Project summary We propose to continue to follow the racially and socioeconomically diverse Henry Ford Health (HFH) Childhood Allergy and the Neonatal Environment (CANOE) cohort. The investigative team has specific interest in the prevention of atopic diseases – including atopic dermatitis (AD), food allergy, asthma and allergic rhinitis – which pose a significant social, financial, and developmental burden for children and are a priority for the ECHO program. The incidence rates and fundamental descriptive epidemiology trends of atopic multimorbidity for children in the US are unknown, although the co-existence of multiple atopic disorders contributes to a significant detriment in health and development, including neurocognitive deficits and poor growth. Clinical practice also lacks an early biomarker to identify the children with atopic multimorbidity phenotypes, including those with AD, food allergy, and asthma with or without allergic rhinitis (referred to herein as severe atopic multimorbidity [SAMM]). Environmental factors may impact risk of atopy, and DNA methylation (DNAm) is influenced by environmental factors and can promote immune pathways towards an allergic phenotype through gene regulation. Limited investigations have been done on placental DNAm, a biologically relevant tissue for assessing prenatal exposures that may influence risk of atopy and act as an early biomarker of SAMM risk. We hypothesize that the incidence rates of SAMM vary based on demographic factors. We also hypothesize that infants at risk of SAMM have differential placental DNAm that may be influenced by environmental factors. The Specific Aims for this proposal are to: (1) Determine ECHO-wide incidence rates and prevalence over time of severe atopic multimorbidity (SAMM) evident by the age of 6 years by demographic factors including age, sex, race/ethnicity, and geography; (2) Determine whether placental DNAm alterations differentiate children with SAMM and if they are influenced by prenatal environmental exposures; and (3) Utilize community health workers and diversity, equity, and inclusion principles to connect and engage with study participants to enhance and complete ECHO study activities and protocols for an additional 7 years; and utilize participant advisors to amplify the voices of participants and overcome challenges with engagement and retention. The data generated by this proposal, combined with ECHO-wide data, will allow for accurate estimates of incidence rates of co-morbid atopic disease phenotypes and is an important step toward understanding how the placenta may influence allergic disease risk. Most importantly, the data and biospecimens that will be generated by this cohort as it ages from birth through middle childhood will be a fundamental asset for the ECHO research platform as numerous investigators all over the country utilize these data to address child health and disease for years to come. Continued follow-up of the HFH CANOE cohort will allow for solution-oriented investigations into causes and contributors to health and disease.

Project narrative Atopic conditions (atopic dermatitis (AD), food allergy, asthma and allergic rhinitis) pose a significant social and financial burden to children and families; however, the fundamental descriptive epidemiology trends for severe atopic multimorbidity or SAAM (AD, food allergy, asthma with or without allergic rhinitis) are unknown for US children, and current clinical practice lacks an early biomarker to identify infants at risk. In conjunction with ECHO-wide committee and working group participation, proposal submissions, and manuscripts, this project will assess incidence rates of SAMM to target populations at risk and use placental DNA methylation to identify potential biomarkers linking social and environmental conditions to disease outcomes. The proposed investigations and scientific collaborations across ECHO will more precisely identify children at risk for multiple atopic co-morbidities which is an important first step in preventing childhood atopic disease co-morbidity and improving the health of children across the US.