Tag Archives: reflux

Ten-Year Trends in Pediatric Pharmacology for Gastroesophageal Reflux and Pediatric Feeding Disorders

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S Hirsch et al. J Pediatr 2025;283:114628. Ten-Year Trends in Pharmacologic Management of Gastroesophageal Reflux Disease and Pediatric Feeding Disorders in Young Children

Methods: Single-center, retrospective cohort study of children less than 2 years (49,483) diagnosed with GERD or PFD (pediatric feeding disorder) between January 2014 and December 2023. Prescriptions were searched for proton pump inhibitors (PPI), H2-receptor antagonists (H2RA), cyproheptadine, erythromycin, metoclopramide, or prucalopride, and procedures were searched for intrapyloric botulinum injections.

Key findings:

  • There was an increasing number of patients seen annually (6516 in 2014 vs 9109 in 2023)
  • The percent of patients receiving any prescription for GERD or PFD declined by almost 50%, from 36.5% in 2014 to 18.7% in 2023 (P < .001)
  • There was a particular decline in PPI prescriptions, with 25.3% of patients receiving PPI in 2014 and 7.1% receiving PPI in 2023 (P < .001)
  • There was also a decline in H2RA prescriptions, with 17.0% of patients receiving H2RA in 2014 and 11.1% receiving H2RA in 2023 (P < .0001).
  • In their discussion, the authors note that: “in contrast to the current findings, prior studies typically have shown increasing PPI prescriptions, with some of these studies demonstrating declining H2RA prescriptions (9-17)…. However, it is notable that 3 more recent international studies did demonstrate declining PPI prescriptions specifically in the final years of the study (18-20).”
  • “Multiple studies have failed to demonstrate efficacy of acid suppression in infants with nonspecific gastroesophageal reflux symptoms, and there is no evidence that acid suppression affects feeding behaviors.(21-23)”
  • “In addition, there has been growing concern about PPI side effects, which include increased infections, decreased bone density, and increased allergy development
    including eosinophilic esophagitis, with numerous recent studies on these risks.(24-26)”

My take: I’ve been a big fan of the aerodigestive research from the pediatric GI group in Boston. This is another useful study showing less use of acid suppression, especially PPIs in young children and infants. This likely indicates better alignment of clinical practice with consensus recommendations that advise against acid suppression as first-line management in this population.

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Gastrointestinal Issues in Rett Syndrome: Key Findings

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FD Ihekweazu, KJ Motil. J Pediatr Gastroenterol Nutr. 2025;80:46–56. Gastrointestinal manifestations of Rett syndrome: An updated analysis using the Gastrointestinal Health Questionnaire

Methods: Parents of 118 females with Rett syndrome (RTT) and 27 unaffected females completed the GHQ.

Key findings:

  • GI symptoms were common in females with RTT, including constipation (81%), gas and bloating (70%), issues with eating, chewing and swallowing (73%), and irritability because of stomach or intestinal problems (53%).
  • Females with RTT commonly used proton pump inhibitors (52%) and laxatives (64%). 
All with p values of <0.001 with the exception of has >3 BM/day which had p value of 0.004

My take: “GI problems are common in RTT and pose a significant medical burden to caregivers.” As such, it is a good idea to screen for treatable disorders including swallow dysfunction, constipation, and reflux.

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Key Advances in 2024: An Overview from GutsandGrowth (Part 2)

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This year I had the opportunity to give a lecture to our group that reviewed much of the important advances that happened in 2024. Here are some of the slides (if you have any trouble reading the slides, you can search for the original blog post using author name).

How to Sort Out Chronic Laryngeal Symptoms and Reflux

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Two recent articles provide some insight into the muddy waters of laryngeal symptoms and reflux which is a much bigger challenge in the adult population than in the pediatric age group.

AJ Krause et al. Clin Gastroenterol Hepatol 2024; 22: 1200-1209. Open Access! Validated Clinical Score to Predict Gastroesophageal Reflux in Patients With Chronic Laryngeal Symptoms: COuGH RefluX

AJ Krause et al. Am J Gastroenterol 2024; 119: 627-634. Diagnostic Yield of Ambulatory Reflux Monitoring Systems for Evaluation of Chronic Laryngeal Symptoms. Thanks to Dr. Benjamin Gold for this reference.

