Tag Archives: Gastroesophageal Reflux

Vonoprazan for Nocturnal Reflux Symptoms

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C Antunes et al. Am J Gastroenterol 2026; 121:1866-1874. Open Access! Vonoprazan Improves Nocturnal Gastroesophageal Reflux Symptoms in Nonerosive Reflux Disease Thanks to Ben Gold for sharing this study.

Methods: This was a prospective, randomized, double-blind, placebo-controlled phase 3 study conducted at 91 centers across the United States. Adults (n=772) with heartburn ≥4 d/wk and without erosive esophagitis were randomized to placebo, vonoprazan 10 mg, or vonoprazan 20 mg. After 4 weeks, subjects on placebo were rerandomized to vonoprazan 10 or 20 mg, and those already on vonoprazan continued the same dose for an additional 20 weeks.

Key findings:

  • Median percentages of heartburn-free nights during the 4-week placebo-controlled treatment period were 45.5% for placebo, 70.4% for vonoprazan 10 mg, and 71.0% for vonoprazan 20 mg.

Discussion Points:

  • “In the few randomized controlled trials available which evaluated the effect of PPIs on nocturnal symptoms, the mean and median rates of heartburn-free nights with different therapies, as well as the placebo response, were similar to what we observed in our study (17–19)…Many of the PPI studies assessing therapies for nocturnal symptoms are limited because of their short follow-up duration, often limited to 2–4 weeks.”
  • Strengths of study: This was a “large multicenter study, placebo-controlled, with a diverse PPI-experienced patient population who presented with reflux symptoms occurring at baseline on approximately 75% of nights.”
  • Limitation: “A limitation of our study, and many previous studies of NERD, is the lack of positive pH testing to document acid reflux as the cause of symptoms. hus, some subjects likely had conditions other than reflux (e.g., functional heartburn) as a cause of their symptoms, which may reduce the overall response rates seen with acid suppression.”
  • “The response rates for nighttime heartburn with vonoprazan were not substantially different between patients who reported previous response to PPIs and those who did not, suggesting that previous PPI response may not be a predictor of response to treatment with vonoprazan. However, this observation was based on a post hoc analysis.”

My take (borrowed from the authors): “Vonoprazan had a rapid effect on nighttime heartburn symptoms which was sustained through 24 weeks.”

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NASPGHAN Paper: Dietary Management in Pediatric Aerodigestive and GI Dysmotility

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K El-Chammas et al. J Pediatr Gastroenterol Nutr. 2026; 83: 748-760. Dietary management and feeding considerations of pediatric aerodigestive and upper gastrointestinal motility disorders.

Oropharyngeal dysphagia (OPD):

  • “Untreated OPD (either penetration and/or aspiration) is associated with persistent symptoms, recurrent respiratory infections, elevations in pulmonary inflammatory markers, and even bronchiectasis”
  • “Because >80% of pediatric aspiration is silent, the presence of symptoms at the time of an aspiration event should not be the determining factor when considering thickening”
  • “Most infants with OPD and aspiration experience improvements in swallow function over time, and thickeners/delivery vehicles can be weaned or changed as swallow function, palate, and caloric needs change. Antegrade aspiration is unlikely to be seen in neurodevelopmentally normal children older than 2 years of age exhibiting persistent lower respiratory tract infections”
  • Table 2 lists common thickeners and key differences. In infants, cereals and gelmix (if >37 weeks gestational age) are recommended. In older age groups, xanthan gum (SimplyThick®), Corn starch (Thick-It®), Tapioca starch, and Tara gum (PuraThick®) are options.
  • “Thickening gastrostomy tube feeds either with commercial thickeners or food improves GI and pulmonary outcomes and reduces the number of gastroesophageal reflux events without prolonging gastric emptying”
  • Table 3 provides specific recommendations including the following: ‘The recommended thickener for formula-fed infants younger than 1 year of age is cereal or purées. Commercial thickeners may be an option for some expressed breast milk- or formula-fed infants under the age of 1 year without comorbidities, depending on institutional practices.”

Esophageal Dysmotility

This section reviews several disorders including achalasia, gastroesophageal reflux, and esophageal atresia.

