Maturation of upstream and downstream esophageal reflexes in human premature neonates: the role of sleep and awake states

Abstract

Jadcherla SR, Chan CY, Fernandez S, Splaingard M. Maturation of upstream and downstream esophageal reflexes in human premature neonates: the role of sleep and awake states. Am J Physiol Gastrointest Liver Physiol 305: G649 -G658, 2013. First published September 5, 2013 doi:10.1152/ajpgi.00002.2013.-We tested the hypothesis that the sensory-motor characteristics of aerodigestive reflexes are dependent on stimulus type and volumes, sleep or awake states, and maturation. Thirteen neonates were studied at 33.6 Ϯ 0.5 wk (time 1) and 37.3 Ϯ 0.5 wk (time 2) postmenstrual age using multimodal provocative esophageal manometry concurrent with video polysomnography. Effects of graded volumes (399 infusions at time 1, 430 infusions at time 2) of midesophageal stimulation with air, water, and apple juice on the sensory thresholds and recruitment frequency of upper esophageal sphincter (UES), esophageal body, and lower esophageal sphincter (LES) reflexes were investigated during sleep and awake states. Sensory thresholds for aerodigestive reflexes between maturational stages were similar. Increased frequency recruitment of UES contractile reflex, LES relaxation reflex, and peristaltic reflexes were noted at time 2 (all, P Ͻ 0.05). Graded stimulusresponse relationships were evident at time 1 and time 2 during awake and sleep states (P Ͻ 0.05). Secondary peristalsis vs. esophagodeglutition response proportions during sleep at time 1 vs. time 2 (P ϭ 0.001) and awake vs. sleep at time 2 (P ϭ 0.02) were distinct. We concluded that sensory-motor effects of esophageal mechanosensitivity, osmosensitivity, and chemosensitivity are advanced in sleep with maturation. Sleep further modulates the frequency recruitment and the type of aerodigestive reflexes.sleep; upper esophageal sphincter; lower esophageal sphincter; peristaltic reflex SLEEP IS BOTH A CRUCIAL AND VULNERABLE physiological state for the developing infant. Although it is essential for conservation of energy and growth, the aerodigestive tract also becomes increasingly susceptible to both retrograde and anterograde aspiration during periods of sleep. Aerodigestive adaptation to these provocations must be maintained; however, the effects of such esophageal provocation during sleep are unclear. Compromise of aerodigestive functions may have serious consequences such as apparent life-threatening events (ALTE) or sudden infant death syndrome (SIDS) (1). It is common practice for infants who have experienced such events to undergo evaluation for esophageal and sleep pathology, as there is often a presumed causal connection between ALTE, SIDS, and aerodigestive pathology with respect to aspiration. These infants are often treated empirically for gastroesophageal reflux disease (GERD) and associated sleep disturbance, using treatments such as caffeine, positional changes, modifications of milk type or density, changes in feeding volumes or feeding methods, medical therapy, or even surgical intervention (2, 6, 25, 36). These treatments have aerodigestive consequences, may be expens...

Effects of Esophageal Acidification on Troublesome Symptoms: An Approach to Characterize True Acid GERD in Dysphagic Neonates

“…The remaining percentage of ascending AREs are associated with symptoms, and may be explained by ineffective, delayed or malfunctioning aerodigestive reflexes in which prolonged and more proximal exposure of the esophagus to refluxed acid may be activating visceral, autonomic and sensory aerodigestive pathways (44, 51, 53, 54). Other explanations may include varying volume of the refluxate and/or sleep state (1, 19, 44, 53–55). …”

The Role of Sleep in the Modulation of Gastroesophageal Reflux and Symptoms in NICU Neonates

“…42 During sleep, primary esophageal clearance mechanism is secondary peristalsis and UES contractile response limiting more proximal ascent. 2 Therefore, the infant is likely to process lesser ascending sensory stimulus spread manifesting in fewer somatic motor responses and preservation of sleep state. 2, 42 Thus there are reductions in physical symptoms during sleep state.…”

“…2 Therefore, the infant is likely to process lesser ascending sensory stimulus spread manifesting in fewer somatic motor responses and preservation of sleep state. 2, 42 Thus there are reductions in physical symptoms during sleep state. Sleep also modulates the recruitment frequency and type of aerodigestive reflexes slowing the clearance mechanisms.…”

“…Sleep also modulates the recruitment frequency and type of aerodigestive reflexes slowing the clearance mechanisms. 2 Impairment of respiratory reflexes is also recognized during sleep with decreased coordination of cardiorespiratory homeostatic control. 43, 44 Collectively these mechanisms may modulate autonomic responses resulting in more frequent cardiorespiratory symptoms during sleep.…”

“…1, 2, 3 Newborns may sleep up to 80% of the time and different sleep states emerge after 28 weeks gestational age. 4, 5 Three stages of sleep are recognized in neonates: active sleep, quiet sleep and indeterminate sleep.…”