The effects of simulated gastroesophageal reflux on infant pig oropharyngeal feeding physiology.

The neural connectivity among the oral cavity, pharynx, and esophagus is a critical component of infant feeding physiology. Central integration of oral and pharyngeal afferents alters motor outputs to structures that power swallowing, but the potential effects of esophageal afferents on preesophageal feeding physiology are unclear. These effects may explain the prevalence of oropharyngeal dysphagia in infants suffering from gastroesophageal reflux (GER), though the mechanism underlying this relationship remains unknown. Here we use the validated infant pig model to assess the impacts of simulated GER on preesophageal feeding parameters. We used high-speed videofluoroscopy and electromyography to record bottle-feeding before and following the infusion of a capsaicin-containing solution into the lower esophagus. Sucking parameters were minimally affected by capsaicin exposure, such that genioglossus activity was unchanged and tongue kinematics were largely unaffected. Aspects of the pharyngeal swallow were altered with simulated GER, including increased thyrohyoid muscle activity, increased excursions of the hyoid and thyroid per swallow, decreased swallow frequency, and increased bolus sizes. These results suggest that esophageal afferents can elicit changes in pharyngeal swallowing. In addition, decreased swallowing frequency may be the mechanism by which esophageal pathologies induce oropharyngeal dysphagia. Although recent work indicates that oral or pharyngeal capsaicin may improve dysphagia symptoms, the decreased performance following esophageal capsaicin exposure highlights the importance of designing sensory interventions based upon neurophysiology and the mechanisms underlying disordered feeding. This mechanistic approach requires comprehensive data collection across the entirety of the feeding process, which can be achieved using models such as the infant pig.NEW & NOTEWORTHY Simulated gastroesophageal reflux (GER) in an infant pig model resulted in significant changes in pharyngeal swallowing, which suggests that esophageal afferents are centrally integrated to alter motor outputs to the pharynx. In addition, decreased swallow frequency and increased bolus sizes may be underlying mechanisms by which esophageal pathologies induce oropharyngeal dysphagia. The infant pig model used here allows for a mechanistic approach, which can facilitate the design of intervention strategies based on neurophysiology.

Impact of volume and rate of milk delivery on coordination of respiration and swallowing in infant pigs.

The coordination of respiration and swallowing is a life-critical function in infants. Varying volume and rate of milk delivery changes swallowing frequency and bolus volume but any impact on swallow-respiration coordination is unknown. Five infant pigs were filmed with simultaneous high speed videofluoroscopy and plethysmography while feeding from an automatic system delivering milk across a range of volumes and frequencies. Swallow inspiration delay, respiratory cycle duration, and distribution of inspiratory and expiratory swallows were calculated. At constant volume, there were more inspiratory phase swallows when frequency increased. At high constant frequency, increasing volume changed swallow-respiration coordination patterns, with increased occurrence of inspiratory phase swallows. Respiratory cycle duration did not change in response to changes in oral milk delivery. These results suggest that the observed pattern of expiratory swallowing in infants is achieved primarily by regulation of milk intake, not modulation of respiratory patterns by oral sensation.

Exploring the interaction of viscosity and nipple design on feeding performance in an infant pig model.

Infant feeding behaviors are modulated via sensorimotor feedback, such that sensory perturbations can significantly impact performance. Properties of the nipple and milk (e.g., nipple hole size and viscosity) are critical sources of sensory information. However, the direct effects of varying milk and nipple properties on infant motor output and the subsequent changes in feeding performance are poorly understood. In this study, we use an infant pig model to explore the interaction between nipple hole size and milk viscosity. Using high-speed videofluoroscopy and electromyography, we measured key performance metrics including sucks per swallow and suck duration, then synchronized these data with the onset and offset of activity of jaw opening and closing muscles. The combination of a small nipple hole and thick milk resulted in negative effects on both suck and swallow performance, with reduced feeding efficiency compared to the other treatments. It also appears that this combination of viscosity and hole size disrupts the coordination between correlates of tongue and jaw movements. We did not see a difference in feeding efficiency between viscosities when infants fed on the large-hole nipple, which may be the result of non-Newtonian fluid mechanics. Our results emphasize the importance of considering both fluid and nipple properties when considering alterations to an infant's feeding system.

Nipple properties affect sensorimotor integration during bottle feeding in an infant pig model.

Infant feeding is a critical neurological milestone in development defined by the coordination of muscles, peripheral nerves, and brainstem nuclei. In infants, milk flow rate is often limited to improve feeding performance without treating the underlying deficiencies in the sucking and swallowing processes. Modification of the neuromotor response via sensory information from the nipple during bottle feeding is an unexplored avenue for physiology-based interventions. In this study, we assessed how differences in nipple hole size and nipple stiffness affect sucking muscle activation and subsequent movement. We fabricated four bottle nipples of varying hole size and stiffness to determine how variation in nipple properties affects the sucking behavior of infant pigs. Our results demonstrate that sensory information from the nipple affects sucking motor output. Nipple hole sizes and stiffnesses with a larger milk flow rate resulted in greater muscle activity and kinematic movement. Additionally, our results suggest that sensorimotor interventions are better directed toward modulating tongue function rather than the mandible movements due to a greater response to sensory information. Understanding how sensory information influences infant feeding is instrumental in promoting effective infant feeding.

