Medical Hypotheses (2007) 68, 1276–1286

http://intl.elsevierhealth.com/journals/mehy

Inappropriate mediastinal baroreceptor reflex as a

possible cause of sudden infant death syndrome –
Is thorough burping before sleep protective?
Christian Flaig *

Landeskrankenhaus Bludenz, Emergency Medicine, Spitalgasse 13, 6700 Bludenz, Austria

Received 14 September 2006; accepted 5 October 2006

This article is dedicated to Magdalena Schaumburger, who died at the age of 20 in a car accident near Bolzano/Italy on
August 20th 2006.

Summary Despite extensive research, a link between the assumed mechanisms of death and known risk factors for
sudden infant death syndrome (SIDS) has not yet been established. Modifiable risk factors such as prone sleeping
position, nicotine exposure and thermal stress and non-avoidable risk factors like male gender and some risky socio-
economic conditions could be detected, but the etiology of SIDS remains unknown. In many SIDS cases
histopathological findings suggest an involvement of vital autonomic control functions and unidentified trigger factors
seem to play a role.
From a hypothetical point of view, a developmental sympatheticovagal imbalance of the cardiovascular reflex
control could cause a predisposition for SIDS. An assumed gastroesophageal trigger impulse is possibly developed during
the first weeks of life and could lead to the infant’s vagal reflex death.
Air swallowed during feeding escapes through the esophagus while the infant is sleeping. The temporarily bloated
esophagus exerts pressure on neighboring mediastinal baroreceptors, which is potentially misinterpreted as a rise in
arterial pressure. The following cardiodepressoric baroreceptor reflex could lead to arterial hypotension, bradycardia
and cardiac arrest. Sleeping in prone position may create an increased thoracic pressure on mediastinal baroreceptors,
causing a more pronounced vagal reflex and an increased likelihood of SIDS. Prone position in connection with soft
objects in the infant’s sleeping environment potentially generates an increased oculobulbar pressure, resulting in an
additional cardiodepressoric condition (Aschner-Dagnini phenomenon).
From the sixth month of life onwards the sympatheticovagal balance seems to have matured sufficiently to
compensate the life-threatening challenges in most infants.
Insufficient postprandial burping could either create another independent modifiable risk factor or present the
missing link to a common trigger mechanism for SIDS. Further investigations may possibly lead to the explicit
recommendation to burp all infants sufficiently and repeatedly before sleep.
c 2006 Elsevier Ltd. All rights reserved.

Abbreviations: SIDS, sudden infant death syndrome; LES, lower esophageal sphincter; UES, upper esophageal sphincter; ALTE,
apparent life threatening event; IHPS, infantile hypertrophic pyloric stenosis; GER, gastroesophageal reflux.
* Tel.: +43 664 3423783.
E-mail address: christian.flaig@cable.vol.at.


0306-9877/$ - see front matter c 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.mehy.2006.10.019
Inappropriate mediastinal baroreceptor reflex as a possible cause of sudden infant death syndrome 1277

