title sub title Gastro-oesophageal Reflux in Infants

EXPERT MONOGRAPH ISSUE 29

Introduction

‘Gastro-oesophageal Reflux’ (GOR) may be defined as ‘the regurgitation of gastric contents into the oesophagus’. It is extremely common in the first twelve months of life. Studies would suggest that it

affects about 50% of healthy babies born at term, and it should be considered to be a normal physiological process in most infants.1 It will typically resolve completely between twelve and eighteen months but often improves within the first year of age.2 If there are negative consequences associated with these episodes, such as respiratory symptoms, evolving oral aversion, slow weight gain or oesophagitis, then the term ‘gastro-oesophageal reflux disease’ (GORD) is used. However, in reality, GORD and GOR may be hard to separate clinically. In those babies whose GOR improves within the first twelve to eighteen months, there is no well-established link with adult-onset GORD.

In infants with recurrent, but uncomplicated regurgitation or ‘posseting’, the history and examination should be sufficient to make the diagnosis. Particular attention should be paid to a detailed feeding history, as overfeeding is a common explanation

Take Home Messages ` Gastro-oesophageal reflux affects about 50% of

healthy babies born at term, and should usually be considered to be a normal physiological process.

` Gastro-oesophageal reflux typically resolves between twelve and eighteen months, but often improves within the first year of age.

` Many studies of infants have suggested that PPIs are no better than placebo in the treatment of gastro-oesophageal reflux.

` Parental reassurance and education, as well as advice about patterns and amounts of feeding, are the mainstays of management.

` Allergy testing and the use of lactose-free milks are unhelpful if atopy is suspected, because the explanation in these infants will most commonly be non-IgE mediated cow’s milk allergy.

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DR RUPERT HINDS MBBS

Dr Rupert Hinds commenced working as Paediatric Gastroenterologist at Monash Medical Centre in March 2009. Prior to this he had worked in the UK as a consultant at King’s College Hospital and St Thomas’s Hospital in London from November 2004. He trained within his speciality in London including at Great Ormond Street Hospital. He manages children and adolescents with gastrointestinal problems and his clinical and research interests include nutrition, hepatology and inflammatory bowel disease. He is now head of the department of gastroenterology at Monash Children’s Hospital as well as Senior Lecturer in Paediatrics at Monash University.

This article discusses the General Practice management of gastro-oesophageal reflux in infants.

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^Dietary management.

IMPORTANT NOTICE: Breast milk is best for babies and provides ideal nutrition. Good maternal nutrition is important for preparation and maintenance of breastfeeding. Introducing partial bottle feeding could negatively affect breastfeeding and reversing a decision not to breastfeed is difficult. Professional advice should be followed on infant feeding. Infant formula should be prepared and used exactly as directed or it could pose a health hazard. The preparation requirements and cost of providing infant formula until 12 months of age should be considered before making a decision to formula feed.

Transitioning advice: A baby may better adapt when changes in feeding are introduced gradually. Alternating between the old and new feeds may ease the transition.

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title sub title

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for these symptoms. The presence of concerning signs or symptoms

suggests either GORD or another diagnosis (see Table 1).3 In GOR,

for the most part, no investigation or treatment will be required.

Parental reassurance and education about GOR, as well as advice

about patterns and amounts of feeding, are the mainstays of

management.

Several studies, both in Australia and elsewhere, have noted

very high prescribing rates of acid suppression for infants by

general practitioners, and in particular, a dramatic increase over

the last ten years in the use of proton pump inhibitors (PPIs). 4,5

The reasons for these increases may include more infants being

diagnosed by general practitioners as having GORD, the trialling

of acid suppression to determine if this improves symptoms, and

insufficient accessibility to well-evidenced guidelines and hence,

the lack of their use.

Many studies of infants have suggested that PPIs are no better than placebo in the treatment of reflux.6 These studies do have their limitations and clearly, there are babies who respond well to their use. However, given that these medications are not without potential side-effects, they should be used with caution. Increased rates of atopic illness, community acquired pneumonia and diarrhoeal illnesses have been described in association with PPI use in infants.7,8 It is important to establish that a baby does have any concerning signs before prescribing these medications. If treatment is unsuccessful, then discontinuation is important. Most authors would recommend a four-week trial of PPIs initially. Studies suggest that doses of at least 1mg/kg to 2mg/kg may be required in order to achieve prolonged acid suppression,9 although this does not always correlate with clinical improvement.

