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Separating Fact from Fiction in Pediatric Medicine: Infant Gastroesophageal Reflux

By now, regular SBM readers should be aware of the Choosing Wisely initiative. Just in case, Choosing Wisely is a campaign developed by the ABIM Foundation to bring together experts from a variety of medical specialties in order to identify common practices that should be questioned by patients and providers, if not outright discontinued. Their ultimate goal was not to establish treatment guidelines or dictate care, but to foster discussion. As I’ve written about in a prior post on the overuse of antibiotics in pediatrics, it doesn’t appear to have caught on. I routinely ask colleagues, residents and students if they are aware of it, and am frequently disappointed by their response.

The American Academy of Pediatrics issued a list of five questionable practices back in February of 2013 and I loved it. All five are important:

  1. Stop treating viruses with antibiotics
  2. Stop prescribing and recommending cough and cold medicines for young children
  3. Stop routine use of CT scans for minor head injuries
  4. Stop routine use of neuroimaging for simple febrile seizures
  5. Stop routine use of CT scans for abdominal pain
  6. While reviewing current evidence-based guidelines on managing gastroesophageal reflux in children for this post, I was surprised to find that in March of this year the AAP had released an additional five questionable practices for Choosing Wisely:

  7. Stop high-dose steroids for the prevention or treatment of bronchopulmonary dysplasia in preterm infants
  8. Stop blindly ordering food allergy screening panels without taking medical history into account
  9. Stop prescribing acid blockers and motility agents for physiologic reflux
  10. Stop surveillance cultures for screening and treatment of asymptomatic bacteriuria
  11. Stop routine use of infant home apnea monitors to prevent SIDS

Naturally, I took number 8 as a sign that I was on the right track.

The problem of gastroesophageal reflux comes up frequently in pediatric medicine, especially during the first few months of a child’s life. Early in our residency training we learn about the existence of the so-called “happy spitter”, the baby who spits up for no apparent reason and without apparent symptoms. We learn to educate worried parents about this phenomenon, jokingly pointing out how this is usually a laundry problem rather than a medical problem. We are taught the signs and symptoms of gastroesophageal reflux disease (GERD) in children of varying ages, the behavioral modifications that might ameliorate the condition and the potential pharmacological and surgical interventions sometimes necessary in severe cases. While reflux is extremely common in babies, GERD is not.

But, as is often the case, something goes wrong after residency. Too many of us begin to alter our approach because of the influence of practicing in the real world and of common hardwired errors in how we interpret reality. Overuse of prescription medications, unnecessary formula hopping and potentially unsafe recommendations on sleep positioning are unfortunately widespread. Our pharmaceutical interventions carry significant risk with little evidence of benefit for most patients, and the combination of stress and a general lack of understanding of the pathophysiology of reflux leads to many parents seeking alternative treatments. Practitioners of irregular medicine are of course more than happy to claim expertise and success in treating what is largely a self-limited condition.

What is gastroesophageal reflux?

Gastroesophageal reflux, henceforth referred to simply as reflux, occurs when stomach contents pass into the esophagus. It is incredibly common in early infancy but occurs throughout the lifespan and is considered a normal aspect of our physiology. It is arguable that 100% of young infants have multiple episodes of reflux daily, with many being clinically silent because the stomach contents only ascend partially up the esophagus and are quickly cleared. Even when the bolus ascends to the oral cavity, infants often simply swallow it back down and caregivers are none the wiser.

But virtually 100% of children will have at least one episode of actual regurgitation (“spitting up”) at some point in early infancy, with most having several. Half of infants under 3 months of age will have a daily episode of regurgitation, and by 4 months of age, which tends to be the peak of incidence and severity, this will occur in two thirds. Incidence drops off steadily after 4 months, with only 5% of infants having daily regurgitation at one year of life. It is very uncommon for children over 18 months of age to still regurgitate, and even less so for them to start spitting up after that age.

