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Updated: Mar 9, 2026
Simultaneous Laryngopharyngeal and Conventional Esophageal pH Monitoring
Published on: December 14, 2020
Dose-Finding Study of Omeprazole on Gastric pH in Neonates with Gastro-Esophageal Acid Reflux Using a Bayesian
Florentia Kaguelidou1,2, Corinne Alberti3,4, Valerie Biran5,6
1Assistance Publique - Hôpitaux de Paris, Department of Pediatric Pharmacology and Pharmacogenetics and INSERM CIC1426, Hôpital Robert Debré, Paris, France.
Insights
The minimum effective dose (MED) of omeprazole for pathological acid reflux in neonates varies by gestational age. Preterm infants (born <32 weeks GA) require 2.5 mg/kg/day, while term infants (born >32 weeks GA) need 1 mg/kg/day.
Area of Science:
- Neonatal Medicine
- Pharmacology
- Gastroenterology
Background:
- Proton pump inhibitors (PPIs) are commonly used for neonatal reflux, but their efficacy is debated.
- Limited trials exist for validating omeprazole dosage in neonates.
- Pathological acid reflux in neonates requires precise dosing for effective treatment.
Purpose of the Study:
- To determine the minimum effective dose (MED) of omeprazole for treating pathological acid reflux in neonates.
- To utilize the reflux index as a surrogate marker for treatment efficacy.
- To establish evidence-based omeprazole dosing guidelines for neonatal populations.
Main Methods:
- A double-blind, dose-finding trial using a Bayesian continual reassessment method.
- Neonates (≥35 weeks postmenstrual age) with a reflux index ≥5% were included and stratified by gestational age.
- Five oral omeprazole doses (1-3 mg/kg/day) were tested, with efficacy measured by reflux index <5% after 72±24 hours.
Main Results:
- Fifty-four neonates with reflux index 5.06-27.7% were analyzed.
- The MED was 2.5 mg/kg/day for preterm neonates (<32 weeks GA; n=30), with 97.7% probability of success.
- The MED was 1 mg/kg/day for term neonates (>32 weeks GA; n=24).
Conclusions:
- Omeprazole dosing for neonatal acid reflux should be validated and individualized.
- Gestational and postnatal ages influence optimal omeprazole dosage.
- Further research is needed to clarify the differential impact of age on omeprazole efficacy.
Objective:
Proton pump inhibitors are frequently administered on clinical symptoms in neonates but benefit remains controversial. Clinical trials validating omeprazole dosage in neonates are limited. The objective of this trial was to determine the minimum effective dose (MED) of omeprazole to treat pathological acid reflux in neonates using reflux index as surrogate marker.
Design:
Double blind dose-finding trial with continual reassessment method of individual dose administration using a Bayesian approach, aiming to select drug dose as close as possible to the predefined target level of efficacy (with a credibility interval of 95%).
Setting:
Neonatal Intensive Care unit of the Robert Debré University Hospital in Paris, France.
Patients:
Neonates with a postmenstrual age ≥ 35 weeks and a pathologic 24-hour intra-esophageal pH monitoring defined by a reflux index ≥ 5% over 24 hours were considered for participation. Recruitment was stratified to 3 groups according to gestational age at birth.
Intervention:
Five preselected doses of oral omeprazole from 1 to 3 mg/kg/day.
Main Outcome Measures:
Primary outcome, measured at 35 weeks postmenstrual age or more, was a reflux index <5% during the 24-h pH monitoring registered 72±24 hours after omeprazole initiation.
Results:
Fifty-four neonates with a reflux index ranging from 5.06 to 27.7% were included. Median age was 37.5 days and median postmenstrual age was 36 weeks. In neonates born at less than 32 weeks of GA (n = 30), the MED was 2.5mg/kg/day with an estimated mean posterior probability of success of 97.7% (95% credibility interval: 90.3-99.7%). The MED was 1mg/kg/day for neonates born at more than 32 GA (n = 24).
Conclusions:
Omeprazole is extensively prescribed on clinical symptoms but efficacy is not demonstrated while safety concerns do exist. When treatment is required, the daily dose needs to be validated in preterm and term neonates. Optimal doses of omeprazole to increase gastric pH and decrease reflux index below 5% over 24 hours, determined using an adaptive Bayesian design differ among neonates. Both gestational and postnatal ages account for these differences but their differential impact on omeprazole doses remains to be determined.
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