Neuromotor markers of esophageal motility in feeding intolerant infants with gastroschisis.

BACKGROUND: Feeding problems in neonates with gastroschisis are commonly attributed to foregut dysmotility. However, the dysmotility mechanisms are not well understood. OBJECTIVE: Our aim was to differentiate the pharyngoesophageal motility characteristics in neonates with gastroschisis compared with the controls. Specifically, the characteristics of swallowing, upper esophageal sphincter (UES), esophageal body, and lower esophageal sphincter (LES) were evaluated during basal state and upon provocation. PATIENTS AND METHODS: Surgically repaired and recovered study infants with persistent feeding difficulties (n = 8; 36 +/- 2 weeks gestational age) and controls (n = 8; 38 +/- 2 weeks gestational age) were evaluated at 40 +/- 2 weeks and 42 +/- 2.5 weeks postmenstrual age, respectively. The basal and adaptive pharyngoesophageal motility characteristics were evaluated using a specially designed esophageal motility catheter with UES and LES sleeves and pneumohydraulic micromanometric water perfusion system at the crib side. Analysis of variance, chi-square, and t tests were applied; data are shown as mean +/- standard deviation, and P < 0.05 was considered significant. RESULTS: Birth weight was less in gastroschisis (P < 0.03, vs controls) and length was less at motility study (P < 0.01, vs controls). The study group (vs controls) needed prolonged respiratory support (21 +/- 23 vs 1 +/- 2 days; P < 0.001) and prolonged gavage feeding (167 +/- 100 vs 9 +/- 16 days; P < 0.01). Compared with the controls, the gastroschisis group had lower frequency (P < 0.05) and poor propagation of spontaneous swallows (P < 0.001), UES relaxation time was shorter (P < 0.05), rate of relaxation was faster (P < 0.001), and esophageal peristaltic propagation velocity was slower (P < 0.05). Upon esophageal provocation with air and liquids, frequency occurrence of the esophageal reflexes was low (P < 0.05) with respect to primary peristalsis, secondary peristalsis, UES contractile reflex, and LES relaxation reflex. CONCLUSIONS: In gastroschisis feeding milestones and respiratory milestones were delayed, basal pharyngoesophageal peristaltic failure was common, adaptive peristaltic reflexes were less frequent and failed to occur, and frequency occurrences of UES and LES responses were impaired. These neuromotor markers may provide clues to define the esophageal motor function abnormalities in infants with an abnormality thought to be limited to the intestine.

Pharyngeal swallowing: defining pharyngeal and upper esophageal sphincter relationships in human neonates.

OBJECTIVE: To test the hypothesis that the sensorimotor characteristics of the reflexes evoked on stimulation with air and water infusions differ by studying the effect of pharyngeal stimulation on pharyngeal-upper esophageal sphincter (UES) interactions in healthy neonates. STUDY DESIGN: Pharyngo-UES-esophageal manometry was recorded in 10 neonates at 39 +/- 4 weeks postmenstrual age. Pharyngeal infusions (n = 155) of air (0.1 to 2.0 mL) and sterile water (0.1 to 0.5 mL) were given. Two types of reflexes were recognized: pharyngeal reflexive swallowing (PRS) and pharyngo-UES-contractile reflex (PUCR). Frequency occurrence, distribution of reflexes, threshold volume, response time, and stimulus-response relationship were evaluated. RESULTS: The reflex response rates were 30% for air and 76% for water (P < .001). PRS was more frequent than PUCR with air and water (P < .05), even though the stimulation thresholds and response latencies were similar. Graded volumes of water but not air resulted in an increased frequency of PRS (P < .01). CONCLUSIONS: PRS is more frequent than PUCR, and the 2 reflexes have distinctive characteristics in air and water stimuli. Both PRS and PUCR have implications for the evaluation of swallowing in infants.

Effect of maturation of the magnitude of mechanosensitive and chemosensitive reflexes in the premature human esophagus.

