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.
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.
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.
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.
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, 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?
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 non acid. In a study of preterm infants with apnea, Magista et al found that 76% of reflux events were only weakly acidic (4<pH<7)
Multichannel intraluminal impedence (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 impedence monitoring is therefore able to detect reflux regardless of pH and provide symptom correlation with parental reports.
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.
Vandenplas Y, Hasall E. Mechanisms of Gastroesophageal Reflux and Gastroesophageal Reflux Disease. Journal of Pediatric Gastroenterology and Nutrition 2006; 35: 119-136.
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