Gestational and postnatal modulation of esophageal sphincter reflexes in human premature neonates.

BACKGROUND: Effects of gestational age (GA) and postnatal maturation on upper and lower esophageal sphincter (UES and LES) reflex development remain unclear. We hypothesized very-preterm (VPT) born neonates (< 32 wk GA) have delayed maturation of UES contractile reflex (UESCR) and LES relaxation reflex (LESRR) vs. preterm (PT) born (32-37 wk GA) neonates. METHODS: Using provocative manometry, effects of 1,263 graded mid-esophageal stimuli (air, liquid) on sensory-motor characteristics of UESCR and LESRR were investigated in 24 VPT-born and 12 PT-born neonates (37.8 ± 0.6 vs. 38.9 ± 0.4 wk postmenstrual age respectively, P = 0.14). RESULTS: In response to liquid stimuli (vs. air), VPT-born neonates displayed prolonged UESCR and LESRR response latencies (P < 0.001) and prolonged UESCR and LESRR durations (P < 0.01); unlike PT-born neonates, who exhibit prolonged LESRR response latency (P < 0.01), but similar UESCR and LESRR durations (P = 0.2). Differences were noted in LESRR duration in VPT vs. PT neonates for air stimuli (P = 0.04). With liquid stimuli, increasing GA was associated with decreasing response onset latencies to UESCR and LESRR (P < 0.05), and increasing LESRR duration (P = 0.02). CONCLUSION: Using GA as categorical or continuous variable, vagus-mediated mechano-sensitive and liquid-sensitive reflex characteristics of UESCR and LESRR are distinct; LESRR differs with varying intrauterine maturation suggesting inhibitory modulation progresses with advancing maturation.

Effects of birth asphyxia on the modulation of pharyngeal provocation-induced adaptive reflexes.

Perinatal asphyxia and aerodigestive symptoms are troublesome. We tested the hypothesis that pharyngeal provocation alters proximal and distal aerodigestive reflex coordination and kinetics in infants with hypoxic ischemic encephalopathy (HIE), compared with healthy controls. Specifically, we characterized the sensory-motor properties of pharyngeal provocation-induced effects on upper esophageal sphincter (UES) and lower esophageal sphincter (LES) reflexes. Ten orally fed controls (32.0 ± 1.5 wk gestation) and 25 infants with HIE (38.1 ± 0.4 wk gestation) were evaluated at 39.7 ± 0.9 and 41.9 ± 0.6 wk postmenstrual age respectively. Pharyngo-esophageal reflexes evoked upon graded water stimuli were tested using water-perfusion micromanometry methods. Analysis included sensory-motor characteristics of pharyngeal reflexive swallow (PRS), pharyngo-UES-contractile reflex (PUCR), esophageal body-waveform kinetics, and pharyngo-LES-relaxation reflex (PLESRR). For controls vs. infants with HIE, median appearance, pulse, grimace, activity, respiration (APGAR) scores were 6 vs. 1 at 1 min (P < 0.001) and 8 vs. 3 at 5 min (P < 0.001). Upon pharyngeal- stimulation, HIE infants (vs. controls) had frequent PUCR (P = 0.01); increased UES basal tone (P = 0.03); decreased LES basal tone (P = 0.002); increased pharyngeal-waveforms per stimulus (P = 0.03); decreased frequency of LES relaxation (P = 0.003); and decreased proximal esophageal contractile amplitude (P = 0.002), with prolonged proximal esophageal contractile duration (P = 0.008). Increased tonicity and reactivity of the UES and dysregulation of LES may provide the pathophysiological basis for pooling of secretions, improper bolus clearance, and aspiration risk. Deficits in function at the nuclear or supranuclear level involving glossopharyngeal and vagal neural networks and respiratory regulatory pathways involved with aerodigestive protection may be contributory.

Upper and lower esophageal sphincter kinetics are modified during maturation: effect of pharyngeal stimulus in premature infants.

BACKGROUND: We hypothesized that changes in proximal and distal esophageal sphincter kinetics evoked upon pharyngeal provocation undergo longitudinal maturation. METHODS: Pharyngeal stimulation-induced reflexes were characterized using novel pharyngo-esophageal motility methods in 19 healthy premature neonates, studied at 34.7 ± 0.8 wk (time-1) and 39.3 ± 1.1 wk postmenstrual age (time-2). Graded volumes of air (290 infusions) and sterile water (172 infusions) were infused to define sensory-motor characteristics of upstream (pharyngeal reflexive swallow, PRS) and downstream (pharyngo-lower esophageal sphincter relaxation reflex, PLESRR) esophageal reflexes. Data displayed as mean ± SE. RESULTS: Threshold volumes were similar with air and water for PRS and PLESRR at time-1 and time-2. Multiple PRS responses were noted with water stimulus and were different between the media (time-1 vs. air, P < 0.0001; time-2 vs. air, P = 0.0003). Dose-response relationships for water were significant (P < 0.01 for PRS and PLESRR time-1 and time-2), but not with air. CONCLUSION: Significantly, the recruitment frequency of PRS and PLESRR increases with maturation, liquid is a superior medium for evoking such swallowing reflexes, and stimulus-response relationships for these reflexes are evident. These changes in aerodigestive protective reflexive activity may indicate differences in modulation of excitatory and inhibitory pathways during longitudinal postnatal maturation.