The use of thickeners (such as starch or carob bean extract) added to formula, or the use of so-called ‘anti-reflux formulas’ that thicken

Gastro-oesophageal Reflux in Infants

Table 1. ‘Red Flag’ Symptoms and Signs that Suggest Disorders Other than Gastro-oesophageal Reflux Disease.

(From the North American Society for Paediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Paediatric Gastroenterology,

Hepatology, and Nutrition).3

Symptoms and signs Remarks

GeneralWeight loss Suggesting a variety of conditions, including systemic infectionsLethargyFeverExcessive irritability/painDysuria May suggest urinary tract infection, especially in infants and young childrenOnset of regurgitation/vomiting >6 months or increasing/persisting > 12- 18 months of age

Late onset as well as symptoms increasing or persisting after infancy, based on natural course of the disease, may indicate a diagnosis other than GERD

NeurologicalBulging fontanel/rapidly increasing head circumference

May suggest raised intracranial pressure for example due to meningitis, brain tumor or hydrocephalus

SeizuresMacro/microcephalyGastrointestinalPersistent forceful vomiting Indicative of hypertrophic pyloric stenosis (infants up to 2 months old)Nocturnal vomiting May suggest increased intracranial pressureBilious vomiting Regarded as symptom of intestinal obstruction. Possible causes include Hirschsprung

disease, intestinal atresia or mid-gut volvulus or intussusceptionHematemesis

Suggests a potentially serious bleed from the esophagus, stomach or upper gut, possibly GERD associated, occurring from acid-peptic disease*, Mallory-Weiss tear† or reflux-esophagitis.

Chronic diarrhoea May suggest food protein-induced gastroenteropathy‡

Rectal bleeding

Indicative of multiple conditions, including bacterial gastroenteritis, inflammatory bowel disease, as well as acute surgical conditions and food protein-induced gastroenteropathy rectal bleeding‡ (bleeding caused by proctocolitis)

Abdominal distension Indicative of obstruction, dysmotility, or anatomic abnormalities

GERD = gastroesophageal reflux diseasc; NSAlD = non-stcroidal anti inflammatory drugs.

*Especially with NSAID use.

† Associated with vomiting.

‡ More likely in infants with eczema and/or a strong family history of atopic disease.

on exposure to gastric acid, have been shown in several studies to reduce the frequency of episodes of regurgitation.10 They would appear to be most effective in mild reflux. In infants with mild reflux, when neither pain nor insufficient weight gain are significant issues, a thickener is worth a trial.

Most of the treatments for GORD are based on guidelines rather than high grade evidence. It is useful to have a consistent and hierarchical approach for doctors to refer to (see Diagram), such as the ‘Paediatric Gastroesophageal Reflux Clinical Practice Guidelines’ from the joint paper3 of the North American Society for Paediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN), and the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN).

Diagram: The Management of the Symptomatic Infant

(From the North American Society for Paediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition).3

Some infants will have reflux symptoms as a consequence of food allergy, most commonly due to cow’s milk. These babies may have a family history of atopy, as well as personal history of other signs supportive of allergy. Examples of these include eczema, or lower gastrointestinal symptoms (such as diarrhoea), particularly in association with the passage of blood (‘allergic colitis’).11 Allergy testing is unhelpful in this setting, as is the use of lactose-free milks, because the explanation in these infants will most commonly be non-IgE mediated cow’s milk allergy. In this setting, it is worth considering exclusion of cow’s milk from the maternal diet in breast fed babies, or a two to four week trial of a protein hydrolysate or amino acid-based feed in babies who are formula-fed.

There is no reason to recommend dietary manipulation

in babies with GOR in the absence of allergy.

