María José Moya

Twenty-four-hour esophageal impedance-pH monitoring in healthy preterm neonates: rate and characteristics of acid, weakly acidic, and weakly alkaline gastroesophageal reflux

OBJECTIVE. Gastroesophageal reflux is a physiologic process and is considered pathologic (gastroesophageal reflux disease) when it causes symptoms or results in complications. It is common in preterm infants and occurs in healthy neonates. Twenty-four-hour pH monitoring commonly is used in children for diagnosis of gastroesophageal reflux disease, and abnormal reflux is considered with detection of increased esophageal acid exposure. However, in neonates, relatively few gastroesophageal reflux episodes cause esophageal acidification to pH <4. Premature infants receive frequent feeds, which can induce a weaker acid secretory response than that observed in older infants and adults. As a consequence, gastric pH may be >4 for prolonged periods, and reflux of gastric contents might be less acidic or even alkaline. Esophageal impedance monitoring can detect weakly acidic and even alkaline gastroesophageal reflux. The role of weakly acidic reflux in the pathophysiology of gastroesophageal reflux disease in preterm infants is not clear. To date, studies that have used impedance-pH in neonates assessed the association between nonacid reflux and cardiorespiratory symptoms, but no impedance data from healthy preterm neonates have been available to determine whether those symptomatic neonates had an increased number of weakly acidic reflux episodes or increased reactivity to a physiologic number of reflux events. Our aim with this study was to provide impedance-pH values for acid, weakly acidic, and weakly alkaline reflux from healthy preterm neonates. METHODS. Esophageal impedance was recorded for 24 hours in 21 asymptomatic preterm neonates by replacing the conventional feeding tube with a specially designed feeding tube that included 9 impedance electrodes (8 French). All neonates were asymptomatic, with spontaneous breathing. Reflux monitoring was performed after comprehensive explanation and on receipt of written parental consent. Esophageal and gastric pH were monitored using a separate parallel pediatric catheter (6 French). According to the corresponding pH change, impedance-detected reflux was classified as acid, weakly acidic, and weakly alkaline. For each infant, the total number of reflux events, the acid exposure and bolus exposure times at 2 cm above the respiratory inversion point, and average proximal extent of reflux were calculated. RESULTS. Twenty-six preterm neonates were recruited into this study. A preliminary analysis was performed, and tracings were classified according to their quality and the presence of technical artifacts (spontaneous pH and impedance drifts, esophageal probe migration, and dysfunction of 1 or more impedance channels). Five studies were excluded because of 1 or more technical artifacts; a total of 21 neonates represent the final cohort included. At birth, the infants had a median postmenstrual age of 32 weeks, and the measurements were performed at a median age of 12 days. The total recording time was 23.7 ± 2 hours. Gastric pH was higher than 4 during 69.3 ± 20.4% of the recording time. The median number of reflux events in 24 hours was 71, 25.4% (range: 0%–53.1%) of which were acid, 72.9% (range: 45.3%–98.0%) were weakly acidic, and 0% (range: 0%–8.1%) were weakly alkaline. Compared with fasting periods, feeding periods tended to be associated with a higher number of total reflux events per hour. The acidity of reflux, however, was significantly different: during fasting, the number of acid reflux episodes per hour was higher, whereas during feeding, the number of weakly acidic reflux episodes was increased. Most reflux events were only liquid, whereas gas was present either mixed with liquid or pure only in 7.7% of all reflux episodes detected. The proximal esophageal segments were reached in 90% of reflux episodes. Reflux-related acid exposure (pH drops associated with impedance-detected reflux) was 1.66% (range: 0%–6.43%), whereas total acid exposure (associated and not associated with reflux detected by impedance) was 5.59% (range: 0.04%–20.69%). There was no relationship between the number or acidity of reflux events and anthropometric parameters such as weight and gestational age. CONCLUSIONS. We present the first study using 24-hour impedance-pH recordings in asymptomatic premature neonates. Previous studies that used pH-metry suggested that neonatal cardiorespiratory symptoms could be related to acid gastroesophageal reflux. However, pH-metry could not detect accurately weakly acidic or nonacid reflux. Our healthy premature neonates had ∼70 reflux events in 24 hours, 25% of which were acid, 73% were weakly acidic, and 2% were weakly alkaline. The number of reflux events per hour (2–3 per hour) was slightly lower than that described in premature neonates with cardiorespiratory events (4 per hour). We confirmed that weakly acidic reflux is more prevalent than acid reflux, particularly so during the feeding periods. In contrast, similar to healthy adults, weakly alkaline reflux was very rare. We confirmed findings from previous studies in which most reflux events were pure liquid during both fasting and during postprandial periods and gas reflux was very rare. As in neonates with cardiorespiratory symptoms, the majority of reflux events in asymptomatic preterms reached the proximal esophagus or pharynx, and there were no differences between acid and weakly acidic reflux. The lack of differences between asymptomatic and diseased infants contravenes the hypothesis for macro- or microaspiration but does not exclude hypersensitivity to reflux as a cause for respiratory symptoms. The acid exposure that was related to reflux events and detected by impedance was significantly lower than the total acid exposure during 24 hours. Increased acid exposure could be attributable to pH-only reflux events or, less frequently, to slow drifts of pH from baselines at ∼5 to values <4. These changes were not accompanied by a typical impedance pattern of reflux but by slow drifts in impedance in 1 or 2 channels. Our findings confirm the need for the use of impedance together with pH-metry for diagnosis of all gastroesophageal reflux events. The relationship between gastroesophageal reflux and cardiorespiratory events in neonates and older infants has been studied extensively. The current evidence for such a relationship is controversial. This study provides values of impedance-pH monitoring for acid, weakly acidic, and weakly alkaline reflux from healthy preterm neonates that can be used for comparison when evaluating gastroesophageal reflux in preterm infants with a cardiorespiratory disease.