SIDS: definition and presentation

Sudden infant death syndrome (SIDS) is the sudden

and unexpected death of an infant under one year
of age which remains unexplained after a thorough
case investigation including performance of a com-
plete autopsy, examination of the death scene, and
review of the clinical history [1].
The predominant hypothesis regarding the etiol-
ogy of SIDS remains that certain infants may have a
maldevelopment or delay in maturation of the
brainstem neural network [2]. These medullary re-
gions are thought to be involved with arousal,
chemosensitivity, respiratory drive, thermoregula-
tion, and blood pressure responses [3]. The discov-
ery of abnormalities in the arcuate nucleus of the
brainstems of some SIDS victims suggests that true
SIDS deaths likely reflect delayed development of
arousal, cardiorespiratory control, or cardiovascu-
lar control [4–6]. When the physiologic stability
of such infants becomes compromised during sleep,
they may not arouse sufficiently to avoid the nox-
ious insult or condition [4,6].
The occurrence of SIDS is rare during the first
month of life, increases to a peak between 2 and
4 months of age, and then declines [2]. The recom-
mendation of the back sleeping position has led to a
dramatic decrease in infant death figures over the
past decade [7]. Additional preventive measures
such as avoiding nicotine exposure, sleeping in opti-
mum room temperature, covering the baby lightly
and sleeping in the parent’s bedroom in his/her
own bed on a firm mattress, breastfeeding, and
using a pacifier at sleep have been suggested [2].
Hypothesis
Aerophagia
When feeding, an infant always swallows some air.
Postprandial care helps this air to escape audibly
from the gastric air bubble. It may be assumed that
infants are not always burped sufficiently. Infants
die from SIDS in various social groups, but certain
living conditions possibly imply a lack of time for
extensive infant care. Some disadvantaged emo-
tional, organisational or socioeconomic conditions
might be responsible for an unintentional deficit
of postprandial care. SIDS questionnaires do not re-
fer to all postprandial infant care habits, and data
concerning the infant’s thorough burping before
his/her last sleep do not exist.
Usually feeding of an infant is followed by a
phase of digestion and sleep, which is dominated
by the parasympathetic nervous system. Redun-
Figure 1 Posterior view of the mediastinum: after its
entry through the upper thoracic aperture the thoracic
part of the esophagus reaches the posterior mediastinum
and crosses the aortic arch, thus forming the middle
esophageal narrowness. After crossing the tracheal
bifurcation it lies adjacent to the left atrium, then
contacting the descendent aorta before passing the
esophageal hiatus of the diaphragm [8], creating multi-
ple contacts with baroreceptors in the walls of aorta,
heart and pulmonary vessels.
dant gastric air can rise during sleep. The gastric
emptying mechanism in connection with the in-
fant’s sleeping position and a changing ratio of chy-
mus and gastric air could theoretically lead to an
ascension of gastric air through the esophagus dur-
ing different phases of sleep.
After passing the lower esophageal sphincter
(LES) the rising air bubble expands the esophagus
and thus should exert pressure on the neighboring
mediastinal baroreceptors. Esophagus and aorta
run adjacent in the posterior mediastinum [8]
(Fig. 1).
In addition to carotid baroreceptors, stretch-
sensitive baroreceptors are also located in the wall
of the aortic arch, the descending aorta, the large
pulmonary vessels, and in the cardiac walls [9].
Basal upper esophageal sphincter (UES) pressure
is highly dependent on the state of arousal, varying
from 18 mmHg during rest to 56 mmHg when the in-
fant is crying [10]. Ascending gastric air has to
override the closing pressure of UES and, conse-
quently, passing air could be temporarily trapped
in the esophagus, resulting in prolonged pressure
on the mediastinal baroreceptors.
1278
Inappropriate excitation of mediastinal
baroreceptors
Arterial baroreceptors are sensitive to stretching of
the walls of the vessels in which the nerve endings
lie [9]. When the dilated esophagus exerts pressure
on the pulsating aortic and/or cardiac walls, the
stretch-sensitive baroreceptors should theoreti-
cally register a sudden increase in transmural
receptor pressure (especially when coinciding with
the systolic pulse wave). Depending on the amount
