Level of agreement: in complete agreement 100%.

Diagnostic tests are ordered for ruling out complications of GERD or evaluating differential diagnoses.2,3

Level of agreement: in complete agreement 100%.

Esophagogastroduodenoscopy (EGD) is not needed for the routine evaluation of infants with GERD2,19,20 because the study does not reflect the frequency of reflux under physiologic conditions, and infants with or without GERD can have episodes of GER seen during the study, making it neither sensitive nor specific. In selected cases, such as infants vomiting bile or with little weight gain, an upper gastrointestinal series can be useful for identifying anatomic anomalies (esophageal stricture, hiatal hernia, intestinal malrotation, infantile hypertrophic pyloric stenosis, prepyloric/antroduodenal membranes, duodenal strictures, tracheoesophageal fistula) and in postoperative fundoplication patients.2–4,20

Level of agreement: in complete agreement 100%.

We do not recommend the use of scintigraphy for diagnosing GERD due to its low sensitivity and lack of standardization of the technique. It can be performed to confirm pulmonary aspiration in patients with refractory respiratory symptoms or with recurrent aspiration pneumonia, but it is not recommended for other reflux symptoms. It can also be used to rule out gastric emptying delay as a causal or precipitating factor of symptoms related to GERD.2–4

Level of agreement: in complete agreement 100%.

Ultrasound is not considered a diagnostic tool for GERD in infants under one year of age. The imaging study is indicated for ruling out other conditions that can manifest with the presence of vomiting, such as infantile hypertrophic pyloric stenosis.21

Level of agreement: in complete agreement 100%.

Evidence is insufficient for recommending the routine use of EGD with biopsy for the diagnosis of GERD in infants and children.2,3 Upper gastrointestinal endoscopy can be of diagnostic benefit in infants that do not respond to empiric treatment. When endoscopy is performed, biopsies should be taken of the esophagus, stomach, and duodenum because they can reveal clinically significant diseases, even when the macroscopic appearance of the mucosa is normal.22 EGD is useful for evaluating the esophageal mucosa and detecting complications of GERD (esophagitis, stricture, Barrett’s esophagus), for diagnosing conditions that predispose to GERD (e.g., hiatal hernia), or for diagnosing conditions that can simulate GERD (eosinophilic esophagitis, infectious esophagitis, etc.).2 In patients with extraesophageal manifestations of GERD, the main indication for EGD is to detect reflux simulators (such as eosinophilic esophagitis, esophageal candidiasis) and to treat esophageal obstructions resulting from coughing and aspiration. In the absence of erosive esophagitis, microscopic esophagitis is insufficient for diagnosing the presence of GERD.2,4 Nevertheless, GERD can exist even with a normal appearing esophageal mucosa and the absence of histologic abnormalities.2

Level of agreement: in complete agreement 92.3%, in partial agreement 7.7%.

Studies of esophageal manometric pressure and lower esophageal sphincter function have been utilized for ruling out esophageal motility disorders, such as rumination syndrome and esophageal achalasia, whose symptoms can simulate those of GERD.23

Level of agreement: in complete agreement 84.6%, in partial agreement 15.4%.

Esophageal pH-monitoring is a quantitative measure of esophageal acid exposure, with established parameters and ranges. It measures the frequency and duration of episodes of acid reflux (pH < 4) through a series of parameters, such as the total number of reflux events in 24 hours, duration of the longest reflux event, or the most important total time with intraesophageal pH < 4 (reflux index: RI).

The pH-monitoring study enables the differentiation between physiologic reflux and pathologic reflux, considering the latter in infants, when the RI is above 10% or there are more than 100 acid reflux episodes in 24 hours, and in children above one year of age, when the RI is above 7% or there are more than 70 acid reflux episodes in 24 hours.13

Intraesophageal 24-h pH-monitoring has high sensitivity and specificity for diagnosing GERD. However, in the large majority of infants and children with reflux, pH-monitoring is not required for making the diagnosis. Indications13,24 for performing pH-monitoring are: 1) when there are symptoms suggestive of GER and progression is unfavorable despite establishing the correct treatment, 2) when it is relevant to determine the relation between GERD and extragastrointestinal symptoms, and 3) as an efficacy control of treatment, whether medical or surgical. Nevertheless, these indications should be individualized, according to the specific situation of each patient.

