Gastroesophageal Reflux in Infants
(Gastroesophageal Reflux Disease [GERD])
Gastroesophageal reflux occurs in almost all infants, manifesting as wet burps after feeding. Incidence of gastroesophageal reflux increases between 2 months and 6 months of age (likely due to an increased volume of liquid at each feeding) and then starts to decrease after 7 months. Gastroesophageal reflux resolves in about 85% of infants by 12 months and in 95% by 18 months. Gastroesophageal reflux disease (GERD), that is, reflux that causes complications, is much less common.
The most common cause of GERD in infants is similar to that of GERD in older children and adults:
LES pressure may transiently decrease spontaneously (inappropriate relaxation), which is the most common cause of reflux, or after exposure to cigarette smoke and caffeine (in beverages or breast milk). The esophagus is normally at a negative pressure, whereas the stomach is at a positive pressure. The pressure in the LES has to exceed that pressure gradient to prevent reflux. Factors that increase this gradient or decrease the pressure in the LES predispose to reflux. The pressure gradient may increase in infants who are overfed (excessive food causes a higher gastric pressure) and in infants who have chronic lung disease (lower intrathoracic pressure increases the gradient across the LES) and by positioning (eg, sitting increases gastric pressure).
Other causes include food allergies, most commonly cow's milk allergy. A less common cause is gastroparesis (delayed emptying of the stomach), in which food remains in the stomach for a longer period of time, maintaining a high gastric pressure that predisposes to reflux. Infrequently, an infant can have recurrent emesis that mimics GERD because of a metabolic disease (eg, urea cycle defects, galactosemia, hereditary fructose intolerance) or an anatomic abnormality (such as pyloric stenosis or malrotation).
Complications of GERD are due mainly to irritation caused by stomach acid and to caloric deficit caused by the frequent regurgitation of food.
Stomach acid may irritate the esophagus, larynx, and, if aspiration occurs, the airways. Esophageal irritation may decrease food intake as infants learn to avoid reflux by eating less. Significant esophageal irritation (esophagitis) may cause mild, chronic blood loss and esophageal stricture. Laryngeal and airway irritation may cause respiratory symptoms. Aspiration may cause recurrent pneumonia.
The main symptom of gastroesophageal reflux is
Caregivers often refer to this spitting up as vomiting, but it is not because it is not due to peristaltic contractions. The spit ups appear effortless and not particularly forceful.
Infants in whom reflux has caused GERD have additional symptoms, such as irritability, feeding refusal, and/or respiratory symptoms such as chronic recurrent coughing or wheezing and sometimes stridor. Much less commonly, infants have intermittent apnea or episodes of arching the back and turning the head to one side (Sandifer syndrome). Infants may fail to gain weight appropriately or, less often, lose weight.
Infants who have effortless spit ups, who are growing normally, and who have no other symptoms (sometimes referred to as "happy spitters") have gastroesophageal reflux and require no further evaluation.
Because spitting up is so common, many infants with serious disorders also have a history of spitting up. Red flags that infants have something other than reflux include forceful emesis, abdominal distention, emesis containing blood or bile, fever, poor weight gain, blood in the stools, persistent diarrhea, and abnormal development or neurologic manifestations (eg, bulging fontanelle, seizures). Infants with such findings require prompt evaluation as described elsewhere in THE MANUAL. Bilious emesis in an infant is a medical emergency because it may be a symptom of malrotation of the intestines and midgut volvulus.
Infants with repeated, forceful emesis should not be presumed to have reflux and should be evaluated for other disorders (see Nausea and Vomiting in Infants and Children) such as with pyloric ultrasonography to assess for pyloric stenosis or brain imaging to assess for causes of elevated intracranial pressure (eg, brain tumor).
Irritability has many causes, including serious infections and neurologic disorders, which should be ruled out before concluding that the irritability is caused by GERD.
Infants who have symptoms consistent with GERD and no severe complications may be given a therapeutic trial of medical therapy for GERD; improvement or elimination of symptoms suggests GERD is the diagnosis and that other testing is unnecessary. Infants can also be given an extensively hydrolyzed (hypoallergenic) formula for 2 to 4 weeks to see whether the symptoms are caused by a food allergy.
Infants who fail to respond to a therapeutic trial, or who present with signs of complications of GERD, may require further evaluation. Typically, an upper GI series is the first test; it may help diagnose reflux and also identify any anatomic GI disorders that cause regurgitation. Finding barium reflux into the mid or upper esophagus is much more significant than seeing reflux into only the distal esophagus. For infants with regurgitation hours after eating, who may have gastroparesis, a liquid gastric emptying scan may be appropriate.
If the diagnosis remains unclear or there is still a question of whether reflux is actually the cause of symptoms such as coughing or wheezing, a pediatric gastroenterologist may do tests using esophageal pH or impedance probes (see Ambulatory pH Monitoring). Caregivers record the occurrence of symptoms (manually or by using an event marker on the probe); the symptoms are then correlated with reflux events detected by the probe. A pH probe can also assess the effectiveness of acid-suppression therapy. An impedance probe has the ability to detect nonacid reflux as well as acid reflux.
