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Gastro-oesophageal reflux in infancy
SYMPOSIUM: NUTRITION
Gastro-oesophageal reflux in infancy
oesophagus, a more upright posture, increased tone of the lower oesophageal sphincter, and a more solid diet.
Gastro-oesophageal reflux disease (GORD) Gastro-oesophageal reflux disease (GORD) is defined as ‘gastrooesophageal reflux associated with troublesome symptoms or complications’ although the authors caution that this definition is complicated by unreliable reporting of symptoms in young children. Gastrointestinal sequelae include oesophagitis, haematemesis, oesophageal stricture formation, and Barrett’s oesophagus. Extra-intestinal sequelae can include acute lifethreatening events and apnoea, chronic otitis media, sinusitis, secondary anaemia, and chronic respiratory disease (chronic wheezing/coughing or aspiration), as well as failure to thrive. Oesophagitis can develop as a result of acid or non-acid reflux and presents with symptoms of crying and irritability in infants and can lead to food aversion. This is likely to be a significant factor in faltering growth seen in some children with GORD.
Vinod Kolimarala R Mark Beattie Akshay Batra
Abstract 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.
Epidemiology GORD is a significant problem for infants in the community and in hospital setting. Determination of the exact prevalence of GORD at any age is difficult because of a lack of specific symptoms but approximately 33% of infants seek medical attention for symptoms suggestive of reflux, of whom up to 20% require diagnostic evaluation. The problem is more pronounced in certain groups like infants born prematurely, infants with neurodisability, with congenital malformations like repaired oesophageal atresia or congenital diaphragmatic hernia, and those with chronic lung disease. Over 50% of children with neurodisability have GORD, due to oesophageal dysmotility and a poorly functioning lower oesophageal sphincter. They have trouble expressing their symptoms, and may also have comorbidities, which may impact on the ability to perform investigations.
Keywords gastro-oesophageal reflux; infancy; oesophagitis; reflux; vomiting
Gastro-oesophageal reflux Gastro-oesophageal reflux (GOR) is the involuntary passage of the gastric contents into the oesophagus. It is a normal physiological phenomenon, particularly common in infancy. Most episodes, in healthy individuals, last less than 3 minutes, occur in the postprandial period, and cause few or no symptoms. It is a very common presentation; both in primary and secondary care setting and can affect nearly 50% of infants less than three months old. Major factors include the high volume of milk ingested compared with older children/adults, posture and the functional immaturity of the lower oesophageal sphincter. The natural history of GOR is generally of improvement with age, with less than 5% of children with vomiting or regurgitation in infancy continuing to have symptoms after the age of 14 months. This is due to a combination of growth in length of the
Pathophysiology The physical barrier between the oesophagus and stomach is provided by the lower oesophageal sphincter (LOS) and the diaphragm. The LOS, or internal sphincter, is a specialised part of the circular smooth muscle of the distal oesophagus. Both components work together to stop refluxing of gastric contents into the oesophagus. The major mechanism of reflux is transient lower oesophageal sphincter relaxation (TLOSR). This is a normal phenomena. Relaxation of LOS occurs in response to swallowing but this is brief and lasts less than 10 seconds. In contrast, in infants with GORD, TLOSR is prolonged (more than 10 secs) and accounts for 75e90% episodes of reflux in infants. Other causes for GORD include abnormal position of LOS as seen in hiatus hernia. This results in inability of diaphragm to contribute to lower oesophageal tone and contraction to prevent reflux. Delayed gastric emptying is felt to be a contributing factor in worsening of reflux and is especially seen in children with neurodisability. It exacerbates GOR by prolonging gastric distension and increasing the frequency of transient LOS relaxation. There is an associated delay in clearance of reflux contents
Vinod Kolimarala MBBS MRCPCH, Speciality Trainee, Paediatric Gastroenterology, Department of Paediatric Gastroenterology, University Hospital Southampton NHS Trust, Southampton, UK. Conflicts of interest: none declared. R Mark Beattie MBBS BSc (Hons) FRCPCH MRCP, Professor in Paediatric Gastroenterology and Nutrition, Department of Paediatric Gastroenterology, University Hospital Southampton NHS Trust, Southampton, UK. Conflicts of interest: none declared. Akshay Batra MBBS MD MRCPCH, Consultant, Paediatric Gastroenterology, Department of Paediatric Gastroenterology, University Hospital Southampton NHS Trust, Southampton, UK. Conflicts of interest: none declared.
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from oesophagus increasing oesophageal exposure to gastric contents, leading to oesophagitis.
Symptoms and signs that may be associated with GORD Atypical symptoms
Symptoms, signs and history Gastro-oesophageal reflux disease can be oesophageal or extraoesophageal depending on the presenting symptoms. The symptoms, signs and typical historical features of GORD are summarised in Tables 1 and 2.
Differential diagnosis Given the frequency of gastro-oesophageal reflux it is easy to forget that other conditions can present with similar features. The commoner alternative diagnoses include: Infection, e.g. urinary tract infection, gastroenteritis, peptic ulcer disease Intestinal obstruction e.g. pyloric stenosis, malrotation, intestinal atresia, Food allergy and intolerances e.g. cow’s milk allergy, soy allergy, coeliac disease Eosinophilic oesophagitis Metabolic disorders e.g. diabetes, inborn errors of metabolism Intestinal dysmotility Drug induced vomiting e.g. cytotoxic agents Primary respiratory disease e.g. asthma, cystic fibrosis Factitious induced illness Child neglect or abuse It is important to remain vigilant for other diagnoses.
Typical symptoms
Signs
Management 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 carefully consider the differential diagnosis, particularly if symptoms persist or worsen. Full assessment of infants is essential including a full feeding history to explore possibility of overfeeding or difficulty with feeding. Careful attention needs to be paid to severity of symptoms, faltering growth and relevant social factors, e.g. parental anxiety and stress. Severe cases need further assessments and investigation. These may include barium study, pH study, impedence study, gastro-oesophageal scintigraphy, gastroscopy and biopsy (described below). Difficult cases require assessment by multidisciplinary team including dietician, speech and language therapist, paediatric gastroenterologist and paediatric surgeon.
Table 1
in oesophageal pH less than 4. Common parameters obtained from pH monitoring include the total number of reflux episodes, the number of reflux episodes lasting more than 5 minutes, the duration of the longest reflux episode, and the reflux index which is the percentage of time when pH was less than 4. Specific indications for pH Study include diagnostic uncertainty in presence of extra oesophageal symptoms, poor response to medical treatment or to quantify the degree of reflux (Figure 1). Interpretation of oesophageal pH studies The North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) consensus recommendation is that a reflux index greater than 7% is abnormal. In general reflux index up to 10% is mild, 10e20% is moderate which is usually controlled by medical therapy and more than 30% is severe and may require surgical intervention. When interpreting studies it is important to consider the following: It is useful to correlate symptoms (e.g., cough, chest pain) with acid reflux episodes and to select those 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 for diagnosis and management of possible extra oesophageal complications of GOR are not well established.
