Infant GORD and reflux: Diagnosis and management

Pharmacological interventions for infant GORD are considered when non-pharmacological measures and lifestyle modifications prove insufficient.

Gastro-oesophageal reflux (GOR, reflux) is a normal physiological process in infants, but when it becomes symptomatic and causes complications, it is called gastro-oesophageal reflux disease (GORD). In clinical practice, the terms reflux and GORD are often used interchangeably. Confirming whether the condition is reflux or GORD poses a challenge due to the absence of a simple, accurate, and reliable diagnostic test. It is therefore difficult to identify infants who have GORD and to estimate the real prevalence and burden of the condition.^1,2

GORD and reflux

Reflux is the involuntary passage of gastric contents into the oesophagus with or without regurgitation and/or vomiting. It is a common occurrence in paediatrics, affecting up to 40 per cent of infants.² Regurgitation is the most frequent symptom of reflux and is present in nearly all cases. It usually starts before eight weeks of age, peaks at around four months, and normally resolves by one year of age. Reflux rarely necessitates extensive investigations and can often be effectively addressed through parental education, support, and guidance._1,3 GORD is when ref lux causes vomiting with refusal to feed; pronounced irritability with feeding; aspiration; chronic cough, wheeze; slow weight gain; and haematemesis.

GORD is not a common cause of unexplained crying, irritability, or distressed behaviour in otherwise healthy infants. The disorder should be differentiated from physiological ref lux, which is common in healthy, thriving babies, and does not require specific investigations or management.³ Symptoms of GORD are frequently non-specific and can imitate or be associated with other conditions common in infancy, such as cow’s milk protein allergy, pyloric stenosis, malrotation, overfeeding, tracheoesophageal fistula, or constipation.

A comprehensive patient history is important for accurate diagnosis and effective treatment .^1,3,4 Several factors are linked to an increased prevalence of GORD, including:^1,2,4

• Premature birth
• Parental history of heartburn or acid regurgitation
• Obesity
• Hiatus hernia
• History of repaired congenital diaphragmatic hernia
• History of repaired congenital oesophageal atresia
• Underlying neuro-disability

Infants and young children lack the ability to articulate their symptoms verbally, necessitating reliance on non-verbal indicators as diagnostic cues. In the case of infants, irritability and back-arching are often interpreted as equivalent to heartburn in older children.¹

Pathophysiology

The pathophysiology of GORD and reflux in infants is multifaceted and involves various anatomical and physiological factors. Understanding the intricate interplay of these factors helps healthcare professionals tailor approaches to managing GORD and reflux in infants, focusing on lifestyle modifications, dietary adjustments, pharmacological therapy, and in severe cases, surgical intervention.

Immature lower oesophageal sphincter: The lower oesophageal sphincter (LOS) is a muscular ring that separates the oesophagus from the stomach. In infants, this sphincter is not fully developed, leading to transient relaxation and increased susceptibility to reflux. The immaturity of the LOS is particularly prominent in the early months of life.^4,5

Delayed gastric emptying: Infants have a slower rate of gastric emptying compared to older individuals. This delayed gastric emptying allows the stomach contents, including stomach acid, to remain in the stomach for more extended periods, increasing the likelihood of reflux.⁵

Liquid diet and composition: The predominantly liquid nature of an infant’s diet, either through breast milk or formula, may contribute to increased reflux. Certain components of the diet, such as fat content, can influence the frequency and severity of reflux episodes.^4,5

Abdominal pressure: Increased intra-abdominal pressure, often associated with crying or straining during bowel movements, can contribute to the movement of stomach contents into the oesophagus.^4,5

Neurological immaturity: The nervous system control over the LOS and other gastrointestinal (GI) functions is still developing in infants. Neurological immaturity may result in inefficient coordination of the muscles involved in swallowing and preventing reflux.⁵

Gut microbiota: The composition of the gut microbiota may influence the occurrence of reflux. Changes in the balance of bacteria in the digestive system could potentially affect the digestive processes and contribute to reflux symptoms.^4,5

Hiatal hernia: Although rare in infants, a hiatal hernia, where a portion of the stomach protrudes into the chest through the diaphragm, can contribute to GORD symptoms.⁵

Epidemiological data Epidemiological data indicates that reflux is prevalent, affecting around 50 per cent of infants under two months, increasing to 60-to-70 per cent in infants aged three-tofour months, and declining to 5 per cent by the age of 12 months.

The male-to-female ratio is approximately 2:1. Infrequent episodes of regurgitation are typically considered physiological and often resolve over time. Pre-term infants face an increased risk of reflux due to the physiological immaturity of the LOS, impaired oesophageal peristalsis, relatively abundant milk intake, and slower gastric emptying. The estimated incidence of reflux in infants born before 34 weeks of gestation is approximately 22 per cent.

