Does maternal immunoglobulin E decrease with increasing order of live offspring? Investigation into maternal immune tolerance

Background Identifying the protective effect of a higher number of siblings is a significant finding in understanding the aetiology of allergic sensitization, asthma, eczema, and hayfever. Knowledge about causes behind the sibling effect may allow us to prevent atopic manifestations. Objective We tested the hypothesis that rising order of live offspring increases maternal immune tolerance (immune non-reactivity) against allergens. To this end, we investigated whether maternal IgE levels are associated with the number of live offspring. Methods In a cohort of 1456 newborns recruited between January 1989 and February 1990 on the Isle of Wight, UK, we determined maternal and cord serum IgE, and the order of live offspring. The data were analysed by means of linear and path analysis. Results Maternal and cord serum IgE were available in 820 mother-infant pairs with birth order information. We found that the number of live offspring significantly reduces maternal IgE. The decline was more prominent in mothers with atopy (n=268). The geometric means of IgE after the first, second, and third or higher delivery were 74.4, 66.6, and 43.0 kU/L, respectively. Findings of path analysis suggest a significant direct effect of birth order on maternal IgE, but no direct effect of birth order on cord serum IgE. Conclusion The findings support that maternal immune tolerance against allergens may increase with increasing order of live offspring and thus pass on a lower risk of developing atopy in children of higher birth order.