Extending the Environmental influences on Child Health Outcomes (ECHO) Cohort through 2030: Rationale and study protocol

Abstract

Early life environmental exposures, even those experienced before conception, can shape health and disease trajectories across the lifespan. Optimizing the detection of the constellation of exposure effects on a broad range of child health outcomes across development requires considerable sample size, transdisciplinary expertise, and developmentally sensitive and dimensional measurement. To address this, the National Institutes of Health (NIH) Environmental influences on Child Health Outcomes (ECHO) Cohort Study is an observational longitudinal pediatric cohort study. In the first phase from 2016-2023, the ECHO Program built a robust platform for investigating prenatal and early life environmental exposures on child health outcomes. Now, the ECHO Program is extending longitudinal follow-up of existing ECHO participants <21 years of age and recruiting and following new pregnant participants <20 weeks gestation and their offspring through 2030. Participants will be enrolled at 72 Cohort Study Sites across all 50 US states, the District of Columbia, and Puerto Rico. Exposure assessments span the biological, chemical/physical, lifestyle, and social environment; child health outcomes focus on five broad domains: pre-, peri-, postnatal; airways; obesity; neurodevelopment; and positive health, or one's physical, mental, and social well-being. Data and biospecimens will be collected annually through August 2030, with an expected total sample size of 60,000 children and their caregivers. The ECHO Cohort Study represents the largest national longitudinal study of children's health in the US. Here, we describe the ECHO Cohort "Cycle 2" observational study arm and the ECHO Cohort Protocol version 3.0 (ECP v3.0), which delineates the data elements, measures, and biospecimens that all ECHO Cycle 2 Cohort Study Sites will collect and analyze.

Fig 1. ECHO Program organizational chart.

The ECHO Program is comprised of an observational study arm, the ECHO Cohort Study described in this manuscript, and the ISPCTN clinical trials arm.

Fig 2. Guiding principles for protocol development.

The ECHO Protocol Task Force began by establishing a set of principles to guide protocol development.

Fig 3. ECHO Cohort Protocol v3.0 development and implementation timeline.

The ECHO Protocol Task Force developed Protocol v3.0 over 19 months, followed by three months of training and culminating in site activation and enrollment in January 2024.

Fig 4. Expected pregnant person enrollment accrual by the end of each month from January 2024 to May 2025.

A total of n = 8,158 pregnant people are expected to be enrolled during the UG3 phase of the ECHO Cohort Study (January 2024 –May 2025), including n = 4,649 pregnant people who self-identify as a race/ethnicity other than non-Hispanic White. By the end of ECHO Cycle 2, n = 20,000 pregnant people are expected to be enrolled.

Fig 5. Expected child enrollment accrual by the end of each month from January 2024 to May 2025 by age band.

“Age band” refers to the developmentally informed age groups of children, where all children within an age band are administered the same set of instruments and specimens within a given calendar year. A total of n = 27,050 children ages 0 to <21 years are expected to be enrolled during the UG3 phase of the ECHO Cohort Study (January 2024 –May 2025), including expected births from new pregnancies, and includes n = 11,650 children who are caregiver or self-identified as a race/ethnicity other than non-Hispanic White.

Fig 6. Graphical depiction of how each birth cohort progresses through age bands, by year they enter the Cycle 2 ECHO Cohort Protocol (ECP) v3.0.

Birth cohort describes the group of children who were born in the same year (“Birth Cohort Year”) and enter the ECP v3.0 at the same age in the same “ECHO Study Calendar Year.” Values represent the child age in the given calendar year for the respective birth cohort. Shaded colors represent the ECP v3.0 age bands, with gray representing children ages 0 to < 36 months.