The effect of stiffness and hole size on nipple compression in infant suckling.

During infant feeding, the nipple is an important source of sensory information that affects motor outputs, including ones dealing with compression of the nipple, suction, milk bolus movement, and swallowing. Despite known differences in behavior across commercially available nipples, little is known about the in vivo effects of nipple property variation. Here we quantify the effect of differences in nipple stiffness and hole size on an easily measured metric representing infant feeding behavior: nipple compression. We bottle-fed 7-day old infant pigs (n = 6) on four custom fabricated silicone nipples. We recorded live X-ray fluoroscopic imaging data of feeding on nipples of two levels of hardness/stiffness and two hole sizes. We tested for differences in nipple compression at the nipple's maximum compression across different nipple types using a mixed model analysis of variance. Stiffer nipples and those with smaller holes were compressed less than compliant nipples and nipples with larger holes (p < 0.001). We also estimated the force applied on the nipple during feeding and found that more force was applied to the compliant nipple with disproportionately larger strains. Our results suggest that infant pigs' nipple compression depends on material type and hole size, which is likely detected by the infant pigs' initial assessment of compressibility and flow. By isolating nipple properties, we demonstrated a relationship between properties and suckling behavior. Our results suggest that sensory information affects feeding behaviors and may also inform clinical treatment of poor feeding performance.

Oropharyngeal capsaicin exposure improves infant feeding performance in an animal model of superior laryngeal nerve damage.

Sensorimotor feedback is critical to safe and effective swallowing. Because of this, sensory interventions have the potential to treat dysphagia. One such treatment may be found in capsaicin, which activates the internal branch of the superior laryngeal nerve (iSLN). The iSLN initiates the pharyngeal swallow, and a more sensitive iSLN should more readily elicit swallowing and improve swallow safety. We explored the neurophysiological mechanism by which capsaicin improves swallow performance using an infant pig model with a unilateral iSLN lesion. Using high-speed videofluoroscopy, we collected oropharyngeal kinematic data while pigs suckled on bottles, before and after applying capsaicin to the posterior tongue and valleculae. We found that capsaicin application decreased maximal bolus sizes, which improved swallow safety. Furthermore, capsaicin improved performance when infant pigs swallowed more moderately sized boluses. However, capsaicin did not change swallow frequency, the number of sucks prior to each swallow, nor total pharyngeal transit time (TPT). Similarly, excursions of the hyoid, thyroid, and posterior tongue were unchanged. TPT and hyoid and thyroid excursions maintained relationships with bolus size post-capsaicin, suggesting that these variables are less sensitive to sensory intervention. The timing and extent of posterior tongue movement were only correlated with bolus size pre-capsaicin, which could imply that capsaicin fundamentally changes in relationships between tongue movements and bolus size. Our results provide insight into the neural control of swallowing and capsaicin's mechanism of action, and suggest that capsaicin may be beneficial in treating acute infant dysphagia.NEW & NOTEWORTHY Chemical sensory interventions alter swallow physiology, which is well-documented in adults but relatively unexplored in infants. Using videofluoroscopy, we found that capsaicin exposure limited infant pigs' bolus sizes to improve swallow performance without changing swallow frequency. Capsaicin increased the likelihood of safe swallowing with more moderately sized boluses and changed relationships between bolus size and tongue movements, which may impact performance. This work highlights the potential role of capsaicin in treating acute infant dysphagia.

Anatomical and physiological variation of the hyoid musculature during swallowing in infant pigs.

The function of a muscle is impacted by its line of action, activity timing and contractile characteristics when active, all of which have the potential to vary within a behavior. One function of the hyoid musculature is to move the hyoid bone during swallowing, yet we have little insight into how their lines of action and contractile characteristics might change during a swallow. We used an infant pig model to quantify the contractile characteristics of four hyoid muscles during a swallow using synchronized electromyography, fluoromicrometry and high-speed biplanar videofluoroscopy. We also estimated muscle line of action during a swallow using contrast-enhanced CT-scanned muscles animated to move with the hyoid bone and found that as the hyoid elevated, the line of action of the muscles attached to it became greater in depression. We also found that muscles acted eccentrically and concentrically, which was correlated with hyoid movement. This work contributes to our understanding of how the musculature powering feeding functions during swallowing.

Increased viscosity of milk during infant feeding improves swallow safety through modifying sucking in an animal model.

