Article written by Mr Thompson
Gastro-oesophageal reflux (GOR) is a symptom not a disease and refers to the involuntary retrograde flow of gastric contents into the oesophagus. It is present in the majority of infants and is illustrated by a spectrum from occasional physiological reflux through to the infant with haematemesis, oesophageal stricture formation, failure to thrive, apnoea, wheezing and even sudden infant death syndrome (SIDS). (Vandenplas 1993) However, despite the recent expansion in diagnostic investigation tools available, most infants have uncomplicated GOR without a definite anatomical, metabolic, neurological or infectious cause, nor an association with serious complications of the GOR itself. Determining which infants would benefit from investigation and treatment to avoid these complications is important to avoid unnecessary and potentially invasive procedures in those in whom physiological reflux would just resolve with time. Approximately 80-85% of infants who have GOR have resolved by 18 months of age and 95% by 2 years of age.
Signs, symptoms and diagnosis:
General common symptoms include irritability, infants labelled with “colic”, feeding refusal, failure to thrive, excessive re-gurgitation and vomiting. Specific symptoms include haematemesis/melaena, anaemia, aspiration, wheezing, apnoea, stridor, torticollis, and even apparent life-threatening events and SIDS. Small amounts of rumination or possetting are common in infancy, but those suffering from significant reflux or vomiting with pathology outside the GI tract (eg. UTI’s, raised intracranial pressure, deliberate poisoning, metabolic conditions etc.) should not be missed.
It is important to realise that there is no clear relationship between symptoms and the severity of GOR or oesophagitis.
Excessive crying or irritability is likely to be associated with pathological GOR over 3 months of age but not when present under 3 months. Pain, which the infant associates with swallowing, may lead to food refusal. Acid, and more commonly non-acid, GOR leads to bronchial constriction, probably mediated by stimulation of the vagal nerve at the distal oesophagitis. Refractory wheezing in infancy and childhood therefore can respond to anti-reflux therapy. (Eid 1994)
Investigation of GOR:
This must be tailored to the question being asked. Indeed, in uncomplicated cases no investigation may be needed, and a trial of simple therapeutic measures may be all that is required, which constitutes a diagnostic measure in itself. Although the place of ambulant oesophageal pH monitoring is receiving critical attention recently, it still remains the gold standard for identification of the temporal relationship between the symptoms and GOR. The reflux index which is the percentage of time below pH 4 over a 24-hour period is also a useful index of GOR.
Advanced endoscopic technology now allows us to perform upper endoscopy on even the smallest infants, but is of course useful only if it will lead to alteration in diagnosis, treatment, or prognosis. The severity of oesophagitis, however, has been shown to determine potential symptomatic relief with medical therapy, eventual requirement for surgery, and overall prognosis. Clearly infants with significant symptoms suggestive of complicated reflux and oesophagitis should be considered for upper endoscopy. This is now a very safe procedure lasting 5-10 minutes under sedation or a short general anaesthetic.
Barium studies of the upper GI tract are only helpful in detecting the presence or absence of anatomical abnormalities, for example, oesophageal strictures, gastric outlet obstruction, and small bowel malrotation. They do not help in the assessment of reflux severity.
Step 1 is the approach which is generally recommended but must be altered depending on symptoms and results of investigations.
1. Possetting mild reflux:
* Simple measures including position, 30o head elevated right lateral position.
* Increased frequency, decreased volume of each feed.
* Milk thickening agents (eg. Nestargel, Carobel) or pre-thickened milks (e.g. (Enfamil AR, SMA Staydown).
* Antacids (Infant Gaviscon) essentially work as thickening agents also.
2. Uncomplicated reflux, unresponsive to above:
* Prokinetic agent such as Domperidone 0.4mg/kg/dose, 3 times daily.
* H2 anagonist such as Ranitidine 1-3mg/kg/dose, 3 times daily.
3. Unresponsive to steps 1 and 2:
* Investigate with pH, endoscopy, barium study as each case dictates (referral to paediatrician with gastro interest or paediatric gastroenterologist).
4. Further drug therapy:
* Add Ranitidine or other H2 blocker (1-3mg/kg/dose 3 times daily).
* If symptoms remain, substitution of cow’s milk protein base formula with casein or whey-hydrolysate milk (eg. Pregestimil, Nutramigen, Pepti-Junior), or even elemental milk (eg. Neocate or Neocate Advance) may be helpful, ideally following small bowel biopsy evidence of cow’s milk sensitive enteropathy.
