The incidence and prevalence of food allergies are believed to be increasing in several countries [1
]. However, the comparison of data from different studies is difficult because criteria to diagnose food allergies, as well as the definitions of groups, vary substantially between studies. Therefore, rates vary from 35% when parental reports are used as criteria to define food allergies, to 1% when proper double-blind placebo-controlled food challenges (DBPCFC) are used [5
A study was conducted in the Isle of Wight in the United Kingdom in order to establish the rates of objectively-assessed food allergies in the 1st
year of life and to compare this with the rate of parental reports. A cohort of 969 infants was recruited between September 2001 and August 2002. Symptoms of food allergies were reported by 132 parents (14.2%) at 3 months, 83 parents (9.1%) at 6 months, 49 parents (5.5%) at 9 months, and 65 parents (7.2%) at 12 months of age [4
]. The cumulative incidence of reported parental perceived food hypersensitivities was 25.8% (250/969; 95% CI, 23.1% to 28.7%) by 12 months of age. Of these, only 14% and 6% were diagnosed with food allergies by means of open food challenges and DBPCFC, respectively. Thus, in this cohort, the incidence of food allergies by the age of 12 months was 2.6% (25/969; 95% CI, 1.7% to 3.8%) on the basis of open food challenge and 1.2% (12/969; 95% CI, 0.6% to 2.2%) on the basis of DBPCFC.
However, the actual occurrence of food allergies may be underestimated because challenge tests may be performed after the development of tolerance. This is a limitation for the method considered the gold standard for epidemiologic studies concerning food allergies. Therefore, the suggestion that the incidence of food allergies in the 1st
year of life ranges from 2% to 3% and symptoms compatible with food allergies found in 5% to 15% of infants may be reasonable and close to reality [1
]. As distinct from other studies, we evaluated the prevalence and incidence of symptoms suggestive of cow's milk allergy according to data collected in the offices of pediatric gastroenterologists. The prevalence of suspected cow's milk allergy was 5.4% in all consultations, and the incidence of new cases was 2.2%. The pediatric gastroenterologists agreed with the diagnostic hypothesis made by the referring pediatrician in 82.0% of the consultations. Although the diagnosis of cow's milk allergy was not established by a milk challenge, patients were started on a cow's milk-free diet, which is the initial approach for this disorder. Nearly one-half of the patients had already received a prescription to eliminate cow's milk protein from their diets when they were seen for the first time by their pediatricians. However, many infants were being fed inappropriate substitutes, such as soy-based infant formulas, extracts with soybean proteins, goat's milk, or even lactose-free cow's milk formula. Only 10.0% of the infants received extensively hydrolyzed or amino acid-based formulas, considered adequate substitutes recommended for infants with cow's milk allergy according to the European Society for Pediatric Allergology and Clinical Immunology (ESPACI), the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), and the American Academy of Pediatrics [7
Approximately one-half of the infants in the study were younger than 6 months of age. In this age group, gastrointestinal manifestations occurred at a greater frequency than in the group of infants older than 6 months of age. As expected, digestive symptoms were the most common (88.7%), including regurgitation and vomiting, colic, diarrhea, and blood in stools. A variety of gastrointestinal allergic disorders typically affect in infants and children. Infants with allergic colitis present small amounts of blood mixed with mucus in their stools. Cow's milk-sensitive enteropathy may present with malabsorption leading to diarrhea and failure to thrive. The most serious form of gastrointestinal food allergy in infants is food protein-induced enterocolitis syndrome which has a symptom complex of profuse vomiting and diarrhoea, and potentially a sepsis-like clinical picture [17
Cutaneous and respiratory symptoms were less frequent, possibly due to the fact that patients were referred to pediatric gastroenterologists. Although the predominant type of clinical manifestation may depend on the type of specialty care where the study patients are enrolled, there is a consensus that gastrointestinal or cutaneous symptoms are the predominant forms of presentation of cow's milk allergy.
A review of the literature did not yield studies with similar designs for comparisons. In a group of 204 infants with cow's milk allergy studied in the 1950s, the most common symptoms were atopic dermatitis in 43% of the cases, vomiting and regurgitation in 38%, colic in 31%, wheezing in 9%, irritability and anorexia in 22%, and constipation in 6% of the cases [18
]. The most remarkable difference from our data is that we observed a greater frequency of allergic colitis and less atopic dermatitis. This current trend is supported by a study conducted in London reporting a reduction in cases of cow's milk allergy associated with intestinal malabsorption due to infectious gastroenteritis [19
The mean z-score deviations, particularly for weight-for-age and height-for-age, suggest that failure to thrive or malnutrition may occur as a consequence of cow's milk allergy. The analysis of weight and height showed greater deficits (< -2.0 standard deviations) than expected (2.5%) according to the CDC-NCHS reference values (2000): specifically, 15.1% of weight-for-age, 11.3% of weight-for-height, and 23.9% of height-for-age z-scores (Table ). The World Health Organization has recently issued new weight and height reference charts for infants who were exclusively breastfed [20
]. These values were not used in our study because our patients were not breastfed, and this may help compare our data with other studies in the literature. A study reporting on a group of 26 Brazilian children demonstrated that 23% had a deficit in weight-for-age, 7.7% had a deficit in weight-for-height, and 11.5% had a deficit in height-for-age when the same diagnostic criteria and reference values were used. These patients were also shown to be receiving a diet with a lower energy intake and calcium content when compared with controls in the same age group and socioeconomic conditions. A nutritionally-inadequate elimination diet may lead to or aggravate anthropometric deficits of infants with symptoms suggestive of cow's milk allergy according to the few studies that investigated this issue [9
]. Our results have shown that height-for-age deficit was the most predominant indicator of nutritional impairment in contrast with the expected predominance of weight-for-age deficit. Similar findings were reported in children with constipation secondary to cow's milk allergy, who presented a mean height-for-age deficit (-0.90 ± 1.24) more pronounced than the weight-for-age deficit (-0.67 ± 1.30) [21
]. It may be possible that due to chronic inflammation secondary to milk allergy, linear growth may be impaired as it is observed in chronic liver disorders [22
In this study, approximately half of the patients referred to the paediatric gastroenterologists were already switched to a substitute infant diet. However, only 16% of patients were receiving extensively hydrolyzed formulas or amino acid-based formulas. The duration of the substitute diet and the efficacy of treatment were variable. Therefore, the nutritional deficit observed in patients at the time of inclusion in the study may be attributable either to the use of inappropriate milk substitutes or to the insufficient duration of treatment for nutritional recovery.
Cow's milk allergy in infants is usually non-IgE mediated, and the diagnostic hypothesis should be raised using clinical symptoms and, if available, functional and morphological markers of gastrointestinal function. Since there are no effective laboratory methods for the diagnosis of this disorder, an elimination diet without allergenic proteins remains the first essential step to make a diagnosis of cow's milk allergy. Clinical follow-up to evaluate the response to treatment (elimination diet) is an essential step in the management of these patients [23
]. After an initial phase of clinical and nutritional recovery, food challenges, when recommended, may provide a definitive diagnosis.