31 Tháng 10 2012 @ 11:46 Sáng 
Trào ngược dạ dày – thực quản ở trẻ nhỏ
Trào ngược dạ dày – thực quản (GOR) là tình trạng tống xuất sữa và các chất khác trong lòng dạ dày vào thực quản một cách dễ dàng (nôn trớ). Cần phải chẩn đoán phân biệt với tình trạng nôn với sự co thắt mạnh mẽ cơ hoành và các cơ thành bụng

Gastro-oesophageal Reflux in Infancy

Hemant Bhavsar, MBBS, DCH, MRCPCH; Mick Cullen, RSCN; R Mark Beattie, BSc, MBBS, MRCP, FRCPCH

WHAT IS GASTRO-OESOPHAGEAL REFLUX?

Gastro-oesophageal reflux (GOR) is the non-forceful regurgitation of milk and other gastric contents into the oesophagus (regurgitation). It should be distinguished from vomiting which is an active process requiring the forceful contraction of the diaphragm and abdominal muscles. It is a normal physiological phenomenon, particularly common in infancy. It is also seen in older children and adults less frequently and only pathological when it occurs in excess.

FUNCTIONAL REFLUX

More than 50% of normal infants regurgitate more than twice a day. Functional reflux is regurgitation without morbidity or clinical signs suggestive of gastro-oesophageal reflux disease (GORD).

Reflux is most common between 1 and 4 months. Major factors include the high fluid volume per kilogram ingested at that age compared with older children/adults, posture and the functional immaturity of the lower oesophageal sphincter. By 12–18 months, most symptomatic reflux will have resolved as the sphincter matures, the infant adopts an upright posture, and is established on a mixed rather than milk-predominant diet.

GASTRO-OESOPHAGEAL REFLUX DISEASE

Gastro-oesophageal reflux disease is defined as ‘gastro-oesophageal reflux associated with troublesome symptoms or complications’. It refers to reflux with significant morbidity including faltering growth, respiratory disease, and oesophagitis or complications of oesophagitis such as stricture. Therefore, within the umbrella termgastro-oesophageal reflux, there is a considerable spectrum with a range of severity from an intermittent nuisance to a life-threatening disease.

Most children with GORD will present in the first year, but there are some who present later with symptoms including heartburn, acid regurgitation, and dysphagia.

REFLUX OESOPHAGITIS

Severe GOR can cause oesophagitis. Oesophagitis implies acid or, rarely, alkali-induced damage to the lower oesophagus. Intake of food by mouth stimulates gastric acid secretion. Reflux of this acid in the lower oesophagus can be painful. GORD is the most common cause of oesophagitis in children.

Crying and irritability may be symptoms of oesophagitis in infants, similar to adults’ complaint of heartburn and chest pain. Children with oesophagitis can develop food aversion as a consequence of experiencing pain when they eat, and food refusal can be the presenting feature. This is likely to be a significant factor in the faltering growth seen in some children with reflux. This can be difficult to diagnose and requires treatment of oesophagitis before dealing with feeding issues.

SYMPTOMS OF GORD

GORD can be oesophageal or extra-oesophageal depending on the presenting symptoms.

Oesophageal

1. Symptoms purported to be due to GORD

  • Especially in infants or younger children or older children without cognitive ability to reliably report symptoms

2. Symptomatic syndrome

  • Older child or adolescent with cognitive ability to reliably report symptoms (typical reflux syndrome)

3. Syndromes with oesophageal injury

  • Reflux oesophagitis, reflux stricture, Barrett’s oesophagus and adenocarcinoma

Extra-oesophageal

1. Definite association

  • Sandifer’s syndrome, dental erosion 2. Possible association
  • Bronchopulmonary – asthma, pulmonary fibrosis, bronchopulmonary dysplasia
  • Laryngotracheal and pharyngeal – chronic cough, chronic laryngitis, hoarseness, pharyngitis
  • Rhinological and otological – sinusitis, serous otitis media
  • Infants – pathological apnoea, bradycardia, apparent life-threatening events

Risk factors for GORD include obesity, neurologic impairment, repaired oesophageal atresia or other congenital oesophageal disease, cystic fibrosis, hiatus hernia, repaired achalasia, lung transplantation, and a family history of GORD.

