A one month old male is brought to your office by his first time parents with a complaint of constant irritability and spitting up. The 2.8 kg (6 pounds, 3 ounce) product of an uneventful full term pregnancy and delivery, he was discharged on the second day of life. He always seems to be hungry, and since his mother is certain that she is not producing enough milk, she has been following the breast feedings with formula for the last 2 weeks. He currently will feed at the breast for 10 minutes, then consume another 4 ounces by bottle. When left with his grandparents, he will finish an entire 8 ounce bottle in 5-10 minutes and they report he will cry if they try to cut him off at the recommended 4-5 ounces. The vomiting generally occurs immediately after feedings. It is not forceful, nor is it blood or bile-tinged. He fills 10 diapers with urine daily, and lately he has been having watery stools, which have further worried his grandparents. Despite all this, he weighed 3.5 kg (7 pounds, 11 ounces) at the two week checkup and he now weighs 4.3 kg (9 pounds, 8 ounces).

Exam: VS are unremarkable. His physical examination is notable only for fussiness when laid supine on the table, with resolution when held upright or in the prone position. You witness effortless regurgitation of 2-5 ml of curdled formula every few minutes during the history and exam since his parents "topped him off" with formula in your waiting room before the appointment as he was beginning to fuss.

Gastroesophageal (GE) reflux is defined by the North American Society for Pediatric Gastroenterology and Nutrition (NASPGN) as the "passage of gastric contents into the esophagus" (1). This is a normal physiologic process including regurgitation (the generally low pressure passage of gastric contents up to the mouth) as opposed to vomiting (the forceful expulsion of gastric contents via the mouth) as the latter is more often associated with obstruction or other significant abnormal alteration of gastric motility involving reversal of the usual gastric emptying phenomenon. Likewise, it is to be differentiated from rumination, which is the purposeful return of gastric contents to the mouth as a response to behavioral issues, most typically beginning in the second half of the first year of life and occurring in neglected infants and children in part as self-stimulatory behavior or as a means of getting attention from an otherwise markedly non-interactive (and usually clinically depressed) caretaker.

GE reflux occurs at all ages, and its consideration is best divided between infantile reflux and reflux in the older toddler/child, as the presentations will differ due to responses available due to developmental stage. It can be a chronic and a recurrent problem.

In infants, the more typical presentation is as above, which the NASPGN label "the happy spitter" (1) who freely regurgitates, but more commonly than not, has no sign of respiratory compromise. With the relatively low acid secretory capability and the constant feeding of early infancy, there is less tendency to irritability suggestive of dyspepsia, though many (like the child in the example) will show some sign, and some will become markedly colicky. The attribution of the colicky behavior to reflux is supported by an increase in fussiness in positions where reflux would be promoted; such as supine or slumped in a mal-positioned baby seat, or at times when reflux can be expected; such as following an overfeeding as in our example.

In toddlers and older children, overt regurgitation is less common as they spend more time upright and typically will have learned eating behaviors favoring solids and minimizing liquids which further help retain most of the feedings in the stomach. The retention is not complete, however, and they more typically present with symptoms or signs suggestive of distal esophageal irritation. Aside from complaints of epigastric pain (in the pre-verbal toddler often indicated as holding the epigastrium or refusing to eat further), they can include drooling (caused by reflex hypersalivation triggered by the acid sensors of the distal esophagus acting via the brainstem on the salivary glands), or pronounced eructation (i.e., belching, representing regurgitation of air co-swallowed with the saliva). The latter two are manifestations of the esophageal protective mechanisms, and can be seen in early infancy presentations, just as many toddlers will still regurgitate freely. In the older child and adolescent, hypersalivation is more commonly manifest as a sleeping behavior (as not all the saliva produced while recumbent is swallowed) and often is accompanied by sleep in specific positions of comfort, the most common of which are prone and left decubitus as these offer some positional advantage to mitigate reflux. These options are not available to the infant (particularly in the face of the American Academy of Pediatrics' "Back to Sleep" campaign against SIDS), often resulting in worsening colicky behavior, as noted in our example.

