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.

Swallow Safety is Determined by Bolus Volume During Infant Feeding in an Animal Model.

Feeding difficulties are especially prevalent in preterm infants, although the mechanisms driving these difficulties are poorly understood due to a lack of data on healthy infants. One potential mechanism of dysphagia in adults is correlated with bolus volume. Yet, whether and how bolus volume impacts swallow safety in infant feeding is unknown. A further complication for safe infant swallowing is recurrent laryngeal nerve (RLN) injury due to patent ductus arteriosus surgery, which exacerbates the issues that preterm infants face and can increase the risk of dysphagia. Here, we used a validated animal model feeding freely to test the effect of preterm birth, postnatal maturation and RLN lesion and their interactions on swallow safety. We also tested whether bolus size differed with lesion or birth status, and the relationship between bolus size and swallow safety. We found very little effect of lesion on swallow safety, and preterm infants did not experience more penetration or aspiration than term infants. However, term infants swallowed larger boluses than preterm infants, even after correcting for body size. Bolus size was the primary predictor of penetration or aspiration, with larger boluses being more likely to result in greater degrees of dysphagia irrespective of age or lesion status. These results highlight that penetration and aspiration are likely normal occurrences in infant feeding. Further, when comorbidities, such as RLN lesion or preterm birth are present, limiting bolus size may be an effective means to reduce incidences of penetration and aspiration.

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.

Changes in the coordination between respiration and swallowing from suckling through weaning.

All mammals undergo weaning from milk to solid food. This process requires substantial changes to mammalian oropharyngeal function. The coordination of swallowing and respiration is a crucial component of maintaining airway function throughout feeding and matures over infant development. However, how this coordination is affected by weaning is unknown. In this study, we ask how changes in posture, neural maturation and food properties associated with the weaning affect coordination of respiration and swallowing in a validated infant pig model. We recorded seven piglets feeding before and during the weaning age with liquid milk in a bottle and in a bowl, and solid feed in a bowl. Using videofluoroscopy synchronized with respiration, we found (i) the delay in the onset of inspiration after swallowing does not change with head position, (ii) the delay is different between solid food and bowl drinking at the same age and (iii) the delay increases over time when bottle feeding, suggesting a maturational effect. Significant changes in aerodigestive coordination occur prior to and post-weaning, resulting in distinctive patterns for liquid and solid food. The interplay of maturational timelines of oropharyngeal function at weaning may serve as a locus for behavioural and life-history plasticity.

Swallow Safety in Infant Pigs With and Without Recurrent Laryngeal Nerve Lesion.

Aerodigestive coordination is critical for safe feeding in mammals, and failure to do so can result in aspiration. Using an infant pig model, we analyzed the impact of recurrent laryngeal nerve (RLN) lesion on aerodigestive coordination and swallow safety at two time points prior to weaning. We used high-speed videofluoroscopy to record 23 infant pigs longitudinally at two ages (7 days, 17 days) feeding on barium milk. We measured respiration with a plethysmograph and used the Infant Mammalian Penetration-Aspiration Scale (IMPAS) to identify unsafe swallows. We tested for changes in swallow safety longitudinally in control and lesion pigs, and whether there was any interaction between the four different groups. On postnatal day 7, lesioned pigs exhibited differences in the frequency distribution of IMPAS scores relative to control pigs on day 7, and 17 day old lesion and control pigs. There were longitudinal changes in performance following RLN lesion through time, suggesting that the impact of RLN lesion decreases with time, as older lesioned pigs performed similarly to older control pigs. We found minimal differences in the impact of aerodigestive coordination on swallow safety, with shorter delays of inspiration onset reflecting higher rates of penetration in young lesioned pigs. Healthy pigs aspirated at a similar rate to those with an RLN lesion indicating that the occasional occurrence of dysphagia in infants may be a normal behavior.

Reduced Coordination of Hyolaryngeal Elevation and Bolus Movement in a Pig Model of Preterm Infant Swallowing.

Preterm infants often have dysphagia. Because reducing lifetime cumulative exposure to radiation in the context of diagnosis and treatment is a continuing goal of all medical fields which use X-ray imaging, efforts exist to reduce reliance on the gold standard diagnostic tool for dysphagia, VFSS. Alternatives, such as video of external hyolaryngeal movement using video recordings of the anterior surface of the neck, must be evaluated and validated against videofluoroscopy, a task for which non-human animal models are appropriate. In this study, we tested the hypotheses that (1) swallows could be identified equally well from video of external hyolaryngeal movement and bolus movement in videofluoroscopy, and that (2) the two measures would be tightly temporally linked in both term and preterm infant pigs. We recorded 222 swallows in simultaneous and precisely synchronized high-speed videofluoroscopy and high-speed camera films of 4 preterm and 3 term infant pigs drinking milk from a bottle. In term pigs, the two measures consistently identified the same swallows in each image stream. However, in preterm pigs there was a high rate of false positives (~ 10% per feeding sequence) and false negatives (~ 27% per feeding sequence). The timing of hyolaryngeal elevation (external video) and bolus movement (videofluoroscopy) was correlated and consistent in terms pigs, but not in preterm pigs. Magnitude of hyolaryngeal elevation was less in preterm pig swallows than term pig swallows. Absence of epiglottal inversion in preterm pigs was not linked to variation in the timing of the two swallow events. Video of external hyolaryngeal movement, though a reliable swallow indicator in term infant pigs, was unreliable in preterm infant pigs. The coordination of swallowing events differs in preterm and term infant pigs. More research is needed into the distinctive biomechanics of preterm infant pigs.

Premature birth impacts bolus size and shape through nursing in infant pigs.

