Gastroesophageal reflux is the movement of gastric contents into the esophagus. It may be physiologic or pathologic. When pathologic, it is also known as gastroesophageal reflux disease (GERD). GERD is reflux that causes complications such as irritability, respiratory problems, and poor growth. Diagnosis is often made clinically and could include a trial of dietary change or in some instances a trial of acid-suppressing medication, but some infants require an upper gastrointestinal contrast x-ray series, use of esophageal pH and impedance probes, and sometimes endoscopy. Gastroesophageal reflux requires only reassurance. Treatment of GERD begins with modification of feeding and after-feeding positioning; some infants require acid-suppressing medications such as proton pump inhibitors or H2 blockers. Antireflux surgery is needed only for the most severe cases.
Gastroesophageal reflux occurs in almost all infants, manifesting as wet burps after feeding and/or spit-ups (the non-forceful return of milk or gastric contents to the esophagus, pharynx, and mouth). The 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), ie, reflux that causes complications, is much less common.
Etiology of Reflux in Infants
The most common cause of GERD in infants is similar to that of GERD in older children and adults:
The lower esophageal sphincter (LES) fails to prevent reflux of gastric contents into the esophagus.
LES pressure may transiently decrease spontaneously (inappropriate relaxation), which is the most common cause of reflux, or after exposure to agents such as cigarette smoke or caffeine (in beverages or breast milk). The baseline esophageal pressures is normally negative, whereas the baseline stomach pressure is positive. 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. For example, the pressure gradient may increase in infants who are overfed (an excessive volume of food causes a higher gastric pressure) and in infants who have chronic lung disease (lower intrathoracic pressure increases the gradient across the LES) and may increase because of positioning (eg, sitting increases intra-abdominal and gastric pressure).
Other causes include food allergies, most commonly cow's milk protein 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, , galactosemia, hereditary fructose intolerance) or an anatomic abnormality (such as pyloric stenosis or malrotation).
Complications of GERD
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, pharynx, 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 lead to esophageal stricture and food refusal. Laryngeal and airway irritation may cause respiratory symptoms such as tachypnea, wheezing, or stridor. Aspiration may cause recurrent pneumonia.
Symptoms and Signs of Reflux in Infants
The main symptom of gastroesophageal reflux is
Frequent regurgitation (spitting up, wet burps)
Caregivers often refer to this spitting up as vomiting, but it is not actually vomiting because it is not due to gastric 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. GERD can cause iron deficiency anemia.
Diagnosis of Reflux in Infants
Clinical evaluation
Typically upper gastrointestinal (GI) series
Sometimes esophageal pH measurement or endoscopy
Infants who have effortless spit-ups, who are growing normally, and who have no other symptoms (sometimes referred to as "happy spitters") have physiologic 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, iron deficiency anemia, and abnormal/delayed development or neurologic manifestations (eg, bulging fontanelle, seizures, hypotonia, hypertonicity). Infants with such findings require prompt evaluation. Bilious emesis in an infant is a medical emergency because it may be a symptom of intestinal malrotation, which leads to a 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) by doing, for example, pyloric ultrasonography to assess for pyloric stenosis or brain imaging to assess for causes of elevated intracranial pressure (eg, brain tumor).
Irritability, a common symptom of GERD, 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 but no severe complications may be given a therapeutic trial of acid-reducing medication for GERD. Improvement or elimination of symptoms suggests that GERD is the diagnosis. If the infant continues to improve, other testing is likely unnecessary. Infants with suspected food allergy 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 do not respond to a therapeutic trial, or who present with signs of complications of GERD (eg, iron deficiency anemia) may require further evaluation. Typically, an upper GI contrast x-ray 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, and thus are suspected of having 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 and is needed because some patients may be still affected by reflux even when the acid is properly buffered by medication and the refluxate is not acidic.
Upper GI endoscopy and biopsy are sometimes done to help diagnose infection or food allergy and to 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.
Treatment of Reflux in Infants
Modifying feedings
Positioning
Sometimes acid-suppressive therapy
Rarely surgery
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 do require treatment, typically beginning with conservative measures.
Modifying feedings
Thickened feedings
Smaller, more frequent feedings
Sometimes hypoallergenic formula
For breastfed infants, changing the mother's diet
As a first step, most clinicians recommend reviewing proper feeding techniques (eg, volume of feedings, proper burping, positioning); if correction of technique is not enough, feedings can be thickened 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 often must be enlarged to allow adequate flow.
Providing smaller, more frequent feedings helps keep the pressure in the stomach down by giving the stomach less volume and the chance for better emptying and often 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 (30 to 60 mL) 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 (hydrolyzed protein formulas) can even be helpful for infants who do not have a food allergy by improving gastric emptying.
Cow's milk protein allergy can occur in breastfed infants and can be a cause of GERD. A trial of placing the mother on a strict cow's milk protein–free diet for several weeks may be helpful. If symptoms do not respond, referral to a gastroenterologist is recommended.
All children should be kept away from caffeine and tobacco smoke.
Positioning
After feeding, infants are kept in an upright, non-seated 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) and other sleep-related death.
Acid-suppressive therapy
Three classes of drugs have been used in infants with GERD who do not respond to feeding modification and positioning:
Proton pump inhibitors (PPI)
Promotility medications
The North American and European specialty societies recommend that infants and children with GERD unresponsive to feeding and positioning modifications be given a proton pump inhibitor (PPI) (1). If PPIs are unavailable or cannot be used, an H2 blocker can be given. These medications are not
baclofen may be tried before doing surgery on infants who are unresponsive to acid-blocking medications (1). Of the other agents, bethanechol, domperidone, and metoclopramide2
Surgery
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/vomiting also may have to be corrected surgically.
Treatment references
1. Rosen R, Vandenplas Y, Singendonk M, 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 Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr 66(3):516-554, 2018. doi: 10.1097/MPG.0000000000001889
2. Tillman EM, Smetana KS, Bantu L, Buckley MG: Pharmacologic Treatment for Pediatric Gastroparesis: A Review of the Literature. J Pediatr Pharmacol Ther 21(2):120-32, 2016. doi: 10.5863/1551-6776-21.2.120
Key Points
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), iron deficiency anemia, or impaired growth.
Clinicians recommend prescribing a therapeutic trial of feeding modifications and after-feeding positioning if GERD symptoms are mild.
Consider testing with an upper gastrointestinal contrast x-ray series, gastric emptying scan, esophageal pH probes, or endoscopy for infants with more severe GERD symptoms or for whom a therapeutic trial is not helpful.
If the response to therapy is not satisfactory, consider gastroparesis and measure gastric emptying using a gastric emptying scan.
Acid suppression with a proton pump inhibitor or H2 blocker may help infants with significant GERD.
Most infants with GERD respond to medical therapy, but a few require surgical therapy.
More Information
The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition: Pediatric gastroesophageal reflux clinical practice guidelines (2018)