There appears to be some benefit in dietary manipulation for breast-feeding mothers with babies affected by colic, particularly a maternal hypoallergenic diet. However, there is no reason to recommend dietary manipulation in babies with GOR in the absence of allergy. Infants who have any concerning signs present, and/or who show a lack of response to simple measures (such as appropriate positioning, avoiding overfeeding), may need a referral to a paediatrician or paediatric gastroenterologist for further investigation. However, the vast majority of infants with GOR will have a self-limiting condition and explanation and reassurance should be sufficient management.

References

1. Davies I, Burman-Roy S, Murphy MS. Gastro-oesophageal reflux disease in children: NICE guidelines. BMJ 2015;g7703. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4707563/

2. Hegar B, Dewanti NR, Kadim M, Alatas S, Firmansyah A, Vandenplas Y, et al. Natural evolution of regurgitation in healthy infants. Acta Paediatr. 2009;98:1189-93. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1651-2227.2009.01306.x

3. Rosen R, Vandenplas Y, Singendonk M, Cabana M, DiLorenzo C, Gottrand F, 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 for Paediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2018 Mar;66(3):516-554. Available from: https://insights.ovid.com/crossref?an=00005176-201803000-00033

4. Kirby CN, Segal AY, Hinds R, Jones KM, Piterman L. Infant gastro-oesophageal reflux disease (GORD): Australian GP attitudes and practices. J Paediatr Child Health 2016 Jan;52(1):47-53. Available from: https://onlinelibrary.wiley.com/doi/full/10.1111/jpc.12983

5. Blank ML, Parkin L. National Study of Off-label Proton Pump Inhibitor Use Among New Zealand Infants in the First Year of Life (2005-2012). J Pediatr Gastroenterol Nutr. 2017 Aug;65(2):179-184. Available from: https://insights.ovid.com/crossref?an=00005176-201708000-00010

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Gastro-oesophageal Reflux in Infants

6. Van der Pol RJ, Smits MJ, van Wijk MP, Omari TI, Tabbers MM, Benninga MA. Efficacy of Proton-Pump Inhibitors in Children With Gastroesophageal Reflux Disease: A Systematic Review. Pediatrics 2011 May;127(5):925-35. Available from: http://pediatrics.aappublications.org/content/127/5/925

7. Safe M, Chan WH, Leach ST, Sutton L, Kei L, Krishnan U. Widespread use of gastric acid inhibitors in infants: Are they needed? Are they safe? World Journal of Gastrointestinal Pharmacology and Therapeutics 2016;7(4):531-539. Available from: https://www.wjgnet.com/2150-5349/full/v7/i4/531.htm

8. Mitre E, Susi A, Kropp LE, Schwartz DJ, Gorman GH, Nylund CM. Association Between Use of Acid-Suppressive Medications and Antibiotics During Infancy and Allergic Diseases in Early Childhood. JAMA Pediatr. 2018;172(6):e180315. Available from: https://jamanetwork.com/journals/jamapediatrics/article-abstract/2676167

9. Ward RM, Kearns GL. Proton Pump Inhibitors in Pediatrics: Mechanism of Action, Pharmacokinetics, Pharmacogenetics, and Pharmacodynamics. Paediatric Drugs 2013;15(2):119-131. Available from: https://link.springer.com/article/10.1007%2Fs40272-013-0012-x

10. Horvath, A. Dziechciarz P, Szajewska H. The effect of thickened-feed interventions on gastroesophageal reflux in infants: systematic review and meta-analysis of randomized, control trials. Paediatrics, Dec. 122(6):e1268-77.Erratum in Pediatrics. 2009 Apr; 123(4):1254. Available from: http://pediatrics.aappublications.org/content/122/6/e1268

11. Nielsen RG, Bindslev-Jensen C, Kruse-Andersen S, Husby S. Severe gastroesophageal reflux disease and cow milk hypersensitivity in infants and children: disease association and evaluation of a new challenge procedure. J Pediatr Gastroenterol Nutr. 2004 Oct; 39(4):383-91.

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Gastro-oesophageal Reflux in Infants

Editorial TeamMedical Editors: Dr Linda Calabresi, Dr Vivienne Miller Managing Editor: Karina Lozada Editorial Assistant: Neil Harris Commissioning Editor: Dr Ramesh Manocha