Sudden infant death syndrome ( SIDS) is the greatest cause of infant deaths ranging 
from ages one month to one year. Most of these deaths occur before the age of six months. 
Normally, any unexplainable infant death is considered to be due to SIDS. Numerous 
attempts have been made to discover the exact cause of this syndrome. However, the only 
known pathology is that SIDS is due to a dysfunction or abnormality in the cardiac and/or 
respiratory systems. To this point, an exact and definite cause has not been named. This 
paper will attempt to present several of the proposed and hypothesized causes of SIDS.

	First of all, it is necessary to understand some of the important features of this 
syndrome (Naeye, 1976). As mentioned initially, SIDS deaths occur in infants ages one 
month to one year. Also, 90% to 95% of these infants die during sleep, and most of these 
deaths are silent. One-third to one-half of the SIDS victims have been found to have a mild 
infection (normally respiratory in nature) prior to death. SIDS has also been found to be in 
part associated with a low socioeconomic status, and it is more common among 
non-whites.  Although SIDS seems to be associated with a low socioeconomic status, 
SIDS is not caused by malnutrition. A more recent article also reported that more male 
infants were victims of SIDS than females ( Becker 361 ). Finally, SIDS has been more 
often associated with prematurely born infants. This seems to suggest that developmental 
immaturity may present a likely situation for the development of SIDS. Each of these 
characteristics must be considered when forming hypotheses for the possible cause of 
SIDS.

	Initially, research on SIDS centered around the performance of an autopsy upon the 
infant. However, little conclusive evidence was found in these post-mortem infants. 
Possible post-mortem characteristics of SIDS victims have been found to be normal in 
comparison with post-mortem non-SIDS infants of the same age. Furthermore, no 
abnormalities in the growth and morphology of the lungs and hearts of SIDS infants have 
been found. Therefore, in more recent years, research has shifted from the actual death 
and autopsy findings to chronic abnormalities found within these infants prior to death.

	The list of proposed chronic abnormalities is lengthy. To this date, research has 
confirmed the following: 1) SIDS is due to a dysfunction of the cardiac and/or respiratory 
systems, and 2) the death of the infant is due to hypo-ventilation of the lungs and periods 
of complete cessation of breathing or apnea. Hypo-ventilation and apnea cause 
hypo-perfusion of the tissues with necessary oxygen. Ischemia of tissues results and 
eventually causes death. Research now centers around discovering the cause of infant 
hypo-ventilation and apnea.

	Hypothesized causes of SIDS generally have fallen into three basic categories: 
1) causes related to the respiratory system; 2) causes related to the cardiac and circulatory 
system; and 3) causes related to levels of various circulating substances (enzymes, 
neurotransmitters, viruses) within the body"

	First of all, most SIDS research has been focused upon the neuronal control of the 
respiratory system. As mentioned previously, the post-mortem lungs of SIDS victims 
showed no evidence of abnormal development. Therefore, research has centered upon the 
control of respiration. Three systems of neural respiratory control exist: the motor system, 
the mechanoreceptor system, and the chemoreceptor system (Armstrong, Sachis, Bryan, 
and Becker, 1982). The motor system forms the central core of respiration. These neurons 
actually cause consistent respiration to occur. This system is composed of the dorsal 
motor nucleus of the vague, the nucleus of the solitary tract, the nucleus ambiguus, the 
nucleus retroambiguus, the reticulospinal tracts, the cervical and thoracic anterior horns of 
the spinal cord, the vagus nerve, and the hypoglossal nucleus. The mechanoreceptor 
system travels via the vagus nerve and glossopharyngeal nerve. This system regulates 
the rate and volume of respiration by sensing the amount of stretch or the amount of 
irritation present within the lung tissue. The third system is composed of chemoreceptors. 
These receptors sense the levels of various gases within the body. The peripheral 
receptors include the aortic and carotid bodies while the central receptors are believed to 
be located within the ventral medulla oblongata. These receptors information travels via the 
glossopharyngeal and vagus nerves.