Upper GI endoscopy and biopsy are sometimes done to help diagnose infection or food allergy and detect and quantify the degree of esophagitis. Laryngotracheobronchoscopy may be done to detect laryngeal inflammation or vocal cord nodules. Previously, the presence of lipid-laden macrophages and/or pepsin in bronchial aspirates was thought to help diagnose reflux and aspiration. However, lipid-laden macrophages are now recognized to be of no benefit, and pepsin measurement has low sensitivity and specificity.
For infants with gastroesophageal reflux, the only necessary treatment is to reassure caregivers that the symptoms are normal and will be outgrown. Infants with GERD require treatment, typically beginning with conservative measures.
As a first step, most clinicians recommend thickening feedings, which can be done by adding 10 to 15 mL (1/2 to 1 tbsp) of rice cereal to 30 mL of formula. Thickened formula seems to reflux less, particularly when the infant is kept in an upright position for 20 to 30 minutes after feeding. Thickened formula may not flow through the nipple properly, so the nipple orifice may need to be cross-cut to allow adequate flow.
Providing smaller, more frequent feedings helps keep the pressure in the stomach down and minimizes the amount of reflux. However, it is important to maintain an appropriate total amount of formula per 24-hour period to ensure adequate growth. In addition, burping the infant after every 1 to 2 oz can help decrease gastric pressure by expelling the air the infant is swallowing.
If conservative measures fail, a hypoallergenic formula should be used in formula-fed infants for 2 to 4 weeks because these infants may have a food allergy. Hypoallergenic formula can even be helpful for infants who do not have a food allergy by improving gastric emptying. All children should be kept away from caffeine and tobacco smoke.
After feeding, infants are kept in an upright, nonseated position for 20 to 30 minutes (sitting, as in an infant seat, increases gastric pressure and is not helpful).
For sleeping, left lateral positioning and elevation of the head of the crib are no longer recommended because of safety concerns. Regardless of the presence of reflux, the only recommended sleeping position for infants is supine, which has been shown to reduce the risk of sudden infant death syndrome (SIDS).
Three classes of drugs have been used in infants with GERD who do not respond to feeding modification and positioning:
A 2018 consensus practice guideline from North American and European specialty societies recommends that infants and children with GERD unresponsive to feeding and positioning modifications be given a proton pump inhibitor (PPI). If PPIs are unavailable or cannot be used, an H2 blocker can be given. These drugs are not recommended simply for treatment of crying/distress and/or visible regurgitation. A typical PPI regimen is lansoprazole 2 mg/kg orally once a day. For infants who respond, the drug is continued for several months and then tapered and stopped.
Promotility (prokinetic) drugs are theoretically beneficial by speeding gastric emptying and thus reducing the volume of gastric contents and amount of time the contents are present to be refluxed. Possible agents include baclofen, bethanechol, cisapride, domperidone, erythromycin, and metoclopramide. The consensus practice guideline recommends against use of promotility drugs as first-line treatments, although baclofen may be tried before doing surgery on infants who have failed acid-blocking drug treatment. Of the other agents, bethanechol, cisapride, domperidone, and metoclopramide are not recommended because of their potential for adverse effects. For infants who have gastroparesis, erythromycin may be used. Some clinicians are using amoxicillin/clavulanate for its promotility properties, but this is not included in the consensus guidelines.
Infants with severe or life-threatening complications of reflux that are unresponsive to medical therapy can be considered for surgical therapy. The main type of antireflux surgery is fundoplication. During this procedure, the top of the stomach is wrapped around the distal esophagus to help tighten the lower esophageal sphincter. Fundoplication can be very effective at resolving reflux but has several complications. It can cause pain when infants vomit (eg, during acute gastroenteritis), and if the wrap is too tight, infants may have dysphagia. If dysphagia occurs, the wrap can be dilated endoscopically. Some anatomic causes of reflux also may have to be corrected surgically.
Most reflux in infants does not cause other symptoms or complications and resolves spontaneously by age 12 to 18 months.
Gastroesophageal reflux disease (GERD) is diagnosed when reflux causes complications such as esophagitis, respiratory symptoms (eg, cough, stridor, wheezing, apnea), or impaired growth.
Prescribe a therapeutic trial of feeding modifications and after-feeding positioning if GERD symptoms are mild.
Consider testing with an upper gastrointestinal series, gastric emptying scan, esophageal probes, or endoscopy for infants with more severe GERD symptoms or for whom a therapeutic trial is not helpful.
Acid suppression with a PPI or H2 blocker may help infants with significant GERD.
Most infants with GERD respond to medical therapy, but a few require surgical therapy.
Pediatric gastroesophageal reflux clinical practice guidelines from the Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition