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Managing Gastro-Oesophageal Reflux Disease

Cite this article as:
Sarah Davies. Managing Gastro-Oesophageal Reflux Disease, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.29563

Isobel is a 10 week old, exclusively breast-fed, baby girl. She is brought into the Emergency Department with a history of frequent vomiting and poor weight gain. Her examination is normal, but when you ask Isobel’s exhausted-looking mother to put her to the breast, she becomes fractious and fussy, pulling away, arching her back, and taking very little feed at all.  

What are you going to do? 

At face value, this familiar presentation sounds like gastro-oesophageal reflux disease (GORD), although the differential for a ten-week old with vomiting and weight loss is wide.

Gastro-oesophageal reflux (GOR) is …the effortless retrograde passage of gastric contents into the oesophagus, with or without overt regurgitation. 

It is:

  • Physiological, due to low tone in the immature lower oesophageal sphincter
  • Common, occurring in up to 50% infants under 6m
  • Frequent – can happen up to x6/day

Gastro-oesophageal reflux disease (GORD) can be diagnosed clinically when GOR is accompanied by troublesome symptoms that affect everyday functioning (eg crying, back-arching, food refusal) and may lead to complications (eg failure to thrive).

Alternative diagnoses should be considered when there are additional red flag features (see below) indicative of a different pathology and under these circumstances, investigations should be tailored to rule these in or out.

*Some red flags overlap with symptoms directly related to GORD. The number, duration and severity of these should inform your decision to investigate on a case by case basis

As Isobel has symptoms of GORD with faltering growth you check her head circumference (which is appropriate), dip a urine (which is negative), and send some bloods for a faltering growth screen (although you strongly suspect they will come back as normal). You explain to Isobel’s mother that there is a stepwise approach to the management of GORD starting with non-pharmacological measures.

So, in the absence of red flag symptoms, do I need to prove its GORD?

In short, no. There is no single gold standard test for the diagnosis of GORD, hence the emphasis on clinical diagnosis. 

Invasive testing does have a place, though it is rarely the job of an ED clinician to be considering this. 

Endoscopy is used under the guidance of a Paediatric Gastroenterologist, for infants who fail to respond to optimal medical management. This will diagnose erosions and eosinophilic oesophagitis. 

pH MII (multi-channel intraluminal impedance) monitoring is used in children whose symptoms persist despite optimal medical therapy with normal endoscopy.   For a great explanation of this technique this previous DFTB post on reflux from 2016

Barium is out. Reliable biomarkers don’t yet exist. Scintigraphy, ultrasound and trial of a proton-pump inhibitor (PPI) are not useful in babies. 

OK, so I only need to investigate if I think there may be another cause for the symptom. But what should be my initial approach to treatment?

  • Positional management?
  • Avoiding overfeeding?
  • Thickening feeds?

Positional management – keeping the baby upright after feeds and elevating the head of the cot to sleep – is often advised for reflux. However, a study by Loots and colleagues in 2014 showed that regurgitation was only reduced through the use of side-lying positions which should NEVER be recommended due to the increased risk of SIDS. Head elevation made no difference at all despite some evidence that it can be beneficial in adults. 

And whilst a common-sense approach would support a move to smaller more frequent feedings and keeping a baby upright for 20-30 minutes after a feed, there isn’t any good quality evidence that confirms this. 

Feed thickeners have been shown repeatedly to reduce the frequency of visible regurgitation episodes in babies with reflux and in some studies to decrease cry/fuss behaviour too. They are safe and come highly recommended as a first-line intervention for babies with troublesome reflux. If you are going to advise a thickener for a breastfed infant, it’s important to suggest a carob bean-based product, such as Carobel, because the amylase in breast milk will digest the rice cereal-based thickeners such as Cerelac.  

Acupuncture, probiotics, massage, hypnotherapy have not yet been adequately studied for us to say one way or another if they are of any benefit. And alginates, probably the most familiar to us being Gaviscon? We’ll cover those shortly.

The key thing to remember for any intervention, is to reserve these for your patients with GORD. Happy, thriving, refluxy babies, typically outgrow their symptoms as they transition to solid food and should be left well alone

OK, but what if my patient has tried these already? What should I advise next? 

First, check how long they have persisted with the intervention. 

One of the biggest reasons for the simpler interventions not to help with GORD is that they are not given enough time to make a difference. Having said that, if a tired parent is repeatedly confronted with a grizzly, uncomfortable baby who is refusing to feed, asking them to persevere for two weeks with an intervention they don’t think is helping, may be practically difficult to achieve. 

In the UK, we have a choice of two key guidelines to help us with the next steps in reflux management.  

  1. NICE, last updated 2019

OR

  1. ESPGHAN/NASPGHAN 2018 joint consensus guidelines which are endorsed and recommended by our own BSPGHAN
  • European Society of Paediatric Gastroenterology, Hepatology and Nutrition
  • North American Society of Paediatric Gastroenterology, Hepatology and Nutrition
  • British Society of Paediatric Gastroenterology, Hepatology and Nutrition

Except that these guidelines differ a little on the advice they give for when simple measures don’t help…

NICE recommend a trial of Gaviscon first, and if that doesn’t work 4-8 weeks of a PPI such as omeprazole, and only then suggest a trial of cow’s milk protein exclusion (either through use of a hydrolysed formula or maternal dairy exclusion in breastfed infants) as a last resort, if reflux does not improve after ‘optimal medical management’. 

NASPGHAN/ESPGHAN on the other hand, suggest that ALL infants undergo an initial trial of cow’s milk protein exclusion, and only if this fails do they suggest the use of a PPI or hydrogen receptor antagonist (H2RA) such as Ranitidine. The bottom line is, that no-one has looked at the efficacy of a cow’s milk protein-free diet for symptom relief in babies presenting with reflux as the single symptom of cow’s milk protein intolerance (CMPI).  

The NASPGHAN team argues, that whilst there is no evidence on the topic, there are a number of babies with CMPI manifesting as reflux only who will benefit from this approach. They suggest eliminating cow’s milk protein from an infant’s diet for a minimum of 2 weeks, ideally four. If symptoms resolve and reappear on reintroduction then the diagnosis is clear. 

NASPGHAN then suggest babies who do not respond should be referred to secondary care services and started on a time-limited trial of PPI. 

This is largely so that infants are not left struggling on inadequate therapy for long periods of time, but also because their review found conflicting evidence around the benefit and side effect profile of these medications for young children. 

In six studies looking at PPI versus placebo, four studies showed no difference in regurgitation or other reflux associated symptoms between intervention and control groups. Three studies comparing H2RAs to placebo did show some benefit of the intervention, however, these studies were all in older children with biopsy-proven erosive oesophagitis up to 8 years of age.  Two studies showed endoscopic and histological and clinical features of GORD were reduced with H2RA over placebo, but these were in mixed-age groups including children up to 8 years old.

All studies showed a similar profile of side effects and between drug and placebo arms, however, one study demonstrated an increased rate of infection, in particular lower respiratory tract infection and diarrhoea in the PPI group. 

Given these findings, NASPGHAN cautiously recommends PPI or H2RA therapy in babies who have troublesome reflux despite trying a number of other non-pharmacological management options. 

Their key message is around early referral to secondary care, giving sufficient time for any one intervention to work, and making sure children are appropriately followed up.

So, what should I do? 

Given the somewhat conflicting advice outlined by these two well-respected groups, you could be left feeling unsure how to manage your next case. However, the genuine gap in the evidence market here does mean you are free to exercise your own clinical judgment and tailor your decision making to each individual refluxy baby, whilst empathetically taking on board the thoughts and preferences of the family.  This could, for some babies and parents, be medicine in itself. 

And what about alginates?

Two studies in the large literature review by the NASPGHAN/ESPAGHN group, compare Gavsicon to placebo. They show a reduction in visible regurgitation but no difference in reflux-associated symptoms. Furthermore, infants treated with alginate and then undergoing pH MII for 24 hours, showed no difference in the frequency of regurgitation events between groups. 

