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SummaryGastro-esophageal reflux in childrenReference: Rybak A, Pesce M, Thapar N, Borrelli O. Int J Mol Sci 2017; 18: 1671. DOI: Introduction Gastro-esophageal reflux (GER) refers to the involuntary passage of gastric contents into the oesophagus. GER disease (GERD), a condition occurring when GER is associated with troublesome symptoms and/or complications, is one of the most common foregut symptoms across all paediatric age groups. Children with GERD may present with a wide range of gastro-esophageal and extra-oesophageal symptoms and potential complications.In infants, regurgitation is most commonly due to immaturity of the gastro-esphageal junction (GEJ) including a short distance and lack of the acute angle between the oesophagus and the gastric fundus (angle of His), where the food is initially stored after ingestion. Therefore, in this population, a conservative “educate-treat-test” approach to management is often appropriate, whereas overmedicalisation can lead to potential adverse consequences without any benefit of treatment. Nevertheless, there are young patients with potentially severe or persistent GERD who require further attention and treatment.Evolution and natural course of regurgitation in the paediatric age groupIn both adults and children, and especially infants, GER is a normal phenomenon that occurs many times a day. At 1 month of age, approximately 50% to 80% of infants experience one or more regurgitation or vomiting episodes per day, whereas the figure falls to approximately 10% by 1 year of age. In very young infants, regurgitation is exacerbated by a sole or predominant milk-based diet, the recumbent position and the immature GEJ. Infants with GERD and histological changes in the oesophagus are more likely to experience persistent symptoms, histological changes and complications of GERD in later childhood, adolescence and adulthood. Clinical presentation of GERD in the paediatric populationPhysiologic regurgitation (spitting or posseting), where gastric material refluxes up into the oesophagus and commonly into the oropharynx, is common in healthy infants, especially up to the age of four months. However, it is sometimes difficult to distinguish posseting from vomiting and therefore other symptoms and complications should be investigated. In children where there is a concern, a thorough history and examination is required. Symptoms that may indicate GERD or another serious pathology are listed in Table 1. Table 1. Symptoms suggestive of serious pathology and GERD in children Nonspecific symptoms suggesting serious pathologyGERD symptomsAge <2 yearsAge 3-17 yearsWeight loss or inadequate weight gainCrying and fussiness during and after feedingEmesis and/or haematemesisIrritabilityAnaemiaBad breath, gagging or choking at the end of feedingSleeping disturbance and frequent night wakingAbdominal painDental erosionDystonic neck posturing (Sandifer syndrome)DysphagiaApnoeaRespiratory symptoms (aspiration, recurrent pneumonia, chronic stridor, wheezing)Regurgitation and vomitingIrritability with feeds and in postprandial periodBack archingCryingFood refusalCoughApnoeaRegurgitation and vomitingHeartburnNauseaEpigastric pain/stomach acheCough and wheezingConditions that may predispose to severe, chronic GER include neurologic impairment, obesity, anatomical anomalies such as oesophageal atresia, hiatal hernia or achalasia, cystic fibrosis, lung transplantation, and a family history of GERD, Barrett’s oesophagus or oesophageal adenocarcinoma. GERD and food allergy The prevalence of food allergy in children is estimated at 6-8%, the most common of which in early childhood is cow’s milk protein allergy (CMPA). Regurgitation and vomiting are common manifestations of food allergy. However, GERD and CMPA may co-exist and the overall association between the two conditions may be as high as 55%. Children with comorbid food allergy may respond poorly to pharmacologic treatment for GERD, and there have been suggestions that alteration of gastric pH by treatments for GERD may predispose to food allergy.GERD and respiratory symptomsGERD may be associated with respiratory symptoms, including higher incidences of cough, sinusitis, laryngitis, asthma, pneumonia and bronchiectasis, although a direct relationship between GERD and at least some of these pathologies remains to be confirmed. Because cough and respiratory symptoms in children with GERD may be related to several different mechanisms, including aspiration of gastric contents, reflux-associated vagal reflexes and sensitisation of the central cough reflex, treatment based on acid suppressants may be less effective in this group of patients. GERD and extraintestinal symptomsConditions in which GERD might be suspected or related to high