Investigations Oesophageal pH monitoring 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 (i.e. acid reflux) in the lower oesophagus and monitors the frequency and duration of reflux into the oesophagus. It is a microelectrode passed through the nose and down the back of the throat to sit 3 e5 cms above the lower oesophageal sphincter and records for a set period, usually 24 hrs. A reflux episode is defined as the drop
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Wheeze/intractable asthma Cough/stridor Cyanotic episodes Generalised irritability Sleep disturbance Neuro-behavioural symptoms e breath holding, dystonia, seizure like events Worsening of pre-existing respiratory disease Apnoea/apparent life threatening events/ sudden infant death syndrome Excessive regurgitation/vomiting Nausea Weight loss/faltering growth Irritability with feeds, arching, colic/food refusal Dysphagia Chest/epigastric discomfort Excessive hiccups Haematemesis/anaemia e iron deficient Aspiration pneumonia Oesophageal obstruction due to stricture Oesophagitis Oesophageal stricture Barrett’s oesophagus Laryngeal/pharyngeal inflammation Recurrent pneumonia Anaemia Dental erosion Sandifer syndrome
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There are several limitations to pH studies. These include: pH studies are unable to detect anatomical abnormalities (e.g. stricture, hiatus hernia, 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. There is potential for technical difficulties and reproducibility is poor. 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.
History required in an infant with suspected GORD Pattern of vomiting (predominant symptom) Frequency/amount Associated pain/discomfort Is the vomit forceful? Does the vomit contain blood or bile Are there any associated constitutional symptoms e.g. fever, lethargy, diarrhoea Feeding and dietary history Amount/frequency (overfeeding) Preparation of formula Recent changes in feeding type or technique Position during feeding Burping Behaviour during feeding Choking, gagging, cough, arching, discomfort, food refusal Medical history Prematurity Birth weight, growth and development Past surgery, hospitalizations Respiratory illnesses, especially croup, pneumonia, asthma Other respiratory symptoms including hoarseness, hiccups, Apnea Features of atopy Other chronic conditions Medications Current, recent, prescription, nonprescription Family psychosocial history and family set up Sources of stress Postpartum depression Maternal or paternal drug use Family medical history Significant illnesses Family history of gastrointestinal disorders Family history of atopy Growth chart including height, weight, and head circumference
Combined multiple intraluminal impedance (MII) and pH monitoring Some of the limitations of the pH study in detecting nonacid reflux and proximal reflux can be overcome by combining it with intraluminal impedance monitoring. This measures changes in the electrical impedance (i.e. resistance) between multiple electrodes located along an oesophageal catheter. Oesophageal impedance tracings are then analyzed for the typical changes caused by liquid, solid, air or mixed bolus and can differentiate between antegrade and retrograde flow. MII reflux episodes can be categorized as acidic (pH less than 4 lasting 4 seconds or more), weakly acidic (pH4-7) or weakly alkaline (pH7). Studies on the normal values in infants and children are lacking. Normal values are results of consensus agreements, data extrapolation and studies on symptomatic children. ESPGHAN EURO-PIG suggests up to 100 reflux episodes in Infants aged less than 1 and oesophageal acid exposure time up to 10% and up to 70 episodes in children more than 1 year and oesophageal exposure time less than 3% is regarded as normal.
Table 2
Figure 1 An example of a pH study in an infant showing moderate reflux. PAEDIATRICS AND CHILD HEALTH xxx:xxx
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common in children with cerebral palsy in whom vomiting may reflect an overall gut dysmotility rather than GORD.
The indications are the same as those for pH monitoring. MIIpH recording provides more information than simple pH measurement because it allows the study of non-acid reflux, extent of reflux and the temporal association between symptoms and reflux. MII still has the following limitations: high cost; limited contribution to medical therapeutic implications; and lack of evidence-based parameters for the assessment of GOR and especially symptom association in children (Figure 2).
Oesophageal manometry: measures the pressures and peristaltic contractions in the oesophagus. It is now increasingly used to help in the diagnosis of pathological reflux and has a role in identifying the position of lower oesophageal sphincter and assessing its morphology and function. The transient relaxation of the sphincter can be better defined with high resolution manometry and provocative tests with multiple swallows help assess severity. Its main role lies in looking for conditions, which can mimic GORD, e.g. achalasia or other motor disorders of the oesophagus such as diffuse oesophageal spasm, Chagas disease, isolated hypertensive lower oesophageal sphincter.
Radiological investigations Barium swallow: assesses the patient over only short periods and may therefore miss pathological reflux or overdiagnose physiological reflux. It is therefore neither a sensitive or specific test. Its main role is in detecting anatomical abnormalities such as hiatus hernia, intestinal malrotation, oesophageal stricture or web, atypical pyloric stenosis, gastric web, duodenal web or volvulus.
Gastroscopy and biopsy: is used in children with suspected oesophagitis. Upper gastrointestinal endoscopy is a useful investigation and should be considered in all children with severe symptomatic reflux. Presence of active oesophagits either macroscopically or on histology is the most specific test for GORD though normal oesophageal histology does not exclude significant gastro-oesophageal reflux. The histological features include an increased eosinophil count, intrapapillary blood vessel dilatation, intraepithelial bleeding, basal cell hyperplasia, dilated intercellular spaces, and enhanced cellular proliferation. Endoscopic biopsy is important to identify or rule out other causes of oesophagitis and to diagnose and monitor Barrett oesophagus.
Gastro-oesophageal scintigraphy: uses continuous evaluation for up to an hour after radiolabelled meal. Food or milk labelled with 99Technetium is given to the infant and stomach and oesophagus are scanned. The standards for interpretation of this test are poorly established and it is not recommended for the routine evaluation of paediatric patients with suspected GORD. Its main role is in the assessment of gastric emptying times to identify the group of children with foregut dysmotility and delayed gastric emptying. It also has a limited role in diagnosis of pulmonary aspiration in patients with chronic and refractory respiratory symptoms. Delayed gastric emptying is especially
Figure 2 Combined MII and pH monitoring demonstrating acid reflux in an infant.
