Table 1. Inclusion and exclusion criteria.
| Inclusion criteria | Exclusion criteria |
|---|---|
| –Infants <13 months of age | –Infants <2,500 g at birth |
| –Clinical history or strong suspicion of an allergic reaction to cow’s milk protein with at least one of the following gastrointestinal symptoms: | –Infants <37 weeks of gestation requiring premature formula at study entry |
| (i) Chronic poor weight gain after dietary inclusion of cow’s milk protein | –Infants with severe concurrent illness |
| (ii) Frequent regurgitation or vomiting, whereby symptoms are related to the cow’s milk protein | –Infants with functional gastrointestinal symptoms, where atopy and food allergy is not suspected |
| (iii) Extended periods of diarrhea with a negative stool examination (lab test-negative) | –Infants with (auto)immune and gluten-sensitive enteropathy |
| (iv) Soft stool constipationa (with/without perianal rash not due to infection) | –Infants with FPIESb |
| (v) Blood in stool | –Behavioral disorders with food aversion or food phobia |
| (vi) Iron deficiency anemia due to occult or macroscopic blood loss in stool not due to infection | –Infants who have acute chronic diarrhea secondary to confirmed infectious gastroenteritis (lab test-positive) |
| (vii) Endoscopically confirmed eosinophilic enteropathy | –Infants who have undergone gastrointestinal surgery (e.g., bowel resection, stoma) |
| (viii) Persistent distress or colic (>3 h/day, at least 3 days/week over a 3-week period) | –Infants with Down’s syndrome or other syndromes, where functional gastrointestinal disorders are common |
| –If performed results of specific IgE tests and/or SPT for cow’s milk protein are negative | –Use of probiotic bacteria or probiotic containing drinks/supplements/formula 4 weeks before study |
| –Expected minimum study formula intake per day at the end of week 2, 500 ml (0–6 months), 450 ml (6–8 months), and 350 ml (≥9 months) | –Use of systemic antibiotics or antimycotics 4 weeks before study |
FPIES, Food Protein-Induced Enterocolitis Syndrome.
a
Soft stool constipation is a term used when a subject uses excessive straining to pass liquid or soft stool (with an occasional hard plug).
b
FPIES, which is associated with very severe symptoms, was excluded to reduce subject heterogeneity.