of eructated air and the fluctuation of the esopha-
geal air bubble, various mediastinal baroreceptors
are likely to be stimulated (Fig. 1).
The corresponding afferent impulse pattern
could potentially be misinterpreted as a rise in
arterial pressure, followed by a cardiodepressoric
reaction. A comparable interpretation of barore-
ceptor excitation is known from the external mas-
sage of the carotid sinus (carotid sinus reflex) and
from mediastinal baroreceptors (Valsalva reflex).
Increased stretching augments the firing rate of
the receptors and nerves, and recruits additional
afferent nerves. Being both proportional and dif-
ferential sensors, baroreceptors react more
strongly to sudden than to slow changes in arte-
rial pressure. In the normal operating range of
arterial pressure, even a slight (supposed) change
in blood pressure causes a strong reaction in auto-
nomic reflexes to readjust the arterial pressure
[9].
The extra-carotid baroreceptors transmit their
afferent information along with the vagal nerves
to the nucleus tractus solitarii of the brain stem,
which in turn projects to efferent cardiovascular
neurons in the medulla. The efferent limbs of the
baroreflex loop consist of sympathetic and para-
sympathetic fibres to the heart as well as to blood
vessels. The excitation of baroreceptors leads to an
activation of parasympathetic and to an inhibition
of sympathetic neurons.
It has been suggested that disordered autonomic
control could be involved in SIDS [4,11].
SIDS has been suspected to be an equivalent of
neurocardiogenic syncope, which clearly involves
an inappropriate peripheral vasomotor response
to a postural challenge, by allowing blood pressure
to fall while failing to develop a compensatory
tachycardia [12].
The most consistent circulatory effect of sleep is
a reduction in vasomotor tone, reflected by a fall in
resting blood pressure and a decrease in peripheral
vascular resistance [13,14]. This is associated with
a reduced heart rate, a reduced central venous re-
turn, and a reduction in cardiac output, indicating
Flaig
a dramatic sleep induced alteration in barorecep-
tor function, because a similar combination of
events while awake is associated with an increase
in heart rate, with sympathetic activation and
peripheral vasoconstriction [13,14].
In the case of a temporarily bloated esophagus,
the resulting inappropriate baroreceptor-reflex
would strike a sleeping organism that is already in
vagal mode, and thus cause a fatal counteraction.
It may be hypothesized that in some infants an
immature central reflex control could fail to com-
pensate this baroreceptor-mediated challenge,
resulting in arterial hypotension, progressive bra-
dycardia and/or cardiac arrest.
Cardiorespiratory recordings from infants who
died at home while on a memory-equipped cardio-
respiratory monitor, showed a prefinal progressive
bradycardia with continued breathing movements
to be the most frequent terminal event [15]. Exper-
imental data in sleeping infants showed that distal
esophageal balloon distension caused a significant
prolongation of the RR-interval [16].
A basic analogy between the mediastinal barore-
ceptors and those in the carotid sinus is obvious.
When stimulated externally (e.g. by carotid sinus
massage in adults), vagal reactions like a significant
drop of blood pressure, bradycardia and sometimes
even a cardiac arrest can be triggered. According
to the Valsalva reflex, the transmural baroreceptor
excitation should result from the cumulative ef-
fects of intravasal and extravasal pressures. Taking
into consideration the known carotid and extracar-
otid baroreceptor effects, the assumed esophageal
pressure on mediastinal baroreceptors could theo-
retically be a pathophysiological equivalent for
the vagal death of the infant.
Discussion
Modifiable risk factors
Sleeping position
Sleeping in prone position has shown to be the most
important single risk factor for SIDS [17].
In prone position the gastric air bubble is local-
ized in the fundus near LES [18], ready for esopha-
geal ascension (Fig. 2), which might cause an
increased likelihood of a gastroesophageal trigger
mechanism for SIDS. In supine position gastric air
moves to the distal part of the stomach [18], creat-
ing a lower probability of escaping through the
esophagus (Fig. 2), which could help explain the
decreased likelihood of the occurrence of SIDS in
supine position.
Inappropriate mediastinal baroreceptor reflex as a possible cause of sudden infant death syndrome 1279