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Compound alginates: (e.g. Gaviscon Infant-Rickett Benckiser) are effective for symptomatic treatment for GOR. Infant gaviscon works by reacting with gastric acid to form a viscous gel. Infant Gaviscon comes in a dual sachet and each half is a dose. 1 dose for babies weighing less than 4.5 kg and 2 doses for those more than 4.5 kg given a maximum 6 times a day. Infant gaviscon can be added to formula 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. Occasionally they can cause constipation and bloating. They should be used with caution in children with renal impairment as the product contains sodium and can cause hypernatraemia. An overdose can lead to a bezoar formation which may require surgical removal.
The indications for endoscopy in GORD include: Gastrointestinal bleeding which can present as haemetemesis or malena Failure of resolution of symptoms beyond 1 year of age despite medical therapy Faltering growth Food aversion Suspected Sandifer’s syndrome
Management Most patients with physiological gastro-oesophageal reflux are managed in primary care by the health visitor and general practitioner and do not require any specific treatment. Nonpharmacological measures include: Review of feeding and feeding practice e checking for overfeeding, trial of smaller more frequent feeds, too small or too large a teat (both of which can cause air swallowing). Review of feeding posture e 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 infants death syndrome (SIDS). In infants from birth to 12 months of age with reflux, the risk of SIDS generally outweighs the potential benefits of prone sleeping. In children more than 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 e 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. Extensively hydrolysed or amino acid based formula e Infants with persistent symptoms with associated red flags like blood in stools, history of eczema or atopy could have non IgE mediated cow’s milk protein intolerance and may benefit from a 2e6 week trial of elimination diet. This can be done by elimination of cow’s milk in maternal diet in breast fed infants. In bottle fed infants extensively hydrolysed formula should be used. Soya formulae should be avoided as there is 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 less than 6 months.
Acid suppression agents: include H2-receptor blockers and proton pump inhibitors. 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. There are several studies that have suggested that H₂-antagonists are efficacious in children. Ranitidine is the most commonly used H2-receptor blocker. Ranitidine is well tolerated and has a low incidence of side-effects (common side-effects include fatigue, dizziness or diarrhoea). Oral ranitidine provides symptomatic relief and endoscopic improvement of oesophagitis in children with GORD. Dosage for neonates is between 2 and 3mg/kg TDS. Child 1e5 months 1e3mg/kg TDS. Child 6 months-2 years 2e4mg/kg BD. Proton pump inhibitors (PPI) such as omeprazole and lansoprazole are a group of drugs that irreversibly inactivate Hþ/Kþ ATPase: the parietal cell membrane transporter. This increases the pH of gastric contents and decreases total volume of gastric secretion, thus facilitating emptying. Side effects reported with long term use include hypomagnesemia, gastric fundal polyps and small increase in risk of osteoporotic fractures. Omeprazole is the most commonly used PPI and is shown to be effective in children with GORD resistant to ranitidine. For healing of erosive oesophagitis and relief of symptoms, PPIs are superior to H2-receptor blockers. Omeprazole is available as dispersible tablets or capsules given once daily. The tablet can be gently mixed or dispersed (not crushed) or the capsule broken for ease of administration in children. Dosage is 0.7e1.4 mg/kg per day although higher doses can be used, up to 3mg/kg. When acid suppression is required, the smallest effective dose should be used. Most patients require only once-daily PPI. Lansoprazole is the other commonly used PPI. Dosage 0.5e1mg/kg OD a maximum dose of 15mg OD can be used.
Drug treatment Drug treatment is indicated in children with severe symptomatic reflux or signs and symptoms suggestive of gastro-oesophageal reflux disease. The major pharmacological agents currently used for treating GORD in children are gastric acidebuffering agents, mucosal surface barriers, and gastric anti-secretory agents. Acid suppressant agents are the mainstay of treatment for all but the patient with occasional symptoms. The potential adverse effects of acid suppression, including increased risk of communityacquired pneumonias and GI infections, need to be balanced against the benefits of therapy.
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Prokinetic drugs: can be helpful in some circumstances. Gastroesophageal reflux is primarily a motility disorder, and the use of pharmacologic agents that improve oesophageal and gastric motility are conceptually attractive as therapies. Unfortunately, the currently available prokinetic medications have only modest efficacy in relieving GORD symptoms, and the side effect profile makes them less useful clinical practice. Examples include metoclopramide, domperidone, and erythromycin.
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surgery, which include recurrence of reflux (10%), retching, bloating, dumping and intestinal obstruction. Some children have a high risk of needing surgery. These include children with neurodisability, those with respiratory disease with intractable reflux (e.g. oesophageal atresia, bronchopulmonary dysplasia), Children with complication of oesophagitis such as stricture or Barrett’s oesophagus and those who have had a tracheo-oesophageal fistula repair.
Domperidone is a dopamine-receptor (D2) blocker that has relatively fewer side effects but case reports of extrapyramidal side effects exist, as well as an effect on the QT interval (prolongation). Domperidone acts to increase lower oesophageal sphincter pressure improve oesophageal clearance and promote gastric emptying. Domperidone is commonly used in clinical practice either as part of empirical medical therapy of gastrooesophageal reflux disease or if delayed gastric emptying has been demonstrated on nuclear scintigraphy. In view of a small increased risk of cardiotoxicity, it is advisable to use domperidone in lower doses and only in cases with overt vomiting secondary to reflux. All infants should have an ECG to rule out prolonged QT interval before starting treatment and should be referred to a specialist if treatment is required for greater than 3 months.
Gastro-oesophageal reflux and neurodisability Paediatric neurodisability is an umbrella term for conditions associated with impairment of the nervous system, including conditions such as cerebral palsy, and epilepsy. Potential causes of feeding difficulties include bulbar weakness, primary or secondary aspiration, reflux oesophagitis, widespread gut dysmotility, mobility and posture problems, poor nutritional state and constipation. These children require careful multidisciplinary assessment by a feeding team including dietetics, speech and language therapy, occupational therapy and the neurodevelopmental paediatrician. 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. Therapeutic strategies include explanation and reassurance, trial of anti-reflux therapy, prokinetic agents such as domperidone and in some cases with marked dysmotility it may be necessary to give feeds by continuous infusion via gastrostomy or gastro-jejunal route. A milk free diet for a trial period of 2e4 weeks can be helpful. Hydrolysed protein formula feeds/MCT predominant feeds may be given as a milk substitute.
Buffering agents (magnesium hydroxide and aluminium hydroxide) and sucralfate: are useful for occasional heart burn. 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.
