Ross Haslam

Mechanisms of gastro-oesophageal reflux in preterm and term infants with reflux disease

Background: Transient lower oesophageal sphincter relaxation (TLOSR) is the predominant mechanism of gastro-oesophageal reflux (GOR) in healthy infants but the mechanisms of GOR in infants with GOR disease (GORD) are poorly understood. Aims: To measure the occurrence of TLOSR, GOR, and gastric emptying (GE) rate in preterm and term infants with GORD. Patients: Thirty six infants were studied and grouped as normals or GORD based on a routine clinical assessment and confirmation of an assessment of GORD by reflux symptom charts and oesophageal pH monitoring. Methods: A micromanometric assembly incorporating a micro pH electrode recorded oesophageal motility and pH. GE rate was determined using the 13C-octanoic acid breath test. Results: TLOSR was the predominant mechanism of GOR, triggering 50–100% of GOR episodes (median 91.5%). Abdominothoracic straining significantly increased the occurrence of GOR in association with TLOSR. In infants with GORD, the number of TLOSRs overall was similar to normals but the proportion of TLOSRs accompanied by acid GOR was significantly higher than in normals (16.5% v 5.7%, respectively; p<0.001). Infants with GORD had a similar GE rate to normals. Conclusions: In infant GORD, acid reflux associated TLOSRs are abnormally common and likely to be a major contributing factor to the pathophysiology of GORD. Infants with GORD do not have delayed GE.

Esophageal body and lower esophageal sphincter function in healthy premature infants

BACKGROUND & AIMS Gastroesophageal reflux is a common problem in premature infants. The aim of this study was to use a novel manometric technique to measure esophageal body and lower esophageal sphincter pressures in premature infants. METHODS Micromanometric feeding assemblies (OD, < or = 2 mm) incorporating 4-9 manometric channels were used in 49 studies of 27 premature neonates. Esophageal body motility was recorded at three sites for 20 minutes after feeding. Twenty attempts (one per minute) were made to stimulate swallowing via facial stimulation (Santmyer reflex). In 32 studies lower esophageal sphincter pressures were recorded (sleeve) for 15 minutes before and after feeding. RESULTS Peristaltic motor patterns were less common than non-peristaltic motor patterns (26.6% vs. 73.4%; P < 0.0001) that comprised 31.1% synchronous, 34.6% incomplete, and 6.3% retrograde pressure waves. Reflex swallowing was elicited more frequently in neonates older than 34 weeks postconceptional age than in younger infants (33.4% vs. 20.4%; P < 0.05). Mean lower esophageal sphincter pressure was 20.5 +/- 1.7 mm Hg before and 13.7 +/- 1.3 mm Hg after feeding (P < 0.0005). CONCLUSIONS Premature infants show nonperistaltic esophageal motility that may contribute to poor clearance of refluxed material. In contrast, the lower esophageal sphincter mechanisms seem well developed.

Caffeine for Apnea of Prematurity trial: benefits may vary in subgroups

OBJECTIVE To determine whether the benefits of caffeine vary in three subgroups of 2006 participants in the Caffeine for Apnea of Prematurity (CAP) trial. STUDY DESIGN Post-hoc subgroup analyses were performed on the basis of: (1) indication for commencement of study drug: treat apnea, prevent apnea, or facilitate extubation; (2) positive pressure ventilation (PPV) at randomization: endotracheal tube (ETT), noninvasive ventilation, or none; and (3) timing of commencement of study drug: early or late (< or =3 versus >3 days). Outcomes assessed were those showing treatment effects in the original analyses. We investigated the consistency of caffeine effects by using regression models that incorporated treatment/subgroup factor interactions. RESULTS There was little evidence of a differential treatment effect of caffeine in subgroups defined by the clinical indication for starting study drug. The size and direction of the caffeine effect on death or disability differed depending on PPV at randomization (P = .03). Odds ratios (95% CI) were: no support, 1.32 (0.81-2.14); noninvasive support, 0.73 (0.52-1.03); and ETT, 0.73 (0.57-0.94). Adjustment for baseline factors strengthened this effect (P = .02). Starting caffeine early resulted in larger reductions in days of respiratory support. Postmenstrual age at time of discontinuing PPV was shorter with earlier treatment (P = .01). Mean differences (95% CI) were: early, 1.35 weeks (0.90-1.81); and late 0.55 weeks (-0.11-0.99). Adjustment for baseline factors weakened this effect (P = .03). CONCLUSIONS There is evidence of variable beneficial effects of caffeine. Infants receiving respiratory support appeared to derive more neurodevelopmental benefits from caffeine than infants not receiving support. Earlier initiation of caffeine may be associated with a greater reduction in time on ventilation.

