Menin D, Ballardini E, Panebianco R, Garani
G, Borgna-Pignatti C, Oster H, Dondi M. Factors
affecting yawning frequencies in preterm
neonates. PLoS One 2022;17(5):e0268083.
Abstract
Yawning is a long neglected behavioral
pattern, but it has recently gained an
increasing interdisciplinary attention for its
theoretical implications as well as for its
potential use as a clinical marker, with
particular regard to perinatal neurobehavioral
assessment. The present study investigated the
factors affecting yawning frequencies in
hospitalized preterm neonates (N = 58), in order
to distinguish the effects of hunger and
sleep-related modulations and to examine the
possible impact of demographic and clinical
variables on yawning frequencies. Results showed
that preterm neonates yawned more often before
than after feeding, and this modulation was not
explained by the amount of time spent in quiet
sleep in the two conditions. Moreover, second
born twins, known to be more prone to neonatal
mortality and morbidity, showed increased
yawning rates compared to first born twins.
Overall, our results are consistent with the
hypothesis that yawning frequencies in preterm
neonates are modulated by separate mechanisms,
related e.g. to hunger, vigilance and stress.
These findings, although preliminary and based
only on behavioral data, might indicate that
several distinct neuropharmacological pathways
that have been found to be involved in yawn
modulation in adults are already observable in
preterm neonates.
Résumé
Le bâillement est un comportement
longtemps négligé, mais il a
récemment fait l'objet d'une attention
interdisciplinaire croissante pour ses
implications théoriques ainsi que pour
son utilisation potentielle en tant que marqueur
clinique, en particulier dans le cadre de
l'évaluation neurocomportementale
périnatale. La présente
étude a examiné les facteurs
affectant la fréquence des
bâillements chez les nouveau-nés
prématurés hospitalisés (N
= 58), afin de distinguer les effets des
modulations liées à la faim et au
sommeil et d'examiner l'impact possible des
variables démographiques et cliniques sur
la fréquence des bâillements. Les
résultats ont montré que les
nouveau-nés prématurés
bâillaient plus souvent avant
qu'après l'alimentation, et que cette
modulation n'était pas expliquée
par le temps passé en sommeil calme dans
les deux conditions. De plus, les jumeaux de
deuxième naissance, connus pour
être plus enclins à la
mortalité et à la morbidité
néonatales, ont montré des taux de
bâillement plus élevés que
les jumeaux de première naissance. Dans
l'ensemble, nos résultats sont
compatibles avec l'hypothèse selon
laquelle la fréquence des
bâillements chez les nouveau-nés
prématurés est modulée par
des mécanismes distincts, liés par
exemple à la faim, à la vigilance
et au stress. Ces résultats, bien que
préliminaires et basés uniquement
sur des données comportementales,
pourraient indiquer que plusieurs voies
neuropharmacologiques distinctes, dont on a
constaté l'implication dans la modulation
des bâillements chez les adultes, sont
déjà observables chez les
nouveau-nés
prématurés.
Introduction
Yawning is a phylogenetically conserved
behavior, virtually ubiquitous in vertebrates
[1] that can be observed in isolation or
in bursts, often accompanied by stretching of
the upper limbs [2]. This behavioral
pattern has been long neglected by scholars, but
recently it has been gaining increasing
interdisciplinary attention [3]. This
interest is partly due to its peculiar position
at the crossroads of very different phenomena.
In fact, yawning frequencies in humans have
been found to be modulated by different
conditions, including hunger [4, 5],
arousal and circadian rhythms [6, 7],
thermoregulation [8], pain [9]
and stress [10]. Moreover some
neurological pathologies [11] as well as
the intake of specific drugs [12, 13]
can result in variations in yawning rates. This
behavior is also contagious in humans as well as
in other strongly social species, e.g. apes
[14, 15] and dogs [16, 17], and
this fact has led some scholars to consider
yawning as a potential window into the origins
of motor contagion and social interaction
[3].