Infants experiencing frequent aspiration, the entry of milk into the airway, are often prescribed thickened fluids to improve swallow safety. However, research on the outcomes of thickened milk on infant feeding have been limited to documenting rates of aspiration and the rheologic properties of milk following thickening. As a result, we have little insight into the physiologic and behavioral mechanisms driving differences in performance during feeding on high viscosity milk. Understanding the physiologic and behavioral mechanisms driving variation in performance at different viscosities is especially critical, because the structures involved in feeding respond differently to sensory stimulation. We used infant pigs, a validated animal model for infant feeding, to test how the tongue, soft palate, and hyoid respond to changes in viscosity during sucking and swallowing, in addition to measuring swallow safety and bolus size. We found that the tongue exhibited substantive changes in its movements associated with thickened fluids during sucking and swallowing, but that pharyngeal transit time as well as hyoid and soft palate movements during swallowing were unaffected. This work demonstrates the integrated nature of infant feeding and that behaviors associated with sucking are more sensitive to sensorimotor feedback associated with changes in milk viscosity than those associated with the pharyngeal swallow, likely due to its reflexive nature.

Does birth weight affect neonatal body weight, growth, and physiology in an animal model?

Infant birth weight affects neuromotor and biomechanical swallowing performance in infant pig models. Preterm infants are generally born low birth weight and suffer from delayed development and neuromotor deficits. These deficits include critical life skills such as swallowing and breathing. It is unclear whether these neuromotor and biomechanical deficits are a result of low birth weight or preterm birth. In this study we ask: are preterm infants simply low birth weight infants or do preterm infants differ from term infants in weight gain and swallowing behaviors independent of birth weight? We use a validated infant pig model to show that preterm and term infants gain weight differently and that birth weight is not a strong predictor of functional deficits in preterm infant swallowing. We found that preterm infants gained weight at a faster rate than term infants and with nearly three times the variation. Additionally, we found that the number of sucks per swallow, swallow duration, and the delay of the swallows relative to the suck cycles were not impacted by birth weight. These results suggest that any correlation of developmental or swallowing deficits with reduced birth weight are likely linked to underlying physiological immaturity of the preterm infant.

Sucking versus swallowing coordination, integration, and performance in preterm and term infants.

Mammalian infants must be able to integrate the acquisition, transport, and swallowing of food to effectively feed. Understanding how these processes are coordinated is critical, as they have differences in neural control and sensitivity to perturbation. Despite this, most studies of infant feeding focus on isolated processes, resulting in a limited understanding of the role of sensorimotor integration in the different processes involved in infant feeding. This is especially problematic in the context of preterm infants, as they are considered to have pathophysiological brain development and often experience feeding difficulties. Here, we use an animal model to study how the different properties of food acquisition, transport, and swallowing differ between term and preterm infants longitudinally through infancy to understand which processes are sensitive to variation in the bolus being swallowed. We found that term infants are better able to acquire milk than preterm infants, and that properties of acquisition are strongly correlated with the size of the bolus being swallowed. In contrast, behaviors occurring during the pharyngeal swallow, such as hyoid and soft palate movements, show little to no correlation with bolus size. These results highlight the pathophysiological nature of the preterm brain and also demonstrate that behaviors occurring during oral transport are much more likely to respond to sensory intervention than those occurring during the "pharyngeal phase."NEW & NOTEWORTHY Physiological maturation of infant feeding is clinically and developmentally significant, but seldom examined as an integrated function. Using longitudinal high-speed videofluoroscopic data, we found that properties of sucking, such as the length of the suck, are more sensitive to swallow physiology than those associated with the pharyngeal swallow itself, such as hyoid excursion. Prematurity impacted the function and maturation of the feeding system, resulting in a physiology that fundamentally differs from term infants by weaning.

The effect of preterm birth, recurrent laryngeal nerve lesion, and postnatal maturation on hyoid and thyroid movements, and their coordination in infant feeding.

Movements of the hyoid and thyroid are critical for feeding. These structures are often assumed to move in synchrony, despite evidence that neurologically compromised populations exhibit altered kinematics. Preterm infants are widely considered to be a neurologically compromised population and often experience feeding difficulties, yet measuring performance, and how performance matures in pediatric populations is challenging. Feeding problems are often compounded by complications arising from surgical procedures performed to ensure the survival of preterm infants, such as damage to the recurrent laryngeal nerve (RLN) during patent ductus arteriosus correction surgery. Here, we used a validated infant pig model for infant feeding to test how preterm birth, postnatal maturation, and RLN lesion interact to impact hyoid and thyroid excursion and their coordination. We filmed infant pigs when feeding using videofluorscopy at seven days old (1-2 months human equivalent) and 17 days old (6-9 months human equivalent) and tracked movements of the hyoid and thyroid on both days. We found that preterm birth impacted the coordination between hyoid and thyroid movements, but not their actual excursion. In contrast, excursion of the two structures increased with postnatal age in term and preterm pigs. RLN lesion decreased thyroid excursion, and primarily impacted hyoid movements by increasing variation in hyoid excursion. This work demonstrates that RLN lesion and preterm birth have distinct, but pervasive effects on feeding performance in infants, and suggest that interventions targeted towards reducing dysphagia should be prescribed based off the etiology driving dysphagia, rather than the prognosis of dysphagia.