The main limitation of pH-monitoring is that it does not detect the presence of nonacid reflux, an entity that can appear in over half of infants with reflux. Likewise, it does not detect the extension of the reflex in the esophagus and it is difficult to establish the correlation between the symptoms experienced and the acid events, given that there is no consensus as to the time during which said events and symptoms are related, resulting in a low association between abnormal results of esophageal monitoring and GERD in this age group.25–27 In addition, the clinical symptoms of irritability, bradycardia, or desaturation episodes sometimes attributed to GERD in infants are poorly correlated with episodes of acid reflux.27

Despite those limitations, these studies can be useful in special rare situations, such as infants with mild episodes of severe symptoms (such as apnea, bradycardia, cough, or desaturation). In such a context, they are utilized together with the monitoring of respiratory rate, heart rate, or oxygen saturation to determine whether there is a temporal relation between reflux episodes and those events.28

Level of agreement: in complete agreement 84.6%, in partial agreement 7.7%, in disagreement 7.7%.

When esophageal reflux monitoring is performed, the ideal technique is to measure both the esophageal pH and the multichannel intraluminal impedance, on a single device, for 24 hours. Multichannel intraluminal impedance associated with pH monitoring (MII-pH) is recommended as the preferred technique for measuring gastroesophageal acid and nonacid reflux. Compared with pH-monitoring, impedance has the advantage of being independent of the pH value, and consequently is better adapted to measuring reflux, especially in the postprandial period when reflux is buffered, and for detecting the symptoms associated with nonacid or weak acid reflux. MII-pH is currently considered the gold standard for evaluating the symptoms of GERD.29 Its indications are the same as those for esophageal pH-monitoring. Currently, there are some indices that allow us to determine whether there is a correlation between reflux events and the symptoms recorded through statistical correlations, but normal reference values are not yet available.

Its indications are:

• •

  To correlate symptoms with acid and nonacid reflux events.

• •

  To clarify the role of acid reflux in the etiology of esophagitis and other signs and symptoms suggestive of GERD.

• •

  To determine the efficacy of acid suppression.

Level of agreement: in complete agreement 92.3%, in partial agreement 7.7%.

A PPI diagnostic test is based on the hypothesis that the symptoms are related to acid. PPI use in controlled trials showed no symptom improvement compared with placebo. Regardless of trial duration, the administration of a PPI cannot be recommended for infants as a therapeutic test,30 nor are there sufficient data for recommending a PPI trial in patients with extraesophageal symptoms that are possibly related to GERD.22

Level of agreement: in complete agreement 100%.

Parental education and support are essential, emphasizing that regurgitation is a physiologic and self-limited process and that symptoms are resolved in 98% of cases before the first year of life. Understanding the natural history of regurgitation can help reduce parental anxiety, medical referrals, and overtreatment.2–5

Level of agreement: in complete agreement 100%.

Studies show that exclusively breastfed infants, especially between 2 and 6 months of age, have less probability of experiencing regurgitation, suggesting that maternal breastfeeding is a protective factor,7,31 as well as being associated with faster resolution.32 Some studies have shown that partially breastfed infants (i.e., infants that are both breastfed and bottle-fed with formula)7,31,33 have more reflux events, compared with exclusively breastfed infants, whereas other studies have reported no difference,34–37 as also occurs with the introduction of complementary feeding.31,37

Level of agreement: in complete agreement 100%.

Early hunger signs are recognized when infants display behaviors, such as sticking out their tongue, touching their mouth with their hands, sucking their fist, and searching for the breast when awake. Crying is a late hunger sign and promotes aerophagia. Satiety signs are a relaxed body with open fists, voluntary release of the nipple, turning the head away or closing the lips when offered the breast, sucking slowly, or falling asleep at the breast.38 The ability of the infant to self-regulate milk consumption has been postulated as a factor associated with reduced reflux, which is also a reason why the manner in which infants are breastfed can influence the incidence of reflux. Directly breastfed infants have a greater capacity for self-regulating milk intake, compared with infants that have mixed feeding or are bottle-fed.31 An important effect of bottle feeding is that caretakers can ignore satiety signs, increasing the possibility of the infant’s receiving a larger volume of milk, which can result in a higher probability of developing reflux. Reflux can cause anxiety in both the infant and caregiver, leading to changes in the infant’s feeding behavior, even interrupting maternal breastfeeding.8 Breastfed infants with GERD can have feeding problems,39 which can lead the caretaker to utilize the bottle, in an attempt to alleviate the anxiety of the infant. In addition, exclusively breastfed infants often have fewer and shorter reflux episodes,7,8 with faster gastric emptying.4 These factors can lead to a lack of perception of reflux severity by the caregiver, and so it is reported less often.8

Infants with physiologic reflux have normal feeding behavior and generally feed frequently. In contrast, one of the concerning alarm signs in the evaluation of children with GERD is precisely food refusal, which can cause failure to thrive.

