Advances in the management of infant colicAll infants experience gastroesophageal reflux (GER) with the prevalence typically peaking at 4-5 months of age and resolving without intervention by 13-14 months of age.1 If an otherwise healthy infant (3 weeks–12 months of age) experiences regurgitation, with no retching, haematemesis (blood in vomit), apnoea (temporary stopping of breathing), more than twice per day for over 3 weeks, they may be diagnosed with functional infant regurgitation.

While functional infant regurgitation can cause caregiver anxiety, leading to caregivers often seeking help from their physician, many infants fulfil these criteria and functional infant regurgitation is unlikely to impact on an infant’s growth.2-4 However, interventions are available to minimize the frequency of reflux and ameliorate the concerns of caregivers.2

Differentiating GER from gastroesophageal reflux disease (GERD)

As GER is a post-meal phenomenon present in all infants, differentiating GER from GERD is a diagnostic challenge for paediatricians. The key difference between normal reflux and GERD, as defined by European and North American Societies for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN and NASPGHAN) guidelines, is when the “reflux of gastric contents is the cause of troublesome symptoms and or complications.”2,5 In children, this can manifest as weight loss, respiratory symptoms, irritability, oesophagitis and vomiting necessitating medical care.2

However, it is important to note that GERD is rare, with one large study reporting a prevalence of 0.5% amongst infant patients with regurgitation.6 Therefore, if an infant presents with troublesome reflux, it is necessary to exclude other causes before making a definitive diagnosis of GERD.

Managing infants with GER

Because the majority of infants who experience GER do not have an underlying disease, pharmacotherapy is not indicated, although there is some evidence that infants who present with persistent regurgitation (>3 months) are more likely to have GER symptoms at 9 years of age.1 However, many caregivers will opt to seek medical help in managing reflux.3,4

Lifestyle interventions can reduce the frequency of regurgitation and may mitigate caregiver concerns and reduce the risk of GER symptoms later in life. For example, feeding techniques to reduce the frequency of vomiting and reflux include smaller, frequent meals. Additionally, not bouncing the infant after a feed and avoiding applying pressure to the abdomen may decrease the frequency of regurgitation.

However, in cases of persistent vomiting and discomfort, GER may be a symptom of allergy or intolerance. Accordingly, the ESPGHAN and NASPGHAN guidelines recommend the following interventions for the management of GER2:

  • Exclude cow milk allergy in the case of recurrent vomiting These patients may benefit from a 2–4 week trial of extensively hydrolyzed formula instead of cow milk formula.
  • Use a thickened formula (using bean gum, cereals or starch from rice or potato) This can reduce visible vomiting and regurgitation episodes, but may not reduce the frequency of reflux.7

However, cow milk allergy is not common, and while bean gum milk formulae have demonstrated greater weight gain in infants, infants with functional regurgitation on normal diets still gain weight within a healthy range. A meta-analysis including 14 randomized controlled trials concluded that regular milk formulae have no significant negative effect on growth compared with thickened milk formulae.7

The ESPGHAN and NASPGHAN guidelines also emphasize that while prone positioning does reduce reflux over supine positioning, prone positioning is associated with an increased risk of sudden infant death syndrome, and is therefore not recommended as a method of reducing reflux.2

In older children and adolescents, lifestyle interventions to reduce GER symptoms include weight reduction, avoiding large meals, not smoking and avoiding chocolate and alcohol. However, many of these interventions have only been evaluated in adult studies.2

Pharmacotherapy for infants with GERD

In infants, therapeutic agents to treat the symptoms of GERD include prokinetic agents (typically domperidone), proton pump inhibitors (PPIs) and antacids. However, a systematic review has concluded that there is limited evidence for the efficacy of domperidone in managing GERD in children aged <18 years.8,9 Additionally, prokinetics can have severe side effects, including hyperprolactinaemia, rash, headache and diarrhoea, which must be considered before prescribing. Consequently, the NASPGHAN and ESPGHAN guidelines conclude that there is insufficient evidence to support the use of prokinetic agents in infants with GERD.2

Currently, there are three PPIs approved for GERD in children. However, caution is warranted as current clinical trials to support the use of PPIs typically include a heterogeneous study population with variable study designs and no common endpoint. Additionally, acid suppression in children can increase their susceptibility to infections such as pneumonia, enterocolitis and Clostridium difficile-associated disease.10-12 Consequently, pharmacotherapies should only be considered for infants with confirmed GERD.

Summary

Reflux is a common phenomenon present in all infants and rarely is the result of underlying disease.6 Accordingly, the primary strategy to treat reflux involves reassuring caregivers that this is a normal developmental feature and will reduce with time.2,5

References

  1. Martin, A.J. et al. Natural history and familial relationships of infant spilling to 9 years of age. Pediatrics, 2002. 109(6): p. 1061-67.
  2. Vandenplas, Y. et al. Pediatric gastroesophageal reflux clinical practice guidelines: Joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroenterol Nutr, 2009. 49: p. 498-547.
  3. Hegar B, et al. Natural evolution of regurgitation in healthy infants. Act Paediatr, 2009. 98(7): p. 1189-93.
  4. Nelson, S.P. et al. Prevalence of symptoms of gastroesophageal reflux during infancy. A pediatric practice-based survey. Pediatric Practice Research Group. Arch Pediatr Adolesc Med, 1997. 151(6): p. 569-72.
  5. Sherman, P.M. et al. A global, evidence-based consensus on the definition of gastroesophageal reflux disease in the pediatric population. Am J Gastroenterol, 2009. 104(5): p. 1278-95.
  6. Campanozzi, A. et al. Prevalence and natural history of gastroesophageal reflux: pediatric prospective survey. Pediatrics, 2009. 123(3): p. 779-83.
  7. Horvath, A. et al. The effect of thickened-feed interventions on gastroesophageal reflux in infants: systematic review and meta-analysis of randomized, controlled trials. Pediatrics, 2008. 122(6): p. e1268-77.
  8. Pritchard, D.S. et al. Should domperidone be used for the treatment of gastro-oesophageal reflux in children? Systematic review of randomized controlled trials in children aged 1 month to 11 years old. Br J Pharmacol, 2005. 59(6): p. 725-29.
  9. Tighe, M. et al. Pharmacological treatment of children with gastro-oesophageal reflux (Review). Cochrane Database Syst Rev, 2014. 11: CD008550.
  10. Dial, S. et al. Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease. JAMA, 2005. 294(23): p. 2989-95.
  11. Guillet, R. et al. Association of H2-blocker therapy and higher incidence of necrotizing enterocolitis in very low birth weight infants. Pediatrics, 2006. 117(2): p. e137-42.
  12. Canani, R.B. et al. Therapy with gastric acidity inhibitors increases the risk of acute gastroenteritis and community-acquired pneumonia in children. Pediatrics, 2006. 117(5): p. e817-20.