Key Dates

Related Announcements

PA-20-272 - Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)

PA-18-935 - Urgent Competitive Revision to Existing NIH Grants and Cooperative Agreements (Urgent Supplement - Clinical Trial Optional)

NOT-OD-21-090 - Notice of Correction to NOT-OD-21-071

Issued by

Office of The Director, National Institutes of Health (OD)

Purpose

The Office of the Director of the National Institutes of Health (NIH), on behalf of the NIH Maternal Mortality Task Force, announces the opportunity for investigators with relevant active NIH-supported grants to address the following scientific priorities for Implementing a Maternal health and PRegnancy Outcomes Vision for Everyone (IMPROVE) in the context of the ongoing COVID-19 pandemic for pregnant persons and up to one year postpartum:

• Understand the effects of SARS-CoV-2 infection and the COVID-19 pandemic on maternal mental health, well-being, functioning and quality of life
• Identify psychosocial and behavioral health risk factors related to the COVID-19 pandemic that affect maternal mental health and functioning outcomes
• Address the impact of structural racism and discrimination (SRD) on maternal health outcomes in the context of COVID-19

IMPROVE aims to understand the biological, behavioral, environmental, sociocultural, and structural factors that affectpregnancy-related and pregnancy-associated morbidity and mortality by building an evidence base for improved care and outcomes. This initiative will promote research to address health disparities associated with pregnancy-related and pregnancy-associated morbidity and mortality (MM).

Over a 25-year period, the global maternal mortality ratio (MMR) declined from 385 per 100,000 live births in 1990 to 216 deaths per 100,000 live births in 2015, a relative decline of 44 percent. In contrast, in the United States (U.S.) the MMR increased during the same period and is currently the highest among developed nations. An estimated 700 persons die each year in the U.S. from conditions related to or associated with pregnancy or childbirth, and over 50,000 experience severe maternal morbidity (SMM). High rates of pregnancy-related and pregnancy-associated MM and SMM disproportionately affect specific racial/ethnic populations. In particular, Black or African American (AA) and American Indian/Alaska Native (AI/AN) pregnant or postpartum persons are 2 to 4 times more likely to die from pregnancy-related causes compared to White persons. Furthermore, Black or African American, Hispanic/Latina/x, Asian, Pacific Islander, and American Indian/Alaska Native persons all have higher incidence of SMM compared to White persons. Age, disabilities, and geographical disparities also affect MM/SMM, as do social determinants of health (SDoH), including education and socioeconomic standing. Another important SDoH is SRD, or macro-level conditions (e.g., residential segregation) that limit opportunities, resources, and well-being of less privileged groups on the basis of race/ethnicity and/or other statuses, including but not limited to gender, sexual orientation, gender identity, disability status, social class or socioeconomic status, religion, national origin, immigration status, limited English proficiency, or physical characteristics or health conditions.

Many of these populations are also disproportionately affected by the COVID-19 pandemic. Pregnant persons have an increased risk of severe COVID-19 disease and are more likely to experience adverse pregnancy outcomes when infected with SARS-CoV-2. Compared to those who gave birth without COVID-19, infected pregnant persons experienced a considerably higher risk of in-hospital death, thrombotic events, preterm birth and preeclampsia, with the highest risk experienced by Black or African American and Hispanic/Latina/x, older persons, and those living in geographic areas without adequate maternity care. Additionally, pregnant Asian and Native Hawaiian/Pacific Islander persons experienced a disproportionately higher risk for ICU admission. Prior to the COVID-19 pandemic, higher rates of preterm birth and pregnancy-associated or -related maternal morbidity and MM have been experienced by Black or African American persons, who also show elevated rates of anxiety and depression in the prenatal period. The risk of anxiety and depression following adversity is increased in pregnancy, and the COVID-19 pandemic places pregnant persons at risk for adverse emotional health outcomes. Black or African American women were more likely to report negative impact on jobs, knowing people who died from COVID-19, and worrying about dying from COVID-19.