Enteral feeding In infants with faltering growth who are not responding to usual medical treatments a period of enteral tube feeding (ETF) should be considered. This ensures slow delivery of feeds and thus reduced distension of stomach and subsequent reflux. When tube feeding is started small oral stimulation in the form of small amount of oral feeds (milk or solids) should be continued. Post pyloric feeding, is reserved for severe cases not responding to other forms of management and associated with complications. As the stomach is bypassed there is no distension of stomach and there is reduction in reflux of gastric contents. This is particularly helpful in children with failure to thrive, severe oesophagitis and reflux related pulmonary aspiration. Continuous post pyloric feeding is most commonly used in children with neurodisability where the volume of feed is limited because of discomfort associated with feeding.
Gastro-oesophageal reflux and respiratory disease Gastro-oesophageal reflux has been associated with significant respiratory symptoms in infants and children. There is a complex relationship between asthma and gastro-oesophageal reflux, manifested by a bidirectional cause and effect. One postulated mechanism for gastro-oesophageal reflux mediated airway disease involves micro-aspiration of gastric contents that leads to inflammation and bronchospasm. However, experimental evidence also supports the involvement of oesophageal acideinduced reflex bronchospasm, in the absence of frank aspiration. In such cases, gastrooesophageal reflux therapy using either H2-blockers or proton pump inhibitors 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 gastro-oesophageal reflux and apparent life-threatening events is somewhat controversial and probably only relevant if the infant vomits, chokes or goes blue during or immediately after feeds.
Surgery The commonest operative intervention is fundoplication done laparoscopically or via open procedure. Children with co morbidities, particularly neurodisability who have the most severe GORD are at the highest risk for operative morbidity and postoperative failure. Before surgery it is essential to rule out nonGORD causes of symptoms and ensure that the diagnosis of chronic-relapsing GORD is firmly established. Indications for surgery include: Failure of optimal medical therapy Extra oesophageal manifestation (asthma, cough, chest pain, recurrent pulmonary aspiration of refluxate) Complication of GORD (e.g. Barrett’s oesophagus or oesophageal stricture) It is important to provide families with appropriate education and a realistic understanding of the potential complications of
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Barrett’s oesophagus
Mutalib M, Rawat D, Lindley K, et al. BSPGHAN Motility working Group position statement: paediatric multichannel intraluminal pH impedance monitoring eindications, methods and interpretation. Front Gastroenterol 2017; 8: 156e62. Nelson SP, Chen EH, Syniar GM, Christoffel KK. Prevalence of symptoms of gastroesophageal reflux during infancy. A pediatric practice-based survey. Pediatric Practice Research Group. Arch Pediatr Adolesc Med 1997 Jun; 151: 569e72. Rosen R, Vandenplas Y. Paediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American society for paediatric Gastroenterology, Hepatology, and nutrition and the European society for pediatric gastroenterology, hepatology, and nutrition. J Pediatr Gastroenterol Nutr 2018; 66: 516e54. Rudolph CD, Vandenplas Y. Paediatric gastro-oesophageal reflux clinical practice guidelines: joint recommendation of NASPGHAN and ESPGHAN e J Pediatr Gastroenterol Nutr 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; https://doi. org/10.1038/ajg.2009.129. Tighe M, Afzal NA, Bevan A, Hayen A, Munro A, Beattie RM. Pharmacological treatment of children with gastro-oesophageal reflux. Cochrane Database Syst Rev 2014 Nov 24; 11. Tighe MP, Beattie RM. Managing gastro-oesophageal reflux in infancy. Arch Dis Child 2010; 95: 243e4. Tighe MP, Cullen M, Beattie RM. How to use: a pH study. Arch Dis Child Educ Pract Ed 2009; 94: 18e23.
This refers to the presence of metaplastic columnar epithelium in the lower oesophagus thought to be a consequence of longstanding gastro-oesophageal reflux disease. There is an increased risk of adenocarcinoma of the oesophagus. It is rare in childhood and requires aggressive medical treatment, of the gastro-oesophageal reflux and regular endoscopic surveillance. Surgery (fundoplication) is often considered.
Case study 1 A 7 week old baby formula fed baby presented with history of vomiting after most feeds and excessive crying. Vomiting was variable quantity, non-projectile and non-bilious. The child was thriving very well. There was no abnormality seen on examination. A careful feed history revealed he was having nearly 200mlg/kg of formula feed. Parents were reassured and the volume of feeds was reduced. Symptoms resolved in 3 weeks. He continued to thrive and was discharged from follow-up. Over feeding is frequently seen in formula fed infants and a careful feeding history allows for an accurate diagnosis and helps in avoiding unnecessary treatments.
Case study 2 An 11 month old with cerebral palsy and seizure disorder presented with history of poor weight gain, recurrent vomiting and episodic crying. She was born at 25 weeks of gestation and had periventricular leukomalacia. 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 proton pump inhibitors with improvement in her symptoms. Her symptoms were secondary of acid reflux in her oesophagus in response to gastric acid secretion associated with meal times. Her feeding improved with treatment of the reflux.
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Case study 3 A 4 month old presented with feed refusal, retching, constipation and eczema. Her symptoms failed to improve with anti-reflux therapy and her weight was static. She was referred to specialist clinic and was started on extensively hydrolysed formula. At 6 months she was started on a dairy free diet. Symptoms improved and she showed good catch up growth. Cow’s milk was gradually introduced in her diet from the age of 12 months. 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. Gastro-oesophageal reflux can co-exist but poor a response to anti-reflux therapy should prompt consideration of cow’s milk allergy.
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A FURTHER READING Beattie RM, Dhawan A, Puntis JWL, Batra A, Kyrana E. Oxford specialist handbook in paediatric gastroenterology, hepatology and nutrition. Oxford University Press, 2018.
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Functional reflux is very common in infancy and resolve spontaneously Gastro-oesophageal reflux disease (GORD) is defined as ‘gastro-oesophageal reflux associated with troublesome symptoms or complications. Physiological reflux is a clinical diagnosis and does not warrant further investigation. It is important to consider appropriate differential diagnoses during history taking and examination. Most reflux will respond to simple strategies including reassurance and explanation, feeding advice, feed thickeners and anti-reflux milk. It is important to carefully consider cow’s milk protein allergy and a trial of 2e4 weeks of extensively hydrolysed or amino acid based formula can be considered before starting medical treatment. Medical therapy is by a step up approach with use of H2 blockers, prokinetics, proton pump inhibitors and consideration of a trial of hydrolysed formula. Surgery is required in cases resistant to medical treatment and those with extra oesophageal complications such as recurrent aspiration. Children with cerebral palsy are at increased risk of reflux although many other factors are relevant in the assessment of feeding problems in children with neurodisability
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Gastro-oesophageal reflux in infancy
oesophagus, a more upright posture, increased tone of the lower oesophageal sphincter, and a more solid diet.
