Children are an understudied and vulnerable population. Prescription drugs are often used outside the specifications described in their license in terms of age restrictions and reasons for use. Symptoms of gastroesophageal reflux (GER) and gastroesophageal reflux disease (GERD) are common during childhood and may affect up to 40% of infants and children. Due to the encouraging safety profile and wide use of proton pump inhibitors (PPIs) in adults, coupled with the high prevalence of GER problems in children, children are being increasingly prescribed this class of drugs.
PPIs decrease acid production in the stomach. Only one of the five commercially available PPIs is approved for use in neonates (<1 month old), with the remaining four PPIs approved for use in children >1 years old. Despite these regulatory restrictions, PPIs are being prescribed in infants and children with minimal evidence regarding their safety or effectiveness. Recently, safety concerns have emerged regarding possible harmful effects in children. These safety signals include a potential increased risk for nutritional deficiencies (low iron and vitamins levels), gastroenteritis (infectious diarrhea), and inflammatory bowel disease.
Our study will use the Clinical Practice Research Datalink (CPRD) Aurum to compare the occurrence of iron deficiency anemia, vitamin B12 deficiency, gastroenteritis, and inflammatory bowel disease with PPI use versus histamine H2-receptor antagonist (H2 RA) (another class of acid suppressing drugs) use among children with GER/GERD. We will link these data with hospitalization data.
This study will provide a better understanding of the safety of PPI use in children.
The high prevalence of GER/GERD in children is becoming increasingly recognized. These conditions produce a variety of symptoms, including regurgitation, abdominal pain, and respiratory symptoms that can affect the quality of life of children and their parents. PPIs are acid suppressing drugs that are commonly prescribed for the management of GER/GERD among children. However, limited evidence is available regarding their effectiveness and safety among pediatric patients. A limited number of clinical trials have examined their safety; however, these studies were conducted in small numbers and only examined short-term outcomes.
We will conduct a population-based, retrospective cohort study using CPRD Aurum, linked to Hospital Episodes Statistics Admitted Patient Care data. We will include infants and children aged 6 months to 18 years with a diagnosis of GER/GERD between January 1998 to June 2019. Our primary objective is to compare rates of iron-deficiency anemia among children with GER/GERD currently exposed to PPIs to that of children currently exposed to H2 RAs. Our secondary objectives are to assess 1) the risk of the vitamin B12 deficiency with PPIs versus H2 RAs among children with GER/GERD; 2) the risk of gastroenteritis with PPIs versus H2 RAs among children with GER/GERD; 3) the risk of inflammatory bowel disease with PPIs versus H2 RAs among children with GER/GERD; 4) the risk of outcomes of interest with PPI users versus unexposed children; and 5) the patterns of PPIs prescribing. We will create a cohort of children with incident GER/GERD during the study period. We will classify the cohort members according to their exposure status: 1) exposed to PPIs; 2) exposed to H2 RAs; 3) not-exposed. Cox proportional hazards models with covariates will be used to estimate hazard ratios and 95% confidence intervals. Extensive sensitivity analyses will be performed.
Primary: Iron-deficiency anemia
Secondary: Vitamin B12 deficiency, gastroenteritis, inflammatory bowel disease
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Kristian Filion - Corresponding Applicant - McGill University
Claire Lefebvre - Collaborator - University Of Montreal
Joseph Delaney - Collaborator - University of Manitoba
pauline reynier - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Reem Masarwa - Collaborator - PPD North America
Robert Platt - Collaborator - McGill University
Samuel Igweokpala - Collaborator - McGill University
Reem Masarwa - Collaborator - McGill University
HES Admitted Patient Care