risk of GERD complications in paediatric patients are listed in Table 2. Current diagnostic guidelinesNo single test is sufficient to make a diagnosis of GERD in children, which generally requires a combination of clinical assessment and diagnostic tests. Therefore, in young children, rather than making a clinical diagnosis of GERD, the most important step is to discriminate between physiologic GER and pathological GERD, to identify individuals at high risk of severe GERD and worse outcome, and exclude other potential worrying conditions that can present with regurgitation and vomiting (red flag symptoms). These are listed in table 2.Table 2. Conditions indicating further investigation and managementGERD-promoting conditions with high risk of complications Red flag symptoms requiring further investigation Neurologic impairmentObesityHistory of repaired oesophageal atresiaHiatal herniaAchalasia (post treatment)Chronic respiratory disordersBronchopulmonary dysplasiaIdiopathic interstitial fibrosisCystic fibrosisHistory of lung transplantationPrematurityBilious vomitingGastrointestinal bleedingHaematemesisHaematocheziaConsistently forceful vomitingOnset of vomiting after 6 months of lifeFailure to thriveDiarrhoeaConstipationFeverLethargyHepatosplenomegalyBulging fontanelleMacro/microcephalySeizuresAbdominal tenderness or distensionDocumented or suspected genetic/metabolic syndromeThe diagnosis of GERD in older children and adolescents generally tends to be more straightforward, as they present with the more classical symptoms of heartburn and regurgitation. In older children with classical symptoms and no alarm signs, a ≥50% reduction in symptoms after 2 to 4 weeks trial of proton pump inhibitor (PPI) therapy is highly suggestive of GERD. Invasive tests should generally be avoided in children. However upper gastrointestinal endoscopy and biopsy may be useful where the potential benefits outweigh risks in children with alarm or refractory symptoms of GERD, to exclude complications and to rule out other conditions mimicking GERD. Routine upper gastrointestinal contrast studies are not recommended except where they might be indicated to exclude another pathology (e.g., achalasia, pyloric stenosis). pH-metry combined with multiple intraluminal impedance (MII) is considered the test of choice in children to evaluate the presence of reflux and association between GER and symptoms. TreatmentA. Infants and young children1.After exclusion of alarm symptoms (Table 2), the first-line management approach for GERD in infants and children aged younger than 2 years is conservative measures, including modification of posture and feeding. This may include modifying feeding frequency and volume, making sure that the intake of feed per kg body weight is appropriate, and keeping the child upright or in the prone position, especially after feeding. Where first-line management fails to improve symptoms, and especially where there is a history of personal or family atopy, a 2-4 weeks trial of cow’s milk protein-free diet is advised. If nonpharmacological approaches fail, the patient should be investigated with pH-impedance monitoring. 2. Pharmacological treatment is reserved for patients with objectively assessed GERD and increased oesophageal acid exposure. Anti-secretory drugs, including histamine-2 receptor antagonists (H2RAs) and PPIs are the medications of choice. PPIs have not been approved for use in infants younger than 1 year. Unlike PPIs, because they are associated with tachyphylaxis and tolerance, H2RAs should not be considered for long-term management of GERD. PPIs are more effective and heal erosive oesophagitis more rapidly than H2RAs and are not associated with tolerance when used long-term. They should be prescribed at the lowest effective dose and once daily. Lack of response to pharmacological treatment necessitates careful reassessment and reconsideration of GERD as the cause of symptoms. B. Older children and adolescents with GERDTreatment of GERD in older children is the same as recommended for adults. Lifestyle changes should be advised, including maintenance of a healthy weight, change in eating habits (to smaller frequent meals and avoiding large meals at bedtime) and avoidance of smoking and alcohol. Foods which may trigger GERD and which may be avoided include caffeine, acidic and spicy foods.In the absence of red flag symptoms a 4 to 6 weeks trial of PPI therapy is a reasonable first-line pharmacological approach for older children complaining of typical GERD symptoms. If symptoms improve, then treatment may be continued for 8 weeks and then tapered down. Patients with refractory symptoms those complaining of atypical symptoms should be referred for further investigation. ................
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