Planned Vaginal Birth or Elective Repeat Caesarean: Patient Preference Restricted Cohort with Nested Randomised Trial

A study conducted in Australia provides new data on the outcomes for mother and baby associated with either planned vaginal birth, or elective repeat caesarean section following a previous caesarean section.

Effect of omeprazole on acid gastroesophageal reflux and gastric acidity in preterm infants with pathological acid reflux.

Introduction: Proton pump inhibitor (PPI) therapy is increasingly being used to treat premature infants with gastroesophageal reflux disease (GERD); however, the efficacy of PPI on acid production in this population has yet to be assessed in this patient group. The aim of this study was to determine the effect of 0.7 mg/kg/d omeprazole on gastric acidity and acid gastroesophageal reflux in preterm infants with reflux symptoms and pathological acid reflux on 24-h pH probe. Methods: A randomized, double blind, placebo-controlled, crossover design trial of omeprazole therapy was performed in 10 preterm infants (34–40 weeks postmenstrual age). Infants were given omeprazole for 7 d and then placebo for 7 d in randomized order. Twenty-four-hour esophageal and gastric pH monitoring was performed on days 7 and 14 of the trial. Results: Compared to placebo, omeprazole therapy significantly reduced gastric acidity (%time pH <4, 54% vs 14%, P < 0.0005), esophageal acid exposure (%time pH <4, 19% vs 5%, P < 0.01) and number of acid GER episodes (119 vs 60 episodes, P < 0.05). Conclusions: Omeprazole is effective in reducing esophageal acid exposure in premature infants with pathological acid reflux on 24-h pH probe; however, the far more complex issues of safety and efficacy have yet to be addressed.

Effects of birthweight and oxygen supplementation on lung function in late childhood in children of very low birth weight

Impaired respiratory function has been found frequently in ex‐premature children, but it is unclear which specific factors influence this impairment the most. The aim of this study was to determine the importance of the contributions of birth weight, gestational age, neonatal respiratory disease, and its treatment on subsequent childhood lung function at age 11 years in a cohort of children of very low birth weight (VLBW; ≤1,500 g). Detailed clinical histories were recorded, and lung function was measured in 60% (102 children) of surviving VLBW infants born 1981/1982, and compared with 82 matched control children (birth weight >2,000 g) of similar age.

Characterisation of relaxation of the lower oesophageal sphincter in healthy premature infants.

BACKGROUND: Gastro-oesophageal reflux disease causes significant morbidity in premature infants, but the role of dysfunction of the lower oesophageal sphincter (LOS) in this condition is unclear. METHODS: Oesophageal manometry was performed after gavage feeding in 13 healthy preterm neonates (postmenstrual age > or = 33 weeks) with a perfused sleeve with side hole assembly. Swallow related (both single and multiple) and transient LOS relaxations (TLOSRs) were identified and the characteristics of these events defined. Reflux was identified with manometric criteria (common cavity episodes). RESULTS: Five hundred and eleven relaxation of the LOS were observed, 55% related to single swallows, 23% related to multiple swallows, and 22% TLOSRs. The time to maximal LOS relaxation was longer for TLOSRs than for single or multiple swallows (mean (SEM) 5.0 (0.3) s v 3.0 (0.1) s and 3.3 (0.1) s, p < 0.0001 and p < 0.005). The durations of multiple swallows and TLOSRs were longer than single swallows (12.2 (0.5) s and 11.2 (0.4) s v 5.3 (0.2) s, p < 0.0001). Most of the oesophageal body common cavity episodes (94%) occurred during TLOSRs. CONCLUSIONS: In healthy preterm infants (postmenstrual age > or = 33 weeks) the motor events associated with LOS relaxation were similar to those seen in healthy adults. TLOSRs may be an important mechanism of reflux in premature infants.