OBJECTIVES: To investigate the effect of esophageal mechanosensitive and chemosensitive stimulation on the magnitude and recruitment of peristaltic reflexes and upper esophageal sphincter (UES)-contractile reflex in premature infants. STUDY DESIGN: Esophageal manometry and provocation testing were performed in the same 18 neonates at 33 and 36 weeks postmenstrual age (PMA). Mechanoreceptor and chemoreceptor stimulation were performed using graded volumes of air, water, and apple juice (pH 3.7), respectively. The frequency and magnitude of the resulting esophago-deglutition response (EDR) or secondary peristalsis (SP), and esophago-UES-contractile reflex (EUCR) were quantified. RESULTS: Threshold volumes to evoke EDR, SP, or EUCR were similar. The recruitment and magnitude of SP and EUCR increased with volume increments of air and water in either study (P < .05). However, apple juice infusions resulted in increased recruitment of EDR in the 33 weeks group (P < .05), and SP in the 36 weeks group (P < .05). The magnitude of EUCR was also volume responsive (all media, P < .05), and significant differences between media were noted (P < .05). At maximal stimulation (1 mL, all media), sensory-motor characteristics of peristaltic and EUCR reflexes were different (P < .05) between media and groups. CONCLUSIONS: Mechano- and chemosensitive stimuli evoke volume-dependent specific peristaltic and UES reflexes at 33 and 36 weeks PMA. The recruitment and magnitude of these reflexes are dependent on the physicochemical properties of the stimuli in healthy premature infants.

The relationship between somatic growth and in vivo esophageal segmental and sphincteric growth in human neonates.

BACKGROUND: Measurement of aerodigestive tract length is an important determinant for accurate placement of esophageal probes and gavage tubes at the desired location. The relationship of esophageal body, upper esophageal sphincter (UES) and lower esophageal sphincter (LES) lengths with somatic growth in neonates is not well understood. OBJECTIVES: Our objectives were to (1) evaluate a relationship between segmental esophageal lengths and somatic growth parameters and (2) ascertain the relationship between segmental esophageal lengths and gestational age (GA) and postmenstrual age (PMA) in preterm and full-term born human neonates. DESIGN/METHODS: One hundred esophageal manometry studies were performed in 75 infants (30-60 weeks PMA) and the high-pressure zones of LES and UES identified. The distance from nares to LES and from nares to UES, esophageal body length, length of UES and LES derived from the manometry studies were correlated with somatic growth parameters. Growth rate of different esophageal segments was also determined in 26 subjects that underwent longitudinal studies. Analysis of variance and linear regression analysis were performed. RESULTS: Seventy-five neonates of 23.0-40.6 weeks gestational age (0.6-4.4 kg) were studied at 29.1-58.6 weeks PMA (1.0-6.4 kg). Significant correlation (P < 0.001) of PMA and physical growth parameters with the growth of nares-LES (R = 0.8), esophageal body length (R = 0.6) and nares-UES (R = 0.4) were noted. Nares-to-LES length increased at a rate of 0.25 cm/wk PMA during 33.0-36.0 weeks of age. CONCLUSIONS: In vivo esophageal segmental lengths correlated strongly with somatic growth parameters and PMA in neonates. We speculate that this approach has many practical applications with the use of esophageal probes and catheters.

Esophageal body and upper esophageal sphincter motor responses to esophageal provocation during maturation in preterm newborns.

OBJECTIVES: We studied the maturation of esophageal body and upper esophageal sphincter (UES) motor responses that protect against reflux in newborns. STUDY DESIGN: The responses of esophageal body and UES on midesophageal provocation were quantified using a micromanometric water perfusion system and a specially designed catheter with a UES sleeve and 5 side-hole recording sites. Eighteen healthy premature infants were studied twice, at 33.4 weeks' and 35.7 weeks' mean postmenstrual ages (PMAs). RESULTS: Mean threshold volumes and the distribution of responses including secondary peristalsis, UES pressure increase, and primary peristalsis were similar for air and liquids. Secondary peristalsis and UES pressure increases were volume dependent for both studies, but their characteristics changed as PMA increased in that (1) completely propagated secondary peristalsis with liquids increased; (2) proximal esophageal contraction duration was shorter for air and liquids; and (3) propagating velocity for liquids was faster. CONCLUSIONS: Esophageal and UES motor responses to abrupt midesophageal provocation are present as early as 33 weeks' PMA, and the response-characteristics improve during development. Reflexes that may facilitate esophageal clearance include (1) secondary peristalsis; (2) esophago-UES-contractile reflex; and (3) esophago-deglutition response.