DIFFERENTIAL DIAGNOSIS OF GORD

  • Infection, eg, urinary tract infection, gastroenteritis, peptic ulcer disease
  • Intestinal obstruction, eg, pyloric stenosis, malrotation, intestinal atresia
  • Food allergy and intolerances, eg, cow’s milk allergy, soy allergy, coeliac disease
  • Eosinophilic oesophagitis (EO)
  • Metabolic disorders, eg, diabetes, inborn errors of metabolism
  • Psychological problems, eg, anxiety, irritable bowel syndrome
  • Intestinal dysmotility, eg, primary achalasi secondary to neurodisability
  • Drug-induced vomiting, eg, cytotoxic agents
  • Primary respiratory disease, eg, asthma, cystic fibrosis
  • Rumination

APPROACH TO THE MANAGEMENT OF GOR

1. Physiological reflux is common in infancy and is a clinical diagnosis. For most parents, reassurance that the condition will resolve without treatment is all that is needed. It is important to consider the differential diagnosis.

2. Full assessment of infants is essential, including a full feeding history, to explore the possibility of overfeeding or difficulty with feeding. Careful attention needs to be paid to severity of symptoms, faltering growth and relevant social factors, eg, parental anxiety and stress (Table 1).

3. Severe cases need further assessments and investigation. These include barium study, pH study, impedance study, milk scan, oesophagoscopy, and oesophageal biopsy (described below).

4. There is a step-up approach to management.

5. Difficult cases require assessment by a multidisciplinary team including dietitian, speech and language therapist, paediatric gastroenterologist and paediatric surgeon.

INDICATIONS FOR INVESTIGATION OF PRESUMED GOR

  • Need to confirm the diagnosis
  • Faltering growth
  • Excessive vomiting
  • Features suggestive of oesophagitis
  • Abnormal electrolytes/acidosis
  • Unexplained or difficult-to-control respiratory disease

HOW TO INVESTIGATE GOR?

Barium Radiology

Barium swallow assesses the patient over only a short period and can therefore either miss pathological reflux or overdiagnose physiological reflux. It is however an important test to rule out large hiatus hernia, oesophageal stricture or web, atypical pyloric stenosis, gastric web, duodenal web, malrotation, volvulus, or other anatomical causes of recurrent vomiting.

pH Study

This is considered by many to be the gold standard investigation test for acid reflux. It is a valid quantitative measure of oesophageal acid exposure, with established normal ranges.

Specific Indications for pH Study

  • Diagnostic uncertainty
  • Poor response to medical treatment
  • If surgery is being considered
  • Children in whom doing the test will lead to a change in management
  • Symptoms suggesting occult reflux
  • Unexplained or difficult-to-control respiratory disease
Physiological Basis and Technique of Using pH Probe

Acid reflux into the oesophagus occurs in all infants as a physiological phenomenon and is only significant when it occurs in excess. The pH probe is designed to measure acidity (ie, acid reflux) in the lower oesophagus. The test relies on the infant/child being off anti-reflux therapy in the 48–72-hour period running up to the test.

The pH probe is a microelectrode passed through the nose and down the back of the throat to sit above the lower oesophageal sphincter. An acid reflux episode is defined as an oesophageal pH of < 4 for a specified minimum duration, usually 15–30 seconds. A set period, usually 24 hours, is recorded, with a note made of the number of episodes, frequency of episodes, and the relationship of reflux to eating, position, sleeping or activity, and especially symptoms. The most sensitive marker of acid reflux on pH study is the reflux index, defined as the percentage of time that oesophageal pH is < 4. This has been validated in several studies. pH study reports are shown in Figures 1 and 2.

  • The North American Society of Pediatric Gastroenterology, Hepatology and Nutrition consensus recommendation is that a reflux index > 7% is abnormal. In general, reflux index up to 10% is mild, 10–20% is moderate which is usually controlled by medical therapy and > 30% is severe which often requires surgical intervention.
  • It is useful to correlate symptoms (eg, cough, chest pain) with acid reflux episodes and to select infants and children with wheezing or respiratory symptoms in whom GOR is a causative/aggravating factor.
  • The sensitivity, specificity and clinical utility of pH monitoring in the diagnosis and management of possible extra oesophageal complications of GOR are not well established.
Limitations of the Test

There are several limitations to pH studies, as follows:

  • pH studies are unable to detect anatomical abnormalities (eg, stricture, hiatus hernia or malrotation) or aspiration.
  • Non-acid reflux will not be detected. This should be borne in mind with non-acidic feeds, such as infant formula, and, in particular, when infants are continuously fed.
  • The changes in environment, diet and behaviour as a result of investigation and admission to hospital may impact on the result.
  • Reproducibility is poor.
  • There is potential for technical difficulties.
  • pH studies provide no objective measures of inflammation and thus are less useful than endoscopy and biopsies for the diagnosis and grading of oesophagitis.
  • The severity of pathologic acid reflux does not correlate consistently with symptom severity or demonstrable complications.