Reproducibility of the 13C-octanoic acid breath test for assessment of gastric emptying in healthy preterm infants

BACKGROUND The 13C-octanoic acid breath test has been used to measure gastric emptying in preterm infants, but the reproducibility of the test has not been evaluated in this population. METHODS Fifty-six paired breath test analyses were performed on 28 healthy preterm infants 1 to 5 days apart using the same food type, volume, and energy content for each paired sample. Breath samples were taken before the feeding, at 5-minute intervals after feeding for 30 minutes, then each 15 minutes for 4 hours. Samples were analyzed using an isotope-ratio mass spectrometer, and 3C recovery was used to calculate values for gastric-emptying coefficient and gastric half-emptying time. RESULTS There was no significant difference between test results on different days in the paired samples studied. gastric-emptying coefficients for the first and subsequent samples were 2.6+/-0.1 (mean+/-SEM) and 2.7+/-0.1, respectively, and half-emptying times were 44.5+/-3.7 minutes and 41.4+/-3.2 minutes. CONCLUSION The 13C-octanoic acid breath test is a reliable, noninvasive, and reproducible measure of gastric emptying in preterm infants that should have wide application for use in this population.

Pharmacodynamics and Systemic Exposure of Esomeprazole in Preterm Infants and Term Neonates with Gastroesophageal Reflux Disease

OBJECTIVE To characterize the pharmacodynamics and systemic exposure of esomeprazole in 26 preterm infants and term neonates with symptoms of gastroesophageal reflux and pathologic acid exposure. STUDY DESIGN Enrolled patients received oral esomeprazole 0.5 mg/kg once daily for 7 days. Twenty-four-hour esophagogastric pH-impedance monitoring was performed at baseline and on day 7. Pharmacokinetic analysis was performed on day 7. Symptoms occurring during the baseline and day 7 studies were recorded on a symptom chart. RESULTS There were no significant differences from baseline to day 7 of therapy in the frequency of bolus reflux, consistency of bolus reflux (liquid, mixed, or gas), extent of bolus reflux, or bolus clearance time. Acid bolus reflux episodes were reduced on therapy (median 30 vs 8, P < .001), as was the reflux index (mean % time esophageal pH < 4, 15.7% vs 7.1%, P < .001). The estimated geometric mean of area under the plasma concentration time curve during the dosing interval and observed maximum plasma concentration was 2.5 micromol x h/L and 0.74 micromol/L, respectively. The number of gastroesophageal reflux symptoms recorded over 24 hours was lower on therapy (median 22 vs 12, P < .05). CONCLUSIONS In preterm infants and term neonates esomeprazole produces no change in bolus reflux characteristics despite significant acid suppression.

Reduced corticomotor excitability and motor skills development in children born preterm

•  Children born preterm commonly experience motor and cognitive difficulties, but the physiology underlying this dysfunction is unknown. •  We used transcranial magnetic stimulation techniques and age‐appropriate assessments of motor skills development to investigate neurodevelopment in 151 children born between 25 and 41 weeks of gestation. •  Reduced gestational age at birth was associated with a reduction in corticomotor excitability that persisted in late childhood, poorer development of manual dexterity skills and reduced hemispheric lateralization of hand preference. •  We suggest this reduced corticomotor excitability at least partly reflects reduced white matter integrity and functional connectivity in the brain regions subserving movement control. •  These findings show that preterm birth, which is increasingly common, impacts neuromotor development and related physiology into adolescence. Whether this altered neurophysiology and motor function persists in adulthood is unknown.