20.4 Gastro-oesophageal reflux and Helicobacter pylori infection

This chapter discusses gastro-oesophageal reflux (GOR), a very common clinical problem in infants and children, and Helicobacter pylori, an infectious agent that colonizes the stomach in more than 50% of the world’s population. H. pylori infection is acquired in early childhood but its disease manifestations usually do not occur until adulthood. It is possible there may be a relationship between the two, and this will be discussed.

Gastro-oesophageal reflux

GOR can be defined as the spontaneous or involuntary passage of gastric content into the oesophagus. The origin of the gastric content can vary and includes saliva, ingested food and fluid, gastric secretions, and pancreatic or biliary secretions that have first been refluxed into the stomach (duodenogastric reflux). Gastro-oesophageal reflux disease (GORD) can be defined as significant symptoms or damage arising as a result of GOR. The difference between physiological reflux and GORD is often blurred by the anxiety engendered in parents, particularly first-time parents, by symptoms such as vomiting and irritability. Physiological reflux manifested by spilling, regurgitation and occasional vomiting is seen in more than 60% of healthy infants by 4 months of age, resolves in the majority by 12 months and rarely leads to GORD. Conservative management is important, particularly in an otherwise healthy infant, so as not to label the condition as a disease state when in fact it is not.

The symptoms of GORD in children aged 3–18 years range in frequency from 1.8% to 22%, and are more refractory and associated with complications such as pain, vomiting, haematemesis, oesophagitis, stricture, growth failure, swallowing difficulties, respiratory symptoms and apnoea.

Pathophysiology (Box 20.4.1)

The main barrier to GOR is the pressure gradient across the lower oesophageal sphincter (LOS) which is formed by the intrinsic LOS (thickened smooth muscle of the lower oesophagus) and the extrinsic striated muscle of the crural diaphragm. Both components work together to generate LOS pressure. The current understanding of LOS function suggests that a pressure of 5–10 mmHg above intragastric pressure is sufficient to maintain an antireflux barrier. Transient lower oesophageal sphincter relaxation (TLOSR) is the major mechanism responsible for GOR in infants, children and adults. A TLOSR is defined as an abrupt decrease in LOS pressure unrelated to swallowing or oesophageal body peristalsis.

Box 20.4.1 Pathophysiological mechanisms of gastro-oesophageal reflux in infants, children and adolescents

• Delayed volume clearance

• Impaired primary or secondary peristalsis

• Reduced pressure wave amplitude

• Increased occurrence of GOR

• Transient LOS relaxation

• Straining

• LOS sphincter hypotonia

• LOS pressure drift

• Delayed gastric emptying

LOS, lower oesophageal sphincter.

Modified from Davidson GP, Omari TI 2001 Pathophysiological mechanisms of gastroesophageal reflux disease in children. Curr Gastroenterol Rep 3:257–262.

Abdominal straining, which occurs frequently in infants, probably exacerbates GOR only when there is simultaneous TLOSR, because both LOS tone and the crural diaphragm are inhibited. The neuroregulation of TLOSR is controlled via a vagovagal reflex. Feeding is a potent stimulus for TLOSR, evidenced by the fact that, in children with GORD, TLOSRs increase from four per hour in the fasting state to eight per hour in the fed state.

Normal oesophageal body peristalsis facilitates clearance of refluxed material including acid. Disordered peristalsis can lead to prolonged acid exposure and oesophageal damage.

The role of gastric emptying in the pathophysiology of GORD is not clear. Delayed gastric emptying could exacerbate GOR by prolonging gastric distension and increasing the frequency of TLOSRs. There are some children at the severe end of the GORD spectrum in whom delayed gastric emptying may be an issue, especially those with neurological or respiratory disease.

Clinical manifestations

There are many causes of regurgitation and vomiting in infants and children, both within the gastrointestinal tract and external to it. The more common causes are outlined in Box 20.4.2.

Box 20.4.2 Causes of regurgitation and vomiting in infants and children

Gastrointestinal tract

• Peptic ulcer disease/gastritis

• Duodenum

• Malrotation

• Duodenal ulcer

• Superior mesenteric artery syndrome

• Small intestine/colon

• Infectious diarrhoea

• Intussusception

• Soy or cow’s milk protein intolerance

• Meconium ileus

• Inflammatory bowel disease

• Appendicitis

• Other organs

• Hepatitis

• Gallbladder disease

• Pancreatitis

Extra-intestinal disorders

• Generalized sepsis

• Rumination

• Intoxications

• Intracranial lesions (e.g. tumour, hydrocephalus)

• Adrenal insufficiency

• Metabolic disorders

Regurgitation can be defined as effortless spilling of gastric content that is usually benign. Vomiting, on the other hand, is a forceful emptying of gastric content that should always be explained. The content of the vomitus is important because of the likely cause, as is the age at onset. Bile staining implies small bowel obstruction and should be examined immediately. Blood staining implies ulceration or gastritis.

Table 20.4.1 highlights the symptoms suggestive of GORD in infants and children. Symptoms do vary according to age. Infants more frequently regurgitate but have also been shown to have reflux-related neurobehavioural symptoms including irritability, crying, fussiness and back-arching but not gagging. More serious complications include apnoea, acute life-threatening events and recurrent chest disease secondary to aspiration. Chronic cough without associated lung disease is unlikely to be reflux-related.

Table 20.4.1 Symptoms suggestive of gastro-oesophageal reflux disease in infants and children

	Infants	Children
Vomiting
Gastrointestinal	Feeding difficulties	Waterbrash
	Failure to thrive	Nausea
	Malnutrition	Dysphagia
	Cow’s milk protein intolerance
Respiratory	Cough, stridor	Chronic cough
	Cyanotic episodes
	Apnoea
	Acute life-threatening events
Acid reflux
Gastrointestinal	Apnoea, cyanotic episodes	Heartburn
	Colic, irritability	Oesophageal obstruction
	Sleep disturbance	Dysphagia, odynophagia
	Flexion patterns after feeds	Night waking
	Hiccoughs	Haematemesis
	Iron deficiency
Respiratory	Apnoea, cyanotic episodes
Respiratory	Stridor
Neurobehavioural	Sandifer syndrome
Neurobehavioural	Seizure-like events (similar to infantile spasms)

Older children, usually over the age of 8 years, can describe common symptoms such as heartburn, chest pain, and a sick or sour taste in the mouth, implying refluxate. Some younger children may complain of a hot feeling in the chest, abdomen or throat.

GORD is a common problem in neurologically impaired children and, although regurgitation is the most likely symptom, problems such as recurrent chest disease, feeding difficulties and food refusal, anaemia, weight loss and behavioural changes can all be manifestations of GORD.

There are many potential extra-oesophageal manifestations of GORD; these are highlighted in Table 20.4.2 and need to be considered as they may be the only presenting symptom or sign. Ear nose and throat manifestations such as otitis media, sinusitis and dental erosions are now being recognized. Although a link between many extra-oesophageal manifestations and GORD has been identified, causality has not been proven, and data supporting improvement in symptoms with GORD treatment are sparse.

Table 20.4.2 Potential extra-intestinal manifestations of gastro-oesophageal reflux disease

Pulmonary	Ear, nose and throat	Other
Asthma Chronic bronchitis Bronchiectasis Pulmonary fibrosis Pneumonia	Chronic cough Laryngitis Hoarseness Pharyngitis Sinusitis Vocal cord granuloma Recurrent granuloma	Dental erosions Non-cardiac chest pain Sleep apnoea