The main finding of our study was that breastfeeding delayed the onset of celiac disease and that breastfeeding at the time of gluten introduction had a significant protective effect against the disease. Early introduction of gluten, before the fourth month, did not result in an earlier onset of the disease. Neither breastfeeding nor the timing of gluten introduction affected the severity of the disease.
We found that breastfeeding, although generally short, reduced the risk of celiac disease occurrence in the first year of life. Some observational studies claimed that breastfeeding at the time of gluten introduction and longer breastfeeding were associated with delay and prevention of the disease (5
). However, Norris et al, in a study including children with high risk for autoimmune diseases, found no protective effect of breastfeeding (6
). D’Amico et al showed that children with celiac disease who had been exclusively breastfed had a delayed onset and less severe disease symptoms than those who had not been exclusively breastfed (7
). All of these studies, including ours, clearly point to the importance of breastfeeding for the delay of celiac disease in infancy.
Another important environmental factor is timing of gluten introduction, as well as the amount of gluten in weaning food (6
). In our study, gluten introduction before the fourth month was not associated with an earlier onset of celiac disease, but the introduction after 6 months delayed the disease. These older infants had also been breastfed longer. According to the literature, the optimal period in which food antigens, such as gluten, should be introduced in order to maximize tolerance is between the fourth and sixth month (3
). It is unclear whether the predominant risk factor for celiac disease is infant’s age at the time of gluten introduction or the amount of gluten consumed (6
). Some studies point to the importance of continuing breastfeeding at the time of gluten introduction (7
). It is not clear from either our or other studies whether the timing of gluten introduction is the sole explanatory variable that predicts age at celiac disease onset. Nevertheless, it is safe to conclude that continuing breastfeeding at the time of gluten introduction is important for protection against the disease.
According to our research, longer breastfeeding, especially breastfeeding at the time of gluten introduction delays the onset of the disease. This effect occurs through various mechanisms. A small amount of gluten in breast milk helps induce oral tolerance, as is the case with all other food allergens. Due to protective factors in human milk, gastrointestinal infections are rare and less severe in breastfed infants than in those who are not breastfed (16
). This is a very important point because gastrointestinal infections can additionally increase permeability of the gut by causing inflammation or by other mechanisms. In this way, gastrointestinal infections allow that large amounts of gluten fragments cross the intestinal wall and exceed the oral tolerance capacity. In addition, human milk provides many bioactive factors, including antimicrobial and anti inflammatory agents, enzymes, hormones, and growth factors, many of which are involved in gut maturation and development of the infant’s innate and acquired immunity (17
). Our results further suggest that breastfeeding indirectly delays the age at diagnosis of celiac disease by delaying gluten introduction. One-fourth of the infants in our study had been breastfed at the time of gluten introduction, and they developed the disease later than the infants who had not been breastfed at the time of gluten introduction, which speaks in favor of the protective effect of consuming human milk while introducing other food antigens.
Our results showed that gluten introduction before the fourth month did not affect the onset of disease, but gluten introduction after the sixth month delayed it. We cannot be sure that the effect is solely based on delaying the introduction of gluten, because this group of infants was breastfed longer and was breastfed during gluten introduction. Another possible factor, which we did not measure, was the amount of gluten consumed by the infants.
None of the early feeding practices that we measured was associated with the severity of the celiac disease, as assessed based on the occurrence of anemia, secondary lactose intolerance, weight loss, and longitudinal retardation. All our patients had had symptoms for a long time, and the age at onset was critical for growth, especially for weight loss. Weight loss is an indicator of recent nutritional disturbances, and serious weight loss was detected in nearly one-fourth of our patients. Length in 4 infants was below the fifth percentile, indicating prolonged malnutrition. The frequency of anemia in our study (51%) was higher than the 17% reported in previous research (19
). The reason for this may be the younger age of our participants and the long duration of symptoms before the diagnosis. All our patients had severe villous atrophy, which led to the malabsorption of important nutriments and may be the reason why early feeding practices did not influence the occurrence of anemia or secondary lactose intolerance.
The role of environmental factors in the expression of celiac disease, especially early feeding practices, warrants further investigation. In the present study, we analyzed their influence on a homogeneous group of infants diagnosed with classic form of celiac disease. The relationship between certain genetic backgrounds and celiac disease expression is well explained in the study by Mearin et al, especially with regard to the age at onset (20
). Although we did not look at their genetic predisposition, all our patients were most likely genetically predisposed to early clinical expression of the disease. In the light of current recommendations for infant feeding, it is important to point out the favorable role of breastfeeding at the time of introduction of new food antigens, including gluten, in helping to establish oral tolerance.