NIH is committed to understanding the range of environmental influences on child health and development. A new program under development for fiscal year 2016, Environmental influences on Child Health Outcomes (ECHO), aims to investigate prenatal, perinatal, and postnatal environmental exposures on pediatric development and health outcomes with a particular focus on exposures that will have a significant impact on public health. To accomplish this, NIH proposes to support multiple synergistic, longitudinal studies using existing study populations, called cohorts. The studies will look at a range of different environmental exposures (e.g., physical, chemical, biological, psychosocial, etc.) among the cohorts using standardized research questions and the effects of these exposures on four key pediatric outcomes – upper and lower airway; obesity; pre-, peri-, and postnatal outcomes; and neurodevelopment.
A Request for Information was released on July 13 and multiple webinars and roundtable meetings were held over the past month to solicit feedback from the broader research community. Drawing upon the feedback from these recent outreach activities, NIH is considering the following issues for the ECHO plan:
- The feasibility of conducting studies that look at factors that influence genes without modifying their sequence (known as epigenetics), and whether epigenetics should be included as a core element for all studies
- The best approaches and methods to harmonize and standardize data collection and analysis across the cohorts
- How best to approach the incorporation of basic research into these studies; particularly, whether support should be limited to those basic mechanistic studies that can only be done using human cohorts
- How best to address intervention research, and whether it should be supported as a component of the plan
We’d like your feedback on how best to address these issues in the ECHO plan.
The Feedback site will accept comments on these topics through September 8. Comments received via the Feedback site may be considered by the NIH as it plans the ECHO program, but NIH will not respond to comments.
The comment period is closed.
re: ECHO RFI
please also don’t forget intermediate markers of behavior and stress manifesting physically (see the work of Blackburn, Adler, Epel and colleagues of stress on telomeres/telomerase as well as the work of Boyce and colleagues of prenatal and perinatal stress on primary/baby tooth development).
furthermore, with respect to interventions, please consider encouraging multi-level interventions.
Number 1. Epigenetics should be included- with measures of biomarkers of exposure, dose, response, and susceptibility. Metabolomics has a great potential to reveal biomarkers and mechanisms that arise from factors that do, or do not, involve modification of gene sequence.
Number 2. Methods such as predictive analytics and latent variable modeling for complex mixtures should be included. The use of standardized protocols, reporting, and archival practices with consortium working group membership will be essential for harmonization.
Number 3. Model systems should be included. The conduct of dose and time to response studies in rodent models, with assessment of biological fluids and tissues for markers of exposure, internal dose, biologically effective dose, early biological response, and susceptibility, will provide the framework and knowledge for developing specific hypotheses for testing in human cohorts. Findings from analysis of samples from cohorts will also provide a means to generate hypotheses that can be tested in model systems.
Number 4. Intervention experts should be involved, for example, to develop communication/education approaches for reducing exposure, or develop nutritional intervention strategies.
In preparation of a future RFA on the this subject, I strongly suggest to include suitable model systems with short generation times, such as Drosophila and C. elegans, because of their general conservation of genetic pathway and because with them rapid progress can be made in transgenerational genetic and epigenetic studies.
Yes to all 4 approaches. Do not leave epigenetics out. I am especially interested in future interventions. I worked with special needs population birth-3 for 11 years and NICU for 2 years. I am supportive of any efforts which cover exposure to refineries, water
Treatment facilities, and high highway traffic areas. Will you need data collection in Oklahoma? I would be interested.
1. Studies on consumption of fruit/herbal extracts by pregnant mothers during the full term should be included.
2. Basic research using mice or other animals should be an essential component.
3. EPIGENETIC gene regulation is a must.
The RFI does not mention pre-conception environmental exposure or paternal exposure. Was this intentionally omitted in the description (please see RFI statement below)?
Going forward, the overarching goal of the FY 2016 plan is to leverage and expand extant cohorts to address new research questions to investigate the longitudinal impact of prenatal, perinatal, and postnatal environmental exposures on pediatric health outcomes with high public health impact. – See more at: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-117.html#sthash.561fAutq.dpuf
Thank you for your comments. Once the Requests for Applications are published, we encourage investigators to submit applications on pre-conception environmental exposures, as this time period would absolutely be relevant to the ECHO program.
