants and comparing the data with data from placentae from SIDS infants. The information obtained will help us understand why SIDS infants show altered patterns of growth and development whilst inside mum.

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.

Multiple Serotonergic Brainstem Abnormalities in Sudden Infant Death Syndrome
– Dr David Paterson, Boston Children’s Hospital

Research from David Paterson and his colleagues at Boston Children's Hospital into "Multiple Serotonergic Brainstem Abnormalities in Sudden Infant Death Syndrome" (see below) generated much excitement in the press in November. The research was part funded by the Trust and we are delighted to be included in the positive outcomes. Sudden infant death syndrome is the leading cause of postneonatal infant death in the United States as well as in Scotland and, despite intensive research, the causes of SIDS remain unknown. Previous research has suggested that abnormalities in the brainstem area that regulates breathing may play a role in SIDS.

The researchers analysed frozen samples of the medulla from 31 infants who died from SIDS and from 10 infants who died from causes other than SIDS. These were then compared. The authors write "We found that the abnormalities in SIDS are more extensive than previously suggested".

This study strengthens the hypothesis that brainstem dysfunction is associated with SIDS and may lead to death by a failure of respiratory responses.

This study also found reduced receptor binding in male compared with female SIDS cases, an observation that may help explain why males are more vulnerable to SIDS. These abnormalities were documented during the era of stringent public messages on risk reduction, including that for supine sleep position.

The majority (65 percent) of the SIDS cases in this data set, however, were sleeping prone or on their side at the time of death, indicating the need for continued public health messages on safe sleeping practices. The researchers speculate that the increased risk of SIDS in the prone or face-down position may reflect the infants' inability to respond to the challenge to breathe in the face-down position.

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.