Although in most children reflux is an uncomplicated and physiologic (normal) process, there are a variety of disease states and anatomical abnormalities that promote reflux or cause symptoms which might be confused for it. It is always very important for a child’s pediatrician or family doctor to evaluate them for any red flags such as bile-stained or bloody vomit, or vomiting that is consistently forceful in nature. Many neurologic conditions and systemic illnesses can result in either pathologic vomiting or increase the likelihood of severe symptomatic reflux in children of all ages.

Why is reflux so common in babies?

A convergence of physiology and anatomy occurs at the distal end of the esophagus which acts to limit retrograde movement of stomach contents. When not swallowing, the muscular tissue of the esophagus at the entry point into the stomach tends to remain contracted. This entry point occurs just beneath the diaphragm in most individuals, the pressure from which adds to the increased resting tone of the esophageal muscle. The angle of entry of the esophagus into the stomach is rather acute as well, leading to it being squeezed shut by a distended stomach.

In healthy people of all ages, but particularly infants, the normal high resting tone of the lower esophageal sphincter relaxes for no apparent reason during the time between feeds. This can occur upwards of 30 times each day in a young infant, likely because of general immaturity of many such processes. Older children and adults have the benefit of gravity when these events occur. When upright, all that tends to escape is gas in the form of a burp. But an infant is supine for significant periods of time and the entry point of the esophagus into the stomach is frequently covered with liquid breast milk or formula.

Young infants consume their entire caloric intake in the form of liquid, often taking in as much as 180 milliliters per kilogram each day. For a 75 kg adult that would equal just under 14 liters of fluid. And young infants feed much more frequently than older children and adults, so their stomachs are very full much of the day. Try drinking a couple of liters of milk every 3-4 hours. This extreme gastric distention increases the likelihood of transient relaxation events. Add to all this the fact that the angle of esophageal entry into the stomach is more obtuse than in older kids and adults, which is why distention of the stomach doesn’t squeeze it shut as effectively.

What is physiologic reflux, and more importantly, what isn’t it?

Physiologic reflux, even when the episodes of regurgitation are frequent, doesn’t result in weight loss or significant difficulty with feeds. The episodes of spitting up are typically not associated with crying or unusual movements, and there usually are not any red flags for a more concerning disease process. Reassurance really is the best approach as this almost always resolves on its own within a few months.

But parents will sometimes report that their otherwise “happy spitter” with physiologic reflux has difficulty sleeping or persistent nasal congestion. More common are complaints of general fussiness or irritability which have already been attributed to reflux in the minds of the caregivers. These symptoms, however, are very unlikely to be related to reflux, a revelation that I find most parents and often other medical professionals have great difficulty accepting.

As you can probably imagine with such subjective concerns, there are many different potential causes of apparent discomfort in an infant ranging from the benign to the life-threatening. And as with infant colic, psychosocial factors must always be taken into account since they can alter parental perception of reality and exacerbate, if not cause entirely, the subjective symptoms being attributed to reflux in a baby. With colic, how long and how severe the episodes of crying truly are is often warped by parental stress and sleep deprivation. How many times each day that a baby regurgitates, and the degree of fussiness during or between those episodes, is no different. Few parents are going to keep a detailed reflux diary.

There really is little in the way of solid evidence linking reflux to pain in the overwhelming majority of babies. Parents and physicians have historically made assumptions based on adult data and “experience”, but a review of the literature reveals a different story. Most studies have not supported the connection, even those that evaluate infants using monitoring of esophageal pH. And the best placebo-controlled studies have found that medications which decrease the production of gastric acid have no better impact than placebo on parental perception of infant irritability.

There are conservative and low risk behavioral and dietary interventions that can be recommended when reassurance fails or when parental quality of life is significantly affected. Unfortunately, these are often only discussed in the mildest cases of reflux. And prescription medications are far too quickly recommended despite a lack of evidence of efficacy, hence their inclusion on the AAP Choosing Wisely list.

The vast majority of episodes of reflux are very brief, and even if there is a significant acid component it is quickly cleared by the esophagus. And a layer of mucous is typically present which protects the esophageal lining from any injury. These normal protective mechanisms can be overwhelmed, particularly in children with neurological and anatomical risk factors, but significant symptoms related to reflux can occur, although uncommonly, even in otherwise-healthy babies leading to a diagnosis of GERD.