Gastro-oesophageal reflux disease (GORD) Gastro-oesophageal reflux disease (GORD) is defined as ‘gastrooesophageal reflux associated with troublesome symptoms or complications’ although the authors caution that this definition is complicated by unreliable reporting of symptoms in young children. Gastrointestinal sequelae include oesophagitis, haematemesis, oesophageal stricture formation, and Barrett’s oesophagus. Extra-intestinal sequelae can include acute lifethreatening events and apnoea, chronic otitis media, sinusitis, secondary anaemia, and chronic respiratory disease (chronic wheezing/coughing or aspiration), as well as failure to thrive. Oesophagitis can develop as a result of acid or non-acid reflux and presents with symptoms of crying and irritability in infants and can lead to food aversion. This is likely to be a significant factor in faltering growth seen in some children with GORD.
Vinod Kolimarala R Mark Beattie Akshay Batra
Abstract 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.
Epidemiology GORD is a significant problem for infants in the community and in hospital setting. Determination of the exact prevalence of GORD at any age is difficult because of a lack of specific symptoms but approximately 33% of infants seek medical attention for symptoms suggestive of reflux, of whom up to 20% require diagnostic evaluation. The problem is more pronounced in certain groups like infants born prematurely, infants with neurodisability, with congenital malformations like repaired oesophageal atresia or congenital diaphragmatic hernia, and those with chronic lung disease. Over 50% of children with neurodisability have GORD, due to oesophageal dysmotility and a poorly functioning lower oesophageal sphincter. They have trouble expressing their symptoms, and may also have comorbidities, which may impact on the ability to perform investigations.
Keywords gastro-oesophageal reflux; infancy; oesophagitis; reflux; vomiting
Gastro-oesophageal reflux Gastro-oesophageal reflux (GOR) is the involuntary passage of the gastric contents into the oesophagus. It is a normal physiological phenomenon, particularly common in infancy. Most episodes, in healthy individuals, last less than 3 minutes, occur in the postprandial period, and cause few or no symptoms. It is a very common presentation; both in primary and secondary care setting and can affect nearly 50% of infants less than three months old. Major factors include the high volume of milk ingested compared with older children/adults, posture and the functional immaturity of the lower oesophageal sphincter. The natural history of GOR is generally of improvement with age, with less than 5% of children with vomiting or regurgitation in infancy continuing to have symptoms after the age of 14 months. This is due to a combination of growth in length of the
Pathophysiology The physical barrier between the oesophagus and stomach is provided by the lower oesophageal sphincter (LOS) and the diaphragm. The LOS, or internal sphincter, is a specialised part of the circular smooth muscle of the distal oesophagus. Both components work together to stop refluxing of gastric contents into the oesophagus. The major mechanism of reflux is transient lower oesophageal sphincter relaxation (TLOSR). This is a normal phenomena. Relaxation of LOS occurs in response to swallowing but this is brief and lasts less than 10 seconds. In contrast, in infants with GORD, TLOSR is prolonged (more than 10 secs) and accounts for 75e90% episodes of reflux in infants. Other causes for GORD include abnormal position of LOS as seen in hiatus hernia. This results in inability of diaphragm to contribute to lower oesophageal tone and contraction to prevent reflux. Delayed gastric emptying is felt to be a contributing factor in worsening of reflux and is especially seen in children with neurodisability. It exacerbates GOR by prolonging gastric distension and increasing the frequency of transient LOS relaxation. There is an associated delay in clearance of reflux contents
Vinod Kolimarala MBBS MRCPCH, Speciality Trainee, Paediatric Gastroenterology, Department of Paediatric Gastroenterology, University Hospital Southampton NHS Trust, Southampton, UK. Conflicts of interest: none declared. R Mark Beattie MBBS BSc (Hons) FRCPCH MRCP, Professor in Paediatric Gastroenterology and Nutrition, Department of Paediatric Gastroenterology, University Hospital Southampton NHS Trust, Southampton, UK. Conflicts of interest: none declared. Akshay Batra MBBS MD MRCPCH, Consultant, Paediatric Gastroenterology, Department of Paediatric Gastroenterology, University Hospital Southampton NHS Trust, Southampton, UK. Conflicts of interest: none declared.
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from oesophagus increasing oesophageal exposure to gastric contents, leading to oesophagitis.
Symptoms and signs that may be associated with GORD Atypical symptoms
Symptoms, signs and history Gastro-oesophageal reflux disease can be oesophageal or extraoesophageal depending on the presenting symptoms. The symptoms, signs and typical historical features of GORD are summarised in Tables 1 and 2.
Differential diagnosis Given the frequency of gastro-oesophageal reflux it is easy to forget that other conditions can present with similar features. The commoner alternative diagnoses include: Infection, e.g. urinary tract infection, gastroenteritis, peptic ulcer disease Intestinal obstruction e.g. pyloric stenosis, malrotation, intestinal atresia, Food allergy and intolerances e.g. cow’s milk allergy, soy allergy, coeliac disease Eosinophilic oesophagitis Metabolic disorders e.g. diabetes, inborn errors of metabolism Intestinal dysmotility Drug induced vomiting e.g. cytotoxic agents Primary respiratory disease e.g. asthma, cystic fibrosis Factitious induced illness Child neglect or abuse It is important to remain vigilant for other diagnoses.
Typical symptoms
Signs
Management 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 carefully consider the differential diagnosis, particularly if symptoms persist or worsen. Full assessment of infants is essential including a full feeding history to explore possibility of overfeeding or difficulty with feeding. Careful attention needs to be paid to severity of symptoms, faltering growth and relevant social factors, e.g. parental anxiety and stress. Severe cases need further assessments and investigation. These may include barium study, pH study, impedence study, gastro-oesophageal scintigraphy, gastroscopy and biopsy (described below). Difficult cases require assessment by multidisciplinary team including dietician, speech and language therapist, paediatric gastroenterologist and paediatric surgeon.
Table 1
in oesophageal pH less than 4. Common parameters obtained from pH monitoring include the total number of reflux episodes, the number of reflux episodes lasting more than 5 minutes, the duration of the longest reflux episode, and the reflux index which is the percentage of time when pH was less than 4. Specific indications for pH Study include diagnostic uncertainty in presence of extra oesophageal symptoms, poor response to medical treatment or to quantify the degree of reflux (Figure 1). Interpretation of oesophageal pH studies The North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) consensus recommendation is that a reflux index greater than 7% is abnormal. In general reflux index up to 10% is mild, 10e20% is moderate which is usually controlled by medical therapy and more than 30% is severe and may require surgical intervention. When interpreting studies it is important to consider the following: It is useful to correlate symptoms (e.g., cough, chest pain) with acid reflux episodes and to select those 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 for diagnosis and management of possible extra oesophageal complications of GOR are not well established.