Inflammation inhibits muscarinic signaling in in vivo canine colonic circular smooth muscle cells.

We investigated the effects of experimental colitis on the muscarinic signaling properties and contractile behavior of canine colonic circular smooth muscle. The hypotheses that inflammation 1) inhibits in vivo muscarinic receptor mediated contractions, and 2) alters receptor density or receptor-binding affinities were tested. Muscarine was infused close-intra-arterially in seven conscious dogs during normal and experimental colitis states. Colonic circular muscle contractions were recorded via surgically attached strain gauge transducers. Muscarine stimulated phasic contractions in a dose-dependent manner, whereas colitis was inhibited. The inhibitory concentration 50% dose of M(3) receptor inhibitor was several times lower than that of M(1), M(2), and M(4) inhibitors during normal and colitis. However, inflammation induced a significant leftward shift in the circular muscle inhibitory dose-response curve of M(2) inhibitor. Muscarinic receptor density and binding analyses in isolated circular muscle cells was done in normal and colitis states. Inflammation significantly decreased maximum binding from 4082 fmol/mg to 2708 fmol/mg, whereas affinity constant remained unaffected. The conclusions were that 1) spontaneous and muscarine-activated in vivo phasic contractile activity of colonic circular muscle cells is primarily mediated by M(3) receptors; 2) inflammation was associated with a shift in M(2) receptor potency, due chiefly to a decrease in receptor density; and 3) this inhibitory effect was seen in normal and inflamed states, suggesting the importance of M(2) receptor. These findings suggest that changes in muscarinic response during colitis may contribute to the abnormal motility seen with inflammatory bowel disease.

Gastroesophageal reflux in the neonate.

Physiologic GER may be a maturational phenomenon, because infants outgrow this over time. Many aspects of GERD in neonates and young infants remain incompletely understood, however, particularly the pathophysiology and long-term problems in high-risk neonates. Diagnostic and therapeutic availability is vital in infants with GER and airway compromise, apnea events, or chronic lung disease. Although most infants improve with conservative therapy, there is a dire lack of ideal pharmacologic agents that work on all the mechanisms of GER with the least consequences. Studies that permit diagnosis not only of the disease but also of the causal mechanism, better feeding strategies, and prevention of morbidity from GERD will be beneficial.

Effect of erythromycin on gastroduodenal contractile activity in developing neonates.

BACKGROUND: The occurrence of phase III of migrating motor complexes in neonates is inversely related to gestational age, and it can be triggered in some infants by the motilin receptor agonist erythromycin. After intragastric erythromycin, the authors determined 1) the occurrence and characteristics of phase III of migrating motor complexes, 2) the antral and duodenal motor responses, and 3) the dose-response relation among preterm and full-term infants. METHODS: Using an unbalanced, repeated measures design, 25 preterm and term infants were given two of three doses of intragastric erythromycin: 0.75, 1.5, and 3.0 mg/kg. Motor activity was recorded 3 hours before and 2 hours after each dose using a continuous water perfusion manometry system. RESULTS: Erythromycin failed to induce phase III of migrating motor complexes in infants younger than 31 weeks' gestation; however, it induced phase III in a dose-dependent manner among infants whose gestational ages were 32 weeks and older ( P < 0.05). Erythromycin significantly increased the amplitude and frequency of antral contractions in term infants and significantly increased the duodenal contraction amplitude in older preterm and term infants, but these effects were absent in younger preterm infants. CONCLUSIONS: The ontogenic emergence of the motilin receptor-mediated induction of phase III occurs by 32 weeks' gestation, whereas the non-motilin-mediated response of increased antroduodenal motor activity is not observed until term. Therefore, early use of erythromycin as a prokinetic agent may not be useful in very preterm infants, partially useful in older preterm infants, and useful in full-term infants.