Gastro-oesophageal reflux

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7.3 Gastro-oesophageal reflux

Daryl Efron

Essentials

1 The infant presenting with regurgitation/vomiting needs to have alternative causes considered, before concluding that the diagnosis is GOR.
2 GOR is a normal physiological phenomenon to which infants are particularly prone.
3 Infants with benign GOR appear healthy and thriving. If the child appears unwell, another cause should be considered.
4 Infants and children with uncomplicated GOR do not need any investigations.
5 Complications of GOR include failure to thrive, reflux oesophagitis, apnoea, aspiration pneumonia, and recurrent aspiration with chronic lung disease.
6 Antacids and antisecretory therapies can be helpful in reflux oesophagitis.

Introduction

Gastro-oesophageal reflux (GOR) is the regurgitation of gastric contents into the oesophagus. It is a normal physiological phenomenon at all ages. In most cases it is a benign self-limited condition which spontaneously resolves over a variable time period, usually in infancy. The refluxed gastric contents are generally rapidly cleared from the oesophagus without causing any significant clinical symptoms. Complications warranting medical intervention are uncommon. When complications do occur, it is referred to as GOR disease (GORD).

Pathophysiology

During periods of raised intra-abdominal pressure such as straining, there are a number of protective mechanisms which help to prevent GOR. These include contraction of the diaphragmatic crura around the lower oesophagus in the region of the lower oesophageal sphincter (LES), as well as compression of the intra-abdominal segment of the oesophagus. Many episodes of GOR are associated with transient relaxations of the LES.

In infants the LES is located above the diaphragm, rendering the above protective mechanisms ineffective. Therefore, infants are especially prone to GOR, particularly in the early months of life. However, with anatomical and physiological maturation, the natural history is of symptom resolution by late infancy in the vast majority. GOR is unusual in children older than 18 months.1

Some children are particularly predisposed to develop GORD. These include premature infants, children with neurological conditions, such as cerebral palsy or neurodegenerative disorders, and children with anatomical anomalies such as tracheo-oesophageal fistula. These children have poor oesophageal motility with reduced clearance of refluxed gastric contents.

History

The cardinal symptom of GOR is visible regurgitation of milk post-feeds. This is usually called vomiting, although in GOR the expulsion of gastric contents is generally by an effortless spill, whereas true vomiting involves forceful contraction of abdominal wall musculature. In GOR, the regurgitation is not particularly forceful and the milk usually soils the child’s clothing. Likewise, the physiological ‘posseting’ of milk, which is common after feeding, usually just spills onto the child’s chin region. This is in contrast to the more projectile vomiting of pyloric stenosis, where the milk often propels to a more distant location.

The history is crucial in considering potential differential diagnoses and in identifying complications. Careful questioning regarding the relationship of vomiting to feeds, the content of regurgitated material (e.g. is there blood or bile?), apparent associated distress, and feeding behaviour, is essential. Episodic irritability related to feeds may indicate GOR, although the association between irritability and GOR in infants is generally weak. Atopic features such as eczema and a family history raise the possibility of cows’ milk protein allergy. A history of associated fever suggests an infective cause. Seizures and poor feeding raise the possibility of a metabolic or neurological disorder. Inquiry about associated symptoms such as poor weight gain and respiratory symptoms including apnoea, or wheezing is important to screen for potential complications. Onset of vomiting after 6 months of age is unusual in GOR and suggests an alternative cause.

Examination

Infants with benign GOR demonstrate a robust general condition. They appear well and are thriving. If the child appears unwell or lethargic another cause for the symptoms needs to be carefully considered. The presence of abdominal distension, abnormal tone, or hepatosplenomegaly suggests alternative diagnoses including anatomical anomalies, neurodevelopmental dysfunction or metabolic disorders. A pyloric tumour should be specifically palpated for in young infants. Note that occasionally, in a young infant with known GOR, a change in the character of the vomiting may indicate another evolving diagnosis on a background of GOR, such as pyloric stenosis or a urinary tract infection (UTI). Serial weight measurements should be plotted on the child’s growth chart. Respiratory examination is important to identify signs of bronchospasm or recurrent aspiration, which may complicate GOR. Conjunctival pallor indicates anaemia, which may be secondary to reflux oesophagitis. The urine should be screened by microscopy and culture for an occult UTI causing vomiting.

Differential diagnosis

There are many causes of vomiting in children, and it is important to consider a number of alternative causes that may mimic GOR (see Chapter 7.8 on Diarrhoea and vomiting). These include: infection, e.g. urinary tract infection, gastroenteritis; surgical conditions, e.g. malrotation and volvulus, pyloric stenosis, intussusception; metabolic disorders, e.g. inborn errors, diabetes; food allergy and raised intracranial pressure, e.g. hydrocephalus, posterior fossa tumour, subdural haematoma (Table 7.3.1).