Figure 2 Sleeping positions: radiographs of the stomach of a child (12 weeks of age) in prone and in supine position

(reproduced with permission from Pediatrics, Oct 2001; 108: e70., Copyright c 2001 by the AAP). Prone position: most
of the contrast fluid is localized in the distal part of the stomach. The gastric air bubble is localized in the proximal part
near LES, ready to escape through the esophagus. Supine position: The contrast fluid has moved to the fundus. Gastric
air has moved to the antrum, which keeps it from ascending through the esophagus.

Prone sleeping has a measurable effect on circu-
latory control, with a reduction in vasomotor tone
resulting in peripheral vasodilatation, a lower blood
pressure, and a higher resting heart rate [14].
The dramatically higher SIDS rate in prone posi-
tion could theoretically be promoted by a compres-
sion of the mediastinal organs between the
sternum and the thoracic vertebral column, caused
by gravitation and the compliant anterior chest
wall. Due to the more confined thoracic space the
pressure on mediastinal baroreceptors, generated
by a temporarily bloated esophagus, as well as
the corresponding vagal impulse pattern should
be more pronounced in prone position.
Non-prone sleeping position
SIDS infants are found dead in various positions,
most of them prone. The hypothesized gastro-
esophageal trigger mechanism should also operate
in supine and side position, but compared to sleep-
ing prone the cartilaginous rib cage is more likely
to be passively expanded in a non-prone position.
Theoretically, there should be less pressure on
the mediastinal organs and baroreceptors, and
the corresponding vagal firing rate should be less
pronounced in supine and side position, when the
esophageal wall exerts pressure on the neighboring
structures.
There are no data available referring to intra-
thoracic, mediastinal, abdominal and intragastric
pressure values in different infant sleeping
positions.
Side sleeping position
When an infant is placed for sleep in side position
and he/she rolls over into prone position during
sleep there is an exceptionally high risk of SIDS
[19]. The infant’s sleeping position is unstable
when in a lateral sleep situation [20].
Gastric anatomy causes an ascension of the gas-
tric air bubble to ‘‘save’’ gastric compartments in
the left (antrum) as well as in the right (fundus]
side sleeping position, which keeps it from esopha-
geal ascension, because the esophago-gastric junc-
tion is in a clearly lower anatomical position in both
lateral sleep situations.
The localisation of the gastric air bubble is rela-
tively stable in both side positions, but it changes,
when the infant rolls to the prone position later on.
The consecutive accumulation of gastric air in the
fundus [18] near LES (Fig. 2) and the higher pres-
sure on the epigastric area in prone position possi-
bly lead to an eruption of air during a later and
potentially even more vulnerable phase of sleep.
If the infant rolls over into a supine position, he/
she is saver [20]. Gastric air moves to the distal
part of the stomach [18] (Fig. 2) and there is no
additional external abdominal or thoracic pressure.
Soft sleeping surfaces and loose bedding
There is a strong interaction between prone sleep-
ing position, a soft bedding surface and SIDS [21].
Epidemiologic studies identified other soft sur-
faces, such as pillows, quilts, comforters, sheep-
skins, and porous mattresses, as a significant risk
factor, particularly when placed under the sleeping
infant [6].
In prone position there is increased pressure on
the anterior thoracic and abdominal walls. When
the mattress is soft, the cartilaginous rib cage
and the more compliant anterior abdominal wall
are likely to create a subtle epigastric step be-
tween anterior thoracic and abdominal wall levels.
Even though slight, when caused by a soft sleeping
surface, or more pronounced when the infant rests
on soft objects, such as pillows, loose bedding or
stuffed toys, it is likely to lead to an increased epi-
gastric pressure and thus to a favored eructation of
1280
gastric air compared to sleeping on the back and/
or on a firm mattress.
Prone position, soft bedding and a potential
oculocardiac reflex
It is recommended to avoid all soft materials in the
infant’s sleeping environment, as their presence
seems to be potentially hazardous [2].
The combination between prone position and fa-
cial resting on a soft sleeping surface possibly gen-
erates additional vagal activity, due to pressure
exerted on the orbital region and the bulbus oculi.
Sleeping in prone position is likely to lead to a tem-
porary and solid resting of the orbito-ocular region
on a soft sleeping surface or on soft objects such as
pillows, loose bedding, quilts, comforters and
stuffed toys. The potentially resulting oculocardiac
reflex is a well-recognized vagal phenomenon, also
known as Aschner-Dagnini-Reflex. It causes a de-
crease of arterial pressure and heart rate, and pro-
longed asystoles [22]. Several investigators have
found, that infants who had survived an apparent
life-threatening event (ALTE) showed an exagger-
ated response to vagal stimulation, as evidenced
by marked bradycardia in response to oculobulbar
pressure [22,23]. There are no data available refer-
ring to a possible connection between prone posi-
tion, increased eyeball pressure, and SIDS.
Increased external oculobulbar pressure might
be harmful as another single factor, independent