In the first study, there were a total of 856 adults, 304 in the training cohort and 552 in the validation cohort. Key finding: In the validation phase, the COuGH RefluX score had an area under the curve of 0.67 (95% CI, 0.62–0.71), with 79% sensitivity and 81% specificity for proven GERD. Graphical abstract from the first study:

In the second study, the authors retrospectively examined 813 adults with chronic laryngeal symptoms over a 5 year period comparing . The diagnostic yield for prolonged wireless pH testing (n=296) was compared to 24-hour pH-impedance monitoring (n=532) off anti-secretory agents. Key finding: the prolonged wireless pH testing had a yield of 50% compared to 27% for the 24-hr pH-impedance testing.

My take: In the 1st study, the scoring system of cough, obesity, globus sensation, hiatal hernia, regurgitation, and male sex provides a good idea about the likelihood of reflux. In the 2nd study, the authors conclude that prolonged wireless pH testing may be preferrable due to higher diagnostic yield. However, the more proper conclusion is that we still don’t know the best way to determine when reflux causes chronic laryngeal symptoms or even the best way to measure reflux.

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Improved Efficacy with Vonoprazan for Severe Esophagitis

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Briefly noted:

Q Zhuang et al. The American Journal of Gastroenterology  :10.14309/ajg.0000000000002714, March 22, 2024. Comparative Efficacy of P-CAB vs Proton Pump Inhibitors for Grade C/D Esophagitis: A Systematic Review and Network Meta-analysis

In this meta-analysis, 24 studies met criteria. Key findings:

  • Vonoprazan (20 mg) had the lowest rates of treatment failure: 6% in the initial treatment phase, and 21% in the maintenance phase of healing of grade C/D esophagitis
  • Vonoprazan had similar risk of incurring adverse events, severe adverse events, and withdrawal to drug when compared with PPI.

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Arching in Infants Not Due to Reflux

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M Njeh, S Jadcherla et al. J Pediatr 2024; 264: 113760. The Irritable Infant in the Neonatal Intensive Care Unit: Risk Factors and Biomarkers of Gastroesophageal Reflux Disease

This study analyzed “pH impedance testing in the NICU in 516 infants with symptoms of arching and irritability. A nurse was assigned to document episodes of arching and irritability during the study.”

Key findings:

  • Acid reflux and impedance bolus characteristics were not significantly different between infants with >72 and ≤72 arching/irritability events (P ≥ .05)
  • Arching/irritability events had an 8% sensitivity for reflux (3062/39,962). The specificity of arching/irritability for NOT being reflux was 94% (246,462/262,534)
  • Oral feeding was associated with more arching and irritability than tube feeding

R-A Deregenier. J Pediatr 2024; 264; 113844 (commentary) Rethinking Infant Irritability and Arching

“The study found that <10% of the clinical episodes were associated with acid reflux but episodes of arching and irritability were more common in infants with preterm birth, neurologic injury, or chronic lung disease.”

My take (in part, borrowed from authors): “Acid GER disease is unlikely the primary cause of arching/irritability and empiric treatment should not be used when arching/irritability is present.” Unfortunately, getting physicians to curtail the use of ineffective acid blockers in infants is a not making headway (Unfavorable Trends in Reflux Management of Infants) There is definitely enough material with reflux to devote a whole MythBusters show.

In addition to not being the main reason for arching,

  • Reflux is not a frequent reason for BRUEs
  • Reflux cannot be reliably-identified by ENTs. Red airway appearance is NOT indicative of reflux (poor specificity, poor sensitivity)
  • Reflux in infants does not improve with PPIs (more than placebo)
  • Fundoplication does not result in fewer hospitalizations or improve pulmonary outcomes
  • Treating reflux does not improve asthma and probably does not help throat symptoms either
  • Many kids (and adults) with “reflux” don’t have reflux

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Lisbon

Understanding Reflux/Airway Disease and Potential Role of Airway Impedance

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A recent blog post, Airway Impedance to Objectively Assess Airway Mucosal Integrity, reviewed a study by Rosen et al (R Rosen et al. J Pediatr 2023; 256: 5-10) which used a novel approach in assessing airway disease using airway impedance.

This month’s Journal of Pediatrics provides a terrific commentary by my partner, Jose Garza. Open Access: Airway Impedance: In Search of a New Tool (DOI:https://doi.org/10.1016/j.jpeds.2023.01.007).

