Case Scenario

A two-month-old full-term, formula-fed infant presents for the first well-child examination since the newborn period. The child’s parents are concerned because the infant spits up at least four times per day. The contents resemble curdled milk (nonbloody, nonbilious), and the spit-up is non-projectile. The infant is gaining weight and following the 75% weight curve for age. The parents report that the infant gets fussy every day around 5:00 p.m. The mother has a 10-year-old child who was prescribed antireflux medications around this age and is wondering if these medications should be prescribed for her infant.

Clinical Commentary

Gastroesophageal reflux, or the regurgitation of gastric contents, occurs in up to two-thirds of healthy infants.¹ Gastroesophageal reflux begins approximately two to three weeks after birth and peaks between four and five months of age. Physiologic reasons for increased reflux in infants include an underdeveloped angle of His (the angle between the greater curvature of the stomach and esophagus), inadequate gastric accommodation, prolonged supine positioning, and a liquid diet. Symptoms usually resolve completely by one year of age.² By one year of age, muscles in the lower esophagus strengthen, the esophagus lengthens, and esophageal and intestinal motility coordination improves. Normal developmental milestones, such as head control, sitting up, and the introduction of solid food, help improve gastroesophageal reflux symptoms. Infants who experience reflux without discomfort or other problems are sometimes referred to as “happy spitters.”

The North American Society for Pediatric Gastroenterology, Hepatology & Nutrition has developed guidelines to help clinicians differentiate gastroesophageal reflux from gastroesophageal reflux disease (GERD).³ The guidelines define GERD as reflux that involves pain, poor weight gain, or mucosal injury on upper endoscopy.^3,4 Although changes in weight and endoscopy findings can be evaluated objectively, the assessment of pain (e.g., crying, grimacing, arching) is subject to parent and clinician interpretation. It can be challenging for parents and clinicians to distinguish manifestations of GERD-related pain from other conditions, such as dyschezia or colic.⁵ Clinicians can feel pressure to treat gastroesophageal reflux with medications even though it is a benign condition. One-fourth of parents of infants with gastroesophageal reflux perceive the symptoms as troublesome.¹ Clinicians are subject to commission bias, which is the tendency to act even when inaction leads to an identical or better outcome.⁶

ANTIREFLUX MEDICATIONS

Clinicians may prescribe histamine H₂ receptor antagonists (H2RAs) or proton pump inhibitors (PPIs) to reduce the perceived discomfort associated with gastroesophageal reflux. These medications decrease the acidity in gastric contents but do not improve regurgitation in the absence of GERD.^3,7,8 In many cases, treatments have not been proven more effective than placebo.^8–10

Although the medical community once viewed H2RAs and PPIs as benign medications, there are now concerns about the short- and long-term effects.^11,12 In the short term, these medications have been linked to necrotizing enterocolitis and sepsis in preterm and low-birth-weight infants.^13–20 Full-term and normal-birth-weight infants are at increased risk of lower respiratory tract and gastrointestinal infections.^8,21 In the long term, there is a link between acid suppression and alteration in the microbiome and higher rates of allergies, asthma, and obesity.^22–25 PPI and combination H2RA/PPI therapy have been linked to a higher risk of fractures in children, with earlier initiation and longer duration of treatment associated with the highest risk.²⁶ Patients treated with acid-suppressing medication incur more than $2,300 in additional health care costs compared with healthy patients.²⁷

CHOOSING WISELY

The American Academy of Pediatrics and Choosing Wisely have recommended against the use of antireflux medications for infants with reflux that is effortless, painless, and not affecting growth.^12,28 Antireflux medications are listed in the Choosing Wisely top five lists from the American Academy of Pediatrics section on perinatal medicine and the Society of Hospital Medicine.^12,28

ALTERNATIVE TREATMENT

Because some parents perceive gastroesophageal reflux as problematic, nonpharmacologic alternatives may be offered. Burping the infant at regular intervals, offering smaller and more frequent feedings, and keeping the infant upright for 30 minutes after a feed may be helpful. However, it can be logistically challenging to keep an infant upright for an extended period when feeding every two to four hours.

Parents may consider thickening formula or expressed breast milk with an infant oat cereal. Rice cereal was historically used for this purpose, but concerns about arsenic contamination have limited its use.²⁹ Thickening has been shown to decrease the frequency of reflux episodes.³⁰ Adding a thickener to formula increases the caloric density of the milk, which can be helpful in underweight infants but can cause excessive weight gain in normal-weight and over-weight infants. The effort required to thicken expressed breast milk instead of breastfeeding may not be worthwhile because of the benign nature of gastroesophageal reflux. Antireflux formulas that are made with rice starch work by becoming more viscous once they encounter stomach acid. Xanthan gum (e.g., SimplyThick) has been associated with necrotizing enterocolitis and is not recommended as a thickener for infants.³¹

Patient Perspective

Overmedication is a cause for concern, especially when it affects the youngest and most vulnerable. Almost all babies spit up (in our experience, at least), but new parents may be alarmed when their baby exhibits symptoms they did not expect. Parents habituated to television advertisements or those who, as in this scenario, experienced antireflux medications freely given to infants in years gone by may reasonably expect a pharmacologic solution. Parents want the best for their children.

Many parents quickly retract their request for a prescription when advised that antireflux medications have not shown effectiveness for infants and could increase the risk of infections, bone fractures, and other unknown effects. But even new parents know their children best, and their concerns should never be taken lightly. Parents often crave information; clear and detailed explanations can go a long way toward creating a positive relationship between the family and physician. Families are more likely to feel heard and supported if they can leave the office with a plan to help control reflux episodes, an understanding that this is a common and usually transitory phase of infant development, and knowledge of signs that could indicate a more serious condition and should precipitate a return visit.

Resolution of Case

A thorough history finds that the infant’s crying is not associated with the spit-up episodes and tends to occur in the afternoons and evenings. The likely cause is colic, which peaks around six weeks of life. The parents are reassured that their child is healthy with normal growth and development, and that reflux is common and often self-resolves. The parents are informed that frequent burping, upright positioning, and thickened feedings may decrease the frequency of spit-ups, and antireflux medications, such as H2RAs or PPIs, are not needed, do not prevent spit-ups, and may cause short- and long-term health problems.