Level of agreement: in complete agreement 92.3%, in partial agreement 7.7%.

A complete evaluation carried out by trained personnel to assess the breastfeeding technique employed is important and includes positioning, attachment (latch-on), milk transfer, and effective sucking to optimize breastfeeding and prevent regurgitation.

The overproduction of maternal milk can cause symptoms of regurgitation, aerophagia due to superficial latching, gas, colic, explosive stools, choking, cough, crying during feeds and/or breast refusal.40

Aerophagia in the breastfeeding infant can promote regurgitation, especially in cases in which the feeding technique fails, such as shallow latch and inadequate seal around the breast due to poor attachment, and when there are anatomic problems, such as ankyloglossia, bubble palate, and short labial frenulum.41,42

Excessive volumes of milk during feeds can cause regurgitation, and so some documents2–4 recommend considering offering lower volumes and more frequent feeds, without incurring risks or extra costs. However, not all infants accept that, and with direct breastfeeding, the ingested volume cannot be measured, making other measures, such as choosing a position that does not exert intra-abdominal pressure, burping after feeding, and maintaining an upright position 15 to 20 minutes after feeding, possibly more useful. Keeping the infant in the same position for 30 minutes after feeding may help reduce regurgitation.43,44

Level of agreement: in complete agreement 84.6%, in partial agreement 15.4%.

Current guidelines for GERD recommend thickening as a first-line approach for treating GERD in infants and young children.2,3 It thickens the feeds, so they stay in the stomach longer, reducing the risk of regurgitation. MII-pH studies on otherwise healthy full-term infants have shown that thickeners decrease visible regurgitation by reducing the maximum height reached by the refluxate.45,46 Several studies utilizing different types of feeding thickeners, with trials varying from 1 to 8 weeks, showed no superiority of one over the other.45 The use of thickeners reduced reflux to 2 episodes/day and reduced parental anxiety most likely due to the placebo effect.47 Thickeners can sometimes cause diarrhea because of the increase in osmolality and weight gain from high caloric density. Paradoxically, the slowing of gastric emptying can increase reflux symptoms in some infants. There is no evidence that thickeners are useful in premature infants and some studies report a higher incidence of necrotizing enterocolitis.48

Commercial formulas are preferred to standard thickened formulas because of their better viscosity, digestibility, and nutritional balance. In the Mexican market, different anti-regurgitation (AR) formulas are available that contain pregelatinized starch from rice, tapioca, potato, and corn, as well as carob flour and xanthan gum, among others. However, as mentioned above, there are currently no clinical trials that compare one thickener with another. Oatmeal and rice cereals are an excellent option for thickening formulas because they are effective, accessible, and inexpensive, but they are not recommended for thickening breastmilk because its amylase dissolves them.

Level of agreement: in complete agreement 84.6%, in partial agreement 15.4%.

Cow’s milk protein allergy (CMPA) is a common entity in pediatric consultation and shares symptoms with GERD, which can make the differential diagnosis difficult. Therefore, despite the lack of evidence supporting their routine use in the management of GERD symptoms, some guidelines suggest utilizing extensively hydrolyzed formulas or amino acid-based formulas for two to four weeks. If there is a favorable result, an oral challenge should be carried out to confirm or rule out the diagnosis of CMPA. This conduct is not justified in the infant with regurgitation. The elimination of cow’s milk protein from the maternal diet can aid in reducing reflux symptoms, in addition to improving esophageal acid exposure and mucosal integrity,49 and so breastfed infant patients can benefit from said strategy.

Level of agreement: in complete agreement 92.3%, in disagreement 7.7%.

Due to the association of the prone and left lateral positions with a risk for crib death, those positions are not recommended.2,3,50 In addition, seated or semi-seated positions for infants under one year of age have not been shown to be efficacious in the management of GER, due to the increase in muscle tone and intra-abdominal pressure.51

Level of agreement: in complete agreement 92.3%, in disagreement 7.7%.

Alginates are natural polysaccharides isolated from brown seaweed. Alginate-based formulations act on GER through chemical and physical mechanisms. In the presence of gastric acid, they react forming a low-density viscous gel that tends to float, the so-called gel rafts. Upon finding that calcium increases the strength of the raft, pharmaceutical formulations have been developed with calcium carbonate. How calcium increases raft strength is attributed to its capacity to cross-link alginic acid polymers, enabling the gel to form an “eggbox” structure that gives it great strength. On the other hand, bicarbonate can also be added to alginates, which act as a carbon dioxide (CO2) production system, in such a way that the CO2 bubbles that form in the presence of gastric acid, remain trapped with the gel matrix, converting it into a foam that floats.52

Using aluminum-free formulations and considering the sodium content (variable according to different commercial products) is recommended for prolonged use, particularly in premature neonates and children with kidney disease.