The article first describes the history of identifying gastroesophageal reflux: “the first attempt to detect GER was in 1884 by Reichman, who lowered a sponge into the esophagus of a patient with heartburn and showed that it contained acid when retrieved. He found that fluid expressed from the sponge was acidic in persons with heartburn and alkaline in normal controls. The first in situ measurement of acid reflux in the esophagus is credited to Tuttle and Grossman 2 in 1958.”

With the development of multi-channel impedance, the concept of reflux has shifted in young children: “non-acid reflux events are more important to the development of symptoms than acid events.”

With regard to Rosen et al, the commentary reiterates that “measuring laryngeal mucosal integrity [using impedance] is safe and feasible in children with extraesophageal symptoms.” The study showed “no correlation between otolaryngology airway inflammation scores with airway impedance, further emphasizing the fact that we need to move away from these scores, as they have failed to show correlation with GERD and with laryngeal mucosal integrity.”

“The authors did find a decrease in airway impedance in patients with history of aspiration; those who aspirated more textures had lower median airway impedance. Therefore, not all airway inflammation is the result of reflux and oropharyngeal dysphagia–associated aspiration can cause GER-like symptoms and airway inflammation. Aspiration can be silent, and if we do not look for it, we are not going to find it.”

“Another group of patients with low airway impedance comprised patients receiving PPIs, which makes it clear that acid is not what is affecting the airway. Otherwise, PPIs would improve airway impedance.” 

My take (borrowed from author): “It is not yet clear whether measuring airway impedance will eventually become a widespread test with clinical applicability. However, the concepts advanced in this report are clearly a step in the right direction.”

Place Massena, Nice, France

More Proof That Transpyloric Feeds Protect the Lungs

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B Srivatsa et al. J Pediatr 2023; 255: 175-180. Transpyloric Feeding is Associated With Improved Oxygenation Compared With Gastric Feeding Among Nonintubated Extremely Low Birth Weight Infants

As noted in a previous blog, transpyloric (TP) feedings are equivalent to a fundoplication in reducing reflux. As such, it is not surprising that it is used in premature infants to minimize reflux-associated respiratory problems including aspiration and potentially mitigate bronchopulmonary dysplasia.

In this retrospective study with 56 extremely low birth weight infants, the authors analyzed oxygen saturation (SpO2) and action of inspired oxygen (FiO2) data (measured at 1-minute intervals) for 96 hours before and after institution of TP feeds.

Key findings:

  • No significant differences were observed in any oxygenation measures during TP vs gastric feeding among 14 intubated infants.
  • Among 42 nonintubated patients, significant improvements were observed in the median SpO2/FiO2 ratios (P = .001), median titration index (P = .05), median number of hypoxemic episodes (P = .02), and median severity of hypoxemic episodes (P = .008) after TP tube placement.

Discussion:

  • The authors note that a prior study (J Perinat Med 2021; 49: 383-387) had shown improvement in SpO2/FiO2 ratios in intubated patients (n=33). This discrepancy between the two studies could be due to differences in patient population, ventilation technique (high frequency vs conventional) and higher level of power due to more intubated subjects in the prior study.
  • The exact mechanism of improvement in oxygenation is a matter of speculation. “Does TP feeding in nonventilated patients result n fewer or less severe GER events, leading to less pulmonary microaspiration or laryngospasm?…Does aerophagia, more common among nonintubated patients on positive pressure support, exacerbate GER events and is it ameliorated with TP feedings?” It is also possible that TP feedings result in improvement due to a reduction in esophageal reflux mediated bronchoconstriction.

My take: TP feedings have been very helpful in clinical practice, especially in infants with feeding difficulties, reflux, and respiratory issues. Most of these problems are transitory. This study provides granular data showing the significant improvements in oxygenation following the initiation of TP feedings among non-ventilated ELBW.

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Does Positioning Help Infants with Reflux?

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IM Paul et al. JPGN Reports 2023; 4(2):p e312. Open Access! Pilot Study of Inclined Position and Infant Gastroesophageal Reflux Indicators

Methods: Healthy infants aged 1–5 months with gastroesophageal reflux disease (GERD) (N = 25) and controls (N = 10) were enrolled into one post-feed observation. Infants were monitored in a prototype reclining device for consecutive 15-minute periods in supine position with head elevations of 0°, 10°, 18°, and 28° in random order. Continuous pulse oximetry assessed hypoxia (O2 saturation <94%) and bradycardia (heart rate <100).