During the last decades, several theories
have been formulated to explain the evolutionary
origins of yawning, each identifying different
modulating factors as the core function of this
behavioral pattern, including arousal/vigilance
[1, 18], brain thermoregulation
[19], cortisol levels regulation
[20], empathy and social interaction
[3, 21]. Despite this tendency to trace
the origins of yawning back to a single
function, recent studies have highlighted in
some primates a surprising morphological and
temporal variability in yawns, associated with
different conditions and social contexts
suggesting that yawning might serve different
functions in different circumstances
[24]. On the other hand, although these
theories have been often presented as competing
explanatory alternatives, several scholars have
highlighted the need of distinguishing proximate
and ultimate explanations when investigating
mechanisms underlying the manifestation of
yawning behavior [25]. In particular,
advocates of the brain cooling hypothesis have
argued that, while, e.g., empathy, familiarity
or communication might serve as proximal
mechanisms explaining yawning modulation, the
ultimate function(s) of yawning is likely
physiological and should be able to explain
proximate mechanisms as well [26].
Yawning is also an ontogenetically primitive
behavior, observed in human fetuses from the
eleventh gestational week [18, 27] as
well as in preterm and full-term neonates
[28, 29]. However, very few studies have
investigated the dynamics of yawning modulation
in early development [28, 30, 31]. The
study of yawning in fetuses and preterm neonates
is particularly relevant to the investigation
into the ultimate function of yawning, not only
because it makes it possible to investigate the
ontogenetically primary functions of yawning,
but also because the very existence of fetal
yawning has been proposed as evidence against
the brain cooling hypothesis, based on the fact
that the mother controls thermoregulation of the
fetus [32]. Gallup and Eldakar
[33], however, have argued that yawning,
similarly to other behavioral patterns, might
serve different functions (if any) during
prenatal life than after birth. With regard to
this hypothesis, studying preterm neonates (i.e.
born before having completed the 37th week of
gestation) could allow us to distinguish
maturational and environmental aspects of the
early functional development of yawning.
Moreover, as yawning is related to different
homeostatic processes [7], detailed
analysis of yawning may also help to identify
potential applications to neurobehavioral
assessment [34, 35].
The present study aims to investigate the
factors affecting yawning frequencies in
hospitalized preterm neonates, in order to
distinguish the effects of hunger and
sleep-related modulations and to explore the
possible impact of demographic or clinical
variables on yawning frequencies. In particular,
since hunger has proven to modulate spontaneous
behavior (including hand-mouth coordination) in
full-term neonates and infants
[36&endash;38], we asked whether a
similar trend can be established for yawns, by
observing the spontaneous behavior of preterm
neonates before and after feeding. If confirmed,
the increase in yawning rates prior to feeding
would be consistent with a role in brain
thermoregulation, as there is evidence, although
limited, that feeding in preterm neonates is
integrated into a heat production episode
[39&endash;40].
Prior animal research, in fact, has shown
that yawns are triggered during rises in
brain/body temperature [41] and result
in a reduction of facial temperatures
[42]. Moreover, the frequency of yawning
increases during rising ambient temperature and
diminishes at low ambient temperatures
[43]. Similarly, warming of the carotid
arteries increases yawning while cooling of this
blood flow to the brain decreases yawning
[44]. A secondary question concerned the
degree to which any modulation observed before
vs. after feeding could be ascribed to
differences in behavioral states. In fact,
preliminary observations indicate that yawning
is generally absent during quiet sleep (QS),
both in neonates [28, 30] and fetuses
[35]. Evidence of the effects of other
behavioral states is limited. Moreover, quiet
sleep (QS) has been found to be the only
behavioral state that shows stability in the
perinatal period, and can be identified more
reliably than active or REM sleep, especially
when scored based on behavioral analysis alone
[45, 46]. By scoring QS periods, easily
identifiable even without relying on
physiological data, we were therefore able to
examine the potential effect of the total time
spent in QS on yawning frequencies in preterm
neonates, and to investigate whether this
sleep-related modulation accounts for the
difference between yawning before and after
feeding.
