Epidemiology of multimorbid pediatric atopic and airway diseases and the impact of prenatal maternal environmental exposures and placental epigenetics - 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.