from the hypothesized difficulties of some infants
to lift their heads, leading to rebreathing of respi-
ratory carbondioxide [24,25] when placed prone.
On a firm sleeping surface the osseous margin of
the orbita is less likely to permit external eyeball
pressure because, from an anatomical point of
view, the anterior pole of the bulbus does not over-
top the external osseous orbital level. Any soft ob-
ject, placed in the infant’s sleeping environment,
could be potentially hazardous, because the orbital
margin cannot defend external oculobulbar impres-
sion from soft objects, e.g. stuffed toys or pillows.
An oculocardiac reflex might promote depressoric
cardiovascular responses as well as cumulative ef-
fects from additional vagal stimuli (including ther-
mal stress, nicotine-related acetylcholinergic vagal
responses and the assumed mediastinal barorecep-
tor reflex) during sleep.
Nicotine
Nicotine exposure may promote the assumed gas-
troesophageal trigger mechanism as well as central
autonomous imbalance.
In adults cigarette smoking has been shown to
decrease lower esophageal sphincter (LES) pres-
Flaig
sure by 19–42% [26], but there are no data avail-
able for infants. Hypothesizing the same
pharmacological effect also for infants, a lowered
resistance of LES against ascending gastric air could
partially explain nicotine as a risk factor for pas-
sively exposed infants.
The affinity of nicotine with the vegetative
receptors in the brain stem [27] and the peripheral
chemo [28] – and/or baroreceptors and the result-
ing pharmacological effects on the autonomous
nervous system are likely to have a disturbing ef-
fect on the sympatho-vagal balance [29] and thus
on the ability of an infant to compensate an inap-
propriate vagal reflex.
Thermal stress
There is some evidence that the risk of SIDS is asso-
ciated with the amount of clothing or blankets on
an infant, the room temperature, and the season
of the year [6,30]. Dead infants are often found
with signs of hyperthermia [31] (higher core-tem-
perature; clothing, cover, and mattress wet from
transpiration). Bedsharing [32] as well as covering
the infant too much and a warm sleeping environ-
ment lead to thermal stress [33] and thus are likely
to cause reactive vasodilatation as a result of ther-
moregulation. Poor vasomotor tone would be exac-
erbated by overheating [12] and could increase the
risk of SIDS, when an additional cardiodepressoric
baroreflex strikes the vulnerable organism.
The flattening of SIDS incidences during the
colder months should be a result of a change in
parental infant care behaviour following preven-
tive recommendations such as avoiding prone posi-
tion and thermal stress.
Sleeping-environment
An infant is safer when he/she sleeps in the par-
ent’s bedroom and in his/her own bed [34].
The presence of the parents with the corre-
sponding social, tactile, visual (light), and acoustic
stimulation favors a lighter quality of the infant’s
sleep, preferred arousability and thus a basic sym-
pathovagal condition better able to cope with a
cardiovascular depressor reflex.
Bottle-feeding
There is no consistent opinion on the validity of
breastfeeding as a protective factor against SIDS
[35].
In both feeding methods, the infant’s sufficient
belching before sleep could be the vital measure
to reduce the risk of gastric air as a potential trig-
ger of SIDS. There is a higher rate of aerophagia in
formula feeding compared to breastfeeding, which
might theoretically cause a more risky situation
Inappropriate mediastinal baroreceptor reflex as a possible cause of sudden infant death syndrome 1281
especially for those infants who suffer from a rela-
tive lack of postprandial care.
In most developed countries breastfeeding is
associated with socioeconomic advantage [36],
which in turn could indicate a link to generally
advantaged environmental infant care conditions.
When adjustment is made for socioeconomic fac-
tors, the protective effect of breastfeeding is less
apparent [35], but there still remains a lack of
explanation as to how infant death rates depend
on sociodemographic factors. Yet there are no data
available that link the caregivers’ infant feeding
habits, the extent of specific postprandial care
and the emotional, social, economic and educa-
tional backgrounds.
Childcare facilities
Nonparental caregivers do not always follow the
parents’ wishes when caring for their babies. The
unaccustomed prone position is more likely to oc-
cur in daycare or other settings outside the home
and highlights the need for all infant caretakers
to be educated about appropriate sleeping posi-
tioning [34]. Even after educational measures, fol-
lowed by changes in infant sleeping positioning, the
number of SIDS cases in childcare settings remains
unproportionally high [37]. Additional, yet-uniden-
tified factors are suspected in child care that place
infants in those settings at higher risk for SIDS [37].
Specific data concerning differences in post-
prandial infant care habits between parental and
nonparental caregivers do not exist and retrospec-
tive investigations may be difficult. Differences in
feeding and caring habits between parental and
nonparental caregivers should be expected,
although they are not scientifically proven, and
there should be noticeable emotional varieties in
e.g. postprandial caring, hugging, kissing, gently
patting and rubbing the infant’s back while pa-
tiently waiting for his/her belch.