Key findings:

  • Overall, 17 (68%) infants had 80 episodes of hypoxia (median 20 seconds duration), 13 (54%) had 33 episodes of bradycardia (median 22 seconds duration), and 15 (60%) had 28 episodes of regurgitation.
  • For all 3 outcomes, incident rate ratios were not significantly different between positions, and no differences were discovered for observed symptoms or infant comfort.

Limitations: This was a one-feeding study with a small number of infants

My take: This study shows a high frequency of transient hypoxia and bradycardia in healthy infants with regurgitation. In addition, there was not improvement in reflux parameters in the inclined position.

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Tucson Botanical Gardens

Incredible Review of GERD, BRUE, Aspiration, and Gastroparesis

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Recently, Rachel Rosen gave a terrific review of reflux and reflux-related entities as part of our annual William (Billy) Meyers lectureship.  This lecture information would be helpful for every pediatric gastroenterologist as well as every pediatrician, pediatric ENT, pediatric pulmonologist, pediatric SLP and lactation specialist.  It puts to rest many obsolete ideas about reflux and its management. Some of her points have been covered by this blog previously (see links below) and by her bowel sounds podcast (see link below).   Some errors of omission and transcription may have occurred as I took notes during this lecture. 

Main points:

Reflux

  1. Using the label “GERD” increases the likelihood that an infant will be prescribed acid blockers; this phenomenon is noted as well with SLP and lactation specialist team members.  Everyone needs to be careful about ascribing infant symptoms to “reflux disease”
  2. AR formulas need acid to increase their viscosity (don’t use PPIs in infants taking AR formulas). Also, AR formula viscosity is hindered when mixed with breastmilk (don’t mix with breastmilk)
  3. Most infants with reflux have nonacid reflux.  PPIs do not help nonacid reflux
  4. PPIs are associated with increased aspiration and infection risks.  Acid suppression has been associated with increased risk of allergic diseases
  5. Rumination can look a lot like reflux on pH probe studies
  6. Reflux hypersensitivity, and functional heartburn can result in similar symptoms as reflux (can be distinguished with pH testing)
  7. Pepsin can increase lung inflammation and can be increased by PPI use
  8. Red airway appearance is NOT indicative of reflux (poor specificity, poor sensitivity)
  9. If having symptoms with transpyloric feedings, this indicates that the symptoms are NOT due to reflux; transpyloritc feedings have similar efficacy as a fundoplication
  10. Avoid fundoplication.  It does not result in fewer hospitalizations or improve pulmonary outcomes.  It can result in a number of complications
  11. Consider genotyping for CYP2C19 pharmacogenetics in patients receiving chronic PPI.  Those with rapid metabolism could benefit from higher doses.  Those with slow metabolism could benefit from lower doses.  Higher doses of PPIs increase risk for infections
  12. Bolus feedings result in fewer problems than continuous feedings

Delayed Gastric Emptying (Gastroparesis)

  1. Delayed GE is associated with increased lung bile acids.  This is important in lung transplant recipients and increased lung bile acids is seen more commonly in those with frequent admissions for respiratory issues
  2. In Dr. Rosen’s experience, prucalopride is currently the most useful promotility agent in documented gastroparesis

BRUE:

  1.  Infants with BRUE need to be tested for aspiration, not prescribed PPIs.
  2.  VSS (aka OPMS) has the highest yield of any test in infants with BRUE (~72% abnormal testing in one study). 
  3. Silent aspiration is common -don’t rely on SLP bedside assessment.
  4. Even with this diagnosis, many infants are still prescribed PPIs which increase the risk of complications (more hospitalizations, more infections, possible increase in allergies)

Aspiration:

  1. There are a number of potential etiologies, though most infants have aspiration due to neurological reasons (most transitory and improved by 7 months of age)
  2. In Boston, less than 5% with aspiration on VSS required GT placement
  3. Thickeners can be very helpful.  Practitioners need to know the differences (don’t use Simply Thick in 1st year of life due to NEC risk)

Chronic Cough:

  1. ~10% of kids with chronic cough have eosinophilic esophagitis (who have seen GI in Boston)

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Cacti at Tucson Botanical Gardens