What is gastroesophageal reflux disease?

True GERD can present in a variety of ways depending on the age of the child, but is notoriously difficult to diagnose with any real certainty in a baby. An infant, for instance, doesn’t have the capacity to describe their heartburn. In babies, symptoms traditionally attributed to GERD are difficulty feeding or even feeding refusals, frequent episodes of arching of the back and crying that occur when a child regurgitates, and poor weight gain. In reality, GERD is an uncommon cause of these problems in infants, and many children are diagnosed with GERD simply based on parental descriptions of what the child does and the assumption that their behaviors are a result of pain from acid induced injury to the esophagus.

When babies fail to thrive, typically evident in poor or absent weight gain, GERD should be a diagnosis of exclusion because the most common causes are psychosocial in nature and there are a variety of other medical conditions that need to be ruled out with a thorough history taking, physical exam and targeted diagnostic testing. Respiratory symptoms that are often attributed to GERD include apparent life-threatening events (blue baby, trouble breathing, terrified caregiver), cough, recurrent pneumonia and wheezing. While certainly possible, persistence of these issues requires investigation for other causes, recurrent viral respiratory infections being considerably more common than true GERD in a young infant.

There are a few diagnostic modalities used to evaluate children with suspected GERD or some other condition presenting in a similar fashion. These techniques are infrequently used in infants, however, because of either poor sensitivity and specificity or their invasive nature. We can, using probes placed in the esophagus, quantify the pH and impedance. This can tell us when reflux happens and if it is acidic, but in infants this information doesn’t mean much because apparent symptoms often don’t correlate well with measured reflux events because they usually aren’t caused by the reflux. But this type of investigation can be helpful when a child has the sudden onset of severe symptoms to see if they really do occur at the same time as reflux, although there is still the possibility of a coincidence.

Imaging, specifically what is known as an upper gastrointestinal series, should never be used for routine reflux because it involves a large amount of ionizing radiation and will only reveal what we already know: infants reflux. We don’t need to see it in real time with contrast-laden formula to prove it. This technique is reserved for when there are red flags for an underlying anatomical abnormality. Unfortunately, I still see the occasional perfectly healthy baby who has been diagnosed with reflux using fluoroscopy. Ultrasound imaging of the stomach is also sometimes useful when infants have red flags.

The gold standard in diagnosing GERD, because it allows direct visualization and the ability to take tissue biopsies, is endoscopy. Inserting a scope down the esophagus is usually reserved for when a patient doesn’t respond to less invasive interventions, such as lifestyle modification, medications and dietary changes, and even then it is more about ruling out non-GERD causes of symptoms. It isn’t perfect though. Findings on biopsy do not correlate well with presence or resolution of symptoms in babies.

What is the science-based approach to treating infant reflux/GERD?

To stress again, reassurance is often all that is needed when a baby spits up, and even when there is some concern that they might have mild to moderate GERD. So-called lifestyle modifications are all that is needed in more troublesome cases, even if all that they really do is buy a little time while the reflux resolves on its own. The risks associated with these modifications are very low. If a baby is exposed to cigarette smoke, stop it. Give smaller feeds. Feeds may need to be given a little more frequently or formula can be concentrated to give more calories per ounce, allowing a smaller volume feed. Many babies with reflux are simply overfed, particularly if they are on formula, but this can occur with breastfeeding as well. If breast milk oversupply is a possible issue, lactation experts do have methods of dealing with this.

In general, hopping from formula to formula is not recommended. The differences between competing standard formula brands are clinically meaningless with extremely rare exceptions. But in babies with mild-moderate GERD, many experts recommend an empiric trial of removing cow’s milk from the diet because milk protein allergy is a common GERD mimic. A specialized formula can be used which contains broken down “hypoallergenic” proteins or the mother can attempt to remove dairy from the diet although that can be difficult to achieve and maintain.