NIH ECHO program RFC
Here is why Intervention research should be a component of the plan because it is akin to the macro stress test the banking system used to uncover systemic risk early on. The validity of the methodology that establishes causal versus correlation between the environmental factors and pediatric outcomes requires a means to test the validity of the approach used in establishing it. Intervention research provides that “stress test like” tweak to test the systematic assumptions in the methodology.
It is established that environmental and behavioral factors that influence the fetus in utero, perinatal and post natal periods has a profound effect on the early and subsequent childhood development.
The exponential evolution of the ‘omic ‘ data and the rapidly expanding field of biomedical informatics, should be harnessed to capture, analyze and make inferences from the data.
The currently established consortium of data coordinating centers under ‘ PEDSNET ‘ includes about 8/9 well established Pediatric centers around the country and some have included genomic profiles into their EMRs. Since a large de- identified data base is already established we should tap into the system.
Using this data base a geo-spatial distribution of the most common problems encountered within populations has to be established and stratified according their disease severity as a base line.
Once the base line is established socio- economic, environmental factors, access to care, availability of recreational facilities , dietary patterns and availability of early childhood education facilities has to be correlated to each specific population under study.
This may give an initial impetus to initiate a comprehensive study
protocol under the concept of ‘epigenitics’ , and perform a comparative analytical study.
Does human physical contact (or some lack of it) affect the expression of certain genes?
Does disruption of key relationships during infancy and/or early childhood (such as a parent leaving for military service or other job, or even parent having to return to work right after birth) affect gene expression?
More to the point, do these physical/emotional stressors turn on or increase the expression of genes for diseases (diabetes, bipolar,…)?
Here are some additional suggestions from members of the Society of Clinical Child and Adolescent Psychology as well as my research team, underscoring the value of including measures of sleep — sleep is a core construct that goes through marked developmental changes, and is tightly connected to immune functioning, growth, obesity, cognitive functioning, and emotional systems. Circadian functions are also a major entry in the Research Domain Criteria (RDoC) matrix.
Additional, collated comments appended:
*I think it would be interesting to look at temperamental match/mismatch between parent and child. I am guessing they will look at attachment, though it isn’t explicitly stated, but I think as kids get older, the similarities of interest/disposition they have with mom/dad can be important.
*I’m guessing “built environment” includes schools – I think this is important, how big is your school, what opportunities are available, etc…
*In terms of natural environment – park access, population density, access to good grocery stores, maybe weather (mostly thinking about seasonal affective issues)
In terms of the focus areas, I’d be interested in physical fitness – not just lack of obesity. Also, creativity. Related to both physical fitness and creativity, I think kids’ interests/activities would be good to look at – I have a bias here, but I think the fact that every kid I see from the age of 2 up is playing with some kind of video game is going to be detrimental to imagination and fitness over time.
In terms of sleep, my guess is that they will look at duration and maybe napping. I think also including sleep problems – co-sleeping, insomnia, nightmares, sleep walking – could be very interesting.
I think sleep is definitely an area that should be given more attention. Collecting information on sleep cuts across some of the Core Elements (i.e., typical early development, environmental influences) as well as a lot of the focus areas. In terms of what to measure for sleep, I think sleep duration, sleep problems, and collecting information on school commitments – school start time, average amount of homework, time spent in extra curricular activities – may also be a good way to gauge time available for children to sleep. Another good area to collect information on is nutrition – maybe asking about what kids are eating, when they’re eating, how many meals, etc.? I think this coupled with the sleep area gives a good picture of environmental factors as well as individual factors.
I would like to comment briefly on two of the issues raised. First, with respect to #2, I recommend that in the selection of measures, serious consideration be given to the PheNX Toolkits. The Toolkits were specifically designed to facilitate cross-study and cross-cohort comparisons and analyses. Second, with respect to #4, if properly designed, embedded interventions offer strong tests of the causal impact of particular interventions and the assumed mechanisms on which they are based.