Investigations Oesophageal pH monitoring 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 (i.e. acid reflux) in the lower oesophagus and monitors the frequency and duration of reflux into the oesophagus. It is a microelectrode passed through the nose and down the back of the throat to sit 3 e5 cms above the lower oesophageal sphincter and records for a set period, usually 24 hrs. A reflux episode is defined as the drop
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Wheeze/intractable asthma Cough/stridor Cyanotic episodes Generalised irritability Sleep disturbance Neuro-behavioural symptoms e breath holding, dystonia, seizure like events Worsening of pre-existing respiratory disease Apnoea/apparent life threatening events/ sudden infant death syndrome Excessive regurgitation/vomiting Nausea Weight loss/faltering growth Irritability with feeds, arching, colic/food refusal Dysphagia Chest/epigastric discomfort Excessive hiccups Haematemesis/anaemia e iron deficient Aspiration pneumonia Oesophageal obstruction due to stricture Oesophagitis Oesophageal stricture Barrett’s oesophagus Laryngeal/pharyngeal inflammation Recurrent pneumonia Anaemia Dental erosion Sandifer syndrome
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There are several limitations to pH studies. These include: pH studies are unable to detect anatomical abnormalities (e.g. stricture, hiatus hernia, 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. There is potential for technical difficulties and reproducibility is poor. 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.
History required in an infant with suspected GORD Pattern of vomiting (predominant symptom) Frequency/amount Associated pain/discomfort Is the vomit forceful? Does the vomit contain blood or bile Are there any associated constitutional symptoms e.g. fever, lethargy, diarrhoea Feeding and dietary history Amount/frequency (overfeeding) Preparation of formula Recent changes in feeding type or technique Position during feeding Burping Behaviour during feeding Choking, gagging, cough, arching, discomfort, food refusal Medical history Prematurity Birth weight, growth and development Past surgery, hospitalizations Respiratory illnesses, especially croup, pneumonia, asthma Other respiratory symptoms including hoarseness, hiccups, Apnea Features of atopy Other chronic conditions Medications Current, recent, prescription, nonprescription Family psychosocial history and family set up Sources of stress Postpartum depression Maternal or paternal drug use Family medical history Significant illnesses Family history of gastrointestinal disorders Family history of atopy Growth chart including height, weight, and head circumference
Combined multiple intraluminal impedance (MII) and pH monitoring Some of the limitations of the pH study in detecting nonacid reflux and proximal reflux can be overcome by combining it with intraluminal impedance monitoring. This measures changes in the electrical impedance (i.e. resistance) between multiple electrodes located along an oesophageal catheter. Oesophageal impedance tracings are then analyzed for the typical changes caused by liquid, solid, air or mixed bolus and can differentiate between antegrade and retrograde flow. MII reflux episodes can be categorized as acidic (pH less than 4 lasting 4 seconds or more), weakly acidic (pH4-7) or weakly alkaline (pH7). Studies on the normal values in infants and children are lacking. Normal values are results of consensus agreements, data extrapolation and studies on symptomatic children. ESPGHAN EURO-PIG suggests up to 100 reflux episodes in Infants aged less than 1 and oesophageal acid exposure time up to 10% and up to 70 episodes in children more than 1 year and oesophageal exposure time less than 3% is regarded as normal.
Table 2
Figure 1 An example of a pH study in an infant showing moderate reflux. PAEDIATRICS AND CHILD HEALTH xxx:xxx
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common in children with cerebral palsy in whom vomiting may reflect an overall gut dysmotility rather than GORD.
The indications are the same as those for pH monitoring. MIIpH recording provides more information than simple pH measurement because it allows the study of non-acid reflux, extent of reflux and the temporal association between symptoms and reflux. MII still has the following limitations: high cost; limited contribution to medical therapeutic implications; and lack of evidence-based parameters for the assessment of GOR and especially symptom association in children (Figure 2).
Oesophageal manometry: measures the pressures and peristaltic contractions in the oesophagus. It is now increasingly used to help in the diagnosis of pathological reflux and has a role in identifying the position of lower oesophageal sphincter and assessing its morphology and function. The transient relaxation of the sphincter can be better defined with high resolution manometry and provocative tests with multiple swallows help assess severity. Its main role lies in looking for conditions, which can mimic GORD, e.g. achalasia or other motor disorders of the oesophagus such as diffuse oesophageal spasm, Chagas disease, isolated hypertensive lower oesophageal sphincter.
Radiological investigations Barium swallow: assesses the patient over only short periods and may therefore miss pathological reflux or overdiagnose physiological reflux. It is therefore neither a sensitive or specific test. Its main role is in detecting anatomical abnormalities such as hiatus hernia, intestinal malrotation, oesophageal stricture or web, atypical pyloric stenosis, gastric web, duodenal web or volvulus.
Gastroscopy and biopsy: is used in children with suspected oesophagitis. Upper gastrointestinal endoscopy is a useful investigation and should be considered in all children with severe symptomatic reflux. Presence of active oesophagits either macroscopically or on histology is the most specific test for GORD though normal oesophageal histology does not exclude significant gastro-oesophageal reflux. The histological features include an increased eosinophil count, intrapapillary blood vessel dilatation, intraepithelial bleeding, basal cell hyperplasia, dilated intercellular spaces, and enhanced cellular proliferation. Endoscopic biopsy is important to identify or rule out other causes of oesophagitis and to diagnose and monitor Barrett oesophagus.
Gastro-oesophageal scintigraphy: uses continuous evaluation for up to an hour after radiolabelled meal. Food or milk labelled with 99Technetium is given to the infant and stomach and oesophagus are scanned. The standards for interpretation of this test are poorly established and it is not recommended for the routine evaluation of paediatric patients with suspected GORD. Its main role is in the assessment of gastric emptying times to identify the group of children with foregut dysmotility and delayed gastric emptying. It also has a limited role in diagnosis of pulmonary aspiration in patients with chronic and refractory respiratory symptoms. Delayed gastric emptying is especially
Figure 2 Combined MII and pH monitoring demonstrating acid reflux in an infant.
