Transplacental Antimicrobial Antibodies and Childhood Asthma: Maternal Nativity as an Upstream Factor.

Abstract

Early-life microbial exposure to microbes may play a role in asthma development. This study tests the hypothesis that mothers born in low-income countries might have been exposed to diverse microbes-leading to greater diversity and higher levels of transplacental anti-microbial antibodies, thereby conferring protection against asthma in offspring. In the prospective Boston Birth Cohort, IgG antibody reactome against microbes (2740 species; 1311 genera) was profiled in cord blood, using Phage ImmunoPrecipitation Sequencing. Multinomial regression models were applied to examine the associations of cord blood IgG reactome with child risk of physician-diagnosed atopy and asthma. Mediation analysis was performed to examine the inter-relationships among maternal nativity, IgG reactome and risk of developing childhood asthma. This report included 943 mother-child dyads enrolled at birth and followed prospectively. Compared to children of US-born mothers, children of foreign-born mothers had a lower prevalence of asthma (17.5% vs. 30.5%) and greater diversity of cord blood IgG antibodies against hundreds of microbes (FDR < 0.05). Cord blood seropositivity to peptides or proteins from 6 microbes was inversely associated with the risk of asthma in children, and children with more seropositivity to these microbes were at a lower risk of developing asthma (p < 0.001). IgG seropositivity to A. actinomycetemcomitans, H. pylori, S. flexneri, and T. parva each mediated 17%-62% of the association between maternal nativity and child risk of asthma. In this US prospective birth cohort, maternal transplacental IgG reactivity to four microbes (A. actinomycetemcomitans, H. pylori, S. flexneri and T. parva) was associated with a lower risk of childhood asthma, and partly explains the lower risk of asthma in children of mothers born outside the US.