National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney
Funding Opportunity Title
Mechanistic Insights from Birth Cohorts (R01)
R01 Research Project Grant
Funding Opportunity Announcement (FOA) Number
Companion Funding Opportunity
Catalog of Federal Domestic Assistance (CFDA) Number(s)
93.847, 93.865, 93.838, 93.839, 93.399
Funding Opportunity Purpose
This Funding Opportunity Announcement (FOA) is intended to support novel research on how prenatal exposures contribute to the etiology of chronic diseases and health conditions later in life. The goal of this FOA is to stimulate research by leveraging existing birth cohorts to address targeted mechanistic questions regarding the normal and abnormal developmental origins of organ systems and/or diseases of interest to the participating NIH Institutes and Centers.
February 6, 2013
Open Date (Earliest Submission Date)
May 5, 2013
Letter of Intent Due Date(s)
(Changed to 30 days prior to the Application Due Date per NOT-DK-13-010), Originally May 5, 2013
Application Due Date(s)
Standard dates apply, by 5:00 PM local time of applicant organization.
AIDS Application Due Date(s)
Scientific Merit Review
Standard dates apply
Advisory Council Review
Standard dates apply
Earliest Start Date
Standard dates apply
May 8, 2016
Due Dates for E.O. 12372
Required Application Instructions
It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.
Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information
Emerging epidemiological evidence has shown that prenatal exposures such as placental function, maternal over- or under-nutrition, maternal physical activity behaviors, and maternal sleep disorders may be associated with an increased risk of chronic diseases in the offspring, either as a child or adult. Little is known about the mechanisms by which such prenatal exposures lead to diabetes or obesity, renal, pulmonary, or cardiovascular or hematologic disease, neurodevelopmental disorders, or reproductive health (i.e. fertility). A number of studies over the past ten years in sheep, rodents, and non-human primates have provided evidence that alterations in nutritional, metabolic, immune and hormonal milieu in utero can have profound long-term effects on offspring. Although there is increasing evidence for the roles of inflammatory pathways and epigenetic modifications, the mechanisms by which these effects are transmitted from mother to offspring have not been fully elucidated. Given the evidence pointing towards the role that alterations in the intrauterine environment have in the future pathophysiology of the offspring, it is necessary to better understand: 1) The factors in utero that mediate these effects; 2) The critical periods in prenatal exposure/development that have untoward effects; and 3) The measurements/biomarkers along the developmental path that can predict disease in the offspring. Ultimately, a better mechanistic understanding of how prenatal exposures contribute to the etiology of chronic diseases and health conditions later in life will allow for the development of effective interventions during pregnancy or early life that may have a profound impact on disease prevention and the future health of the offspring.
Scope and Areas of Research Interest
Proposed studies must take advantage of existing (or accruing) birth cohorts, with well-characterized pregnancies, such that targeted mechanistic questions regarding the developmental origins of diabetes or obesity, renal, pulmonary, or cardiovascular or hematologic disease, neurodevelopmental disorders, or reproductive health (i.e. fertility) can be addressed. Applications that address diseases that are not within the mission of the participating Institutes and Centers (ICs) are not appropriate to this announcement. A description of the existing cohort(s) to be used must be included in the application. Cohorts that are ongoing, but have not completed enrollment, could also be used. This announcement would not fund the originally-planned cohort but could, for example, fund ancillary data collection while the cohort is accruing. The establishment of new cohorts is not appropriate for this announcement; nor will the funding of infrastructure for follow-up visits of an existing cohort be allowed. This announcement seeks existing mother/child cohorts that have a rich depth of phenotypic information, including clinical data and bio-specimens starting in early pregnancy. Data on pre-pregnancy measures in the mother (and, if available, in the father) would also be desirable.
Applications should focus on potential mechanisms that mediate the developmental origins of human disease. Measures should come from analysis of stored or readily collectable samples from mother or offspring (such as cord blood, placenta, tissue, blood, serum, saliva, or urine). Applicants are encouraged to include specific measures, collected at defined times along the prenatal to postnatal life continuum, that will provide insight into the potential mechanistic links between maternal metabolism and fetal exposures during pregnancy and subsequent disease in the offspring. In addition to using existing and new samples for mechanistic studies, there should be a measure of disease, or disease risk, in the offspring.
Applications submitted to this FOA should target diabetes or obesity, renal, pulmonary, or cardiovascular or hematologic disease, neurodevelopmental disorders, or reproductive health (i.e. fertility). Research areas may include, but are not limited to, the following topics.
Potential applicants are strongly encouraged to contact the relevant Scientific/Research Contact listed in Section VII. Agency Contacts to discuss specific topics.
It is anticipated that there will be an investigators’ meeting in the Bethesda, MD area shortly after awards are made so that investigators can share study plans and discuss whether there are common measures that should be conducted in all funded studies. Thereafter, there will be an annual investigators’ meeting to share plans, findings and issues of common interest. Each applicant should include funds for attending these meetings in his/her budget.
Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
Application Types Allowed
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards
The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
Application budgets are limited to less than $500,000 in direct costs per year and need to reflect actual needs of the proposed project.