Several studies have shown that there is a subgroup of infants with cow’s milk protein allergy who present with regurgitation and vomiting – symptoms that are indistinguishable from reflux. Some studies suggest that the two conditions may be causally related. Breastfed infants are less likely to have reflux than formula-fed infants, and breastfeeding is also associated with more rapid resolution of reflux.^4,5 GORD is more prevalent in children with obesity, neurological impairment, congenital heart disease, abnormalities of the GI tract, congenital diaphragmatic hernia, and chromosomal abnormalities. Obesity is an important predisposing factor, and is associated with increased transient relaxation of the LOS and higher intra-gastric pressure.

“Infants and young children lack the ability to articulate their symptoms verbally, necessitating reliance on non-verbal indicators as diagnostic cues. In the case of infants, irritability and back-arching are often interpreted as equivalent to heartburn in older children”

There is an increased concordance of reflux in monozygotic twins compared with dizygotic twins, suggesting genetic factors might have a role to play in the aetiology.⁴

Clinical presentation

Clinical manifestations vary according to age, with regurgitation the most prevalent symptom found in nearly all cases. While reflux may be present at birth, regurgitation might not become prominent until the second or third week of life, reaching a peak at four months when oral intake increases. The regurgitation is typically effortless, exacerbated after feeding, especially when the infant is in a reclined position or when abdominal pressure is applied.

Approximately 25 per cent of infants experience regurgitation four or more times a day, with some infants regurgitating more than six times daily.^4,6,7 Besides regurgitation, infants and young children with GORD may display symptoms such as irritability, excessive crying, poor appetite, feeding refusal, gagging, failure to thrive, sleep disturbance, chronic cough, wheezing, stridor, grimacing, opisthotonus, and torticollis. Sandifer syndrome, a condition that causes the infant to have uncontrollable muscle spasms after they eat, characterised by spasmodic torsional dystonia involving arching of the back, neck torsion, and lifting of the chin, is a highly specific indicator of GORD.

In Sandifer syndrome, it is thought that the arching of the back and rigid opisthotonic posturing provide relief from the discomfort caused by the acid reflux.^4,6,7

Complications

Complications vary with age. Severe regurgitation can lead to calorific loss and failure to thrive. GORD is linked to rumination, protein-losing enteropathy, and digital clubbing. Acidic reflux may cause peptic oesophagitis, presenting as bleeding, haematemesis, melena, and anaemia. Older children may experience heartburn, water-brash, and dysphagia.

Sleep disturbances are common, potentially due to increased nocturnal acid reflux. Peptic oesophagitis can lead to stricture formation, oesophageal shortening, mucosal dysplasia, and Barrett’s oesophagus.^4,8 Respiratory complications include reactive airway disease, sinusitis, laryngitis, bronchitis, recurrent aspiration pneumonia, and life-threatening events. Acidic stimulation may cause apnoea, leading to cardiac arrest, potentially linking to sudden infant death syndrome (SIDS). GORD is associated with cardiac autonomic dysfunction.^4,9

Recurrent otitis media and chronic tubotympanic disorders are also linked to reflux. In severe cases, reflux reaching the oral cavity can harm oral health, causing dental caries, erosion, and mucosal lesions, fostering the growth of acidophilic bacteria like Streptococcus mutans and Candida albicans.^4,10

Diagnosis

In most cases, diagnostic studies are not necessary to diagnose reflux and GORD in infants. The diagnosis is primarily clinical. A thorough clinical history and a complete physical examination remain the cornerstone of diagnosis. When the diagnosis is ambiguous or when complications are suspected, further investigations may be warranted.^4,11

Investigations for GORD such as barium contrast radiography, pH probe, and endoscopy are rarely necessary, and should only be considered on an individual basis after the infant has been assessed by a paediatrician.³ Using an upper GI series for diagnosing reflux in infants and children is not recommended, as the test lacks both sensitivity and specificity.

An upper GI barium contrast study does not accurately represent the frequency of reflux in normal physiological conditions. However, the test can be valuable for identifying anatomical abnormalities such as oesophageal stricture, oesophageal extrinsic compression, achalasia, antral web, pyloric stenosis, duodenal web, duodenal stenosis, hiatal hernia, malrotation, and annular pancreas, all of which may contribute to vomiting.⁴

There is no evidence to support oesophagogastric ultrasonography as a diagnostic tool for GORD in infants and children. It may be used to detect conditions such as pyloric stenosis, which may mimic GORD.⁴ Oesophageal pH and intraluminal impedance monitoring are rarely helpful in informing clinical management. Although this monitoring can demonstrate the degree of acid and non-acid reflux, determining the degree of reflux does not correlate well with severity of symptoms or complications.⁴