	The respiratory control centers have become so important in SIDS research due to the 
discovery of gliosis within the brain stem. The brain stem is the site of exit for the 
glossopharyngeal and vagus nerves and is also the site of the vital medullary respiratory 
groups of neurons. Gliosis is the result of neuronal injury or disease. The injury causes a 
hypertrophy of astroglial cells resulting in a gliotic scar. The scar left in place of the 
degenerated neuron has no neuronal activity. The presence of gliosis within the brain stem, 
having been reported by numerous researchers, leads one to believe that the prolonged 
apneic spells present in SIDS patients lead to gliosis. As those neural tissues are deprived 
of their oxygen supply, the neurons degenerate and are replaced by a gliotic scar. Gliosis 
has also attributed to hypovasculature within the medulla of SIDS victims Hypovasculature 
leads to ischemia of those neural tissues which leads to gliotic scars. Hypoxia within the 
SIDS infant may also result in decreased metabolism. This idea coincides with findings that 
SIDS victims show a decrease in postnatal growth. (Peterson, Benson, Fisher, Chinn and 
Beckwith, 1974). Furthermore, gliosis of the medullary respiratory control centers suggest 
that the apnea may result from a dysfunction of the respiratory controls.

	One respiratory control center which has been of particular interest to researchers has 
been the peripheral chemoreceptor, the carotid body. The carotid body is sensitive to 
arterial levels of oxygen, carbon dioxide, and hydrogen ions and is, thus extremely vital in 
the control of ventilation. An abnormality here could result in hypoventilation. The 
confusion occurs upon analysis of the carotid body. The carotid bodies of SIDS victims 
have been examined for unique morphological features as well as unique neurosecretory 
granular appearances. While some articles report a definite atrophy of the SIDS carotid 
body in comparison with a control group, others report no size change at all between the 
two groups (Becker, 1990; Perrin, Cutz, Becker, and Bryan, 1984). However, according to 
the most recent article available, "  ...  these static morphological studies on postmortem 
tissues from SIDS victims do not exclude an abnormality of neurotransmitter function on 
the carotid body (Becker, 1990 ). Therefore, neurotransmitter secretion and function may be 
a major factor in causing SIDS. The catecholamine levels of the carotid body have been 
tested and will be discussed momentarily. Therefore, although the carotid bodies of SIDS 
victims appear to be morphologically similar to the control groups, the carotid body may 
present a neurotransmitter dysfunction which leads to an abnormality of respiratory control. 
Further research is necessary to confirm these hypotheses.

	It must also be noted that while the carotid body may be a factor in causing SIDS, 
researchers have also reported an evidence of neuronal immaturity among SIDS victims 
within the respiratory control centers of the medulla. Under normal development, the fetus 
demonstrates a rapid growth of dendritic spines within the medullary reticular formation 
just prior to birth (Becker, 1990). Following birth, the number of dendritic spines normally 
rapidly decreases. It has been reported within several articles that the SIDS victim shows a 
persistence of the dendritic spines following birth. This neuronal immaturity may definitely 
compromise the respiratory capabilities of the SIDS infant.

	Some other areas of SIDS research involving respiratory control have also been 
reported. For instance, it has been noted that there is an increase in brain weight of SIDS 
victims. Rapid neonate brain growth may severely compromise the respiratory control 
centers within the brain stem. Also, not only have lesions containing gliotic scars been 
found associated with the carotid bodies and the brain stem, but they have also been found 
in the subcortical. and periventricular white matter and the vagus nerve (Armstrong, Sachis, 
Bryan, and Becker, 1982). The cortical lesions have been the subject of further research, 
yet the exact pathology is not yet understood (Takashima, Armstrong, Becker, and Huber, 
1978)

	Not only has SIDS research centered around the respiratory control centers, but it has 
also been concerned with the cardiac and circulatory system. First of all, research has 
found that infants with blood group type B appear to have a 1.7 times greater chance of 
being victims of SIDS. The significance of this has not yet been determined (Naeye, 1977).