BACKGROUND: The formation of a bolus of food is critical for proper feeding function, and there is substantial variation in the size and shape of a bolus prior to a swallow. Preterm infants exhibit decreased abilities to acquire and process food, but how that relates to their bolus size and shape is unknown. Here, we test two hypotheses: (1) that bolus size and shape will differ between term and preterm infants, and (2) bolus size and shape will change longitudinally through development in both term and preterm infants. METHODS: To test these hypotheses, we measured bolus size and shape in preterm and term infant pigs longitudinally through nursing using high-speed videofluoroscopy. RESULTS: Preterm infant pigs swallowed smaller volumes of milk. Although term infants increased the amount of milk per swallow as they aged, preterm infants did not. These changes in bolus volume were also correlated with changes in bolus shape; larger boluses became more elongate as they better filled the available anatomical space of the valleculae. CONCLUSIONS: These results suggest that preterm birth reduces the ability of preterm pigs to increase bolus size as they grow, affecting development in this fragile population. These results highlight that studies on term infant feeding may not translate to preterm infants.

Preterm birth disrupts the development of feeding and breathing coordination.

All mammals must breathe and breathe continuously from birth. Similarly, all mammals, including infants, have high functional demands for feeding. However, the pathway that food takes through the pharynx interrupts respiration. The coordination between swallowing and breathing is therefore critical for all infant mammals. Clinically, this coordination differs between term and preterm infants. However, the neurological mechanisms underlying this coordination and how it matures as infants grow are poorly understood. Here, we integrate high-resolution data from multiple physiologic processes across a longitudinal time frame to study suck-swallow-breathe dynamics in a preterm animal model, the infant pig. In doing so, we test the hypothesis that preterm birth will have an impact on some, but not all, behaviors associated with suck-swallow-breath performance. We hypothesize that coordination will be disrupted, reflecting incomplete connections in the brainstem. We found that preterm pigs became rhythmic and mature in sucking and swallowing behaviors, suggesting substantial postnatal maturation in the coordination of these behaviors. However, their ability to coordinate swallowing and breathing never developed. These results have implications for the nature of clinical care of human infants, as well as for how feeding processes develop in mammals. Clinically, they provide a foundation for developing interventions for preterm infants. Additionally, these results suggest that the lack of coordination between swallowing and breathing may be a significant factor in determining the minimum gestation time across mammals. NEW & NOTEWORTHY Preterm infants face a variety of challenges associated with safe feeding, but obtaining high-resolution longitudinal data to understand these challenges in humans is challenging. We used a pig model to acquire high-speed videofluoroscopic and respiratory inductance plethysmograph data throughout the nursing period to show that preterm birth does not have substantial impacts on the ability of infants to perform isolated behaviors. However, it does decrease the ability of preterm infants to coordinate among behaviors during feeding.

Maturation of the Coordination Between Respiration and Deglutition with and Without Recurrent Laryngeal Nerve Lesion in an Animal Model.

The timing of the occurrence of a swallow in a respiratory cycle is critical for safe swallowing, and changes with infant development. Infants with damage to the recurrent laryngeal nerve, which receives sensory information from the larynx and supplies the intrinsic muscles of the larynx, experience a significant incidence of dysphagia. Using our validated infant pig model, we determined the interaction between this nerve damage and the coordination between respiration and swallowing during postnatal development. We recorded 23 infant pigs at two ages (neonatal and older, pre-weaning) feeding on milk with barium using simultaneous high-speed videofluoroscopy and measurements of thoracic movement. With a complete linear model, we tested for changes with maturation, and whether these changes are the same in control and lesioned individuals. We found (1) the timing of swallowing and respiration coordination changes with maturation; (2) no overall effect of RLN lesion on the timing of coordination, but (3) a greater magnitude of maturational change occurs with RLN injury. We also determined that animals with no surgical intervention did not differ from animals that had surgery for marker placement and a sham procedure for nerve lesion. The coordination between respiration and swallowing changes in normal, intact individuals to provide increased airway protection prior to weaning. Further, in animals with an RLN lesion, the maturation process has a larger effect. Finally, these results suggest a high level of brainstem sensorimotor interactions with respect to these two functions.

Effects of support diameter and compliance on common marmoset (Callithrix jacchus) gait kinematics.

Locomotion is precarious in an arboreal habitat, where supports can vary in both diameter and level of compliance. Several previous studies have evaluated the influence of substrate diameter on the locomotor performance of arboreal quadrupeds. The influence of substrate compliance, however, has been mostly unexamined. Here, we used a multifactorial experimental design to investigate how perturbations in both diameter and compliance affect the gait kinematics of marmosets (Callithrix jacchus; N=2) moving over simulated arboreal substrates. We used 3D-calibrated video to quantify marmoset locomotion over a horizontal trackway consisting of variably sized poles (5, 2.5 and 1.25 cm in diameter), analyzing a total of 120 strides. The central portion of the trackway was either immobile or mounted on compliant foam blocks, depending on condition. We found that narrowing diameter and increasing compliance were both associated with relatively longer substrate contact durations, though adjustments to diameter were often inconsistent relative to compliance-related adjustments. Marmosets also responded to narrowing diameter by reducing speed, flattening center of mass (CoM) movements and dampening support displacement on the compliant substrate. For the subset of strides on the compliant support, we found that speed, contact duration and CoM amplitude explained >60% of the variation in substrate displacement over a stride, suggesting a direct performance advantage to these kinematic adjustments. Overall, our results show that compliant substrates can exert a significant influence on gait kinematics. Substrate compliance, and not just support diameter, should be considered a critical environmental variable when evaluating locomotor performance in arboreal quadrupeds.