Gastro-oesophageal Reflux in Infants: Investigating this Common Condition (Part 2)

Current treatment and advice – the evidence

If successful at alleviating symptoms, reflux treatments also help to confirm the diagnosis of reflux.


In a recent draft guideline NICE does not recommend positional treatment in sleeping infants. This is in line with guidance from the Department of Health, which states that infants should be placed on their back when sleeping. However, additional positional studies have shown reflux, measured by pH probe, reduced to the greatest degree with the infant in the prone position (tummy), followed by the left lateral (left side), right lateral (right side) and supine (back) positions. However, other researchers claim that lying laterally (either side) is an unstable position for infants, and using pillows to maintain is not recommended.

Elimination of cow’s milk and cow’s milk products

Guidelines produced by NICE recommend a two-week trial of the following:

-  If a breastfed infant, advise the mother to eliminate cow’s milk and cow’s milk product from her diet. This should be replaced with soya milk fortified with calcium supplement. If the infant does not respond, the mother may be advised to avoid soya by a specialist. This is because some children with cow’s milk protein allergy/intolerance (CMPA) are also hypersensitive to soya.

-  If a formula fed infant, advise a hydrolysed Formula.

These recommendations are based on expert opinion from two narrative reviews and international guidelines. The literature identifies that hydrolysed formula is also effective in improving symptoms of colic, which is often mistaken for physiological reflux because of the symptom overlap.

Recent guidance from NICE has called for a randomised controlled trial (RCT) investigating the effectiveness of hydrolysed formula. This is due to many infants remaining on hydrolysed formula for extended periods based on a subjective assessment alone, and resource implications related to increased expense of hydrolysed formula in comparison to cow’s milk.

Frequency and feed volume, thickeners and alginates

In the treatment of formula-fed infants NICE recommend reducing the overall feed volume (if excessive for the infants weight). Followed by a trial of either: smaller, more frequent feeds or thickened formula (for example, containing rice starch, corn starch, locust bean gum or carob bean gum).

If this proves unsuccessful a 1-2 week trial of an alginate (Gavsicon Infant) is recommended. This latter therapy is also recommended by NICE in the treatment of breastfed babies. Alginate’s such as Gaviscon Infant prevent reflux by increasing viscosity of gastric contents.

A recent systematic review performed by Cochrane analysed five randomised controlled trial (RCT) evaluating Gaviscon Infant in the treatment of Infantile Reflux. The largest RCT assessed 90 infants (0-12 months) and found a significant reduction in number and severity of vomiting episodes with Gaviscon Infant compared to placebo. No serious adverse effects were reported in any of the five studies. The reviewers state that there is weak-moderate evidence indicating that Gaviscon Infant improves symptoms of physiological reflux. However, a caveat to this statement, is that more studies are required to prove the long-term safety of Gaviscon Infant.

gorgeous newborn baby sleeping

Acid suppression therapy – increased level of prescription despite disparity of evidence

Within the clinic setting I have observed that infants in this population are commonly prescribed the following medications in this order: Gaviscon Infant, acid suppression medications Ranitidine (histamine antagonist, H2) and Omeprazole (proton pump inhibitor, PPI). Current evidence provided by Cochrane concludes that in terms of efficacy, the best evidence for treatment of physiological reflux relates to Gaviscon Infant. What evidence underpins the prescription of this commonly prescribed pharmacological acid suppression treatment?

The primary class of acid suppression medications are H2 antagonists and PPIs. A retrospective audit investigating dispensing data for PPIs and prescribing patterns in infants, over a 10 year period (2002-2011), indicated that PPIs were being prescribed as a last resort to treat normal infant behaviour (crying, back arching and posseting) and this use should be discouraged. This overuse of acid suppression therapy is coupled with concern regarding the long-term adverse effects of these medications.

A recent systematic review has produced guidelines for feeding very low birth weight infants. The researchers state that observational data suggests that gastric acid suppression is associated with serious adverse events in neonates. They conclude that there is little justification for pharmacological acid suppression in the treatment of GORD. The literature also reflects other less severe adverse events including an increase risk of gastrointestinal tract and pulmonary infections in infants.

There is evidence within the literature that H2 antagonists and PPIs have been shown to reduce gastric enzyme activity allowing for healing of oesophagitis. This is supported by the new draft guidelines by NICE and the recent systematic review by Cochrane. This latter review concluded that both ranitidine and omeprazole appear to be efficacious in the treatment of GORD in children over one year of age. The reviewers did not identify any RCTs evaluating the use of ranitidine in infants (less than one year of age). In addition weak evidence for the efficacy of omeprazole in infants with GORD was reported. Their findings also revealed that omeprazole improves the pH probe markers of GORD, although improvement in pH probe markers do not clearly correlate with reduction of symptoms, especially in infants.

In contrast to this evidence, the new NICE draft guidelines recommend ‘considering’ a 4-week trial of an H2 antagonist or PPI for infants. This guideline states that this should be offered in those with regurgitation, with one more of the following: unexplained feeding difficulties (for example, refusing feeds, gagging or choking), distressed behaviour and faltering growth. The use of the word ‘consider’ reflects the strength of the evidence and whether or not to have the intervention at all. According to NICE  ‘consider’ directs the health care professional to be aware that prescribing the intervention is more likely to depend on the patient’s values and preferences than for a strong recommendation. They specify that these medications should not be offered to treat infants presenting with regurgitation only.

Disparity exists between evidence and current practice and as a result acid suppression therapy is often empirically started within the clinical setting. This observed trend is supported by research showing that this therapy has been prescribed in record levels in infants (less than one year of age).

Final thought

Due to the controversy and difficulty in defining and effectively diagnosing between physiological reflux and GORD, these terms are subsequently being used interchangeably by health professionals and patient families. This is usually under the encompassing term of “reflux”. This may contribute to heterogeneity of opinion and disparity within research and clinical settings. In terms of pharmacological therapy, it seems imperative to clearly distinguish between physiological reflux, GORD and oesophagitis to avoid unnecessary treatment of a self limiting, transient condition, whereby the risk to benefit ratio may be imbalanced.