When the environmental, organisational, or
emotional circumstances are disadvantaged it
might sometimes be understandably difficult for
caregivers to feed an infant patiently and to burp
him/her sufficiently after every meal. Uninten-
tional improper burping of an infant and its possi-
ble consequences could be the key for a better
understanding of the high SIDS rate in childcare
facilities.
Pacifiers may help infants to belch
When an infant is placed for sleep pacifier use has a
significant protective effect against SIDS [38]. Pac-
ifier use even seems to reduce the risk of known
risk factors such as prone or side position and
cosleeping with a mother who smoked [39].
From a hypothetical point of view and suspect-
ing a gastroesophageal trigger mechanism to be in-
volved in SIDS, pacifier use could cause an
activation of oropharyngeal muscles, which, as a
part of the mechanism of swallowing and propul-
sive peristalsis, is accompanied by a temporary
relaxation of the upper esophageal sphincter. UES
relaxation and increased esophageal motility could
theoretically result in a decreased likelihood of
trapped esophageal and/or gastric air. Non-nutri-
tive sucking before falling asleep and/or during a
lighter stage of sleep could favor the safe release
of gastric air in infants who were not burped suffi-
ciently before, thus protecting the infant from a
postprandial trigger mechanism during a later, dee-
per and more vulnerable phase of sleep.
Non-avoidable risk factors
Socio-economic factors
SIDS occurs more frequently in families with a low
socio-economic status [40]. There is a strong corre-
lation with parental unemployment and the level of
parental education, late or no prenatal care, young
maternal age and higher parity and there is an in-
creased risk for infants of single mothers and for
multiple births [41]. There is a significantly higher
risk for infants of parents from certain ethnic back-
grounds [42], and for infants in child care settings
[37].
Exploring all these sociodemographic findings
carefully, various conditions could hypothetically
show a connection: one could say that a difficult
social and family situation can lead to the caregiv-
ers’ being under emotional and/or organisational
stress. It may be assumed that disadvantaged living
conditions sometimes cause a lack of time for
extensive infant care. Thus, some apparently unal-
terable risk factors can theoretically be seen in
connection with improper burping as another risk
factor for SIDS.
The level of parental education as well as late or
no prenatal care can be interpreted in connection
with the general access and/or attention to infant
care recommendations. Very young maternal age
and/or unintentional pregnancy are likely to lead
to social stress and emotional overloading with
the potential risk of less attentive infant care hab-
its. Yet there are no data available to support this
theoretical view.
Caregivers who suffer from a relative lack of
environmental support, like some single mothers
and mothers with twins or multiple births could
be more likely to be demanded in several cases at
the same time. During and after the time-consum-
ing feeding of the infant their attention is likely to
1282
be claimed by concurrent challenges, resulting in a
lack of time for the infant’s thorough burping.
No data has been presented yet which would
investigate a connection between the extent of
postprandial infant care and the occurrence of
SIDS. Certainly more detailed research could lead
to evidence which proves that disadvantaged socio-
economic conditions entail organisational and
emotional deficits for some aspects of social inter-
action (including infant care) as opposed to an
optimum social and economic environment.
SIDS on weekends
The relative accumulation of SIDS deaths on week-
ends could be a result of the parents’ wish to take
up social life again [43]. The caregiver’s need for
children to fall asleep in the evening without delay
is more urgent than during the week. And, possibly,
the infant is being fed less patiently and uninten-
tionally given less postprandial care than would
be the case on ‘‘normal’’ days.
SIDS in male infants
Male infants are 30–50% more likely than infant
girls to be affected by SIDS [44]. Suspecting a gas-
troesophageal trigger mechanism to be involved in
the genesis of SIDS, an association between differ-
ences in the postnatal development of the gastric
muscles in male infants and the hypothesized trig-
ger factor should be evaluated. The frequency of
infantile hypertrophic pyloric stenosis (IHPS) is al-
most five times higher in male than in female in-
fants [45]. After four weeks of life the usual
symptoms start with vomiting after retroperistaltic
waves of the gastric muscles. A significant coinci-
dence of SIDS and IHPS has been observed in Swe-
den [18].
From a hypothetical point of view gender-
related neuromuscular abnormalities or subtle dif-
ferences in the development of male gastric mus-
cles could form part of the pathophysiological
connection with the significantly higher rate of
male SIDS mortality. The higher probability of
stomach contents (chymus and/or gastric air) mov-
ing retrogradually during sleep could theoretically
promote an esophageal bloating mechanism which
triggers SIDS in some male infants.
Whooping cough, IHPS and SIDS
Whooping cough has been suggested to be a trigger
factor for SIDS, the proposed mechanism being
unrecognized episodes of apnoea [46]. Infants