Table 7.3.1 Differential diagnosis of GOR

Urinary tract infection Gastroenteritis Surgical: volvulus, PS, intussusception Food allergy Neurological Metabolic: inborn errors Raised intracranial pressure

Complications

GOR may result in serious complications and is then referred to as GORD.

Failure to thrive

Some infants with GOR have poor weight gain, which may extend to failure to thrive (crossing two major centiles on a growth chart). This may result from reduced intake – either related to dysphagia or parental reduction of feed volumes offered, in an attempt to minimise regurgitation – or from inadequate absorption of ingested food due to excessive losses.

Respiratory

A number of respiratory complications may occur with GOR. Recurrent aspiration (often silent) results in chronic wheeze or cough, and alveolar disease may develop, with signs of tachypnoea and increased work of breathing. Exposure of the oesophageal mucosa to acid can trigger reflex bronchospasm, and persistent asthma symptoms may occasionally be related to GOR.2 Intermittent (or even isolated) episodes of aspiration can cause pneumonia. Reflux of gastric contents into the upper airway can result in laryngospasm, presenting as an obstructive apnoea or apparent life-threatening event (ALTE).3 However, it is unusual to be able to demonstrate an association between GOR and ALTE.

Oesophagitis

Reflux oesophagitis has become a popular clinical diagnosis given to infants presenting with excessive crying behaviour (so-called ‘silent reflux’). There are many causes for infant distress, (including temperamental factors, food allergy) and peptic oesophagitis is only responsible for a minority of cases of infant distress.4 These infants may have episodes of blood in the vomitus or develop iron deficiency anaemia due to the red cell loss. Rarely, an infant may develop feed aversion due to the distress of GOR.

Sandifer syndrome is abnormal trunk and neck posturing of infants in response to oesophageal pain due to refluxed gastric acid. These uncommon episodes can be quite stereotypic, such that they may be confused with seizures.

Investigations

In the majority of cases, a careful history and examination will clarify the likely diagnosis of GOR. Investigations may be required to exclude differential diagnoses, when the diagnosis is unclear.

Serum biochemistry including an acid base, to exclude the evolving metabolic hypokalaemic, hypochloraemic alkalosis of pyloric stenosis, and urine microscopy and culture to screen for a UTI, are relevant first-line tests in the vomiting infant. If the history or biochemistry is suggestive, a pyloric ultrasound should be performed to rule out pyloric stenosis.

Well and thriving infants and children with uncomplicated GOR should not be subjected to any investigations. There are a number of investigations that may be helpful in selected clinical situations. However, the interpretation of studies of oesophageal function and their clinical relevance is not straightforward.

Some children may require admission under a paediatrician for observation of feeding and the presence of regurgitation and consideration of further tests to clarify the diagnosis.

Barium meal and follow through is used to exclude anatomical problems such as malrotation of the small bowel. The observation of GOR merely demonstrates that the infant experienced an episode of reflux at the time of the study. The frequency of GOR episodes, their correlation with clinical symptoms, or the presence of complications cannot be determined from a barium study.

Oesophageal pH monitoring over 24 hours provides representative data about the pH at the lower oesophageal mucosa. A number of indices can be calculated from the monitoring: the frequency of GOR episodes; the length of episodes; and the reflux index – the proportion of time sampled that the oesophageal pH was less than 4 (exposure to gastric acid greater than 10% is usually considered abnormal). However, the association of GOR with oesophagitis is not strong. Infants often have abnormal oesophageal pH findings in the absence of histological features of oesophagitis and, conversely, infants with oesophagitis may have no evidence of significant GOR on pH study.4 These infants presumably have an alternative cause for their oesophagitis, such as allergy. The precise role of oesophageal pH studies is contentious. It is a good test to confirm severe GOR prior to embarking on antireflux surgery, and there may be other clinical scenarios where it provides useful information, e.g. in conjunction with monitoring of respiratory rate, heart rate and oxygen saturations in investigation of apnoea or episodic hypoxaemia/bradycardia.

Oesophagoscopy and biopsy may be indicated for evaluating the presence and severity of oesophagitis, as well as to characterise the changes histologically, e.g. peptic, eosinophilic (allergic), Crohn’s disease, Barrett’s oesophagus.

Aspiration of gastric contents into the lungs can be identified by nuclear medicine study using radiolabelled milk (can detect aspiration events up to 24 hours following a feed). A chest X-ray ± computerised tomography scan of the chest can be used to evaluate for chronic lung disease.

Treatment

Children diagnosed with GOR need follow up organised with the local doctor, to ensure no alternative diagnosis is missed and to monitor for complications. Parents need an explanation of the symptoms and to be reassured that the natural history is for spontaneous resolution over months. It is unusual for GOR symptoms to persist beyond 12 to 15 months of age. If there is any doubt about the diagnosis, then a paediatric review should be arranged.

