Sudden infant death syndrome (SIDS) is the most frequent cause of death between 1 month and 1 year of age (Naeye). SIDS is defined as the sudden death of any infant or young child that is unexpected by it’s history, and in which a thorough postmortem examination fails to determine an adequate cause (Hunt 1987). It is important to consider both aspects of this definition in order not to ‘overdiagnose’ SIDS. A mistake of this nature would occur with failure to report a previous history of seizures, or if at the time of the autopsy a differentiation between suffocation due to rebreathing and SIDS was not made (Kemp 1993). One of the major characteristics of SIDS is that of ‘silent death’, which occurs during a sleep period. The majority of SIDS cases are between 1-6 months, with the peak occurrence being between 2-4 months. Boys are affected more often than girls (Becker, 1990).

Although there are many theories in regards to the cause of SIDS, the principle cause has not as yet been identified. Most researchers attribute the underlying mechanism of death to acute respiratory insufficiency occurring predominantly during sleep. Due to the lack of evidence of lung or heart abnormalities, recent studies have focused on the theory of a dysfunction of the neural control of respiration and cardiac function (Becker, 1990). There are currently several branches in this area of research. In this paper I will introduce the involvement and validity of brainstem abnormalities, neurotransmitters, and neural maturational delays.

During infancy (2-8 months), respiratory control is almost entirely dependent on brain stem control (Naeye). Due to the fact that this is also the peak time for SIDS, the hypothesis that abnormalities in this area could account for the fatalities is feasible. A study was conducted by Naeye et al. to determine if the nucleus of the hypoglossal nerve and the nucleus of the vagus nerve showed any abnormalities in SIDS patients. These structures were chosen because it is thought that some victims may have their airway blocked by their tongue during sleep (the hypoglossal is known to control tongue movements), or that possibly cardiac arrhythmia’s may be the cause of SIDS death (due to the vagus nerve) (Naeye). It was found that there were fewer neurons in the hypoglossal nerve nuclei of SIDS victims with abnormally small carotid bodies. This could in fact be an explanation for the obstruction of the airway by the tongue during obstructive apnea (Naeye). An explanation of why there were fewer neurons was not given.

The human brain is not fully developed at birth (Kopp 1992). This plays a role in the aspect of certain neurotransmitters which are vital to the human body. It has been demonstrated that in a normal central nervous system, serotonin declines as well as norepinephrine in the first few months after birth (Becker 1990). In a study conducted by Hilaire et al., it was postulated that increased levels of serotonin might be involved in obstructive apnea, leading to SIDS (Hilaire 1992). The reasoning for this was that serotonin depresses the hypoglossal respiratory output. The results did in fact cause lethal apneas of newborn rats which were injected with L-tryptophan thereby stimulating serotonin synthesis.

There has also been evidence that other neurotransmitters, such as catecholamines, beta-endorphin, met-enkephalin, and substance P ,play a role in SIDS. The carotid bodies have been examined and have shown increased levels of noradrenaline, adrenaline, and dopamine. Dopamine showed the greatest increase in SIDS victims when compared to the control group (Becker). This is of importance because we know that dopamine inhibits respiration by acting directly on the carotid bodies. It also has an inhibitory effect on the carotid body’s response to hypoxia. However, it is not certain if the carotid body catecholamine abnormality is the cause or the result of chronic hypoxia. Evidence indicates that it is the increased release of the neurotransmitters that is the cause of the problem in the carotid bodies.

Substance P (SP) may be another neurotransmitter which is involved in SIDS. SP has been shown to stimulate breathing and has been detected in neural structures such as the solitary nucleus which are involved in the respiration process. It has been proposed that SP is a mediator in the hypoxia respiratory drive. If this is the case, then we would expect to see increased concentrations of SP in the medulla of SIDS victims due to the fact that SIDS victims suffer chronic hypoxia, which would stimulate SP synthesis. This was seen in vivo in a study conducted by Lagercrantz et al. (Lagercrantz).

Neural developmental delay appears to be an important component of SIDS. There is numerous evidence to support this theory. One of the major observations of SIDS is the specific time period at which it occurs, suggesting a developmentally related pathogenesis involving changes in sleep patterns with respiratory and/or cardiac maturation (Becker). There has also been evidence that delayed CNS myelination occurs in SIDS victims. Different regions of the brain region were affected, including those that occur before and after birth (Kinney 1991). It is a simple conclusion then, that the aspect of SIDS affecting myelin formation occurs even prior to birth. This may also play a part in the cardiorespiratory component of SIDS. If the pathways are not properly myelinated, then there is going to be a decreased conduction by those axons which are affected.

The cause of the delayed CNS myelination is unknown at the present time but there are several possibilities that are currently being investigated. One, is that delayed CNS myelination is directly related to cigarette smoking by the mother during pregnancy (Kinney 1991). Although current evidence has not been attained for this possibility, there is a connection between SIDS victims and mothers who smoke. Deficient nutrition is another possibility relating to the delay of CNS myelination. Current research did not provide evidence for this theory at the present time (Kinney 1991).

Further evidence for the theory of delayed maturation of the neuron, is that it has been found that dendritic spines persist in SIDS victims, whereas in normal infants they are not present (Becker 1990). The number of spines reach a maximum number at 34-36 weeks’ gestation and decrease after birth. The presence of the spines in SIDS is thought to impair the higher levels of control for respiration.

The carotid body appears to also be involved with the development of the respiratory process. Prior to birth, the carotid receptors are essentially uninvolved with breathing. Their chemosensitivity increases after birth and is believed to be responsible for postnatal maturation of breathing (Becker). The reasoning for this is due to an experiment in which the carotid bodies of lambs were denervated. Three of the lambs died during the fourth and fifth weeks due to what was thought to be prolonged apnea during sleep. This is similar to what is seen in SIDS victims.

Once again, at the present time, no definitive cause of SIDS has yet been found. It is now believed that it is a result of multiple factors of which some I have discussed in this paper. I believe that the underlying mechanism is in fact located in the central nervous system and that a late maturation is very likely to be an important component of SIDS.

WORKS CITED:

Becker, L. E. (1990) Neural Maturational Delay as a Link in the Chain of Events Leading to SIDS. Canadian Journal of Neurological Sciences. 17(4): 361-369.

Hilaire, Gerard et al. Changes in Serotonin Metabolism May Elicit Obstructive Apnea in the Newborn Rat. Journal of Physiology. 1993; 466:367-382.

Hunt, C. E. and R. T. Broillette. Sudden Infant Death Syndrome 1987 Perspective. The Journal of Pediatrics. May 1987; 110(5): 669-678.

Kemp, J. S. et al. Unintentional Suffocation by Rebreathing: A Death Scene and Physiologic Investigation of a Possible Cause of Sudden Infant Death. Journal of Pediatrics. 1993;122:874-880.

Kinney, H. C. Delayed Central Nervous System Mvelination in the Sudden Infant Death Syndrome. Journal of Neuropathology and Experimental Neurology. January 1991; 50(1):29-48.

Kopp, N. et al. Ontogeny of Peptides in Human Hypothalamus in Relation to Sudden Infant Death Syndrome (SIDS. Progress in Brain Research. 1992;93: 167-185.

Lagercrantz, H. and M. Runold. Hypoxemia and Neuropharmacoloay of Breathing. Marcel Dekker, Inc. 1991.

Naeye, R. L. New Brain Stem and Bone Marrow Abnormalities in Victims of Sudden Infant Death Syndrome. Journal of Perinatology. 9(2):180-183.