ALKALINE REFLUX

The pH study may be falsely negative in the presence of alkaline reflux (reflux of alkaline stomach contents, eg, during continuous feeding/duodenal contents). Either dual pH monitoring (electrode in stomach and oesophagus), oesophageal impedance or a radio-labelled milk scan is required to detect this.

MILK SCAN

This uses continuous evaluation for up to an hour after radio-labelled meal. It is independent of pH so it can detect alkaline reflux. It is performed over a period of up to an hour with a delayed 24-hour film to look for aspiration. The technique is useful for diagnosis of non-acid reflux. It also gives an assessment of gastric emptying which is a useful indicator of overall gut motility. Markedly delayed gastric emptying is common in children with cerebral palsy in whom vomiting may reflect an overall gut dysmotility rather than GORD. Sensitivity for detection of reflux is variable but can approach 95%.

IMPEDANCE

This measures the changes in the electrical impedance (resistance) between multiple electrodes located along an oesophageal catheter. Oesophageal impedance tracings are then analysed for the typical changes caused by liquid, solid, air or mixed bolus. The impedance changes suggestive of retrograde bolus movement indicate reflux. This test is superior to pH monitoring alone for the evaluation of the temporal relation between symptoms and GOR.

OESOPHAGEAL MANOMETRY

This measures the pressure inside the lower part of the oesophagus. It may be abnormal in patients with GORD, but the findings are not sufficiently sensitive or specific to confirm the diagnosis, nor to predict response to medical or surgical therapy. It is useful to confirm a diagnosis of achalasia or other motor disorders of the oesophagus that may mimic GORD.

OESOPHAGOSCOPY AND OESOPHAGEAL BIOPSY

In children with suspected oesophagitis, upper gastrointestinal endoscopy is a useful investigation and should be considered in all children with severe symptomatic reflux. Biopsies need to be taken, as significant histological abnormality may not be obvious endoscopically. An eosinophilic infiltrate is a characteristic of reflux oesophagitis. However, an excess of eosinophils suggests cow’s milk allergic oesophagitis/EO.

Normal oesophageal histology does not exclude GOR.

In children with documented oesophagitis and normal pH study, other diagnoses should be considered.

NON-REFLUX CAUSES OF OESOPHAGITIS

  • Cow’s milk allergic oesophagitis (see above)
  • Eosinophilic oesophagitis
  • Candidal oesophagitis
  • Chemical oesophagitis from caustic ingestion
  • Achalasia
  • Crohn’s disease

TREATMENT OF GOR

Most patients with physiological gastro-oesophageal reflux are managed in primary care by the health visitor and general practitioner.

Simple measures are often effective, including:

  • Explanation and reassurance about the natural history, particularly in the infant who is thriving.
  • Review of feeding and feeding practice, eg, checking for overfeeding, trial of smaller more frequent feeds, and too small or too large a teat (both of which can cause air swallowing).
  • Review of feeding posture – infants have significantly less reflux when placed in the prone position than in a supine position. However, prone position is associated with a higher rate of sudden infant death syndrome. In infants from birth to 12 months of age with reflux, the risk of sudden infant death syndrome generally outweighs the potential benefits of prone sleeping. In children > 1 year, it is likely that there is a benefit to right-side positioning during sleep and elevation of the head of the bed.
  • Use of feed thickeners and use of anti-regurgitation milks – these are useful in reducing the symptoms of GOR and should be considered in children with persistent symptomatic reflux impacting on nutrient intake or through excessive vomiting on lifestyle. They should not be used for healthy children who regurgitate.
  • Cow’s milk allergy is a potential differential and infants with persistent reflux may benefit from a 2–6 week trial of extensively hydrolysed formula. Soya formulae should not be used. There is a significant cross reactivity between cow’s milk and soya protein and because of the presence of phytoestrogens in soya milk, they are not recommended in infants < 6 months.

Drug treatment is indicated in children with severe symptomatic reflux or signs and symptoms suggestive of GORD.