Thickening feeds with rice cereal or oatmeal can help, primarily by reducing the number of regurgitation episodes. It likely won’t treat true GERD, however, but it may help change parental perception of symptoms. It isn’t worth it for breastfeeding mothers, as they would need to pump, thicken and feed via a bottle. Thickening significantly increases the caloric density of the formula or breast milk, so weight gain can become an issue. There are also formulas on the market which are “pre-thickened”. They should be of similar effectiveness theoretically but they haven’t been studied enough to say for certain.

Gravity plays a role in causing reflux, and parents can take advantage of it also. Although not well studied, keeping a baby completely upright for 10-20 minutes after each feed is often recommended to reduce reflux episodes. There is no real downside other than the extra time involved. I’ve seen many parents, and a number of medical professionals, who have extrapolated from the likelihood that upright positioning helps to placing a child in, or recommending, partial supine positioning. Sitting in an infant seat actually increases the likelihood of reflux, and achieving a partial incline by placing the child on an elevated mattress might increase the chance of rolling onto a prone position before they are developmentally ready. Prone positioning does decrease reflux but it isn’t worth the increased risk of SIDS.

What about those drugs for reflux/GERD?

As a pediatric hospitalist, I’m hardly shy about throwing evil synthetic pharmaceutical agents at kids. But in the case of reflux and most cases of mild-moderate GERD in infants, they aren’t going to help and will only expose the child to the potential side effects. There are times when they are appropriate, however, such as when endoscopy findings reveal significant inflammation or when there are anatomical/medical conditions that increase the likelihood of GERD. When symptoms are severe and don’t respond to conservative measures, a trial is also reasonable. But they shouldn’t be continued for more than a couple of weeks without clear improvement. Even surgery is sometimes indicated in the most severe cases of GERD, although that is most likely to be required when a child has a neurologic problem that places them at risk of aspirating feeds into the lungs.

As I stated earlier, most babies can’t reliably be diagnosed with GERD because the symptoms are based on parental report for the most part. Parental report can only really be suggestive of GERD. We know that these symptoms almost always respond to lifestyle changes/placebo and regurgitation episodes decrease quickly after 4 months in most infants. There are many studies demonstrating that the conservative approach is best and that medications which decrease or stop acid production often aren’t better than placebo, particularly for the perception of general fussiness.

But these medications are some of the most commonly prescribed in infants, with use of newer (meaning more expensive and more potent) proton pump inhibitors increasing dramatically over the past ten years. This wouldn’t be an issue if they were only prescribed for babies that were more likely to have actual esophageal injury because PPIs are more effective at stopping acid production and allowing the esophagus to heal. They were a game changer in the adult population, where GERD and heartburn are much more easily diagnosed. Many infants are placed on older histamine type 2 receptor blockers, which decrease acid production but don’t stop it. They also have the downside of tachyphylaxis, where a drug loses effectiveness over time, in this case allowing acid production to rebound. They are considerably cheaper though.

What are the risks? Antacids are generally avoided in babies because of the lack of efficacy and risk of toxicity. H2 blockers are pretty safe but lose effectiveness after a few weeks. PPIs are where the real risk is, increasing the likelihood of pneumonia and intestinal infections such as the dreaded Clostridium difficile. Stomach acid plays a role in killing potentially pathogenic bacteria after all. When I was a resident, the drug metoclopramide was all the rage and it used to drive me nuts. It is a prokinetic agent that can enhance emptying of the stomach. Delayed emptying is only rarely a problem in healthy kids and the risks of this medication are considerable, including impressive dystonic muscular contractions and increased risk of seizures.

What about an alternative approach to infant reflux/GERD?

It is a good thing that infant reflux is a generally self-limited and benign condition, although it is often frustrating when excessive parental concern becomes the predominant issue. But most, if not all, pediatricians would much rather work hard to reassure the parent of a well child than have a suffering child. Unfortunately, a combination of many factors frequently lead parents to seek out alternative approaches to infant reflux.