Diagnosis should be reconsidered if any of the following red flag signs and symptoms are present: Vomiting that is bilious, onset >six months of age, or is consistent and forceful; Significant diarrhoea or constipation; Fever or lethargy; Abdominal rigidity; Hepatosplenomegaly; Bulging fontanelle and/or increasing head circumference. Infants should be referred to a specialist when regurgitation becomes persistently projectile; there is bile-stained vomiting or haematemesis; there are new concerns such as signs of marked distress, feeding difficulties or poor weight gain; and there is persistent, frequent regurgitation beyond the first year of life .¹

Current recommendations do not support an empiric trial of proton pump inhibitors (PPIs) as a diagnostic test for GORD in infants and young children because symptoms suggestive of GORD are not/less specific in children of this age group. The North American Society for Paediatric Gastroenterology, Hepatology, and Nutrition and European Society for Paediatric Gastroenterology Hepatology and Nutrition suggest a four-to-eight week trial of PPIs in older children with typical symptoms of GORD, such as heartburn, retrosternal or epigastric pain, as a diagnostic test for GORD.⁴

Treatment

In most cases, no treatment is necessary for reflux apart from reassurance of the benign nature of the condition.

Thickened feedings, postural therapy, and lifestyle changes should be considered if the regurgitation is frequent and problematic.⁴ Therapy for paediatric GORD is based on a combination of conservative measures; ie, lifestyle and dietary modifications, pharmacological and, rarely, surgical treatment. Management strategies should be tailored to the severity of symptoms, the age of the infant, and any underlying medical conditions.¹

“Therapy for paediatric GORD is based on a combination of conservative measures; ie, lifestyle and dietary modifications, pharmacological and, rarely, surgical treatment”

Lifestyle and dietary modifications Positioning: Holding the infant in a head-elevated position for 20-to-30 minutes after feeding may reduce reflux. Prone sleeping or inclining the sleep surface is not recommended in infants due to the risk of SIDS.^3,12

Feeding practices: Smaller, more frequent feeds and avoiding overfeeding can help manage symptoms.^3,12

Thickened feeds: Thickening the formula or breast milk may reduce the frequency of regurgitation. In bottle-fed babies, thickened feeds may reduce the frequency of vomiting. Anti-reflux formulas are pre-thickened, or a thickening agent can be added to standard formula or expressed breast milk. Thickened feeds can contribute to constipation.

Gaviscon Infant should not be given to premature infants, young children who are ill with a high temperature, diarrhoea, vomiting, or if already using a food thickener.³ Maternal diet for breastfeeding mothers: Mothers may be advised to make dietary changes, such as avoiding spicy foods, caffeine, and acidic foods, as these can contribute to reflux.4 Formula selection: For formula-fed infants, switching to a hydrolysed formula may be recommended.^4,12

Tailored approaches for GORD – contemplate cow milk protein exclusion. Up to 40 per cent of infants displaying GORD symptoms may have non-immunoglobulin (Ig) E mediated cow milk protein allergy (CMPA). Symptoms typically manifest within a few weeks of exposure to cow milk protein. No distinct features predict the response to dietary changes, and investigations are unhelpful in diagnosing CMPA.

If CMPA is suspected, infants should undergo a two-week trial of strict cow milk protein elimination from their diet, with referral to a paediatrician arranged.⁴

Pharmacological interventions

In general, pharmacotherapy is not indicated in the treatment of uncomplicated reflux in infants as symptoms tend to resolve with time. Pharmacological interventions for infant GORD are considered when non-pharmacological measures and lifestyle modifications prove insufficient in managing symptoms.⁴

Anti-reflux medicines reduce the severity of the reflux by improving the motility of the oesophagus and stomach. They may also reduce acidity so that the reflux is less damaging to the oesophageal lining. They are generally only used if other treatment options like thickeners do not work. Domperidone helps tighten the sphincter at the end of the oesophagus where it joins the stomach.

This helps stop food from flowing back into the oesophagus. It comes in liquid or suppository form for infants and children, and is only available on prescription.¹³

Acid-suppressive medications: In more severe cases, acid-suppressive medications, such as PPIs or histamine-2 receptor antagonists (H2RAs), may be required.

While the use of these medications in infants is a subject of ongoing research, and caution is advised due to potential side-effects, both H2RAs and PPIs have been demonstrated to be safe and effective for infants and children in reducing gastric acid output. According to a 2017 systematic review comprising 23 randomised placebo-controlled trials involving 1,598 children, both H2RAs and PPIs proved to be effective in treating paediatric GORD, particularly in cases involving reflux oesophagitis.