  • Reflux: In infants with reflux, “thickening of feeds can reduce overt symptoms such as vomiting but does not decrease reflux events.” Also, in this population, “a trial of maternal cows’ milk elimination, extensively hydrolyzed or amino-acid based formulas (in more severe cases with intractable symptoms) may be appropriate”
  • Achalasia: “There are no clear guidelines on the management of feedings in pediatric or adult patients with achalasia…Patients should be encouraged to eat in an upright position and to minimize eating for several hours before bedtime. A liquid or purée may be required with the guidance of a dietitian to ensure adequate nutritional intake while waiting for the diagnosis and definitive management of achalasia”
  • Esophageal atresia: “Only 28% of children with EA are consuming age‐appropriate food textures within the first 2 years of life, with that improving to 70% of children over 5 years of age…Many infants with EA require gastrostomy tube placement because they cannot safely tolerate oral feeding or meet caloric requirements”
  • Table 4 summarizes recommendations for esophageal dysmotility, including “children with esophageal dysmotility should avoid foods with a high risk for esophageal obstruction/irritation, eat in an upright position, and avoid eating several hours before bedtime”

Gastric Dysmotility

  • “Most pediatric cases are idiopathic or post-viral, with less common causes being drug-induced or post-surgical”
  • “While dietary modification is often considered first-line therapy in patients with mild gastroparesis, it often results in suboptimal improvement in symptoms in clinical practice. Small, frequent meals and maintaining a post-prandial upright position may be better tolerated.74, 75 Liquids typically empty from the stomach faster than solids76; therefore, increasing liquid calories and switching from solid to liquid calories later in the day may help patients with their symptoms.”
  • “Fatty, acidic, spicy, and high-fiber foods can exacerbate symptoms in patients with gastroparesis as they delay gastric emptying, exacerbate pain, and promote release of cholecystokinin”
  • “Small-particle diets, consisting of puréed, blended, or finely ground foods, facilitate gastric emptying by reducing mechanical workload on the stomach”
  • “Caution is advised when initiating enteral or parenteral nutrition in patients with gastroparesis given the significant overlap with functional dyspepsia and increased prevalence of feeding intolerance in adolescents with disorders of gut–brain interaction”
  • “In aerodigestive patients with upper gut dysmotility and feeding intolerance, gastrostomy and/or post-pyloric tube placement may provide access to decompress as well as provide nutrition when oral feeding is inadequate to sustain appropriate growth and symptom control”
  • “Blenderized tube feeds may be considered over commercial formulas to help with symptoms, decrease healthcare utilization, and improve quality of life…The American Society for Parenteral and Enteral Nutrition recently published detailed practice recommendations (L Epp et al. Nutr Clin Pract. 2023; 38(6): 1190-1219) providing guidance to medical providers and family pertaining to the use of BTFs regardless of their indication”

My take: This is a useful article regarding potential dietary interventions across a wide range of pediatric GI disorders. Just like medications, dietary interventions can result in complications. As such, the involvement of experienced dietitians and careful follow-up are needed.

Related blog posts:

Dysphagia:

Esophageal dysmotility:

Blenderized Diets:

Gastroparesis:

Here’s Why CYP2C19 Testing May Be Helpful For Refractory Reflux

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Recent pediatric Rome V recommendations suggested the use of CYP2C19 testing in patients with reflux that was not responding to time-limited therapy (link: Rome V Pediatric Upper Gastrointestinal Disorders of Gut-Brain Interaction (Part 1)). The following retrospective study of adults (n=421) at an academic medical center provides a strong rationale.

L Creech et al. Clin Gastroenterol Hepatol 2026; 24: 1550-1557. Open Access! High Prevalence of CYP2C19 Rapid and Ultrarapid Metabolism Among Patients With Gastroesophageal Reflux Disease

Key finding:

  • 44% (n=184) of patients presenting to gastroenterology clinic with gastroesophageal reflux disease who underwent CYP2C19 genotyping were found to be rapid metabolizers (RMs) (38%) or ultrarapid metabolizers (6%)
  • The prevalence of Barrett’s esophagus/erosive esophagitis was higher among ultrarapid metabolizers (24%; n = 5/21) than among normal metabolizers (7%; n = 12/165; odds ratio, 3.5)
  • Among the 184 RMs, 79% (n = 146) had a change in management due to CYP testing results: 65% (n = 120) changed their medication (89 patients were switched to rabeprazole), 22% (n = 41) continued PPI therapy, and 14% (n = 26) increased their PPI dose

Discussion points:

Prevalence of CYP RMs in Other Studies:

  • “Ionovo et al studied over 2 million patients who underwent genetic testing using 23andMe and found that the rate of RMs (∗1/∗17) in the general population was 26.0%, and the rate of URMs (∗17/∗17) was 4.4%.25“
  • “Fricke-Galindo et al analyzed data from 138 studies of over 52,000 healthy volunteers from around the world.26 The highest rates of combined RMs and URMs were reported in the Middle Eastern populations (36%), followed by European (28.6%), African (16.8%), and Asian populations (3.4%).26 The prevalence was 26.7% in the United States.”
  • “Among GI clinical practice guidelines, the 2025 American Society for Gastrointestinal Endoscopy (ASGE) guideline was the first to suggest routine incorporation of CYP testing into the management of patients with GERD.30“
  • “PCABs offer a viable alternative to PPIs in patients who are RMs and should be considered accordingly. PCABs are also not dependent on preprandial dosing and thus are easier for patients to take. However, the cost of PCABs continues to be a limiting factor.”
  • Testing cost: “A typical out-of-pocket price of $250 to $400 and is covered by some insurance.39“
  • Limitations: The study population has a selection bias compared to the general population. Patients referred to a GI clinic are more likely to have treatment-refractory GERD and thus have higher rates of RMs.

My take: In patients with established GERD who are not responding to treatment, CYP testing may be helpful. This is probably true for patients with EoE as well. In patients with GERD who are RMs, options include changing to rabeprazole, higher doses, or possible use of PCABs.

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How Long Should a pH Probe Last to Accurately Diagnose Gastroesophageal Reflux

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RI Rusu et al. Clin Gastroenterol Hepatol 2026; 24: 365-374. Open Access! The Optimal Duration of pH Monitoring: Testing the Validity of Lyon 2.0 Recommendations for Wireless pH Measurement

Background: “The Lyon 2.0 consensus recommends 96-hour wireless pH studies for gastroesophageal reflux disease (GERD) diagnosis…Ninety-six-hour monitoring is not always possible, either for technical reasons (eg, early detachment of the pH sensor) or for practical and financial reasons (48-hour studies are routine and cost-efficient in many centers).”

Methods: Data from 944 patients (16-85 years) with 4-day recordings (Bravo capsule) was reviewed. Patients were classified at 24, 48, and 72 hours against the 96-hour reference standard. Acid exposure time (AET) <4% was conclusively negative, and AET >6% was conclusively positive for GERD.

Key findings:

  • With longer duration, more patients were able to be diagnosed with GERD and fewer patients were in the indeterminate group. The proportion of patients with inconclusive results (AET 4%–6%) reduced from 113 of 944 at 24 hours to 40 of 113 at 96 hours (35% of subgroup; P = .02)
  • Only 3 of 60 patients with LA grade B esophagitis demonstrated physiologic reflux burden across all 96 hours of recording (which indicates that for significant reflux esophagitis, pH monitoring is not needed in most cases)
  • In the associated editorial (pg 306-308), the authors note that “the minimum duration for an effective study seems to be 3 days, because ~90% of conclusively positive studies identified over 4 days would be detected with 72 hours of recording. However, to achieve this, a 4-day study would need to be planned because of potential data loss, reported in almost a third of the cases in this and prior cohorts.”
  • “96-hour wireless monitoring is optimal for ruling out GERD when the pretest likelihood of reflux is low, especially when empiric PPI therapy is ineffective.”

My take: pH probe tests have many limitations. This study reinforces the need for longer studies in many patients when the findings would be equivocal with shorter duration studies.

Related blog post:

#5000: Simple Rule for Deciding When pH Impedance Testing Should Be Done While on Therapy

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Editor’s note: This is the 5000th post on this blog! The first post was on December 7th, 2011.

Iguazu Falls

CP Gyawali et al. Clin Gastroenterol Hepatol 2025; 23: 2459-2467. Open Access! pH Impedance Monitoring on Proton Pump Inhibitor Therapy Impacts Management Decisions in Proven GERD but Not in Unproven GERD

Methods: Prospective 2-center study enrolled adult patients (n=79) with typical reflux symptoms with incomplete PPI response; they were studied both off PPI (wireless pH monitoring) and on PPI (pH-impedance monitoring)

Key findings:

  •  In 60 patients with proven GERD off-PPI, 56.7% had no ongoing GERD on PPI (despite reflux symptoms)
  • In unproven GERD, pH-impedance monitoring on acid suppressive therapy is unable to differentiate non-GERD symptoms from controlled GERD in the majority of patients, or identify patients who could benefit from discontinuation of acid suppression

Discussion points:

  • “Only a small proportion of PPI nonresponders have true GERD, and most have either no GERD or overlap between inconclusive GERD and a non-GERD process such as an esophageal disorder of gut-brain interaction (E-DGBI).10,11“
  • “On-therapy pH-impedance monitoring can identify refractory GERD in patients with previously proven GERD.”
  • “Definitive GERD evidence and persisting symptoms despite optimized PPI therapy is an indication for escalation of management.20… potassium competitive acid blockers provide better healing of advanced grade esophagitis21 as well as faster symptom response in nonerosive reflux disease,22,23 and could be an option”