A systematic review on the efficacy and safety of liquid alginate-based formulations for reducing GER in neonates and infants that includes two studies suggests there is significant symptom improvement with said formulations as intervention. No significant adverse events were observed, signifying that this treatment option is generally safe for use in infants.53

The study by Salvatore et al.54 suggests that alginate can reduce symptoms related to GER in infants, can reduce episodes of acid, nonacid reflux measured through MII-pH. Nevertheless, those authors express the need for conducting randomized, double blind, placebo-controlled trials to confirm their findings, concluding that alginate is a treatment option for symptoms related to GER in infants.

Level of agreement: in complete agreement 92.3%, in disagreement 7.7%.

Despite the wide use of prokinetics in pediatrics for the treatment of GERD, there is still not enough evidence to confirm its efficacy. Systematic reviews on metoclopramide, domperidone, and cisapride have not found solid proof of their efficacy,55–57 and the international guidelines do not recommend their routine use. These medications have potentially serious adverse effects. For example, metoclopramide is associated with extrapyramidal neurologic symptoms and cisapride and domperidone are implicated in cardiac arrythmias. Therefore, adding a drug with debatable efficacy and possible adverse effects is questionable and the risk for adverse effects outweighs the benefit.58

Level of agreement: in complete agreement 100%.

Acid secretion inhibitors, such as the H2 receptor blockers and PPIs have been used for managing irritability in infants with suspected GERD, contrary to international recommendations.59,60

A 2015 systematic review61 and its 2022 update62 conclude that available data suggest that PPIs are not efficacious for treating crying and irritability in infants and their use has been related to an increase in infections, particularly diarrhea caused by Clostridioides difficile, as well as an increase in the risk of fractures.

A prospective study that simultaneously evaluated restlessness, crying, irritability, and GER through symptom quantification and evaluation based on the Face, Legs, Activity, Cry, Controllability (FLACC) scale and MII-pH found a temporal association between crying and GER in half of the episodes of irritability. No significant differences were observed in the FLACC score between episodes of irritability associated with or without GER, and nonacid reflux was perceived to be at least as painful as acid reflux. These results emphasize that acid inhibitors should not be started in infants that present with crying unless there is a clear association with acid GER.63

Level of agreement: in complete agreement 100%.

Data on the prevalence and severity of erosive esophagitis (EE) in young children is limited. The prevalence of EE confirmed by endoscopy and biopsy was reported at 29% in a study on 209 patients with GERD, whose age ranged from 18 months to 10 years and who had no neurologic alterations or congenital esophageal malformations.64 A retrospective review from the Pediatric Endoscopy Database System-Clinical Outcomes Research Initiative (PEDS-CORI) showed that 12.4% of the 7,188 children under 18 years of age that underwent endoscopy presented with EE.65 A retrospective cross-sectional study that collected information from 12 pediatric hospitals in the United States also reported that 9.5% of children one year of age and 7.6% of children 2 years of age had EE.65 Esophagitis can manifest as irritability, nausea, and feeding aversion; it rarely manifests as hematemesis or melena, anemia, weight loss, failure to thrive, or Sandifer syndrome. There is evidence of endoscopic and/or histologic remission, with symptom improvement, in patients that received PPIs.66–68

Level of agreement: in complete agreement 84.6%, in partial agreement 15.4%.

Although it is clear that H2RAs can be beneficial and efficacious in EE or frank gastritis, the majority of infants with GERD do not present with those complications, and so the decision to treat all infants with GERD with H2RAs should not be precipitated, especially given the risks associated with their use. There is no good correlation between symptoms and the presence of reflux esophagitis, nor can any sign or symptom predict which infants would benefit from H2RA use.69,70

Among the H2RAs, cimetidine, ranitidine, famotidine, and nizatidine have traditionally been used in the majority of countries. Famotidine and nizatidine have been authorized for use in children in the United States but not in Europe.

Tachyphylaxis is an important disadvantage that seriously restricts their long-term use.71

Starting in 2019, the US Food and Drug Administration (FDA) found levels of N-Nitrosodimethylamine (NDMA) that exceeded acceptable ingestion limits in many medication batches, including ranitidine. This resulted in the generalized removal of several products and caused concern in patients and physicians, given that NDMA was classified as a possible carcinogen for humans. NDMA can form as a result of ranitidine degradation, especially after the expiration date, but it can also form from ranitidine inside the body. As a precaution, in April 2020, both the FDA and the European Medicines Agency (EMA) ordered manufacturers to remove all prescription and over-the-counter ranitidine products from the market because NDMA levels can increase over time if the medication is stored above room temperature, reaching dangerous levels.72

This same recommendation was adopted in Mexico and ranitidine was removed from the market. Currently there are no formulations of H2RAs for infants.