Characteristics of gastroesophageal reflux and potential risk of gastric content aspiration in children with cystic fibrosis.

Objectives: Increased gastroesophageal reflux (GER) is common in children with cystic fibrosis (CF). We studied the occurrence of acid, weakly acidic (WA), and weakly alkaline (WALK) reflux in children with CF and evaluated a possible surrogate marker for risk of gastric content aspiration. Patients and Methods: Twenty-four children with CF underwent impedance-pH monitoring for detection of acid (pH < 4), WA (pH 4-7), and WALK-GER (pH ≥ 7). In 11 children, cough was objectively recorded with esophageal manometry and the symptom association probability was calculated to determine the reflux-cough relation. Presence of bile acids (BA) was measured in the saliva of 65 patients with CF and 23 healthy children, respectively. Results: Sixteen of the 24 children had increased GER (esophageal acid exposure). The majority of reflux events were acidic in nature. WA reflux was less common and WALK reflux was rare. The sequence reflux-cough was found in 8 of the 11 children and 1 of 11 children had a positive symptom association probability for reflux-cough. The sequence cough-reflux was found in only 3 of the 11 children. Only a small fraction of the total esophageal acid and volume exposure was secondary to cough. Twenty-three of the 65 children with CF had BA in saliva compared with none of the healthy controls. Conclusions: Although WA-GER is uncommon, acid GER is prevalent in children with CF. It is a primary phenomenon and is not secondary to cough. One third of the children with CF have BA in saliva, which may indicate an increased risk for aspiration. However, the impact of salivary BA and potential aspiration on CF pulmonary disease needs further investigation.

Monte Carlo method for the evaluation of symptom association.

Gastroesophageal monitoring is limited to 96 hours by the current technology. This work presents a computational model to investigate symptom association in gastroesophageal reflux disease with larger data samples proving important deficiencies of the current methodology that must be taking into account in clinical evaluation. A computational model based on Monte Carlo analysis was implemented to simulate patients with known statistical characteristics Thus, sets of 2000 10-day-long recordings were simulated and analyzed using the symptom index (SI), the symptom sensitivity index (SSI), and the symptom association probability (SAP). Afterwards, linear regression was applied to define the dependency of these indexes with the number of reflux, the number of symptoms, the duration of the monitoring, and the probability of association. All the indexes were biased estimators of symptom association and therefore they do not consider the effect of chance: when symptom and reflux were completely uncorrelated, the values of the indexes under study were greater than zero. On the other hand, longer recording reduced variability in the estimation of the SI and the SSI while increasing the value of the SAP. Furthermore, if the number of symptoms remains below one-tenth of the number of reflux episodes, it is not possible to achieve a positive value of the SSI. A limitation of this computational model is that it does not consider feeding and sleeping periods, differences between reflux episodes or causation. However, the conclusions are not affected by these limitations. These facts represent important limitations in symptom association analysis, and therefore, invasive treatments must not be considered based on the value of these indexes only until a new methodology provides a more reliable assessment.

The binomial symptom index: toward an optimal method for the evaluation of symptom association in gastroesophageal reflux

The evaluation of symptom association in gastroesophageal reflux is an open problem. The scientific literature reports important deficiencies and clinicians are claiming a new methodology. This article provides an optimal method for the evaluation of symptom association, the binomial symptom index (BSI).

Inter-reflux and bolus clearance times in non-pathologic pediatric patients: data support computational models.