The major pharmacological agents currently used for treating GORD in children are gastric acid–buffering agents, mucosal surface barriers, and gastric anti-secretory agents. Acid suppressant agents are the mainstay of treatment for all but patients with occasional symptoms. The potential adverse effects of acid suppression, including increased risk of community-acquired pneumonias and gastrointestinal infections, need to be balanced against the benefits of therapy.

STEP-UP APPROACH TO MEDICAL TREATMENT OF GOR

Step 1 – lifestyle changes
Step 2 – thickeners/H2 receptor blockers
Step 3 – prokinetics
Step 4 – proton pump inhibitors (PPIs)
Step 5 – consider change in feed/feed regimen
Step 6 – surgery

Compound alginates are effective symptomatic treatment for GOR. Infant aluminum hydroxide/magnesium trisilicate works by reacting with gastric acid to form a viscous gel. It comes in a dual sachet and each half is a dose. One dose for under 4.5 kg and two doses for over 4.5 kg are given for a maximum of six times a day. In infants, aluminium hydroxide/magnesium trisilicate can be added to feed or, for breast-fed infants, dissolved in cooled boiled water and given by spoon after a feed. Chronic use of alginates is not recommended for GORD because some have absorbable components that may have adverse effects with long-term use.

Acid Suppression Agents

Histamine H2 receptor blockers are widely used in the management of reflux. They are safe and well tolerated and can be considered before any further investigation in children who are thriving and in whom the diagnosis is robust. Ranitidine is the most commonly used H2 receptor blocker. Oral ranitidine provides symptomatic relief and endoscopic improvement of oesophagitis in children with GORD. Dose is 2–4 mg/kg twice daily; the syrup can be used (75 mg/5 mL).

Proton pump inhibitors (eg, omeprazole, lanzoprasole) increase the pH of gastric content, decrease the total volume of secretions, and facilitate emptying. For healing of erosive oesophagitis and relief of symptoms, PPIs are superior to histamine receptor blockers. Omeprazole is the most commonly used PPI and is shown to be effective in children with GORD resistant to ranitidine. It is available as dispersible tablets or capsules given once daily. The tablet can be gently mixed or dispersed (not crushed), or the capsule can be broken for ease of administration in children. Dosage is 0.7–1.4 mg/kg per day although higher doses can be used, at up to 3 mg/kg. In practice, twice daily doses are often used. Lanzoprazole is available as dispersible tablets and given in the dose of 0.5–1 mg/kg once daily.

PROKINETIC DRUGS

These drugs increase lower oesophageal spincture pressure, improve oesophageal clearance, and promote gastric emptying. Efficacy data are limited. Examples include metoclopramide, domperidone, cisapride and erythromycin. Cisapride has been withdrawn from use because of concerns about cardiotoxicity. Although the effectiveness of domperidone in children is unproven, it is often used with no serious adverse effects at 0.3–0.6 mg/kg three times daily in children. It can occasionally exacerbate reflux.

OTHER AGENTS

Buffering agents (magnesium hydroxide and aluminium hydroxide) and sucralfate are useful for occasional heartburn. Buffering agents carry significant risk of toxicity and are not recommended for long-term use. Sucralfate binds to inflamed mucosa and forms a protective layer that resists further damage from gastric acid.

CHILDREN WITH SEVERE REFLUX RESISTANT TO MEDICAL MANAGEMENT MAY BENEFIT FROM:

  • Trial of hydrolysed protein formula feed
  • Period of continuous feeding
  • Trial of gastrostomy/gastro-jejunal feeding

SURGERY

Indications
  • Failure of optimal medical therapy
  • Dependence on long-term medical therapy
  • Extra-oesophageal manifestations (asthma, cough, chest pain, recurrent pulmonary aspiration of refluxate)
  • Complication of GORD (eg, Barrett’s oesophagus, peptic stricture)

Surgery is usually fundoplication with consideration of a pyloroplasty if there is delayed gastric emptying. A gastrostomy for feeding is often done at the same time, particularly if there are feeding problems, eg, neurodisability.

Most fundoplications are now done laparoscopically with good results in terms of reduced post-operative complications, reduced stay in hospital, and long-term outcome.

Children with underlying disorders predisposing to the most severe GORD are at the highest risk for operative morbidity and post-operative failure. Before surgery, it is essential to rule out non-GORD causes of symptoms and ensure that the diagnosis of chronic-relapsing GORD is firmly established. It is important to provide families with appropriate education and a realistic understanding of the potential complications of surgery, which include recurrence of reflux (10%), retching, bloating, dumping, and intestinal obstruction.