Level of agreement: in complete agreement 100%.

Antireflux surgery primarily includes fundoplication, as well as other procedures designed to reduce the passage of gastric content into the esophagus. Indications for surgery have not been clearly established, success and failure rates vary widely, and complications frequently occur. Diagnostic tests and surgical considerations depend on the clinical presentation of the patient with the goal of ruling out conditions that present with symptoms of GERD, and in some cases, demonstrate its presence.2–5

Level of agreement: in complete agreement 84.6%, in partial agreement 15.4%.

An alternative to antireflux surgery is transpyloric or jejunal feeding through nasojejunal or gastrojejunal tubes or jejunostomies that reduce reflux by bypassing the stomach.2 Efficacy is variable, and its utility is limited because the tube can easily be dislodged, along with other practical considerations.73

Level of agreement: in complete agreement 100%.

Surgical indications for GERD in pediatrics are at times controversial, especially in infants, due to anatomic and physiologic peculiarities.74 In addition to there being no standardized evaluation of GERD in children that are programmed for surgery, diagnostic tests have limitations.

As previously described, EGD can be useful for ruling out anatomic abnormalities but its usefulness in diagnosing GERD is a subject of debate. The sensitivity of pH-monitoring is low in pediatric patients, given that clinical signs are poorly correlated to its results. Diagnostic yield is improved through MII-pH study, but normal values are not available in pediatrics. Upper gastrointestinal endoscopy does not always show validating pathologic findings of esophagitis for the diagnosis of GERD. Lastly, high-resolution esophageal manometry can be a useful tool, but it is available in very few centers.

Surgical indications for GERD result from an objective analysis of the patient that includes a clinical history specifying symptoms, the search for alarm signs, previous treatments carried out, patient characteristics, and associated diseases, such as esophageal atresia, congenital diaphragmatic hernia, bronchopulmonary dysplasia, and encephalopathy with associated neurologic decline that tends to be related to alterations in the swallow mechanism. Another group of patients are the infants that present with BRUE (previously known as ALTE) or crises of recurrent apnea.75

From the surgical perspective, Nissen fundoplication is the surgical technique of choice in the majority of operated patients, generally through the laparoscopic approach. Nevertheless, although some surgical centers perform hundreds of antireflux operations annually, others debate the need for and efficacy of fundoplication, and instead, promote better medical treatment, noninvasive feeding methods, and other surgical interventions, such as gastrostomy without fundoplication or gastrojejunal feeding.76

In patients with feeding problems due to alterations of the swallow mechanism, poor weight gain, or GERD, the placement of a percutaneous endoscopic gastrostomy (PEG) or surgical gastrostomy can be considered. However, the routine practice of adding fundoplication to those patients is no longer recommended because said procedure increases the risk for complications and does not improve reflux-related results.77–79

If bronchoaspiration-related lung disease is the indication for fundoplication, a comprehensive and multidisciplinary approach is very important because of the difficulty in differentiating retrograde bronchoaspiration (due to GERD) from anterograde bronchoaspiration (due to a swallow disorder). Even though fundoplication can reduce GER, it can also impede esophageal emptying and increase the possibility of aspiration. Transpyloric feeding or feeding through gastrostomy can also be considered in this group of patients.80

Other surgical procedures, such as radiofrequency ablation of the lower esophageal sphincter, endoscopic full-thickness serosa-to-serosa fundoplication, and total esophagogastric dissociation have been described mainly in adults and have not been evaluated in infants. At present, none of these techniques is recommended as primary therapy for GERD in children.2 Total esophagogastric dissociation can be adequate as a rescue procedure in children with neurologic impairment in whom fundoplication has failed, but because of the invasiveness of the procedure, a comprehensive evaluation is required, in order to make the appropriate diagnosis.

Antireflux procedures are more frequently performed in children during the period of life when regurgitation is normal and objective and physiologic measures of GERD are difficult to interpret. To identify significant results after surgery, indications should be clear and standardized. We must clarify the adequate study for infants and young children with GERD and better define “medical treatment failure” in that patient population.75

• •

  There are alarm signs and symptoms suggestive of an underlying gastrointestinal disease

• •

  Patients do not respond to optimal treatment

• •

  Pharmacologic treatment cannot be withdrawn after 6 to 12 months

Level of agreement: in complete agreement 100%.