Alkaline gastroesophageal reflux in infancy

Alkaline gastroesophageal reflux is a rare disorder, although it has been suggested as a cause of esophagitis. However, up to now, there exists no unequivocally accepted diagnostic method for alkaline reflux that can be routinely applied. "Normal ranges" of episodes of pH greater than 7.0-7.5 in asymptomatic as well as in symptomatic infants are proposed. In the asymptomatic infants (n = 83), the mean percentage of time the pH was greater than 7.0 was 1.3 +/- 2.6, and the number of episodes in 24 h with a pH greater than 7.0 was 10.4 +/- 16.4. In the symptomatic group (n = 60), including infants with chronic vomiting, the mean percentage of time the pH was greater than 7.0 was 0.15 +/- 0.5, and the number of episodes with a pH greater than 7.0 was 2.8 +/- 5.5. In all but six infants the percentage of time the pH was greater than 7.5 was less than 0.1. In three of four of these infants (endoscopy was refused by two parents) whose conditions exceeded the cut-off limits, there was a histologically proven esophagitis. To evaluate the proposed "normal" ranges for episodes of pH greater than 7.0 and 7.5, 200 symptomatic children were included in a prospective study. Symptoms were repetitive vomiting (n = 110), excessive crying (n = 53), and chronic respiratory disease (n = 37). Esophagoscopy was performed in 18 babies (9%) because pH monitoring data exceeded the proposed limits for the percentage of time the pH was greater than 7.0.(ABSTRACT TRUNCATED AT 250 WORDS)     

Metoclopramide pharmacokinetics and pharmacodynamics in infants with gastroesophageal reflux

The pharmacokinetics and pharmacodynamics of metoclopramide oral solution were evaluated in six infants (0.9-5.4 months) with gastroesophageal reflux (GER) following the initial and 10th dose of 0.15 mg/kg administered every 6 h. Metoclopramide pharmacodynamics were assessed by pre- and post-dose comparison of esophageal pH monitoring data and clinical evaluation of improvement in GER symptoms. A significant reduction in the number of episodes of pH less than 4 for greater than 5 min and the longest episode of GER was seen between the predose and 10th dose (steady-state) evaluation periods. Four of the 6 patients had a 75% reduction in reflux time and demonstrated improvement in clinical symptoms by the 10th dose. Metoclopramide pharmacokinetics were best characterized by a one-compartment open model following the first and 10th doses. Metoclopramide serum concentrations (mean +/- SD) ranged from 56.2 +/- 23.5 to 32.7 +/- 13.2 ng/ml within a 6-h dosing interval at steady state. There were no significant differences between the first versus tenth dose values for Tmax (2.0 +/- 0.5 versus 2.2 +/- 0.4 h), Kel (0.14 +/- 0.03 versus 0.17 +/- 0.04 h-1), Vdarea (4.9 +/- 0.4 versus 4.4 +/- 0.6 L/kg), or clearance (0.66 +/- 0.16 versus 0.67 +/- 0.13 L/h/kg). The youngest subject (3.5 weeks) had a metoclopramide t 1/2 of 23.1 h following initial dose, which decreased to 10.3 h at steady-state. Care should be exercised in using the 0.15 mg/kg dose in infants less than 1 month of age as prolonged clearance may produce excessive serum concentrations.     

Sonographic diagnosis of gastroesophageal reflux in infancy

The gastroesophageal reflux is a common problem in the pediatric clinical practice in the 1st year of life. Its diagnosis is mainly based on the x-ray and the measurement of the esophageal pH. Our investigation shows the possibility of the ultrasonographical diagnosis of this disturbance. We could demonstrate a good correlation between the x-ray and the ultrasonographical findings. A continuous lasting gastroesophageal reflux which takes more than 5 minutes points to a pathologic reflux pattern with the well known complications. Thus, ultrasonographical investigation should perform before an extensive diagnostic is taken into consideration.     

Cystic fibrosis and gastroesophageal reflux in infancy

Gastroesophageal reflux (GER) was initially diagnosed in two black infants, aged 5 and 9 months, as a cause of their chronic lung disease and failure to thrive. Both infants were treated with bethanechol chloride as part of the management of their GER, but respiratory failure developed in both patients and they required ventilatory support. Both infants had severe air trapping, CO2 retention, difficulty in being weaned from mechanical ventilation, and Staphylococcus aureus cultured from their respiratory tract secretions. These factors led to the suspicion of cystic fibrosis (CF), and this diagnosis was subsequently confirmed by sweat test. The condition of both infants improved substantially on withdrawal of bethanechol therapy and the institution of a regimen of CF care. The early diagnosis of GER in these infants may have led to a delay in diagnosis and treatment of CF.     