Some parents who bring their baby to a chiropractor because of concerns about reflux, for instance, were going to bring their kid in anyway because it fits into their world view. They will buy unproven herbal concoctions, allow deluded theatrical placebo artists to poke their baby with acupuncture needles, and try just about anything they perceive as a natural remedy. It is unlikely that we are going to have much of an impact on that sad reality.

Certainly some parents are just frustrated by a seeming lack of options with conventional medicine. They may be uncomfortable with giving medications to such a young child. They may just be tired, stressed and online, a combination that probably is to blame for the majority of bad medical decisions. But the children of most parents who seek out natural cures for apparent reflux are also cared for by pediatricians and family doctors. These caregivers are simply seeking out additional help and have been fooled by the pretty wrapping paper on the empty box that is alternative medicine. Maybe we can reach these parents before they take the plunge, wasting money or worse, putting their child’s health at risk.

It isn’t that many proponents of irregular medicine don’t provide some useful information for parents. I’ve spent hours investigating the approach of chiropractors, homeopaths, naturopaths, acupuncturists, etc to reflux and found that we frequently agree. Like me, they tend to stress the benign nature of most cases of reflux and the fact that the attributed symptoms tend to resolve on their own. They talk about the conservative recommendations, and even if the details aren’t always exactly right I didn’t see much of anything that was dangerous. If only they stopped there.

As is always the case, there is little time devoted to educating parents on the nuance of a condition like reflux in a baby. This is likely because nuance is not something that alternative medical practitioners understand themselves. They are more about the big picture. Natural is better. Subluxations are to blame for everything. So forth and so on. They get that reflux is almost always benign but not that the symptoms may not even really exist or may not be caused by reflux. They denigrate drugs because they don’t work but fail to realize that their placebo-based interventions are no different, and they absolutely do not have the training to rule out more concerning conditions that might initially cause symptoms similar to GERD.

A good example I found was a discussion of infant reflux by The Holistic Mama. It contains some good advice, but also a great deal of common bogus concepts like detoxing, essential oils and overzealous elimination diets for breastfeeding mothers. One alternative approach to reflux which was completely new to me was the use of hazelwood reflux jewelry. These are similar to the amber teething necklaces that John Snyder wrote about recently in that they seem to work, defy all plausibility and may serve as a choking hazard.

Chiropractic appears to be the most commonly recommended alternative treatment for infant reflux. The proposed mechanism of action is removing nerve interference cause by subluxations acquired during birth. Despite how easily I found a large number of chiropractic practice websites touting success, Pubmed contained only one published paper on the use of chiropractic for infant reflux, which naturally was a case report. Frequently linked to on said chiropractic websites, this report is another perfect example of why anecdotes usually aren’t helpful for much other than generating a hypothesis. The child in question began chiropractic at exactly the same time that reflux tends to peak and then quickly improve. Also the complaints were subjective and could have easily been affected by a variety of placebo effects.

Conclusion

Gastroesophageal reflux is a common complaint, and affects essentially all young infants. The symptoms related to reflux, the most common being general fussiness, are largely subjective and the connection is not well supported in the literature. It is very likely that in many cases of apparent reflux, parental perception of their child’s symptoms is altered by stress and fatigue.

Despite the knowledge that reflux in babies is a normal aspect of physiology, and almost always benign and self-limited, it has unfortunately become medicalized. This has led to a frequent parental demand for relief from healthcare professionals and the overuse of reflux medications. These medications are unlikely to impact the course of infant reflux beyond the effect of placebo on parental perception of the symptoms, and are not risk free. Rarely is direct and clear evidence of esophageal injury found in an infant, but in some cases a tentative diagnosis of GERD is warranted and a trial of acid-reducing medications indicated. In nearly all cases of reflux in infants, and even with suspected GERD, conservative measures are indicated and should be attempted prior to starting medications.

Because reflux is benign and tends to resolve spontaneously, proponents of unproven alternative medical modalities claim to have both success in curing it and, depending on the type of practice, special knowledge about what causes it. What they do not have is any evidence to support treatment recommendations that aren’t already a component of the conventional approach to management. But even when they give semi-reasonable advice it is often jumbled together with misinformation.

Posted in: Science and Medicine

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