who had received systemic erythromycin as a pro-
phylaxis or treatment of a bordetella pertussis
infection showed a higher rate of IHPS [47]. In fact,
in Sweden SIDS mortality significantly followed the
Flaig
prevalence of IHPS [18] and bordetella pertussis
[46].
Gastric hypermotility [48] or subtle pyloric
abnormalities [49], both caused by erythromycin
and potentially leading to a gastroesophageal trig-
ger impulse, might be linked with some SIDS cases.
On the other hand, there could theoretically be
a connection between the infant’s nocturnal
coughing and an increased thoracic pressure that
is exerted on the mediastinal baroreceptors, lead-
ing to a cardiodepressoric reaction (Valsalva-
reflex).
First month of life
It is a popular hypothesis that neuronal immaturity
has an important role in SIDS infants [2,27], but the
rare occurrence of SIDS during the first four weeks
of an infant’s life presents a basic contradiction to
the statement that SIDS is caused by neuronal
immaturity of the central reflex control. Neuronal
immaturity should manifest itself particularly dur-
ing the first weeks of the infant’s life [50], but
the cause of rare SIDS cases during the first month
of life might rather be found in the initially weak
gastroesophageal trigger mechanism. The relative
absence of a relevant trigger impulse seems to pro-
tect the infant’s organism during the first weeks of
life. Referring to the triple risk hypothesis [50],
neuronal immaturity without an adequate trigger
mechanism should not cause a lethal condition.
Right after birth the infant may theoretically not
yet be able to eructate enough air in order to trig-
ger a relevant depressor reflex. The gastric volume
is small and the angle of His between cardia and
esophagus is obtuse in newborns but decreases as
infants develop. The tension of LES, pylorus and
the gastric muscles cannot yet be developed fully.
Relevant amounts of air can probably be kept and
eructated after the first month of life, when LES
and pylorus function more sufficiently and the gas-
tric volume as well as the gastric air bubble have
become big enough to bloat the esophagus. The
increasing amount of eructated gastric air could
cause a more pronounced esophageal distension
and an increased firing rate of mediastinal
baroreceptors.
Preterm infants, low birth weight
Neuronal development in human infants is not
adequately completed even by the time of term
birth [51], especially from an evolutionary point
of view, and compared to other species. The
higher SIDS risk for preterm born infants may
be a result of this developmental neuronal pecu-
liarity in human infants. Neuronal immaturity and
Inappropriate mediastinal baroreceptor reflex as a possible cause of sudden infant death syndrome 1283
vegetative imbalance may be more pronounced
as a developmental indicator in preterm born
and low birth weight infants and may compromise
their circulatory and respiratory capabilities even
stronger.
During early infancy the parasympathetic ner-
vous system (‘‘feed and breed, rest and digest’’)
clearly dominates, as newborns sleep up to 19 h
per day. The sympathetic nervous system (‘‘fight
and flight’’) shows less activity during the first per-
iod of life and could consequently develop at a
slower pace, which might hypothetically cause
the assumed vegetative imbalance in preterm as
well as in term infants. During early infancy the
sympathetic nervous system is possibly not suffi-
ciently matured as an alarm and emergency
system.
Physiologic stability during sleep could be com-
promised, and SIDS infants may not arouse suffi-
ciently to avoid a noxious insult or condition [6].
After six months of life the autonomous nervous
system should be better balanced. Sufficient vege-
tative compensation and/or arousal as an adequate
response to life threatening challenges during sleep
should be developed in most infants, and the
occurrence of SIDS decreases dramatically.
Autopsy
The very definition of SIDS [1] implies that an au-
topsy should not produce any pathological findings
that could explain the infant’s death.
Neither ascending gastric air as a possible trigger
for SIDS nor a resulting progressive bradycardia or
cardiac arrest do leave any relevant post-mortem
traces. Up to 60% of SIDS cases show histopatholo-
gical evidence of varying degrees of hypoplasia of
the arcuate nucleus, an integrative site for vital
autonomic functions [52], which supports the path-
ophysiological link with a developmentally caused
malfunction of the autonomous reflex control.
Post-mortem findings like intrathoracic pete-
chiae, heavy wet organs and an empty bladder
can be found in many SIDS infants. Trying to find
an explanation, a possible connection to similar
pathological findings in some victims of strangula-
tion could hypothetically be attributed to agonal
vegetative reactions following prefinal excitation
of extracarotid baroreceptors in the one and caro-
tid baroreceptors in the other case.
Testability of the hypothesis
The hypothesis offers a speculative, but testable
view of SIDS. Due to the potential risks and the
ethic problems of invasive testing in human infants,
animal experiments should generally be preferred.
The ability to compensate a postprandial cardio-
depressoric challenge can be proven by esophageal
balloon distension in changing mediastinal posi-
tions, with alternating volumes, in prone and su-
pine position and during different phases of sleep