Esophagitis: a frequent consequence of gastroesophageal reflux in infancy

A control group of infants was evaluated to determine criteria for the diagnosis of histologic esophagitis. Based on our observations, histologic esophagitis was defined as four or more intraepithelial neutrophils or one eosinophil per high power field or both. Esophageal biopsy specimens from 33 consecutive infants younger than 2 years who had been examined for clinically significant gastroesophageal reflux (GER) were reviewed for histologic esophagitis. Endoscopy had been performed in each patient, and 4.1 +/- 1.1 (mean +/- SD) biopsy specimens had been obtained above the distal 20% of the esophagus. Twenty (61%) infants had histologic esophagitis, including 15 with intraepithelial eosinophils alone, one with intraepithelial neutrophils alone, and four with both. Older infants (7 to 24 months) with histologic esophagitis were more likely to have moderate to severe inflammation than were infants younger than 7 months of age (P = 0.01). Endoscopic evidence for gross esophagitis was found in six (18%) infants; of these, five had abnormal biopsies, including four with moderate to severe inflammation. Among the 27 infants with a grossly normal esophagus, 14 (52%) had histologic esophagitis, including nine (33%) with moderate to severe inflammation. We conclude that in infants with clinically significant GER: (1) esophagitis is common, (2) histologic esophagitis frequently occurs in the absence of gross endoscopic findings, (3) the likelihood of moderate to severe inflammation increases after 6 months of age, and (4) intraepithelial eosinophils are a sensitive marker for acute inflammation in association with GER.     

Extended pH-monitoring in the evaluation of gastroesophageal reflux in infancy and childhood

Esophageal 24-h pH monitoring was performed in addition to esophagogastrography, esophageal manometry, and esophagoscopy in 66 infants and 12 children from 2–14 years of age with symptoms characteristic of gastroesophageal reflux (GER). In ten infants, ph monitoring was repeated once or twice at intervals of 1 week to 8 1/2 months. The follow-up time for all patients ranged from 2–7 years. Our findings suggest that extended pH monitoring is the most valuable diagnostic procedure under the following circumstances. First, when there are major discrepancies between reported observations and actual symptoms during hospitalization, pH monitoring can clarify the causal relationship. Second, when symptoms are milder but presistent, documentation of prolonged episodes of reflux — overall and during sleep — can aid in determining the urgency of endoscopy. Third, the effectiveness of individual therapeutic measures is best objectivized by means of extended pH monitoring. On the other hand, the procedure is not in defining prognosis or the need for surgical therapy.     

Mechanisms of gastroesophageal reflux and gastroesophageal reflux disease

Gastroesophageal reflux is a physiological phenomenon, occurring with different severity and duration in different individuals. Reflux occurs when this normal event results in the occurrence of symptoms/signs or complications. The pathophysiology of gastroesophageal reflux is complex and diverse, since it is influenced by factors that are genetic, environmental (e.g., diet smoking), anatomic, hormonal, and neurogenic. However, many mechanisms remain incompletely understood. Future research should focus on a better understanding of the physiology of the upper and lower esophageal sphincters, and of gastric motility. The afferent and efferent neural pathways and neuropharmacologic mediators of transient lower esophageal sphincter relaxations and gastric dysmotility require further study. The role of anatomic malformations such as hiatal hernia in children has been underestimated. While therapeutic possibilities are greater in number and largely improved, the outcomes of some treatments are far from satisfactory in many cases. In addition to development of new forms of treatment, research should address better use of currently available medical and surgical treatments.     

Gastro-oesophageal reflux in infancy

Gastro-oesophageal reflux is very common in infancy. It is important to differentiate benign physiological reflux from gastro-oesophageal reflux disease, which is associated with significant morbidity. This review summarises the approach to infants with symptoms and signs of reflux, differential diagnosis, investigations and management including non-pharmacological, pharmacological and surgical treatments. Most infants with physiological gastro-oesophageal reflux do not require any medical management if the infant is thriving. Severe cases require a careful diagnostic work, treatment of associated conditions and aggressive medical management of the reflux. Involvement of the multidisciplinary team is essential and in persistent refractory reflux surgical intervention may need to be considered.     