Chronic use of alginates causes constipation and poses a theoretical risk of milk-alkali syndrome, which is perhaps why the authors suggest use is limited to short term therapy. NICE do recommend a trial of Gaviscon therapy at an early stage in their pathway, as an alternative to feed thickener, but again on a time-limited basis with a planned review. 

Isobel’s mother had already tried two weeks of feed thickener on recommendation from the GP with no improvement. She was keen to avoid medication if possible so you agreed to a trial of dietary cow’s milk elimination for Mum who would continue to breastfeed and give top-ups with a hydrolysed formula if there was still no weight gain in a week. You gave her a sheet of dietary advice to ensure she maintained her own calcium intake and asked her to see the GP in 2 weeks for a review.  

Take home message

  • The vomiting infant has a wide differential – actively look for red flag features and investigate if you are concerned.
  • Infants with GORD need a management plan; infants with GOR, leave well alone
  • Start simply with an intervention that the family are happy to trial
  • Give time for it to work (up to two weeks)
  • Ensure follow-up for all and onward referral for infants who require acid-suppressive medication 

References

  1. Loots et al. Body positioning and medical therapy for infantile gastroesophageal reflux symptoms. Journal of Pediatric Gastroenterology and Nutrition 2014; 59 (2): 237-243. 
  2. Rosen et al. Pediatric Gastroesophageal Reflux Clinical Practice Guidelines: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition and the European Society of Pediatric Gastroenterology, Hepatology and Nutrition. JPGN 2018; 66(3): 516-554. 
  3. Winter et al. Efficacy and safety of pantoprazole delayed release granules for oral suspension in a placebo-controlled treatment withdrawal study in infants 1-11 months old with symptomatic GERD. JPGN 2010; 50: 609-618.  
  4. Orenstein et al. Multicenter, double-blind, randomized, placebo-controlled trial assessing the efficacy and safety of proton pump inhibitor lansoprazole in infants with symptoms of gastroesophageal reflux disease. Journal of Pediatrics 2009; 154: 514-520e4. 
  5. Davidson et al. Efficacy and safety of once daily omeprazole for the treatment of gastroesophageal reflux disease in neonatal patients. Journal of Pediatrics 2013; 163: 692-698.e1-2. 
  6. Winter et al. Esomeprazole for the treatment of GERD in infants ages 1-11 months. JPGN 2012; 55: 14-20. 
  7. Hussain et al. Safety and efficacy of delayed release rabeprazole in 1-11 month old infants with symptomatic GERD. JPGN 2014; 58: 226-236. 
  8. Moore et al. Double-blind placebo-controlled trial of omeprazole in irritable infants with gastroesophageal reflux. Journal of Pediatrics 2003; 143: 219-223. 
  9. Cucchiara et al. Cimetidine treatment of reflux oesophagitis in children: an Italian multi-centric study. JPGN 1989; 8: 150-156. 
  10. Orenstein et al. Ranitidine, 75mg, over the counter dose: pharmacokinetic and pharmacodynamic effects in children with symptoms of gastro-oesophageal reflux. Alimentary Pharmacology and Therapeutics 2002; 16: 899-907. 
  11. Simeone et al. Treatment of childhood peptic esophagitis: a double-blind placebo-controlled trial of nizatidine. JPGN 1997; 25: 51-55. 
  12. Miller et al. Comparison of the efficacy and safety of a new aluminium free paediatric alginate preparation and placebo in infants with recurrent gastroesophageal reflux. Current Medicines and Research Opinion 1999; 15: 160-168. 
  13.  Ummarino et al. Effect of magnesium alginate plus simethicone on gastro-oesophageal reflux in infants. JPGN 2015; 60: 230-235.