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Compound alginates: (e.g. Gaviscon Infant-Rickett Benckiser) are effective for symptomatic treatment for GOR. Infant gaviscon works by reacting with gastric acid to form a viscous gel. Infant Gaviscon comes in a dual sachet and each half is a dose. 1 dose for babies weighing less than 4.5 kg and 2 doses for those more than 4.5 kg given a maximum 6 times a day. Infant gaviscon can be added to formula 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. Occasionally they can cause constipation and bloating. They should be used with caution in children with renal impairment as the product contains sodium and can cause hypernatraemia. An overdose can lead to a bezoar formation which may require surgical removal.
The indications for endoscopy in GORD include: Gastrointestinal bleeding which can present as haemetemesis or malena Failure of resolution of symptoms beyond 1 year of age despite medical therapy Faltering growth Food aversion Suspected Sandifer’s syndrome
Management Most patients with physiological gastro-oesophageal reflux are managed in primary care by the health visitor and general practitioner and do not require any specific treatment. Nonpharmacological measures include: Review of feeding and feeding practice e checking for overfeeding, trial of smaller more frequent feeds, too small or too large a teat (both of which can cause air swallowing). Review of feeding posture e 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 infants death syndrome (SIDS). In infants from birth to 12 months of age with reflux, the risk of SIDS generally outweighs the potential benefits of prone sleeping. In children more than 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 e 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. Extensively hydrolysed or amino acid based formula e Infants with persistent symptoms with associated red flags like blood in stools, history of eczema or atopy could have non IgE mediated cow’s milk protein intolerance and may benefit from a 2e6 week trial of elimination diet. This can be done by elimination of cow’s milk in maternal diet in breast fed infants. In bottle fed infants extensively hydrolysed formula should be used. Soya formulae should be avoided as there is 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 less than 6 months.
Acid suppression agents: include H2-receptor blockers and proton pump inhibitors. 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. There are several studies that have suggested that H₂-antagonists are efficacious in children. Ranitidine is the most commonly used H2-receptor blocker. Ranitidine is well tolerated and has a low incidence of side-effects (common side-effects include fatigue, dizziness or diarrhoea). Oral ranitidine provides symptomatic relief and endoscopic improvement of oesophagitis in children with GORD. Dosage for neonates is between 2 and 3mg/kg TDS. Child 1e5 months 1e3mg/kg TDS. Child 6 months-2 years 2e4mg/kg BD. Proton pump inhibitors (PPI) such as omeprazole and lansoprazole are a group of drugs that irreversibly inactivate Hþ/Kþ ATPase: the parietal cell membrane transporter. This increases the pH of gastric contents and decreases total volume of gastric secretion, thus facilitating emptying. Side effects reported with long term use include hypomagnesemia, gastric fundal polyps and small increase in risk of osteoporotic fractures. Omeprazole is the most commonly used PPI and is shown to be effective in children with GORD resistant to ranitidine. For healing of erosive oesophagitis and relief of symptoms, PPIs are superior to H2-receptor blockers. Omeprazole is available as dispersible tablets or capsules given once daily. The tablet can be gently mixed or dispersed (not crushed) or the capsule broken for ease of administration in children. Dosage is 0.7e1.4 mg/kg per day although higher doses can be used, up to 3mg/kg. When acid suppression is required, the smallest effective dose should be used. Most patients require only once-daily PPI. Lansoprazole is the other commonly used PPI. Dosage 0.5e1mg/kg OD a maximum dose of 15mg OD can be used.
Drug treatment Drug treatment is indicated in children with severe symptomatic reflux or signs and symptoms suggestive of gastro-oesophageal reflux disease. The major pharmacological agents currently used for treating GORD in children are gastric acidebuffering agents, mucosal surface barriers, and gastric anti-secretory agents. Acid suppressant agents are the mainstay of treatment for all but the patient with occasional symptoms. The potential adverse effects of acid suppression, including increased risk of communityacquired pneumonias and GI infections, need to be balanced against the benefits of therapy.
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Prokinetic drugs: can be helpful in some circumstances. Gastroesophageal reflux is primarily a motility disorder, and the use of pharmacologic agents that improve oesophageal and gastric motility are conceptually attractive as therapies. Unfortunately, the currently available prokinetic medications have only modest efficacy in relieving GORD symptoms, and the side effect profile makes them less useful clinical practice. Examples include metoclopramide, domperidone, and erythromycin.
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surgery, which include recurrence of reflux (10%), retching, bloating, dumping and intestinal obstruction. Some children have a high risk of needing surgery. These include children with neurodisability, those with respiratory disease with intractable reflux (e.g. oesophageal atresia, bronchopulmonary dysplasia), Children with complication of oesophagitis such as stricture or Barrett’s oesophagus and those who have had a tracheo-oesophageal fistula repair.
Domperidone is a dopamine-receptor (D2) blocker that has relatively fewer side effects but case reports of extrapyramidal side effects exist, as well as an effect on the QT interval (prolongation). Domperidone acts to increase lower oesophageal sphincter pressure improve oesophageal clearance and promote gastric emptying. Domperidone is commonly used in clinical practice either as part of empirical medical therapy of gastrooesophageal reflux disease or if delayed gastric emptying has been demonstrated on nuclear scintigraphy. In view of a small increased risk of cardiotoxicity, it is advisable to use domperidone in lower doses and only in cases with overt vomiting secondary to reflux. All infants should have an ECG to rule out prolonged QT interval before starting treatment and should be referred to a specialist if treatment is required for greater than 3 months.
Gastro-oesophageal reflux and neurodisability Paediatric neurodisability is an umbrella term for conditions associated with impairment of the nervous system, including conditions such as cerebral palsy, and epilepsy. Potential causes of feeding difficulties include bulbar weakness, primary or secondary aspiration, reflux oesophagitis, widespread gut dysmotility, mobility and posture problems, poor nutritional state and constipation. These children require careful multidisciplinary assessment by a feeding team including dietetics, speech and language therapy, occupational therapy and the neurodevelopmental paediatrician. 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. Therapeutic strategies include explanation and reassurance, trial of anti-reflux therapy, prokinetic agents such as domperidone and in some cases with marked dysmotility it may be necessary to give feeds by continuous infusion via gastrostomy or gastro-jejunal route. A milk free diet for a trial period of 2e4 weeks can be helpful. Hydrolysed protein formula feeds/MCT predominant feeds may be given as a milk substitute.
Buffering agents (magnesium hydroxide and aluminium hydroxide) and sucralfate: are useful for occasional heart burn. 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.