Occasional patients will present with respiratory symptoms as their primary complaint with reflux laryngitis and the contribution of microaspiration of either regurgitated acid or oral secretions (from the hypersalivation) in the exacerbation of chronic asthma is gaining increasing recognition. Though more common as a presenting complaint among older children, it will occur in younger children as well, but is not the more common presentation for any age. A more worrisome presentation is frank aspiration or choking, resulting in pneumonia for the former and symptoms ranging from gagging and sleep interruption to apparent life threatening events (ALTE) for the latter. These more serious conditions require full regurgitation, and are also far less common than the non-respiratory symptoms which require reflux only part-way up the esophagus. The NASPGN have acquiesced to the AAP in dissuading prone sleeping position before 12 months of age, though proning may be used while "awake, particularly in the postprandial period" (1).

GE reflux, and more specifically secondary esophageal irritation (if not frank esophagitis), can result in voluntary reduction in intake in all ages, resulting in classic failure to thrive or frank weight loss. It can result in overt feeding refusal, though it more commonly is manifested as a selective intake, avoiding items which cause pain including acidic and spicy foods, and surprisingly commonly, items with adverse effect on the distal esophagus, including caffeine and chocolate if the examiner questions specifically.

GE reflux must be differentiated from vomiting, as the latter hints at obstruction, and can also arise from metabolic processes (urea cycle defects and Reye syndrome) as well as disease in other organ systems (increased intracranial pressure, pancreatitis, urinary tract infection, or distention of any hollow viscus such as the gallbladder or renal pelvis/ureters). It should also be differentiated from extra-abdominal causes such as post-tussive vomiting, or altered motility due to allergic enteritis or eosinophilic gastroenteritis. In the case above, a one month old with projectile vomiting would suggest pyloric stenosis, but in our case the vomitus is not forceful and has been present from the neonatal period. Projectile vomiting requires an intact lower esophageal sphincter (LES) function to develop adequate intragastric pressure. Since GE reflux is common at this age (>50%), projectile vomiting may not be present in infants with coexisting pyloric stenosis with GE reflux, which may delay the diagnosis of pyloric stenosis.

Three mechanisms produce the majority of GE reflux: 1) Chronically decreased lower esophageal sphincter tone is most common at all ages and can be expected to improve over the first year of life. It is characterized by symptoms which occur more commonly immediately after feedings and further reflect effects of posture or intra-abdominal pressure. 2) Delayed gastric emptying is common among adults due to progressive gastroparesis, particularly with diabetes mellitus, but is less common in children. Characteristically it will produce symptoms which continue for hours after feedings, reflecting the persistently full stomach. 3) Inappropriate LES relaxation is least common of the three, and typically produces more irregular timing of the symptoms, which tend to be more fleeting as the esophageal protective mechanisms are typically more effective in these youngsters than with the other two.

The diagnosis of GE reflux is typically made by a detailed history and physical examination alone. Regurgitation reliably reported or observed with appropriate adjunct symptoms and signs is suggestive of uncomplicated GE reflux. A careful elucidation of a consistent constellation of symptoms can suggest reflux which is not visible (which is also sufficient to trigger the first lines of intervention). It is in situations where significant secondary disease is present (such as recurrent aspiration, stridor suggesting laryngeal irritation, or failure to thrive with or without frank feeding refusal), that subspecialist assistance should be sought at an early stage, even if overt regurgitation makes the diagnosis fairly certain. Efforts should be made to exclude the other items in the differential diagnosis above, but many can be excluded on the basis of a good history and physical examination of the relevant organ systems.

Radiographic studies are not part of the usual initial workup since the absence of reflux on a short radiographic study cannot rule out GE reflux, and the manipulation inherent in the exam can itself trigger regurgitation. The main utility of the upper gastrointestinal contrast study is to search for structural anomalies such as malrotation as well as the much rarer webs and secondary strictures. These are often accompanied by signs of obstruction (though bilious vomiting may be absent if the obstruction is proximal to the mid-duodenum). The exception is the younger patient with signs of tracheomalacia, as the rare vascular ring, trapping both the esophagus and trachea in its grasp during in utero growth, deserves early intervention. Another exception is pyloric stenosis, for which ultrasound provides less invasive evaluation, permitting earlier access to surgery.