The duration of treatment can range from a few weeks to several months. It is advisable to regularly reassess patients with GORD to determine the ongoing necessity of treatment.⁴ PPIs are more effective than H2RAs in reducing gastric acid secretion and are therefore the drugs of choice.4 Medications containing omeprazole are the most commonly used PPIs for children.

To treat symptoms of GORD, children over one month of age may take omeprazole. The dose for infants and young children is based on body weight.¹³ Omeprazole liquid is available as an unlicensed medication in Ireland, and Losec MUPS (omeprazole) can be dissolved in water for infants.13 Pedippi oral suspension (a PPI containing omeprazole) is an infant-specific treatment for GORD now available on the Irish market. Dosage range for omeprazole based on the child’s weight:¹⁴ Child’s body weight 10-20kg: 10mg once daily (max 20mg/day).

Child’s body weight over 20kg: 20mg once daily (max 40mg/day).* *See individual product information leaflet for exact dosage information. Omeprazole must not be taken by patients who are on medicine containing nelfinavir, which is used to treat human immunodeficiency virus infection.¹⁵

Antacids: Antacids such as aluminium hydroxide, calcium carbonate, and magnesium hydroxide are not useful in the treatment of GORD in infants, but may be considered for short-term use in older children and adults for relief of heartburn.⁴ Prokinetic agents: These medications promote the movement of food through the digestive system and may be considered in specific cases.

Metoclopramide enhances the movement of food through the digestive system and may help reduce reflux episodes. However, its use is limited due to concerns about side-effects, especially in the central nervous system. It is usually only considered in specific cases where other measures have failed.4 Alginate-based formulations: Some formulations containing alginate, a natural substance derived from seaweed, are designed to create a protective barrier in the stomach, preventing reflux of stomach contents into the oesophagus. These formulations may be considered in certain situations, but their efficacy in infants is still under investigation.4

Medication considerations and challenges in infants Age and weight considerations: Determining the appropriate dosage for infants can be challenging due to their size and developmental stage. Careful monitoring and adjustment of dosages are essential.4 Safety concerns: The safety of pharmacological interventions in infants is a significant consideration.

Potential side-effects, drug interactions, and the impact on normal growth and development must be carefully assessed.⁴ Short-term vs long-term use: The duration of medication use is an important consideration. While medications may be effective in the short-term, their long-term safety and impact on the developing digestive system are areas for consideration.⁴

“Therapy for paediatric GORD is based on a combination of conservative measures; ie, lifestyle and dietary modifications, pharmacological and, rarely, surgical treatment”

Parental education and support

Specialist referral to a paediatric gastroenterologist or other relevant healthcare professionals may be necessary for complex cases.^2,4 Surgical management of GORD is rarely required. Indications for anti-reflux surgery, usually laparoscopic fundoplication, include life-threatening events such as cardiopulmonary failure, apnoea, and near-miss SIDS attributable to GORD. Children with failure to thrive, oesophagitis, oesophageal strictures, intractable emesis, or chronic problems such as neurological impairment or cystic fibrosis with a significant risk of GORD-related complications who do not respond to medical treatment may also be considered for anti-reflux surgery.⁴

Prognosis Approximately 95 per cent of infants naturally outgrow reflux by the age of 12 months, experiencing the most significant improvement around 8-to-10 months when they begin sitting upright. Infants with neurodevelopmental disabilities and a strong family history of GORD generally face a less favourable outlook compared to those with physiological reflux. Persistent reflux symptoms beyond 18 months of age are indicative of a higher likelihood of developing chronic GORD in children.⁴

REFERENCES 

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10. Sarath Kumar K, Mungara J, Venumbaka N, Vijayakumar P, Karunakaran D. Oral manifestations of gastroesophageal reflux disease in children: A preliminary observational study. J Indian Soc Pedod Prev Dent. 2018;36(2):125-129 
11. Rosen R. Gastroesophageal reflux in infants: More than just a phenomenon. JAMA Paediatr. 2014;168(1):83-89 
12. Health Service Executive. Reflux in babies. Dublin: HSE; 2023. Available at: www2.hse.ie/conditions/reflux-babies/ 
13. Brady E. Gastro-oesophageal reflux in infants and children. Irish Pharmacist. 2022;23(2). Available at: www. irishpharmacist.ie/2022/02/22/gastro-oesophageal-refluxdisease- in-infants-and-children 
14. Health Products Regulatory Authority. Package leaflet: Information for the patient – PEDIPPI 4mg/ml, powder for oral suspension Omeprazole. Dublin: HPRA; 2023. Available at: www.hpra.ie/img/uploaded/swedocuments/c85baa45- bd9e-44a4-a8f3-5bcd81f3fb28.pdf