	Several groups have recorded ECG patterns of SIDS infants in comparison with 
control groups. It has been noted that SIDS victims demonstrate a significant increase in 
heart rate during sleep in comparison with the control groups. Furthermore, during the first 
month of life, an increase in heart rate for SIDS infants was shown in all sleep states; both 
quite sleep and REM sleep. Yet, during the second month of life, the increase was only 
shown to exist in the state of rapid eye movement (REM). Also, heart rate variability has 
been noted in the awake state of SIDS infants. (Schechtman, Harper, Kluge, Wilson, 
Hoffman (1988) and Southall, 1988). In conjunction with these findings, it has been 
reported that the QT interval of the ECG recording is shorter in SIDS infants in comparison 
with a control group. This measurement is true for both quiet sleep and REM sleep. 
(Haddad et el, 1979). These differences are obviously due to a dysfunction of the 
autonomic nervous system. It has been proposed that the increase in heart rate with a 
shortening of the QT interval in SIDS infants may be due to an increase in sympathetic 
impulses in conjunction, with an increase in circulating catecholamine levels. This topic 
will be discussed momentarily. Yet, it is clear from this research that the cardiac system  
most likely plays a role in causing SIDS.
	Analysis has also been made of the circulatory vessels of the SIDS infants; in 
particular, the pulmonary arteries. More than half of SIDS victims analyzed have been
found to contain hypertrophy of the muscle layer of the pulmonary arteries. Alveolar 
hypoxia (lack of oxygen) results in low blood pressure within the vessels. The response 
of the pulmonary arteries is to contract to create more resistance and, thus, increase blood 
pressure. Thus, in SIDS infants under a state of chronic hypoxia, these arteries remain 
under a state of constant contraction. Therefore, the muscle mass of the pulmonary arteries 
is increased. The effect of this also produces a backup of blood in the heart's right 
ventricle. This produces a hypertrophy of the right ventricle as it attempts to pump harder in 
order to evacuate the extra blood.

	Each of these cardiac and circulatory abnormalities (heart rate and the state of the 
pulmonary arteries) may have a deep impact upon the pathology of SIDS. However, one 
final area of research must be considered. This area surrounds the level of various 
circulating substances within the body of a SIDS infants. Some of these substances include 
an increased level of brown (fetal) fat, an increased level of fetal hemoglobin, an increased 
level of dopamine and norepinephrine within the carotid body, a decreased level of 
catecholamines within the brain stem, a decreased level of glucose formed from 
gluconeogenesis (PEPcarboxykinase may be deficient), an increased level of serum 
sodium chloride, an increased level of urea within the vitreous humor, and a possible 
increased level of infectious microbes within the infant. The more prominent of these will 
be further explained.

	Brown fat is found within the fetus and is important for the hypoxic environment 
within the womb in order to deliver oxygen to fetal tissues. However, at birth the brown fat 
is normally replaced by adult fat. Yet in SIDS patients, brown fat persists. This is caused 
by chronic hypoxemia. Also present in the SIDS infant is fetal hemoglobin. Normally at 
birth, fetal hemoglobin is replaced by adult hemoglobin. However, in many SIDS infants, 
levels of fetal hemoglobin are elevated indicating a compromise in delivery of oxygen to 
the tissues (Guilian, Gilbert, and Moss, 1987).

	As mentioned previously in conjunction with both the respiratory and cardiac control 
systems, much research has been reported concerning the catecholamines. Various 
reports have been made. First of all, one article dealt with the activity of two important 
enzymes, dopamine-betahydroxylase (DBH) and phenylethanolamine N-methyltransferase 
(PNMT) (Denoroy et al, 1987). The most important finding concerned PNMT. Its levels 
were decreased in certain areas of the medulla oblongata. It has been proposed that a 
decrease in PNMT may be responsible for not activating the reticular formation to cause an 
awakened condition in the state of chronic hypoxia which a SIDS infant experiences during 
sleep. Thus, respiratory control is altered. Another article reports that the carotid bodies 
demonstrate higher levels of both dopamine and noradrenaline (Perrin et. al, 1984). 
Dopamine in elevated levels causes inhibition of respiration. It is believed that increased 
noradrenaline levels may compromise the function of the carotid bodies. Increase 
catecholarnine levels also may cause the increased heart rate seen in SIDS infants. The 
level of various neurotransmitters in SIDS Infants has been a research topic of great 
interest in recent years. It is possible that the true cause of SIDS lies here.

     Finally, as noted earlier, SIDS infants often present a mild infection prior to death. This 
has been of great concern to many physicians. It has been surmised that numerous SIDS 
deaths may be prevented by protecting infants from exposure to various microbes such as 
bordetella pertussis or respiratory synctial virus. Doctors have cautioned that. care must 
be taken to ensure that an infant's surroundings be extremely sanitary (Southall, 1988).

	Having discussed respiratory and cardiac control in addition to levels of various 
circulating substances, it is evident that no one really knows or understands the true cause 
of SIDS. It is also clear that although the exact pathology is not known, SIDS must 
somehow involve alveolar hypoxia leading to prolonged apneic spells The cause of SIDS 
must lie in the area of the neuronal control of the respiratory and/or cardiac systems. 
Further research must be done to further decipher the root problem found in SIDS.

	 	 
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