The radionuclide gastric emptying study, likewise is not commonly part of an initial workup, as its prime utility is in assessing delayed gastric emptying. Unfortunately, age appropriate standards are not well established, prompting the use of this test in the more severe cases where surgery is already being contemplated (typically fundoplication). Scintigraphic imaging during the hour-long study can also identify reflux visually (but again cannot rule it out due to the short duration of the study) and 24 hour delayed imaging is cited as being of utility in searching for evidence of aspiration.

pH probes offer a means of assessing the frequency and duration of acid reflux, and with the double-sensor probes, the differentiation between regurgitation and reflux only part-way up the esophagus can be made. Twenty-four hour studies are more reliable than those of shorter duration, since reflux varies with activity and sleep state. Their prime utility is in the patient with symptoms which are clear and disruptive who does not have a clear association with visible regurgitation. The classic example is the infant with repeated ALTEs who is found with curdled feedings. The main issue in such patients in establishing causality is determining whether the reflux came first, then the obstruction, then the apnea. It is more common that the apnea came first, then the agonal relaxation of the LES and regurgitation. In such situations, simultaneous multichannel recordings are essential, since the transition from one stage to the next may be only seconds apart, and on such studies many infants with obstructive apneic episodes and known GE reflux have the two occur at completely different times.

Manometric studies have fallen on disfavor, as they do not address the issues of delayed gastric emptying or inappropriate relaxation of the LES.

For the average healthy infant with no threatening complications, the GE reflux can be approached first with basic mechanical measures:

1) Regulate feedings: As in our illustration, overfilling of the stomach is to be discouraged, and in such a patient, I would recommend the bottle feedings be halted if there is ample evidence of sufficiency of breast feedings. This can be reinforced by following the urine output, with most parents being reassured when told that the fluid urinated had to have been absorbed, and the nutrients associated with that fluid can be expected to be absorbed as well. In the bottle-fed infant, the volume can be calculated, but I have found it easier to give the caretakers a means of identifying the volume that would fit in a minimally distended stomach as being roughly a quarter of the abdominal volume as measured between the ribs and the pelvic brim. This forestalls repeated questions of "how much can we feed now?" as the child grows. The feedings also need to be regularly spaced, to avoid overfilling with too closely spaced feedings. This is less of a problem in the exclusively breast-fed infant, but is not eliminated. For the demanding infant, use of suitable pacification (particularly a parental digit) can be helpful. The feedings also need to be evenly paced, to allow enough time for the infant to feel full and cut off the feeding before overfilling occurs. With the bottle-fed infant, thickening of the feedings is possible; in exclusive breast-feeding, the parental digit will again have to be used.

2) Positioning: Maximizing the vertical distance between the mouth (or more particularly the larynx) and the stomach helps minimize reflux and secondary esophageal irritation (i.e., colic). The literature does support prone positioning in this regard, but the cautions noted above regarding SIDS apply. It is worth mentioning to parents, however that infants choose their own sleeping positions once they are able to roll from supine to prone around 4 months of age to avoid many sleepless nights repeatedly rolling their infant back into the supine position only to flip back as soon as he or she is free to do so. Decubitus positioning provides some relief, as can positioning in a recliner (as long as the angle chosen does not cause slumping). There will be times when carrying the infant upright may offer the only relief (particularly after overfeeding).

3) Thickening the feedings may be a consideration in the formula fed infant, and is far less practical in the breast-fed one. In many cases the greater utility of the thickening is in slowing the feeding rate than in any retention within the stomach. Rice cereal is preferred over the recently introduced formulas that thicken when exposed to acid (recall many young infants may not produce much acid). Typical recipes call for one-half to one tablespoon of rice cereal per ounce of formula, which also adds substantially to the overall caloric intake. Thickening to encourage retention in the stomach is of most use in those with evidence of chronic low LES tone (spitting which occurs predominantly shortly after the meal) and can be less than useful in those who have delayed gastric emptying (with spitting which continues for hours after a meal) as it may cause further delay in emptying. In such infants who are formula fed, one of the cheaper partially hydrolyzed formulas may provide the better option, as fluids empty from the stomach faster than curd. In that respect, breast feeding, with its thinner curd, tends to empty faster than most formulas.

In older toddlers and children:

1) Regulate the feedings: Many with secondary esophageal irritation (if not frank esophagitis) will tend to complain of nausea and anorexia in the morning, and skip or minimize breakfast intake. They may or may not eat much lunch, particularly if the school is providing a spicy menu. They often eat more of their daily caloric intake throughout the afternoon and evening. Redistributing the intake to be more evenly spaced during the day will result in less nocturnal acid reflux and is of most utility in those complaining of symptoms after supper or nocturnal waking or morning nausea. Avoidance of after supper snacking can also help.