Patient Groups at High Risk of Needing Surgery
  • Children with neurodisability
  • Respiratory disease with intractable reflux (eg, oesophageal atresia, bronchopulmonary dysplasia)
  • Children with complication of oesophagitis such as stricture
  • Tracheo-oesophageal fistula repair
  • Barrett’s oesophagus
Barrett’s Oesophagus
  • This refers to the presence of metaplastic columnar epithelium in the lower oesophagus thought to be a consequence of long-standing GORD.
  • There is an increased risk of adenocarcinoma of the oesophagus.
  • It is rare in childhood and requires aggressive medical treatment of the GOR and regular endoscopic surveillance.
  • Surgery (fundoplication) is often considered.
GOR and Neurodisability

Children with cerebral palsy commonly suffer from feeding difficulties of which GOR is a component. Assessment of the contribution of GOR requires careful assessment.

There are many potential causes of feeding difficulties in children with neurodisability:

  • Bulbar weakness with oesophageal incoordination
  • Primary or secondary aspiration
  • Reflux oesophagitis
  • Widespread gut dysmotility
  • Mobility and posture, degree of spasticity
  • Poor nutritional state
  • Constipation

Children require careful multidisciplinary assessment by a feeding team including dietitian, speech and language therapist, occupational therapist, and the neurodevelopmental paediatrician. A video barium assessment of the swallow is often indicated. GORD, if present, should be treated aggressively.

Attention to nutrition is of key importance, and many children with feeding difficulties benefit from a feeding gastrostomy. A fundoplication is required if reflux is severe, although in some cases, improved nutritional status will result in improvement of the reflux.

The motility of the gut is a key factor in feed tolerance in children with cerebral palsy who may have delayed gastric emptying which impact significantly on the ability to feed, particularly if nutrition is dependent upon nasogastric or gastrostomy feeding. It is important to recognize this as a separate condition from reflux. Abdominal pain, bloating and constipation are common features of gut dysmotility. Therapeutic strategies include explanation and reassurance, prokinetic agent such as domperidone, laxatives and, occasionally (if there is a need for distal gut deflation), suppositories. It may be necessary to give feeds by continuous infusion. It may also be necessary to consider gastro-jejunal feeding. A milk-free diet for a trial period of 2–4 weeks can be helpful. Hydrolysed protein formula feeds may be given as a milk substitute.

GOR and Respiratory Disease

GOR has been associated with significant symptoms in infants and children. There is a complex relationship between asthma and GOR, manifested by a bidirectional cause and effect.

One postulated mechanism for GOR-mediated airway disease involves micro-aspiration of gastric contents that leads to inflammation and broncho- spasm. However, experimental evidence also supports the involvement of oesophageal acid–induced reflex bronchospasm, in the absence of frank aspiration. In such cases, GOR therapy using either H2 blockers or PPIs has been shown to benefit patients with steroid-dependent asthma, nocturnal cough, and reflux symptoms. Similarly, intrinsic lung disease may, through excessive coughing, result in reflux.

The association between GOR and apparent life-threatening events is somewhat controversial and probably only relevant if the infant vomits, chokes or turns blue during or immediately after feeds.

Eosinophilic Oesophagitis

In infants and young children, EO presents with symptoms similar to those of GORD but fails to respond to conventional acid blockade therapy. In older children, dysphagia and food impaction can occur.

EO is often seen in patients with atopy who have asthma, eczema or chronic rhinitis, or in those with family history of atopic disease. Multiple food antigens can also induce EO.

Endoscopy may reveal a ringed appearance or linear furrows. Standard biopsy findings reveal severe eosinophilic infiltration; more than 15–20 eosinophils per high-magnification microscopic field are necessary for diagnosis. In contrast to GORD, EO involves the mucosa, submucosa and, possibly, the muscularis.

EO is currently diagnosed based solely on endoscopic findings. Standardized skin prick testing and radioallergosorbent testing are not useful in the diagnosis of EO. About two-thirds of children with EO have an increased peripheral eosinophilic count. The exact pathophysiology of EO is unknown, but contact of the allergen with the oesophageal or intestinal mucosa is thought to be the initiating event.

Treatments include those for GOR, trial of dietary elimination, inhaled (swallowed) or oral steroids, anti-inflammatories, and immunosuppression. There is a natural history of relapse, remission and chronicity.