Gastroesophageal Reflux Disease

Cite this article as:
Li-Zsa Tan. Gastroesophageal Reflux Disease, Don't Forget the Bubbles, 2016. Available at:
https://doi.org/10.31440/DFTB.2754

A 5-month-old infant is brought into the Emergency Department by her parents because they feel she has been persistently irritable and back arching after feeds for the last month. They have looked up ‘infant reflux’ on the internet, but upright positioning and changing formulas several times has not made any difference. They are now intensely sleep-deprived and are keen for something to be done for her.

Examination reveals a cheerful baby girl with no signs of being unwell or irritable. She is gaining weight according to her centiles and is developmentally appropriate for age.

Bottom Line

  • Gastroesophageal reflux is a physiological phenomenon
  • Gastroesophageal reflux disease is when the child is symptomatic and results in complications such as poor weight gain
  • 67% of healthy infants have some form of reflux at 4 months of age
  • It is important to consider factors which may worsen reflux or contribute to reflux disease, such as hiatus hernia or eosinophilic esophagitis
  • Most infants will improve on transitioning to solids

What is gastroesophageal reflux disease?

Gastroesophageal reflux (GER) is a physiological phenomenon.  It is defined as the retrograde passage of gastric contents into the esophagus and is a normal physiological phenomenon that occurs in healthy children several times a day after meals and lasts <3 minutes. Reflux disease (GERD) occurs when it results in symptoms and complications.

Regurgitation is the passage of refluxed contents into the mouth. Vomiting is the expulsion of said contents from the mouth.

Primary GER results from a primary disorder of the upper GI tract.

Factors which influence incidence of GOR include: mastication, saliva secretion; swallowing; esophageal clearance; esophageal innervation and receptors; mucosal resistance; LES pressure and relaxation; abdominal esophagus; sphincter position; angle of His; gastric volume and accommodation; gastric emptying; gastric acid output; gastric acid feed buffering; feeding regimen: type frequency and volume; pepsin/trypsin/ bile salts; H. Pylori; intra abdominal pressure; genetic factors; environmental factors; posture; physical activity; sleep state; respiratory disease; medications.

Sometimes GER is protective: e.g. when the stomach is overdistended after a meal GER decompresses it.

Which mechanisms are in place to prevent or limit GERD?

The first line of defense against GERD is the lower esophageal sphincter (LES), and the diaphragmatic pinchcock and angle of His which physically limits the frequency and volume of gastric contents refluxing into the esophagus.

The second defense is esophageal clearance, when gravity and peristalsis remove the contents from the esophagus and secretions serve to neutralise the acid.

The third defence is the esophageal mucosal defence against luminal acid.

How does the LES work?

The LES is an extension of the circular muscle of the esophagus. The anti-reflux barrier consists of the LES and the crural portion of the diaphragm. The esophagogastric angle (or the angle of His) is the angle between the esophagus and the greater curvature of the stomach and is normally acute. It is a functional barrier, and its intraluminal pressure is greater than that of the stomach and esophagus. In adults, it is 3-6 cm long and has a pressure of 20 mmHg. (range 10-40 mmHg). An absolute pressure of <6 mmHg is required for GER.  In infants, the length is only a few millimeters. The LES relaxes 2.5 secs after the initiation of a swallow, and remains open during 10-12 secs until the food bolus passes through. LES pressure is decreased postprandially, and is also decreased by among others: the presence of fat in the duodenum, progesterone, cholecystokinin, glucagon, estrogen, nitric oxide, dopamine, nicotine, alcohol, mint and chocolate.

Most physiologic reflux episodes occur in relation to Transient LES Relaxations  (TLESRs) or when the LES tone adapts inadequately to changes in intra-abdominal pressure. TLESRs are induced by gastric distension and incomplete swallowing (normal mechanism for burping and belching). The larger the meal the more TLESRs, the more reflux episodes! Higher intragastric osmolarity and greater gastric secretory volume also contribute towards more TLESRs which may contribute to the efficacy of Proton Pump Inhibitors and H2 receptor antagonists in decreasing secretory gastric volume and reducing TLESRs.

The angle of His is usually acute. When the angle is obtuse, such as in hiatal hernias, this favors GER episodes

How does esophageal clearance help in reflux episodes?

