In this study, we have found that adverse reactions to milk start early in life. All but one in our cohort presented symptoms before 3 months of age. Symptoms appeared mainly in the gastrointestinal and respiratory organs. The majority of the children had symptoms in more than one organ. We found just one child with IgE-mediated allergy to cow's milk. Half of the children were tolerant to milk at 1 year of age. The premature children had debut of symptoms at the same age as the term children, and they also had the same mixture of symptoms.
In this birth cohort of 555 children, we have found the frequency of adverse reaction to milk to be 4.9%, which is in accordance with Moneret-Vautrin, reporting between 2 and 5%, but somewhat more than Host and Martorell, reporting 2–3% (1
). We found that 17 of 27 (63%) children presented with symptoms during the first month of life. That most of the children had debut of symptoms before 3 months of age is in accordance with earlier studies by Host (1
In our population, the frequency of atopic dermatitis in children with adverse reactions to milk was 37% during the first year of life. We found gastrointestinal symptoms in 66% of the children and respiratory symptoms in 37%. This is all in accordance with other investigators (1
Interestingly, we found just one child with IgE-mediated CMA that is 3.7% of children with adverse reactions to milk. This is much less than that reported by Moneret-Vautrin and Kamelmaz, who reported 14% and 73%, respectively, with IgE-mediated allergy (2
It may be argued that we might have overlooked some children with IgE-mediated allergy to cow's milk. We consider this unlikely, because of the very close follow-up with personal interviews by phone at 1, 4 and 12 months, and also written questionnaires at 6 and 12 months. All children with any symptom, even vague, were invited to an examination, and no one failed to appear. Therefore, we are quite certain that in this birth cohort the frequency of IgE-mediated CMA before 1 year of age is low, that is, 0.2%.
The apparent discrepancy between IgE- and non-IgE-mediated adverse reactions to milk might be explained by an over-diagnosing of non-IgE-mediated reactions. We find this unlikely as the diagnosis was based on convincing results of the elimination/challenge test, with close follow-up in a hospital setting during the procedure. In cases where the result of the challenges was inconclusive, we did not consider this to be an adverse reaction to cow's milk, even though these children might possibly have had an early development of tolerance.
Most of our children were diagnosed between 1 and 4 months of age. In cases of early development of tolerance, we might have lost the diagnosis if the interviews or questionnaires had been postponed until later in the first year of life, as half of the group were tolerant at 1 year. This might explain the large number of non-IgE-mediated adverse reactions.
Another explanation of the apparent discrepancy between IgE- and non-IgE-mediated adverse reactions is the rather surprising finding of respiratory symptoms as the main complaint. In these cases, one could easily overlook the diagnosis by examining the child with regard to respiratory infections or an early debut of asthma.
At 1 year of age, all the children had a planned open provocation at the hospital. Half of the children in our study, 14 of 27, showed no adverse reactions to milk at that age. This is in accordance with earlier studies by Host and Martorell (1
). We find a planned challenge, especially important for an early diagnosis, based on elimination/challenge tests. In the lack of objective criteria, one has to keep in mind that the diagnosis might be wrong, as well as the fact that early tolerance is usual, and therefore, an early challenge is reasonable.
The child with IgE-mediated CMA was not tolerant at 1 year of age.
We find the same frequency and the same symptoms and age of debut in premature and term children. To our knowledge, there is no report in the literature on these topics. At 1 year, 6 out of 13 nontolerant children were premature. More term children than premature children had become tolerant. The difference is not significant; however, the groups may be too small for evaluation. Theoretically, premature children may have a tendency to become tolerant later than term children, due to delayed development of their immune system.
We are aware of the fact that the gold standard for diagnosing food allergy is double-blind, placebo-controlled (DBPC) challenge (13
). In the literature, however, there is support for open elimination/challenge test below the age of 1 (1
). For practical and clinical reasons, we found it impossible to do DBPC challenges in the age group of 1–6 months, when most Norwegian infants are mainly breastfed. It is difficult, for practical reasons, to carry out the DBPC challenge through the mother.
Another possibility for an exact diagnosis is to do the DBPC challenge when the infant is around 1 year of age, and is having it's own meals. We intended to do so, to verify the diagnosis. We did DBPC challenge in eight children, finding that seven had no adverse reactions to milk at that time. Thus, the diagnosis was not confirmed in 1-year-old children. This is not surprising, however, as about 50% of children are tolerant at 1 year of age (1
Consequently, in our opinion, DBPC challenge is not suitable for diagnosing adverse reactions to cow's milk in early infancy.
In conclusions, in our study, we found that adverse reactions to milk are common in infants and occur in 4.9%, regardless of GA at birth. The symptoms often appear during the first month or months of life, even in exclusively breastfed children.
The diagnosis should be considered in infants with gastrointestinal, respiratory and cutaneous symptoms.
If no IgE-mediated allergy is verified, an elimination/challenge test should be carried out. In our study, non-IgE-mediated adverse reactions seemed to be much more common than IgE-mediated reactions in the first year of life.
About half of the children who demonstrated adverse reactions to milk in the first months of life did not show any adverse reactions at 1 year of age. This demonstrates the importance of performing an open challenge at that time.
Children with prevailing allergies might either maintain their symptoms or acquire new or additional symptoms.
For practical, economical and social reasons, it is important to establish when the age of tolerance occurs in a child diagnosed with adverse reactions to milk.