PROJECT SUMMARY Atopic disease is a major public health problem affecting up to 20% of the world’s population, with rising prevalence in recent decades. It is associated with fatal reactions (food allergy), and with significant psychosocial and financial burden for children and families. Environmental and in utero exposures are known risk factors, but little is known about the mechanisms through which exposures may confer risk. One of these known exposures is maternal antenatal anxiety, which has been associated both with elevated markers of allergy risk (such as levels of Immunoglobluin E (IgE)) and with atopic diagnosis in children. Maternal antenatal anxiety has also been linked to immune dysregulation in both mothers and children, and elevated innate immune activity in children at birth may be a key marker of future allergic risk – yet no study has attempted to link dyadic maternal and neonatal immune dysregulation to allergy risk in the same mother-child pairs. In this prospective, longitudinal, observational study, we propose to follow 200 mother-child pairs (132 at risk for clinically significant anxiety and 68 healthy controls) from the second trimester of pregnancy until infants reach 12 months of age. We hypothesize that women with clinically significant antenatal anxiety will demonstrate elevated immune activity compared to healthy controls, that stimulated cells and gene expression from umbilical cord blood in these pregnancies will similarly show evidence of increased immune activity, and that maternal and child immune activity will be associated with markers of allergy risk in children. We will measure immune cell populations and cytokines produced by stimulated cells in mothers and children; will conduct methylation analyses of immune-related genes in the cord blood of children (focusing on known biomarkers of future allergic risk); will measure atopic dermatitis in children; and will measure IgE to common allergens and maternal report of food allergic reactions in children. In addition, we will observe mother-child interactions surrounding feeding to account for elements of the postnatal environment that may contribute to elevated child allergic risk. Our thorough and rigorous experimental plan will help to illuminate pathways that contribute to the association between maternal antenatal anxiety and child allergy risk, and may lead to novel interventions to ameliorate symptoms and risk in both mother and child.

PROJECT NARRATIVE Atopic disease is a major public health problem affecting up to 20% of the world’s population, with a substantial psychosocial and economic burden for children and families and rising prevalence in recent decades; child atopic risk has been associated with maternal antenatal anxiety, yet we know little about the biological mechanisms that may underlie this association. This study will examine both maternal and child immune activity from pregnancy through the first year (through stimulated immune cells, the cytokines they produce, and gene expression in cord blood), and will determine dyadic immune activity and associations with the child’s atopic risk, accounting for elements of anxious parenting in the postnatal environment. These findings will shed light on the biological pathways contributing to risk for atopyin children, and may lead to novel interventions to ameliorate both maternal symptomatology and child risk.