This is influenced by peristaltic waves, gravity and saliva. Swallowed saliva contributes towards neutralising the pH of the refluxed acid. Swallowing itself stimulates antegrade peristalsis which clears the esophageal contents.

Esophageal mucosal resistance against injury to acid consists of:

  • Pre-epithelial: mucous layer, surface bicarbonate ion concentration, unstirred water layer
  • Epithelial defense: The esophagus is lined by moist, partially keratinized stratified squamous epithelium. Tight junctions act as a barrier to molecules passing from lumen to blood.

What are the symptoms of GERD?

GERD can range from minor symptoms such as regurgitation, heartburn and epigastric pain to more complicated disease such as erosive esophagitis or esophageal stricture. Hiatal hernia is the only endoscopic observation that predicts erosive esophagitis.

Reflux disease may also cause respiratory symptoms through micro aspiration. This may manifest as apneas, chronic coughs or chest infections, particularly in neurologically compromised infants.

How common is reflux or regurgitation in normal children?

In healthy infants, the prevalence of regurgitation has been reported at 50% at age 0-3 months, 67% at 4 months then declining to <5% by 10-12 months.  In a study of 509 healthy infants aged 0-11 months, as many as 73 physiologic reflux episodes per day was normal.

How do we investigate GERD?

pH monitoring

Intraluminal pH monitoring measures the frequency and duration of acid esophageal reflux episodes. A drop in intraesophageal pH <4.0 is considered an acid reflux episodes.

pH monitoring has limitations because of its inability to detect nonacidic bolus movement into the esophagus in particular in infants who are fed milk. This is problematic when evaluating reflux as a contributing factor towards respiratory disease in infants. Studies showed that in infants with apparent life-threatening events or apnea, 48% were nonacid. In a study of preterm infants with apnea, Magista et al found that 76% of reflux events were only weakly acidic (4

Impedence technique

Multichannel intraluminal impedance (MII) detects GER episodes based on changes in electrical resistance to the flow of an electrical current between 2 electrodes placed on the MII probe when a liquid, semisolid, or gas bolus moves between them. The combined pH and impedance monitoring are therefore able to detect reflux regardless of pH and provide symptom correlation with parental reports.

Endoscopy

Upper GI endoscopy can also be performed to look for esophagitis (macroscopic and histological changes) and gastritis. As this involves a general anaesthetic in children and has its own risks and complications, endoscopy is not usually a first line investigation for simple suspected reflux disease.

What are the pharmacological options to treat reflux disease?

Proton Pump Inhibitors are the most potent inhibitors of gastric acid secretion, and are superior to H2 Rreceptor antagonistis in healing esophagitis and maintaining remission.

What about other approaches?

There is no clear evidence that upright positioning post feeds helps limit reflux episodes in infants. In fact GER seems to occur most in seated upright position! Changing formulas or from breastfeeding to bottle feeding also does not appear to have an effect on reflux disease.

Thickening feeds under the supervision by a dietician may be useful.

It is important to rule out contributing factors such as concurrent infection in infants, congenital abnormalities such as a hiatus hernia and eosinophilic esophagitis and H pylori infection in older children.

Transitioning to solids usually marks clinical improvement in symptoms.

References

Vandenplas Y, Hasall E. Mechanisms of Gastroesophageal Reflux and Gastroesophageal Reflux Disease. Journal of Pediatric Gastroenterology and Nutrition 2006; 35: 119-136.

Colletti R, Di Lorenzo C. Overview of Pediatric Gastroesophageal Reflux Disease and Proton Pump Inhibitor Therapy. Journal of Pediatric Gastroenterology and Nutrition 2003; 37: S7 – S11.

Mousa HM, Rosen R, Woodley FW, Orsi M, Armas D, Faure C, Fortunato J, O’Connor J, Skags B, Nurko S. Esophageal Impedance Monitoring for Gastroesophageal Reflux. Journal of Pediatric Gastroenterology and Nutrition 2011;52:129 – 139