Preterm birth disrupts the development of feeding and breathing coordination

Abstract

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.

Keywords: aerodigestive; dysphagia; feeding; neonate; premature.

Fig. 1.

Maturation of sucking and swallowing relationships in term (orange) and preterm (blue) pigs through ontogeny. A; sucking rate during feeding (day 7: term n = 386 sucks, preterm n = 420 sucks; day 17: term n = 450 sucks, preterm n = 374 sucks). B: swallow rate (day 7: term n = 158 swallows, preterm n = 96 swallows; day 17: term n = 196 swallows, preterm n = 136 swallows). C: respiratory rate during feeding (day 7: term n = 159 breaths, preterm n = 122 breaths; day 17: term n = 178 breaths, preterm n = 158 breaths) on days 7 and 17. Small black dots are outliers; large black circles are means; box and whisker plots show median and interquartile range; width of each plot indicates the frequency distribution of the data along the y-axis; and lines connecting plots show significant differences identified by mixed models or Tukey’s post hoc analyses when interactions were significant (P < 0.05).

Fig. 2.

The coordination of different behaviors in term and preterm pigs. A: term (orange) and preterm (blue) pigs both decrease the delay of the swallow relative to the beginning of the suck cycle, and preterm pigs exhibit a greater delay than term pigs throughout ontogeny (day 7: term n = 143 swallows, preterm n = 88 swallows; day 17: term n = 174 swallows, preterm n = 158 swallows). B: term pigs begin inspiration shortly after a swallow, and this delay increases through ontogeny, whereas preterm pigs show no coordination between respiration and swallowing through ontogeny (day 7: term n = 106 breaths, preterm n = 65 breaths; day 17: term n = 143 breaths, preterm n = 104 breaths). Small black dots are outliers; large black circles are means; box and whisker plots show median and interquartile range; width of each plot indicate the frequency distribution of the data along the y-axis; and lines connecting plots show significant differences identified by mixed models or Tukey’s post hoc analyses when interactions were significant (P < 0.05).