Gastroesophageal reflux disease in infants is not fully understood. Infants are prescribed medical treatments that may not be effective or that contribute to adverse side effects and lead to concerns and expenses for the parents and healthcare system. Current guidelines recommend cow-milk-protein free diet as a first-line treatment, but these recommendations are based on weak evidence. This study investigate the efficacy of a cow-milk-protein free diet compared to treatment with a proton pump inhibitor (omeprazole)
An increasing number of infants less than one year of age have been referred to the pediatric departments with gastroesophageal reflux in the past decade. Gastroesophageal reflux is a common condition in infants defined as the passage of gastric contents into the esophagus with regurgitation or vomiting. Around 50% of infants younger than four months regurgitate or vomit regularly. In most cases, it is a harmless, self-limiting condition; in 90% of cases, the symptoms diminish before 12 months. However, if reflux leads to troublesome symptoms or complications, it is defined as gastroesophageal reflux disease. Troublesome symptoms may include failure to thrive, back arching, food refusal, regurgitation, and irritability. The prevalence of gastroesophageal reflux disease varies between studies. Infants can be treated medically, and proton pump Inhibitors have been recommended as the first choice. However, within the last few years, there has been concern among pediatricians that too many infants are unnecessarily treated with this medication. There are only a few randomized studies on proton pump inhibitor treatment in children under one year, and most studies do not show a significant effect on symptoms. Side effects of treatment with proton pump inhibitors include symptoms related to the gastrointestinal tract or airways, increased susceptibility to infections, and increased risk of developing allergy later in life. Within the past years, there has been attention to the overlapping of symptoms between gastroesophageal reflux disease and allergy to cow milk protein. Cow-milk-protein allergy is the most common food allergy in early childhood, with an estimated prevalence of 2-3%, and presents with various symptoms predominantly from the skin and gastrointestinal tract. Consequently, cow-milk-protein allergy can be challenging to differentiate from gastroesophageal reflux disease. Cow-milk-protein-allergy is an immune reaction and can be either immunoglobulin E-mediated, presenting with immediate reaction including anaphylaxis, or non-immunoglobulin E-mediated, presenting with delayed symptoms. In addition, it is possible that cow's milk can aggravate gastroesophageal reflux disease with a non-immunologic mechanism. As there is no biomarker to differentiate non-immunoglobulin E-mediated cow-milk allergy from gastroesophageal reflux disease, the diagnosis of non-immunoglobulin E-mediated cow-milk allergy can only be verified by an oral food challenge test preceded by a cow-milk-protein-elimination period. Therefore, in the updated international guidelines, all children with gastroesophageal reflux disease should start with a 2-4-week cow-milk-protein-elimination diet before a proton pump inhibitor is prescribed. However, evidence is scarce on the effect of a cow-milk-protein-free diet in infants diagnosed with gastroesophageal reflux disease.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
96
1 mg/kg /day
Mother on cow milk protein diet or infant on hypoallergenic formula in case of bottle fed
Placebo medicine (appearing substantially like Omeprazole) 1mg/ ml, and continuing nutrition containing cows' milk protein
Paediatric Department, Hospital of Southern Jutland
Aabenraa, Region Syddanmark, Denmark
RECRUITINGBørnelægecentret v/Kasper Dalby
Odense, Region Syddanmark, Denmark
NOT_YET_RECRUITINGH.C Andersen Childrens' Hospital
Odense, Region Syddanmark, Denmark
NOT_YET_RECRUITINGChange from baseline in reflux episodes in the fourth week of active treatment, compared to placebo
Parent-reported reduction in the weekly number of reflux-episodes in the fourth week of active treatment with either PPI or diet, compared to placebo. The outcome is registered daily in an App.
Time frame: Baseline and daily in 4 weeks.
Change from baseline in reflux episodes in the fourth week in the PPI group, compared to the diet group.
Reduction in the number of regurgitation episodes (compared to the run-in period) in the PPI group compared to the diet group
Time frame: Baseline and 4 weeks
Change from baseline in weight
A nurse or physician will perform the measurement on a weight in the clinic/hospital. Measurement unit: gram.
Time frame: Baseline and 4 weeks
Change from baseline in the number of reflux episodes with visible blood
Parent reported weekly number of reflux episodes with visible blood. Registered in MyCap App.
Time frame: 1,2,3,4 weeks
Change from baseline in the number of episodes with discomfort
Parent reported weekly episodes with discomfort 5 minutes after feeding. Registered in MyCap App
Time frame: 1,2,3,4 weeks
Change from baseline in the numbers of episodes with crying
Parent reported weekly numbers of episodes with crying 5 minutes after feeding. Registered in MyCap App
Time frame: 1,2,3,4 weeks
Change from baseline in the number of episodes of refusing breast/ bottle
Parent reported weekly numbers of episodes of refusing breast/bottle. Registered in MyCap App
Time frame: 1,2,3,4 weeks
Change from baseline in the number of episodes with short breathing pauses
Parent-reported weekly numbers of episodes with short breathing pauses. Registered in MyCap App
Time frame: 1,2,3,4 weeks
Change from baseline in the number of episodes with paleness/blue color in face or lips
Parent reported weekly numbers of episodes with paleness/blue color in face. Registered in MyCap App
Time frame: 1,2,3,4 weeks
Change from baseline in the number of episodes with troublesome breathing/cough
Parent reported weekly numbers of episodes with troublesome breathing/cough. Registered in MyCap App
Time frame: 1,2,3,4 weeks
Immunoglobulin E level
Blood positive/negative for specific immunoglobulin E for cows milk protein. Values above 0,35 kU/l are considered positive for cows' milk allergy.
Time frame: 4 weeks after treatment is started
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