2) Positioning is less of a problem once infants pass 6 months of age and can choose to be upright. For older children, the option of elevation of the head of the bed for sleep is often declined as more seem to prefer prone positioning.

3) Avoid agents prone to adversely altering LES tone and functioning such as caffeine and nicotine.

In all age groups, a therapeutic trial to address acid can be of significant diagnostic utility. My personal preference is to use antacids, since this provides immediate pain relief (good reinforcement). Typical therapeutic courses with histamine-2 receptor blockers or proton pump inhibitors run 6-8 weeks with only partial resolution. In infants, the aluminum containing antacids should be avoided since aluminum absorption may cause osteodystrophy. A typical therapeutic trial yields suggestive results within 2 weeks, and can be helpful in determining whether an atypical (but non-threatening) symptom is acid-related.

Beyond these basic steps, the evaluation and therapy diverge based on the dominant symptoms. If delayed gastric emptying is the issue, therapy centers on properistaltic agents and may include a more thorough evaluation of structure and gastric emptying. If pain or other inflammatory signs are dominant (i.e., reflux laryngitis), acid secretion suppression or blockade are the mainstay, and endoscopy (with biopsy) offers the best diagnostic discrimination. These measures typically prompt subspecialist assistance.

Infantile reflux typically presents with overt regurgitation and dyspepsia (colic). These can be expected to improve markedly over the first year of life with the transition to a diet based more on solids than liquids and attainment of a more upright posture. Conversely, GE reflux in the older child tends to present as chronic or recurrent pain, with only secondary signs or symptoms of reflux and no overt regurgitation. It represents a chronic problem, the symptoms of which may run life-long, and if mechanical measures and intermittent acid neutralization do not provide adequate symptomatic relief, long-term medical therapy may be warranted. In either case, in the absence of life-threatening complications, surgical options are not a routine consideration, and generally are considered only in the face of failure of extended and aggressive medical management of significant levels of disease.

Questions

1. True/False: Gastroesophageal Reflux is a rare phenomenon in childhood.

2. For the vomiting infant:
. . . . . a. The parents can be reassured it is a process the child will outgrow as they get older.
. . . . . b. Thickening the feedings sometimes works.
. . . . . c. Proper positioning may be helpful.
. . . . . d. Deserves further evaluation.

3. A one month old second born female presents with worsening of her GE reflux. The regurgitation remains effortless, but is increasing in volume and seems more prominent an hour or so after meals. She has been more demanding of feedings and has had fewer wet diapers over the last few days and is losing weight. Her parents have felt "something moving" in her stomach in the hour after feedings over the last week. What is happening?

4. True/False: A 4 year old with complaints of abdominal pain that disrupt school attendance warrants a two week trial of a proton pump inhibitor.

5. True/False: A diagnosis of pain due to gastroesophageal reflux is likely to lead to a lifetime of expensive medication.

References

1. Rudolph CD, Mazur LJ, Liptak GS, et al. Pediatric GE Reflux Clinical Practice Guidelines. J Pediatr Gastroenterol Nutrition 2001;32(suppl 2):S1-S31.

Answers to questions

1. False. Though most episodes are asymptomatic, reflux is a routine physiologic phenomenon in everyone, at every age. It is gastroesophageal reflux DISEASE that is uncommon in most of childhood.

2. d. Remember regurgitation is effortless, vomiting is forceful and is atypical for uncomplicated GE reflux. It can indicate obstruction or metabolic derangement, and represents a problem that requires an answer in as short a period of time as possible (even if the answer is a diagnosis of routine gastroenteritis).

3. Consider pyloric stenosis, even if only a few of the classic symptoms and signs are present. Waiting for the diagnosis to become more obvious further delays surgical intervention and increases the risk of complications such as hypochloremic alkalosis and dehydration. See differential diagnosis above.

4. This one is arguable, but my personal preference is to start treatment with antacids since it offers a means of immediate relief of any truly peptic pain episode, and younger children are better reinforced by immediacy of the response. Of course a good history and physical should come first to verify the pain does fit a "peptic" pattern, as constipation is more likely at this age.

5. False. The vast majority of uncomplicated pain seems to respond to mechanical measures, avoidance of caffeine, nicotine, and the like, and intermittent antacid use. It is only when the pain episodes remain disruptive more than once weekly that it is generally warranted to proceed to chronic medical therapy, and then only at the minimal doses necessary unless other complications (e.g., Barrett's esophagus) occur.