Previous contributions suggested that gastroesophageal reflux can be modeled in terms of a Poisson process. This study aims to provide empirical data to validate this statement in pediatric patients so that computational models can be broadly used as an alternative for research. A retrospective review of 63 pediatric patients who underwent 24-hour impedance-pH monitoring to discard gastroesophageal reflux disease was conducted in this study. Patients were grouped by age as preterm (21), infants (21), and children (21). All the tracings were analyzed by a trained physician who identified the reflux entry and the bolus clearance time of each episode. The time between reflux episodes was tested against three probability distributions (gamma, exponential and inverse Gaussian) whereas the bolus clearance time was tested against a normal probability distribution. Parameters were estimated using the maximum likelihood method. The Kolmogorov-Smirnov test and the Kullback-Leibler divergence were computed to evaluate the goodness of fit. One-way analysis of variance was applied to compare results along the three groups. Exponential fitting for inter-reflux time was successful in 90.48% of children older than 1 year. The overall reflux rate was 57.58 reflux episodes per day whereas the mean bolus clearance time ranged between 10.87 in preterm subjects and 12.05 in children, showing a good Gaussian fitting. The time between reflux episodes can be modeled in terms of a Poisson process in non tube-fed patients, whereas the bolus clearance time follows a normal distribution in all cases.

El índice de síntomas binomial para la evaluación de la asociación temporal entre síntomas cardiorrespiratorios y reflujo gastroesofágico en neonatos

INTRODUCTION The evaluation of symptom association between gastroesophageal reflux and cardiorespiratory events in preterm infants remains unclear. This paper describes a conservative approach to decision-making of anti-reflux surgery through symptom association analysis. METHODS Forty-three neonates with potentially reflux-related cardiorespiratory symptoms underwent synchronized esophageal impedance-pH and cardiorespiratory monitoring. Three indices were considered to evaluate symptom association, the symptom index (SI), the symptom sensitivity index (SSI) and the symptom association probability (SAP). A conservative strategy was adopted regarding the decision of anti-reflux surgery, and therefore, patients were scheduled for laparoscopic Nissen fundoplication if the three indices showed a positive assessment of symptom association. Retrospectively, these indices and the binomial symptom index (BSI) were contrasted against the decision of anti-reflux surgery using different windows of association. RESULTS Thirteen patients showed positive symptom association but only two underwent anti-reflux surgery. The SI and the SSI showed an increasing trend with the width of the window of association. The SAP was affected randomly by slightly altering the windowing parameters. The BSI showed the best performance with the two-minute window (κ =0.78) CONCLUSIONS: The pathology under study is known to improve with maturity. However, the severity of cardiorespiratory symptoms may threaten the neonates life and therefore, in some occasions, invasive treatments must be considered to protect life. The BSI provides a good prediction of a combination of positive SI, SSI and SAP, which may improve clinical decisions. However, further clinical studies are required to prove the BSI as an optimal predictor of clinical outcomes.

Resultados del descenso endorrectal transanal en la enfermedad de Hirschsprun

OBJECTIVE To present our experience of patients with Hirschsprung disease (HD) operated by transanal endorrectal descent (TED). METHODS A retrospective study performed of TEDs. We correlate fundamentally the aganglionic segment length with: Complications, need for colostomy and surgical approach. RESULTS Between 2003 and 2012 we performed 73 TED (57 men), 78.6% diagnosed in the neonatal period. The aganglionic segment length evidenced in the enema was correlated with surgical findings in 68.9% of cases, being higher in the short forms than in the long segments (80.9 vs. 44%, P<.001). Four patients required preoperative colostomy. The mean age of surgery was 6.3 months (4.5 to 33.7). Short forms represented 64.4% of cases. The abdominal approach was necessary in 10 patients, 9 of these were long/total colonic aganglionic segment. Postoperative enterocolitis presented in 10,9% (9 patients), with no relation with the length of aganglionic or the existence of residual dysplasia. Obstructions occurred in 19.2% of the long form or pancolonic forms. Currently, of the evaluable patients, 5 present constipationand 12 present occasional leakage. CONCLUSIONS TED is the surgery of choice for patients with HD. The majority can be handled by preoperative «nursing» without colostomy. The diagnostic tests of choice are manometry with suction biopsy. No significant correlation was found between enterocolitis and length of aganglionic segment, although we observed a drastic reduction of postoperative enterocolitis, since the introduction of technical changes, such as the use of postoperative rectal tubes and the posterior section of the cuff muscles.

Software for symptom association analysis in pediatric gastroesophageal reflux disease

Gastroesophageal reflux (GER) disease is a serious complication of the upper gastrointestinal tract. Cardiorespiratory symptoms such as apnea, oxygen desaturation and bradycardia may be related to GER. Thus, the recommended diagnostic methodology in pediatric patients requires 24-h synchronized esophageal and cardiorespiratory monitoring. However, there is no computer tool available for this purpose and therefore, researchers and physicians are forced to seek for customized solutions. This paper presents an open source computer program for the analysis of symptom association. It allows a convenient visualization of the biological signals and implements the three main metrics for symptom association, that is, the symptom index, the symptom sensitivity index and the symptom association probability. This software represents a flexible solution and will facilitate caregivers an easy assessment of the existence of temporal association between GER and cardiorespiratory episodes. This would ideally reduce inappropriate medical and surgical treatments and would provide an early diagnosis of the medical condition.