Simple measures

A number of conservative measures are commonly used to reduce the symptoms of GOR. These include posturing (elevation of cot ~30 degrees head up), thickening of feeds,5 and changes to infant formulas. None of these have been demonstrated to modify clinical outcomes.6 A trial of a partially hydrolysed formula may be indicated in GORD, e.g. GOR with failure to thrive. Prone sleeping position is best for reducing GOR7 but is not generally recommended as it as associated with sudden infant death syndrome. Suggesting positioning a towel on the carer’s shoulder may decrease the inconvenience of refluxed milk onto the parent during feeding.

Pharmacological

Pharmacological treatment of otherwise well, thriving infants with uncomplicated benign GOR is not indicated.8

In more severe cases, the pharmacological options include antacids, antisecretory therapies, and prokinetic agents. High-dose antacids can be effective in treating oesophagitis.9 However, prolonged use can be associated with aluminium toxicity and is not recommended. H2-receptor antagonists such as ranitidine have been shown to improve both histological changes and symptoms.10 Proton pump inhibitors have well-demonstrated clinical efficacy in children with reflux oesophagitis11,12 and appear to be safe. Prokinetic agents do not have clear evidence for symptom reduction;13 however, a trial of domperidone or erythromycin may be worthwhile in GORD.

Surgical

Antireflux surgery has a limited role in cases of severe GORD, such as neurologically abnormal infants with recurrent aspiration pneumonia. The operation of choice is usually the Nissen fundoplication. Complications of the procedure include breakdown of the wrap, dysphagia, bloating and gagging. Some surgeons are now performing fundoplications laparoscopically.

Controversies

The role of oesophageal pH studies in the evaluation for reflux oesophagitis is the subject of ongoing debate.
Antireflux medications are not indicated for uncomplicated GOR, and are probably being overprescribed in infancy.
Prokinetic agents have not been consistently demonstrated to reduce symptoms.

References

1 Campanozzi A., Boccia G., Pensabene L., et al. Prevalence and natural history of gastroesophageal reflux: pediatric prospective survey. Pediatrics. 2009;123:779.

2 Balson B.M., Kravitz E.K., McGeady S.J. Diagnosis and treatment of gastroesophageal reflux in children and adolescents with severe asthma. Ann Allergy Asthma Immunol. 1998;81:159-164.

3 Menon A.P., Schefft G.L., Thach B.T. Apnea associated with regurgitation in infants. J Pediatr. 1985;106:625-629.

4 Heine R.G., Cameron D.J.S., Chow C.W., et al. Esophagitis in distressed infants: Poor diagnostic agreement between esophageal pH monitoring and histopathologic findings. J Pediatr. 2002;140:14-19.

5 Horvath A., Dziechciarz P., Szajewska H. The effect of thickened-feed interventions on gastroesophageal reflux in infants: systematic review and meta-analysis of randomized controlled trials. Pediatrics. 2008;122:e1268.

6 Carroll A.E., Garrison M.M., Christakis D.A. A systematic review of nonpharmacological and nonsurgical therapies for gastroesophageal reflux in infants. Arch Pediatr Adolesc Med. 2002;156:109-113.

7 Meyers W.F., Herbst J.J. Effectiveness of positioning therapy for gastroesophageal reflux. Paediatrics. 1982;69:768-782.

8 Khoshoo V., Edell D., Thompson A., Rubin M. Are we overprescribing antireflux medications for infants with regurgitation? Pediatrics. 2007;120:946.

9 Cucchiara S., Staniano A., Romaniello G., et al. Antacids and cimetidine treatment for gastroesophageal reflux and peptic oesophagitis. Arch Dis Child. 1984;59:842-847.

10 Simeone D., Caria M.C., Miele E., et al. Treatment of childhood peptic oesophagitis: A double-blind placebo-controlled trial of nizatidine. J Pediatr Gastroenterol Nutr. 1997;25:51-55.

11 Kato S., Ebina K., Fujii K., et al. Effect of omeprazole in the treatment of refactory acid-related diseases in childhood: Endoscopic healing and twenty-four hour intragastric acidity. J Pediatr. 1996;128:415-421.

12 DeGiacomo C., Bawa P., Franceschi M., et al. Omeprazole for severe gastroesophageal reflux in children. J Pediatr Gastroenterol Nutr. 1997;24:528-532.

13 Augood C., MacLennan S., Gilbert R., Logan S. Cisapride treatment for gastro-oesophageal reflux in children (Cochrane Review). In: The Cochrane Library. Chichester: John Wiley & Sons; 2002. Issue 4

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