Dietary manipulation and induction of tolerance.

Clinical observations have suggested that the development of atopic diseases in childhood may be influenced by breast-feeding and the timing of first exposure to foreign protein, but the controversy is far from being resolved. Early weaning and introduction of foreign proteins (i.e., cow milk) have been associated with an increased prevalence of atopic symptoms in infants with a family history of atopy. Opposite results have been reported, and the effects of early protein introduction in infants not at risk of having atopic symptoms are poorly documented. Research in rodents suggests that perinatal antigen exposure is more likely to prime the immune system than to induce tolerance. Continuous feeding beyond the critical neonatal period leads to induction of tolerance. The immunologic response is dependent on the antigen dose. Protein transfer by breast-feeding can induce tolerance, though in a dose range otherwise associated with priming. The protective effect of antigen avoidance in infancy on the development of cow milk allergy and also on subsequent atopic symptoms is well documented. Protective effects have been observed in infants at risk who either were breast fed or received a hydrolyzed infant formula. Several clinical studies suggest a causative role of neonatal milk exposure in the development of cow milk allergy. Prospective, population-based studies are required to assess the true incidence of food-allergic diseases in childhood.

Effects of brief early exposure to partially hydrolyzed and whole cow milk proteins.

Clinical experience ("the dangerous bottle") and experimental evidence indicate that the early life of an infant is particularly important for the development of the immune responses to food antigens. However, the clinical and immunologic consequences of a brief exposure to, or avoidance of, food antigens during the neonatal period in human infants are poorly understood and documented. We present the preliminary results of a prospective controlled study of 256 normal breast-fed infants randomly assigned to receive (blind) either an adapted formula (Nidina) or a partially hydrolyzed formula (Nidal HA) as a supplement to breast-feeding for a few days when necessary, and to be examined at days 5, 90, 150, and 365. The results indicated that (1) the prevalence of clinical symptoms and of total and specific IgE responses was not statistically different in the two groups of infants and (2) infants fed a hydrolyzed formula had median titers of specific IgG lower than those fed an adapted formula; the difference was significant for alpha-lactalbumin at day 90 (p < 0.005) and for alpha-lactalbumin (p < 0.05), casein (p < 0.05), and hydrolyzed formula (p < 0.01) at day 150. Humoral immune responses of breast-fed infants to food antigens thus appear to be modulated by early, short-term exposure to them.