and age. Experimental testing of distal esophageal
balloon dilatation induced a significant prolonga-
tion of the RR-interval and of the duration of the
respiratory cycle in sleeping infants who were af-
fected by GER [16].
Esophagomanometry could quantify the influ-
ence of prone, supine and side position on medias-
tinal pressure. Defining the localisation and amount
of gastric air in prone, supine, left and right side
position and interpretation of postprandial LES
pressure as well as UES closing pressure in different
sleeping positions might possibly show continuative
results.
Vagal responses through eyeball pressure during
sleep could be demonstrated by using a device for
alternating mechanical protection and exertion of
pressure on the bulbus oculi, preferably in animal
experiments. Alternating or simultaneous inflation
of a preorbital balloon device and an esophageal
balloon tube could simulate the single effect of
soft object eyeball pressure as well as the assumed
cumulative parasympathetic effects from eruc-
tated air in prone position. Investigations in human
infants showed significant bradycardia resulting
from external eyeball pressure [22].
Observation of esophageal pressure and motility
during pacifier use could demonstrate a potential
influence of non-nutritive sucking on the early re-
lease of previously swallowed air.
Data of esophagomanometry from infants af-
fected by gastroesophageal reflux (GER) might
show that infants exposed to second hand smoke
and those who grew up in a nicotine free environ-
ment have a distinct difference in LES pressure.
Measuring the amount of swallowed air after
breastfeeding and after formula feeding and quan-
tifying the gastric air/chymus ratio of sufficiently
belched infants as well as of infants with deficient
postprandial care might lead to continuative
results.
Pathophysiologists might be able to demonstrate
neuromuscular abnormalities or subtle differences
in the development of male and female gastric
muscles during early infancy.
A retrospective review of infant feeding and car-
ing habits in different social groups and family
backgrounds should be carefully evaluated. The
discussion of a possibly unintentional lack of post-
prandial care causing SIDS could be painful and
insulting for parents and caregivers, who have lost
an infant to SIDS.
1284
Conclusions
SIDS-questionnaires and studies in many countries
have presented various data and were followed
by prevention campaigns, leading to decreases in
death figures, but one interesting question has
not yet been asked: Was the infant burped suffi-
ciently before his/her last sleep? There are no data
available referring to the extent of postprandial in-
fant care in different social groups and family
conditions.
Nevertheless, the dogma that SIDS has nothing
to do with spitting up, regurgitation, choking and
belching should be critically re-evaluated, as far
as there is an obvious evidence of outstanding
physiological and epidemiological investigations
concerning esophageal dilatation during sleep and
potentially generated mediastinal interactions.
Could belching during sleep be the missing
trigger factor for SIDS or another modifiable
risk factor?
Corresponding with the triple risk hypothesis [50],
(1) A developmental neuronal immaturity of auto-
nomic reflex control is likely to cause a predis-
position for SIDS in many healthy infants,
(2) The vulnerable period of time is defined by the
development of the assumed gastro-esophageal
trigger mechanism at the beginning and neuro-
nal maturation at the end of this period and,
(3) Insufficient burping could cause a defined
trigger mechanism that is likely to occur
under certain modifiable and socio-economic
conditions.
Extended preventive recommendations
All successful measures to reduce SIDS incidences
during the past decade are almost exclusively im-
proved methods of infant care. Finding reasonable
grounds to suspect another unspectacular yet
potentially harmful factor during infancy, the ex-
plicit recommendation of sufficient and repeated
burping of all infants before sleep might be consid-
ered after further investigations.
Referring to a potentially dangerous oculocar-
diac reflex, even the smallest objects should be
kept out from an infant’s bed. The recommenda-
tion to use a pacifier for sleep could create the
need to improve the design of some pacifiers, since
they might potentially cause increased oculobulbar
pressure, when infants loose them during sleep.
Flaig
Breast- and/or bottle-feeding in the mother’s
bed has to be regarded with scrutiny because there
is the risk of thermal stress and reactive vasodilata-
tion through cosleeping as well as a possible lack of
the opportunity to belch, because mother and child
tend to fall asleep while feeding. When, in addi-
tion, the infant is exposed to second hand smoke
and/or nicotine is being transmitted with the
mother’s milk, the higher probability of a relaxed
LES is more likely to permit the ascension of gastric
air, which, in addition, might increase the risk of a
vagal reflex death for co-sleeping infants.
In any case, the infant suffers no harm if he/she
is given enough postprandial care (even during the
night) and is then returned to his/her own bed in
supine position. There might be more to the old-
fashioned recommendation passed on to genera-
tions of mothers – ‘‘to give their infants time to
belch’’ – than meets the eye.
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