Award Project Period
Scope of the proposed project should determine the project period. The maximum period is 5 years.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations must complete the following registrations as described in the SF424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.
All Program Directors/Principal Investigators (PD(s)/PI(s))
must also work with their institutional officials to register with the eRA
Commons or ensure their existing eRA Commons account is affiliated with the eRA
Commons account of the applicant organization.
All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least 6 weeks prior to the application due date.
Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Program Director(s)/Principal
Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
A team approach representing investigators that have access to the clinical samples and knowledge of the birth cohorts, with investigators having expertise in genomic, epigenomic, metabolomic and/or other in depth mechanistic analysis is encouraged. Given the potential breadth and depth of the data that will be accrued in the proposed studies, evidence of personnel that are qualified to perform the appropriate statistical and bioinformatic analysis should also be provided.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:
Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the “Apply for Grant Electronically” button in this FOA or following the directions provided at Grants.gov.
It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.
For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.
Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.
By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:
The letter of intent should be sent to:
Corinne M. Silva, Ph.D.
Division of Diabetes, Endocrinology and Metabolic Diseases (DEM)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
6707 Democracy Blvd., Room 794
Bethesda, MD 20892-5460
The forms package associated with this FOA includes all applicable components, mandatory and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
Applicants should budget for key investigators to attend an annual 2-day meeting in the Bethesda, MD area, as described in the Funding Opportunity Description.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
In addition to describing the proposed research as outlined in the SF424 Application Guide, a description of the existing cohort(s) to be used also must be included in the Research Strategy.
Letters of Support
A letter indicating approval of the use of birth cohort samples by the appropriate committee or person from the birth cohort study must be included in the grant application. This information should be uploaded as an attachment in Letters of Support.
Resource Sharing Plan
Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:
All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.
Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.
Organizations must submit applications via Grants.gov, the online portal to find and apply for grants across all Federal agencies. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration.
Applicants are responsible for viewing their application before the deadline in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.
The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management (SAM). Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.
Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.
Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Will the studies proposed provide insight into the potential mechanistic links between maternal metabolism and fetal exposures during pregnancy and subsequent disease in the offspring?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Is the appropriate clinical and mechanistic expertise to obtain and analyze samples provided along with the appropriate bioinformatic and/or statistical expertise for data analysis?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project?
Are potential problems, alternative strategies, and benchmarks for success
presented? If the project is in the early stages of development, will the
strategy establish feasibility and will particularly risky aspects be managed? Do the studies address specific measures, at defined times, using already available birth
If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.
Protections for Human Subjects
For research that involves human subjects but does
not involve one of the six categories of research that are exempt under 45 CFR
Part 46, the committee will evaluate the justification for involvement of human
subjects and the proposed protections from research risk relating to their
participation according to the following five review criteria: 1) risk to
subjects, 2) adequacy of protection against risks, 3) potential benefits to the
subjects and others, 4) importance of the knowledge to be gained, and 5) data
and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Human Subjects Protection and Inclusion Guidelines.
Inclusion of Women, Minorities, and Children
When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.
For Renewals, the committee will consider the progress made in the last funding period.
For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
Applications from Foreign Organizations
Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.
Select Agent Research
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Resource Sharing Plans
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).
Budget and Period of Support
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by the Center for Scientific Review, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications:
Applications will be assigned on the basis of established PHS referral guidelinesto the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:
After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH Grants
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.
Cooperative Agreement Terms and Conditions of Award
When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) and financial statements as required in the NIH Grants Policy Statement.
A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
We encourage inquiries concerning this funding opportunity and
welcome the opportunity to answer questions from potential applicants.
GrantsInfo (Questions regarding application instructions and
process, finding NIH grant resources)
eRA Commons Help Desk (Questions regarding eRA Commons
registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
Corinne M. Silva, Ph.D.
Intracellular and Intrauterine Signaling
Division of Diabetes, Endocrinology and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
6707 Democracy Boulevard, Room 794
Bethesda, MD 20892-5460
Megan Mitchell, MPH
Vascular Biology and Hypertension Branch, Division of Cardiovascular Sciences
National Heart, Lung and Blood Institute (NHLBI)
6701 Rockledge Drive
Room 8113, MSC 7940
Bethesda, MD 20892
Uma M. Reddy, MD, MPH
Pregnancy and Perinatology Branch
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
6100 Executive Blvd., Room 4B03F
Bethesda, MD 20892-7510
(Fed X: Rockville MD 20852)
Telephone (direct): 301-496-1074
Telephone (secretary): 301-496-5575
Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).
Senior Grants Management Specialist
Grants Management Branch
National Institute on Diabetes, Digestive
and Kidney Diseases, NIH
Two Democracy Plaza, Suite 708
6707 Democracy Blvd., MSC 5456
Bethesda, Maryland 20892-5456
Office of Grants Management
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Room 7129, MSC 7926
Bethesda, MD 20892-7926
Telephone: 301- 402-3839
Bryan S. Clark, MBA
Chief, Grants Management Branch
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Building 6100, Room 8A01
6100 Executive Blvd.
Rockville, MD 20852
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.
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