CASE STUDY 1

A 5-week-old, term, breast-fed baby presented unsettled in the evenings and at night. She was vomiting (not the whole feed), with episodes of arching. She has continued to gain weight appropriately. Mum was given advice on positioning and feeding, along with explanation and reassurance about the natural history of GOR. The symptoms, however, continued and infant aluminium hydroxide/magnesium trisilicate was started. She continued to thrive. Her reflux gradually improved with time. This infant presumably had functional GOR. There may have been a component of ‘infantile colic’. Infantile colic is poorly understood but, like reflux, generally improves. Symptoms may overlap and can cause considerable anxiety to parents.

CASE STUDY 2

A 3-month-old exclusively breast-fed baby was started on formula milk. He developed symptoms of retching (distress) with most feeds, constipation, and milk refusal. His symptoms failed to improve with anti-reflux therapy and he lost weight. Cow’s milk allergy was considered. He was referred to a specialist clinic where he was started on extensively hydrolysed formula. Weaning was delayed to 6 months, after which he was started on dairy- free weaning solids, with dietetic support. His symptoms improved rapidly and he showed good catch-up growth. Cow’s milk was gradually introduced in his diet from the age of 12 months, after a day case challenge, which he tolerated well. His diet was subsequently normalized. Cow’s milk allergy is the commonest food allergy in infancy and usually resolves by 2 years of life and almost always by 5 years of age. GOR can coexist, but poor response to anti-reflux therapy should prompt consideration of cow’s milk allergy.

CASE STUDY 3

A 2-year-old boy with spastic quadriplegia and intractable epilepsy presented to hospital repeatedly with aspiration pneumonia and poor weight gain. He was nasogastrically fed at home, and parents reported frequent retching and vomiting associated with feeds in spite of being on ranitidine and domperidone. His pH study confirmed severe reflux. He failed to respond to PPIs at good doses and trial of hydrolysed formula feed. He underwent fundoplication with feeding gastrostomy. Post-operatively, his admissions to hospital were reduced. Parents reported good weight gain and improved feed tolerance.

CASE STUDY 4

A 15-month-old baby presented with history of poor weight gain, recurrent vomiting and food refusal from very early age. She was born at term and there was no significant antenatal or medical history. She was particularly distressed at meal times as if she was in pain. Further investigations revealed significant reflux (reflux index 14%) and endoscopic findings of oesophagitis. She was treated with PPIs, with improvement in her symptoms. Her symptoms were secondary to acid reflux in response to gastric acid secretion associated with meal times. Her feeding improved with reflux treatment.

FURTHER READING

Beattie RM, Dhawan A, Puntis JWL. Oxford Specialist Handbook in Paediatric Gastroenterology, Hepatology and Nutrition. Oxford University Press; 2009.

Rudolph CD, Vandenplas Y. Paediatric gastro-oesophageal reflux clinical practice guidelines: joint recommendation of NASPGHAN and ESPGHAN. J Pediatr Gastroenterol Nutr 2009;49:498–547.

Sherman PM, Hassall E, Fagundes-Neto U. A global, evidence-based consensus on the definition of gastro-oesophageal reflux disease in the pediatric population. Am J Gastroenterol 2009;104:1278–1295.

Tighe MP, Afzal NA, Bevan A, Beattie RM. Current pharmacological management of gastro-esophageal reflux in children: an evidence-based systematic review. Paediatr Drugs 2009;11:185–202.

Tighe MP, Beattie RM. Managing gastro-oesophageal reflux in infancy. Arch Dis Child 2010;95:243–244.

Tighe MP, Cullen M, Beattie RM. How to use: a pH study. Arch Dis Child Educ Pract Ed 2009;94:18–23.

© 2011 Elsevier Ltd. Initially published in Paediatrics and Child Health 2011;21(9):394–400.

About the Authors

Hemant Bhavsar is a Speciality Registrar in Paediatric Gastroenterology in the Paediatric Medical unit at Southampton General Hospital, Tremona Road, Southampton, UK. Mick Cullen is a Paediatric Gastroenterology Nurse Specialist in the Paediatric Medical unit at Southampton General Hospital, Tremona Road, Southampton, UK. R Mark Beattie is Consultant Paediatric Gastroenterologist in the Paediatric Medical unit at Southampton General Hospital, Tremona Road, Southampton, UK.

Posted By: bsnguyet
Last Edit: 31 Tháng 10 2012 @ 11:47 Sáng

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