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 remains unclear. We hypothesized very-preterm (VPT) born neonates (< 32 weeks GA) have delayed maturation of UES contractile reflex (UESCR) and LES relaxation reflex (LESRR) vs. preterm (PT) born (32–37 weeks GA) neonates. METHODS: Using provocative manometry, effects of 1263 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 weeks PMA 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). CONCLUSIONS: 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.