Moreover, in order to investigate whether
the hypothesized difference in yawning rates
before and after being fed might be partly or
completely due to a shift in behavioral state
distributions, further analyses were conducted
after excluding QS periods from the considered
observation time. Additionally, the effects of
demographic and clinical variables were assessed
in order to identify possible confounders and
pinpoint developmental trends or
morbidity-dependent yawn modulation. In
particular, the inclusion of a group of twins
allowed us to test the difference between the
first and the second born. The second twin has
in fact been found to be more prone to neonatal
mortality and morbidity, probably because of the
increased risk of hypoxia during delivery
[47, 48]. Second born twins may
therefore be expected to display higher
frequencies of stress-related yawning [9,
10]. Moreover, developmental trajectories of
preterm neonates (i.e., those born before 37
completed weeks of gestation) are to be
understood based on the interaction of three
separate age variables, i.e., gestational age
(GA, the duration of the gestation),
chronological age (CH, the time from birth to
observation) and postmenstrual age (PMA, the sum
GA and CH) [49]. As a consequence, we
tested the potential associations between each
of these three variables, as well as gender, and
yawning frequencies. Finally, because promising
evidence points at yawn duration as a potential
marker of different types of yawns in some
non-human primates [22&endash;24], we
investigated potential differences in yawn
durations before and after feeding.
Discussion Both singletons and twins
displayed higher yawning frequencies before
feeding compared with after feeding, confirming
the hypothesis of a condition-related modulation
of yawning. Because the effect of condition was
still significant after checking for the effect
of the portion of observation time spent in
quiet sleep, and even after excluding
quiet-sleep periods from the analysis, we can
conclude that this modulation is not entirely
explained by a difference in the distribution of
behavioral states but is at least in part
directly due to hunger. This finding is in line
with the existing literature on hunger-related
modulation of yawning frequencies in adults
[4, 5] and shows that this mechanism is
already observable in preterm neonates.
Moreover, this form of modulation is consistent
with the brain cooling hypothesis, as previous
research has shown that feeding in preterm
neonates is integrated into a heat production
episode [39&endash;40]. Moreover, our
results confirmed the absence of yawning during
quiet sleep in preterm neonates [28,
30], showing the importance of considering
quiet sleep for behavioral research in early
infancy.
Finally, the increased yawning frequencies
found in the second born twin, known to be prone
to higher neonatal morbidity [47, 60],
is consistent with the hypothesis that yawning
behavior might be affected by perinatal clinical
conditions [35, 61]. This seems to
confirm that analysis of yawning is a promising
tool for neurobehavioral assessment, potentially
allowing clinicians and researchers to identify
at-risk infants through early observation, both
during the fetal and neonatal periods [62,
63]. Overall, our results are consistent
with the hypothesis that yawning frequencies in
preterm neonates are modulated by two separate
cholinergic-related factors&emdash;respectively,
hunger and sleep-related factors&emdash;as well
as by a possibly ACTH-mediated stress-related
condition (i.e. being a second born twin). These
findings, although preliminary and based only on
behavioral data, might indicate that several
distinct neuropharmacological pathways that have
been found to be involved in yawn modulation
[64] are already observable in preterm
neonates. Furthermore, demographic variables,
including gender and age measures (GA, CH and
PMA) were not found to affect yawning
frequencies, suggesting that the observed
pattern can be generalized to healthy preterm
neonates from at least 32 weeks PMA. These
results represent an advance in efforts to tease
apart the effects of between- as well as
within-subject factors that may influence the
frequency of yawning in preterm neonates. The
findings are consistent with the hypothesis that
yawning in preterm neonates is modulated by
partially autonomous cholinergic and
ACTH-mediated processes.
Future research should address some
limitations of the present study, by
investigating the specific effect of different
behavioral states, including both quiet and
active sleep, as well as the potential
associations between yawning frequencies and
state transitions or instability. Moreover,
additional studies will be needed in order to
directly test the hypothesis that stress and
hunger-related modulations in neonates are in
fact ascribable to cholinergic and ACTH-mediated
pathways, as postulated by Collins and Eguibar
[64]. In particular, further research is
needed to confirm whether the effect of birth
order on yawning rates in twins is due to
stress-related factors associated with birth or
to other variables and whether hunger or
stress-related modulation of yawning can be
explained in terms of brain
thermoregulation.
Finally, although the exploratory analysis
of yawn durations before and after feeding did
not show any difference, other behavioral
studies might be useful to test whether yawns
associated with different conditions and
modulatory mechanisms also present some
particularities in terms of morphology,
intensity or temporal dynamics, as recently
shown for some species of apes [22, 24].