Enteral feeding In infants with faltering growth who are not responding to usual medical treatments a period of enteral tube feeding (ETF) should be considered. This ensures slow delivery of feeds and thus reduced distension of stomach and subsequent reflux. When tube feeding is started small oral stimulation in the form of small amount of oral feeds (milk or solids) should be continued. Post pyloric feeding, is reserved for severe cases not responding to other forms of management and associated with complications. As the stomach is bypassed there is no distension of stomach and there is reduction in reflux of gastric contents. This is particularly helpful in children with failure to thrive, severe oesophagitis and reflux related pulmonary aspiration. Continuous post pyloric feeding is most commonly used in children with neurodisability where the volume of feed is limited because of discomfort associated with feeding.
Gastro-oesophageal reflux and respiratory disease Gastro-oesophageal reflux has been associated with significant respiratory symptoms in infants and children. There is a complex relationship between asthma and gastro-oesophageal reflux, manifested by a bidirectional cause and effect. One postulated mechanism for gastro-oesophageal reflux mediated airway disease involves micro-aspiration of gastric contents that leads to inflammation and bronchospasm. However, experimental evidence also supports the involvement of oesophageal acideinduced reflex bronchospasm, in the absence of frank aspiration. In such cases, gastrooesophageal reflux therapy using either H2-blockers or proton pump inhibitors 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 gastro-oesophageal reflux and apparent life-threatening events is somewhat controversial and probably only relevant if the infant vomits, chokes or goes blue during or immediately after feeds.
Surgery The commonest operative intervention is fundoplication done laparoscopically or via open procedure. Children with co morbidities, particularly neurodisability who have the most severe GORD are at the highest risk for operative morbidity and postoperative failure. Before surgery it is essential to rule out nonGORD causes of symptoms and ensure that the diagnosis of chronic-relapsing GORD is firmly established. Indications for surgery include: Failure of optimal medical therapy Extra oesophageal manifestation (asthma, cough, chest pain, recurrent pulmonary aspiration of refluxate) Complication of GORD (e.g. Barrett’s oesophagus or oesophageal stricture) It is important to provide families with appropriate education and a realistic understanding of the potential complications of
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Barrett’s oesophagus
Mutalib M, Rawat D, Lindley K, et al. BSPGHAN Motility working Group position statement: paediatric multichannel intraluminal pH impedance monitoring eindications, methods and interpretation. Front Gastroenterol 2017; 8: 156e62. Nelson SP, Chen EH, Syniar GM, Christoffel KK. Prevalence of symptoms of gastroesophageal reflux during infancy. A pediatric practice-based survey. Pediatric Practice Research Group. Arch Pediatr Adolesc Med 1997 Jun; 151: 569e72. Rosen R, Vandenplas Y. Paediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American society for paediatric Gastroenterology, Hepatology, and nutrition and the European society for pediatric gastroenterology, hepatology, and nutrition. J Pediatr Gastroenterol Nutr 2018; 66: 516e54. Rudolph CD, Vandenplas Y. Paediatric gastro-oesophageal reflux clinical practice guidelines: joint recommendation of NASPGHAN and ESPGHAN e J Pediatr Gastroenterol Nutr 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; https://doi. org/10.1038/ajg.2009.129. Tighe M, Afzal NA, Bevan A, Hayen A, Munro A, Beattie RM. Pharmacological treatment of children with gastro-oesophageal reflux. Cochrane Database Syst Rev 2014 Nov 24; 11. Tighe MP, Beattie RM. Managing gastro-oesophageal reflux in infancy. Arch Dis Child 2010; 95: 243e4. Tighe MP, Cullen M, Beattie RM. How to use: a pH study. Arch Dis Child Educ Pract Ed 2009; 94: 18e23.
This refers to the presence of metaplastic columnar epithelium in the lower oesophagus thought to be a consequence of longstanding gastro-oesophageal reflux disease. There is an increased risk of adenocarcinoma of the oesophagus. It is rare in childhood and requires aggressive medical treatment, of the gastro-oesophageal reflux and regular endoscopic surveillance. Surgery (fundoplication) is often considered.
Case study 1 A 7 week old baby formula fed baby presented with history of vomiting after most feeds and excessive crying. Vomiting was variable quantity, non-projectile and non-bilious. The child was thriving very well. There was no abnormality seen on examination. A careful feed history revealed he was having nearly 200mlg/kg of formula feed. Parents were reassured and the volume of feeds was reduced. Symptoms resolved in 3 weeks. He continued to thrive and was discharged from follow-up. Over feeding is frequently seen in formula fed infants and a careful feeding history allows for an accurate diagnosis and helps in avoiding unnecessary treatments.
Case study 2 An 11 month old with cerebral palsy and seizure disorder presented with history of poor weight gain, recurrent vomiting and episodic crying. She was born at 25 weeks of gestation and had periventricular leukomalacia. 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 proton pump inhibitors with improvement in her symptoms. Her symptoms were secondary of acid reflux in her oesophagus in response to gastric acid secretion associated with meal times. Her feeding improved with treatment of the reflux.
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Case study 3 A 4 month old presented with feed refusal, retching, constipation and eczema. Her symptoms failed to improve with anti-reflux therapy and her weight was static. She was referred to specialist clinic and was started on extensively hydrolysed formula. At 6 months she was started on a dairy free diet. Symptoms improved and she showed good catch up growth. Cow’s milk was gradually introduced in her diet from the age of 12 months. 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. Gastro-oesophageal reflux can co-exist but poor a response to anti-reflux therapy should prompt consideration of cow’s milk allergy.
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A FURTHER READING Beattie RM, Dhawan A, Puntis JWL, Batra A, Kyrana E. Oxford specialist handbook in paediatric gastroenterology, hepatology and nutrition. Oxford University Press, 2018.
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Functional reflux is very common in infancy and resolve spontaneously Gastro-oesophageal reflux disease (GORD) is defined as ‘gastro-oesophageal reflux associated with troublesome symptoms or complications. Physiological reflux is a clinical diagnosis and does not warrant further investigation. It is important to consider appropriate differential diagnoses during history taking and examination. Most reflux will respond to simple strategies including reassurance and explanation, feeding advice, feed thickeners and anti-reflux milk. It is important to carefully consider cow’s milk protein allergy and a trial of 2e4 weeks of extensively hydrolysed or amino acid based formula can be considered before starting medical treatment. Medical therapy is by a step up approach with use of H2 blockers, prokinetics, proton pump inhibitors and consideration of a trial of hydrolysed formula. Surgery is required in cases resistant to medical treatment and those with extra oesophageal complications such as recurrent aspiration. Children with cerebral palsy are at increased risk of reflux although many other factors are relevant in the assessment of feeding problems in children with neurodisability
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Please cite this article as: Kolimarala V et al., Gastro-oesophageal reflux in infancy, Paediatrics and Child Health, https://doi.org/10.1016/ j.paed.2019.06.002