* Additional medical therapy in the form of Omeprazole, which has recently been licensed for use in children over the age of 2 years, or Cisapride on a named-patient basis post-ECG – both should be initiated by a paediatric gastroenterology centre.
* Surgical intervention if maximum medical management is ineffective (eg. Nissen fundoplication) may be required in severe cases, commonly in those with neurological disability.
GOR and cow’s milk protein intolerance (CMPI)
GOR and CMPI share some of the clinical presentations (eg. vomiting, “colic”, feeding refusal, failure to thrive) and CMPI may occur in up to 40% of infants diagnosed with GOR. (Kelly 1995) A trial of removal of CMP is often considered necessary, but soya milks should not be used to substitute due to 30-35% cross sensitivity of soya with CMP. Casein hydrolysate or elemental milks, (Pregestimil, Nutramagin, Pepti-Junior, Neocate, Neocate Advance) although not particularly palatable, are the milks of choice (as above).
* A spectrum exists from occasional physiological reflux to haematemesis, oesophageal stricture formation, failure to thrive, apnoea, wheezing, and even sudden infant death syndrome (SIDS).
* Pathological reflux is much commoner than previously thought, although 80-90% of infants grow out of it by 2 years.
* Cow’s milk protein intolerance may be contributing to reflux in up to 40% of infants.
* Severe GOR-associated oesophagitis may be accompanied by only mild symptoms.
* Children with refractory wheezing may have GOR.
1. Thomson M. Disorders of the oesophagus and stomach in infants. In: Bailliere’s “Clinical Gastroenterology”. Paediatric Gastroenterology. Ed: Walker-Smith J. 1997;11(3):547-73.
2. Thomson M, Walker-Smith J. Dyspepsia in childhood. In: Bailliere’s “Clinical Gastroenterology”. Ed: Talley N. 1998. 12(4) .
3. Thomson M. Esophagitis Chapter 23;297-316. In: Third Edition of “Pediatric Gastrointestinal Diseases”. Ed Walker, Durie, Hamilton, Walker-Smith. Mosby. 2000.
4. Vandenplas Y, Ashkenazi A, Belli D et al. A proposition for the diagnosis and treatment of gastro-oesophageal reflux disease in children: a report from a working group on gastro-oesophageal reflux disease. Eur J Pediatr. 1993;152:704-711.
5. Eid N, Shepherd R, Thomson M. Persistent wheezing and gastroesophageal reflux in infants. Pediatr Pulmonol. 1994;18:39-44.
6. Kelly K, Lazenby A, Rowe P et al. Eosinophilic esophagitis attributed to gastroesophageal reflux: improvement with an amino acid based formula. Gastroenterol. 1995;109:1503-12.
Figure 1: Gastro-oesophageal reflux treatment algorithm in infants and young children.
Possetting / Mild Reflux
1. Simple Measures:
Position – 30o head-elevated L lateral Trendelenburg
Feeds – ↑freq, ↓vol of each feed
Milk-thickening agents (Nestargel, Carobel) / pre-thickened milks (Enfamil AR, SMA Staydown)
Antacids (Infant Gaviscon)
2. Prokinetic agents:
Prokinetic agent such as Domperidone 0.4mg/kg/dose, 3 times daily.
H2 antagonist such as Ranitidine 1-3mg/kg/dose, 3 times daily.
Investigate as individual case dictates (see text) e.g. pH/OGD/Ba study
4. Consider substituting CMP-based formula with:
caseine-hydrolysate milk (e.g. Pregestimil, Nutramagen, Peptijunior)
or even elemental milk (e.g. Neocate; Neocate Advance)
ideally following small bowel biopsy evidence of cow’s milk-sensitive enteropathy
If CMPI not considered a contributory factor
5. Consider additional medical therapy:
Proton pump antagonist (e.g. omeprazole 0.7-2.7 mg/kg/dose 1xdaily)
(no place for metoclopramide or bethanechol)
(use of misoprostol or sucralfate not yet proven)
5. “Maximum medical therapy” for 6 weeks to 3 months
Max doses of:
No significant symptom resolution
6. Consideration for surgery:
Nissen or Thal or endoscopic fundoplication
(± gastrostomy if significant feeding disorder)