My take:

  1. Simple rule: Only perform on-therapy pH-impedance monitoring in patients with proven GERD
  2. Many patients with GERD symptoms do not have GERD (see posts below)
  3. In patients with documented GERD, on therapy pH monitoring can be helpful in proving refractory GERD which may benefit from alternative treatments

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VISION 5-Year Study Results: Safety of Vonoprazan in Erosive Esophagitis

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N Uemura et al. Clin Gastroenterol Hepatol 2025; 23: 748-757. Open Access! Vonoprazan as a Long-term Maintenance Treatment for Erosive Esophagitis: VISION, a 5-Year, Randomized, Open-label Study

Background: Potassium-competitive acid blockers, such as vonoprazan, provide more potent gastric acid suppression than proton pump inhibitors. However, long-term safety data are lacking for vonoprazan in patients with healed erosive esophagitis. This study with 208 patients provides long-term data on the use of a vonoprazan.

Methods: Open-label study. Patients with erosive esophagitis (EE) received induction therapy (once daily vonoprazan 20 mg or lansoprazole 30 mg; ≤8 weeks). Those with healed EE received maintenance therapy (once daily vonoprazan 10 mg or lansoprazole 15 mg) for 260 weeks (2:1). 

Key findings–Adverse effects:

  • No malignant alterations or gastric neuroendocrine tumors (NETs) were observed; there was 1 adenoma in each group
  • At week 260, significantly more patients taking vonoprazan vs lansoprazole had parietal cell hyperplasia (97.1% vs 86.5%) and foveolar hyperplasia (14.7% vs 1.9%)
  • proportions of patients with ECL cell hyperplasia (4.9% vs 7.7%) and G-cell hyperplasia (85.3% vs 76.9%) were similar
  • Median serum gastrin levels were higher with vonoprazan treatment vs lansoprazole (625 pg/mL vs 200 pg/mL)

Key finding –Efficacy:

  • Overall, the cumulative EE recurrence over 260 weeks was lower in the vonoprazan group (10.8% ) vs the lansoprazole group (38.0%) (P = .001)  

Discussion Points:

  • “Annual endoscopies and biopsies performed in the VISION study are considered objective approaches for detecting upper gastrointestinal diseases and variable lesions, as well as gastric mucosa morphological changes in areas without endoscopically apparent lesions…Although the proportions of patients with parietal cell protrusion and foveolar hyperplasia were higher in the vonoprazan group than in the lansoprazole group over 5 years, the clinical significance of these findings is unclear.”
  • “The safety profiles of vonoprazan and lansoprazole were also comparable, suggesting that long-term use of vonoprazan is as safe as PPIs.”

My take: This study provides some reassurance regarding the risk of using vonoprazan & other potassium-competitive acid blockers. The benefits of controlling erosive esophagitis may outweigh potential safety risks of long-term use. Nevertheless, it will be a while before this class of medications is used extensively in the pediatric age group.

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Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Unfavorable Trends in Reflux Management of Infants & Update on USNWR Rankings

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T Achler et al. J Pediatr 2023; 252: 141-145. Trends and Correlates of Early-Life Exposure to Acid-Suppressant Therapy in Israel (2005-2020)

In this retrospective study from Israel with nearly 600,000 children, key findings:

  • The incidence rate of acid-suppressant medication use increased by 2.8-fold from 18.2 per 1000 in 2005 to 51.0 per 1000 in 2020
  • Primary care providers accounted for 74.8% of prescribing physicians in 2005 vs 96.1% in 2020, whereas the prevalence of prescribing gastroenterologists decreased from 18.8% to 2.8%
  • Other factors associated with increased use: first born child, male sex, multiple births and greater socioeconomic status; this latter group is more likely driven by health-seeking tendency rather than financial disparity due to national health insurance

Comments: This high use of acid suppression medications in infancy has been reported in multiple other studies despite the lack of efficacy in prior studies. Pediatricians, more than pediatric gastroenterologists, may be less familiar with the GERD guidelines and potential adverse effects of acid suppression (including association with an increase food allergies).

My take: This Israeli study shows that pediatric gastroenterologists are using acid blockers less in infants while pediatricians are using them more often. It is interesting that after the first child, parents are less likely to seek medical attention & are more tolerant of reflux symptoms.

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Is Reflux Really a Disease in Premature Infants?