Incompetent lower esophageal sphincter and gastroesophageal reflux in recurrent acute pulmonary disease of infancy and childhood

Fifteen patients with recurrent acute respiratory symptoms were evaluated for gastroesophageal reflux. All 15 had barium esophagrams. Ten of 15 had acid reflux tests performed and lower esophageal sphincter pressures measured. The data were compared to those in 23 patients with no acid reflux and 23 patients with positive acid reflux but no respiratory symptoms. Ten of ten patients with respiratory symptoms who were evaluated by the acid reflux test had positive results. The remaining five demonstrated GER by barium esophagram. LES pressure measurements in the ten patients were 11.3 +/- 1.5 mm Hg, which was significantly lower than the pressures in the acid reflux-negative group (20.3 +/- 1.3 mm Hg, P less than 0.001) but not different than in the patients with GER but no respiratory symptoms (13.9 +/- 1.5 mm Hg, P greater than 0.05). GER secondary to an incompetent lower esophageal sphincter may be one cause of recurrent acute respiratory disease in infants and children.     

Pathophysiology of gastroesophageal reflux and distal esophageal motility in children with gastroesophageal reflux disease

We investigated the mechanisms of gastroesophageal reflux (GER) and esophageal motility during endogenous esophageal acid exposure in 17 patients with reflux disease alone (age range 3-20 months) (group A) and in 10 patients with reflux disease complicated by esophagitis (age range 4-19 months) (group B), by simultaneous recording distal esophageal sphincter relaxation was the predominant mechanism of reflux in both groups of subjects; however, it was more frequent in group B patients (Bpts), whereas reflux episodes due to appropriate sphincter relaxation were detected more frequently in group A patients (Apts). During endogenous acid exposure, primary peristalsis was the most frequent esophageal motor event in all patients; furthermore, its amplitude was significantly higher in Apts as compared with Bpts. Primary peristalsis was more efficacious (rise of intraluminal pH by at least 0.5 unit) in patients with reflux disease alone, whereas nonspecific motor irregularities were more common in children with reflux esophagitis. It is concluded that the major mechanism of GER in patients with reflux esophagitis is an inappropriate sphincter relaxation; reflux due to appropriate sphincter relaxation is associated with less severe reflux disease; and patients with esophagitis exhibit a deranged esophageal motility during spontaneous acid exposure.     

新生儿胃食管反流发病机理的研究

为探讨新生儿胃食管反流（ＧＥＲ）的发病机理，对３８例经钡餐造影诊为ＧＥＲ的患儿进行食管ｐＨ值动态监测和食管动力功能检查，１５例无症状儿作对照组。结果：ＧＥＲ组各项反流指标均显著大于对照组。３８例中１８例为生理性ＧＥＲ，２０例为病理性ＧＥＲ。病理性反流组下食管括约肌压力（ＬＥＳＰ）和屏障压（ＢＰ）均显著低于对照组，而食管功能的其他指标则差异无显著意义。以总ｐＨ值＜４百分时间２．７７％和综合评分８．９２为９５％参考值上限，则ＧＥＲ组病理性反流的检出率为５５．３％（２１／３８），高于对照组的６．７％（１／１５）（Ｐ＜０．０１）。ＬＥＳＰ和ＢＰ的９５％参考值下限分别为８．３９ｋＰａ、８．１５ｋＰａ，对照组无一例ＬＥＳＰ低下，ＧＥＲ组ＬＥＳＰ降低占１５．７％（６／３８），二组差异无显著意义（Ｐ＞０．０５）。提示：新生儿期食管功能已成熟，新生儿ＧＥＲ的发生不单是ＬＥＳＰ降低这一因素，还可能与短暂下食管括约肌松驰有关。     

Medical management of gastroesophageal reflux

Gastroesophageal reflux (GER) is a common problem which can manifest as vomiting, failure to thrive, recurrent pneumonias, asthma, sinusitus, or subglottic stenosis. The medical management plan should be individualized. A "happy spitter" who has no complications of GER may respond well to conservative management, including positioning and thickening of feedings. A child with complications may require treatment with H-2 antagonists or proton pump inhibitors in conjunction with prokinetic agents. Children with gastrointestinal symptoms suggestive of GER who do not respond to antireflux management may need to be treated for eosinophilic esophagitis. Recent studies that assess the effect of medications on recognized complications of GER are reviewed.