Is there a role of early neonatal events in susceptibility to allergy?

Several studies suggest a protective role of bilirubin against oxidative damage during the neonatal period. ADA1*2 allele has been found associated with higher bilirubin levels in newborns and with a protective action against bronchial asthma. Thus the relation between ADA1 and asthma could be mediated by events occurring during the early extrauterine life. Moreover the increased prevalence of allergic diseases in western populations parallels the widespread practice of phototherapy during the neonatal period. These observations prompted us to reevaluate our previous data and show new observations.

Data from 2729 previously studied subjects, from 53 subjects studied at birth and after 30 years and from a survey of phototherapy frequency in four Italian Hospital including 7392 newborns are reported.

ADA1*2 allele carriers are less represented among asthmatic subjects than in controls (p=0.0004). ADA1*2 allele carriers among newborns undergoing phototherapy for hyperbilirubinemia is higher when compared to newborns not undergoing this treatment (p=0.006). In infants treated by phototherapy, the maximum bilirubin level attained during the first few days of life positively correlated with the ADA1*2 allele dose (p=0.001). Among subjects studied at birth, allergic rhinitis and/or conjunctivitis are more frequent among those treated with phototherapy than among those not treated (p=0.046).

These observations support our hypothesis that ADA1*2 allele through an increase of bilirubin level in the neonatal period protects infants from oxidative stress and favours Th2→Th1 switching thus preventing allergic manifestations in later periods of life.