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From Atlanta Botanical Garden

Z Sultana et al. Gastro Hep Advances 2022; 1: 869-881: Open Access! Symptom Scores and pH-Impedance: Secondary Analysis of a Randomized Controlled Trial in Infants Treated for Gastroesophageal Reflux

In the introduction, the authors note: “Gastroesophageal reflux (GER) is a physiological process defined as the passage of gastric contents into the esophagus with or without regurgitation and vomiting, while GER disease (GERD) is pathophysiologic and occurs when GER is associated with troublesome symptoms and/or complications.”

“This distinction between GER and GERD remains enigmatic among survivors in the neonatal intensive care unit (NICU). Reflux-type symptoms (arching, irritability, acute life-threatening events, coughing, failure to thrive, and swallowing difficulties) in this high-risk infant population can be troublesome to the parent and provider, and empiric management using pharmacological and dietary changes are common albeit with consequences.”

Methods: “Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R) and 24-hour pH-impedance data were analyzed from 94 infants…[and] Longitudinal data from 40 infants that received randomized GER therapy (proton pump inhibitor [PPI] with or without feeding modifications) for 4 weeks followed by 1-week washout were analyzed. Relationships between I-GERQ-R and pH-impedance metrics (acid reflux index, acid and bolus GER events, distal baseline impedance, and symptoms) were examined and effects of treatments compared.”

Key findings:

  • Acid-suppressive therapy with feeding modifications had no effect on symptom scores or pH-impedance metrics. Clearance of refluxate worsened despite PPI therapy.
  • Correlations between I-GERQ-R and pH-impedance metrics were weak or non-existent, indicating that physicians cannot depend only on the questionnaire to diagnose and treat GERD in premature infants.

My take: This study shows that reflux symptoms are unreliable in establishing a diagnosis of reflux disease in infants. In addition, medical treatments were not beneficial in infants with abnormal pH-impedance metrics. Perhaps, it is time to acknowledge that we cannot even agree what reflux “disease” is in (premature) infants.

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“Pediatric Formula Basics”

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CHOA Nutrition Support Core Seminar -Thanks to Kipp Ellsworth for organizing this series and sharing content. This lecture is a really good review and would be a great place to start when discussing formulas with medical students and residents.

Link to Webex (49 min): “Pediatric Formula Basics” by Clancy Bryant, MS, RD (March 2, 2021). Password: FbhSgup5

Also, can reach via: Our first Nutrition Support Core Lecture of 2021: “Pediatric Formula Basics” by Clancy Bryant, MS, RD-20210302 1810-1

Key points:

  • This lecture reviewed selection of formulas for infants, children and adolescents; some of the most common formula choices (but not all) were reviewed
  • This talk reviewed reflux guidelines as reflux symptoms often impact decisions on formula choice in infancy. Thickened formulas like Enfamil AR and Similac Spit Up do not work with acid suppression medications.
  • WIC resources (for children <5 years) -can identify through website: https://dph.georgia.gov/WIC/wic-formula-resources
    • WIC script requires 2 ICD-10 diagnosis which are relevant to chosen formula
    • For standard formula, no prescription is needed; if formula is not on WIC formulary, it will not be covered
    • If child is NPO, write for “patient is NPO, please give maximum formula”
  • For cholestatic liver disease: high MCT formulas include pregestamil (55%), Alimentum (33%) and elemental formulas (33-49%)
  • For chylous effusions, very high MCT formulas (83%, 84%) include enfaport and monogen (needs EFA supplementation)
  • Formulas for children and adolescents come in concentrations of 0.6 kcal/mL to 2.0 kcal/mL
    • Reduced calorie formulas (eg. Pediasure Reduced Calorie or Compleat Pediatric Reduced Calorie) are helpful to provide adequate micronutrients/protein in children with hypocaloric needs
  • Blenderized formulas often helpful for children with retching (when given via gastric route); some of these may increase vitamin A levels and beta-carotene (eg. Nourish, Compleat Pediatric Organic Blends). Real food blends are not nutritionally-complete. Harvest is able to run through enteral tube without dilution.
    • For those older than 10 years of age, Liquid Hope is similar to Nourish and Compleat Organic Blends is similar to Compleat Pediatric Organic Blends
  • Low electrolyte formulas, like Renalcal and Renastart, may be useful for children with kidney dysfunction. Corresponding formulas for >10 years of age include Suplena and Novasource Renal
  • Kate Farms is often a good choice for patients with multiple allergies or eosinophilic esophagitis

Some of the slides:

Formulas for 1-10 years of age.

Adult formulas (>10 years):

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