Psychosocial factors and SDoH contributing to pregnancy-related and pregnancy-associated morbidity and MM (e.g., stress, social isolation, mental health, intimate partner violence, substance use, quality of life) may be amplified by the pandemic, particularly in racial/ethnic minorities, less privileged socioeconomic status groups, and other vulnerable populations that have been disproportionately impacted by COVID-19. SRD could have a profound negative impact on maternal health and well-being outcomes during pregnancy and up to one year postpartum in these disproportionately affected and COVID-19 vulnerable populations. Risk could be conferred through intergenerational transmission of effects of stressors related to the COVID-19 pandemic mediated through pregnancy consequences and inequities in healthcare and social service delivery (e.g., poorer healthcare resulting from clinician bias, rationing of care to uninsured patients). Additional structural factors that contribute to negative impacts on disproportionately affected and COVID-19 vulnerable populations include residential segregation that restricts access to healthcare and healthy living environments; occupational segregation that limits access to health insurance, sick or maternity leave, and safe working conditions; and criminal justice inequities that lead to a greater risk of incarceration or fewer legal protections for persons who are victims of violence, among others.

The goal of this NOSI is to accelerate our understanding of the effects of SARS-CoV-2 infection and the COVID-19 pandemic on maternal mental health, well-being, functioning and quality of life. This research will seek to identify psychosocial and behavioral health risk factors related to the COVID-19 pandemic that affect mental health and functioning outcomes during pregnancy and up to one year postpartum and how they may contribute to increased pregnancy-related and pregnancy-associated morbidity and MM. IMPROVE will support research that addresses the impact of SRD in the context of the COVID-19 pandemic on maternal health outcomes for pregnant persons and up to one year postpartum. This new knowledge will advance the IMPROVE long-term goal of risk stratification approaches and mitigation strategies. By encouraging the use of a set of common data elements and outcomes measurement instruments, this initiative will facilitate the creation of a set of harmonized data across existing NIH projects and infrastructure related to the COVID-19 pandemic and pregnant and postpartum persons. NIH expects applicants to include a focus on underrepresented, underserved, and vulnerable pregnant/postpartum populations, address SRD, and to consider community-engaged research approaches.

Areas of Research Interest

NIH is soliciting the submission of applications for Administrative Supplements or Urgent Competitive Revisions to active awards that include or could extend to pregnancy and COVID-19. Applications in response to this NOSI should be aligned with one or more of the areas of interest below. Example research questions are provided for each area of interest:

• Area 1: Investigate the impact of the COVID-19 pandemic on the health, well-being, and functioning of pregnant persons and up to one year postpartum using psychosocial and behavioral research approaches.
  • What unique pregnancy- or postpartum-related factors have the potential to exacerbate (or ameliorate) the overall impact of the COVID-19 pandemic on the mental health and well-being of pregnant and postpartum persons?
  • What strategiescan be used to mitigate or manage depression, anxiety, or substance use among pregnant and postpartum persons to improve the overall well-being of pregnant and postpartum persons and maternal health outcomes?
  • What impact does a positiveCOVID-19 diagnosis have on the mental health and well-being of pregnant and postpartum persons?
  • What are the effects of COVID-19 mitigation strategies (e.g., social distancing, quarantine, business and school closures) on the health and well-being of pregnant and postpartum persons? How do pandemic-influenced factors such work/ income, childcare, family support, access to care/treatment, stress, social isolation, intimate partner violence, family violence, or food insecurityaffect maternal mental health and well-being?
  • What is the impact of the COVID-19 pandemic on pregnant persons with pre-existing chronic conditions (including mental health and substance use disorders)?
  • What is the effect of post-acute sequelae of COVID-19 (PASC) on the health, well-being, functioning and quality of life for pregnant and postpartum persons?
• Area 2: Investigate the impact of SRD in the context of the COVID-19 pandemic on the health and well-being of persons during pregnancy and up to one year postpartum.
  • What are the health consequences, including psychosocial and mental health outcomes, of SRD on pregnancy and maternal health outcomes?
  • What are the multi-generational effects of SRD on pathological pathways or mechanisms involving pregnancy and maternal health outcomes?
  • What are the maternal health consequences of COVID-19- related alterations in antenatal and obstetric care, including the investigation of racial/ethnic inequities and disparities, including access to and quality of care?
  • What are the effects of SRD or health inequities in the context of COVID-19 on maternal health and maternal health outcomes?
  • What are the mechanisms mediating the effects of SRD on maternal health outcomes? What strategies can be used to address SRD and eliminate its adverse effects on maternal health?
  • What is the impact of SRD on the treatment of severe COVID-19 in pregnant persons and on the risk of pre-eclampsia, pregnancy-induced hypertension, immune system dysregulation, on the effect on mental health, and subsequent maternal health outcomes?

• Area 3: Understand how knowledge, attitudes, and beliefs about COVID-19 influence decisions and behaviors related to COVID-19 testing and vaccination during pregnancy and up to one year postpartum.
  • What are the specific needs and opportunities for COVID-19 prevention and testing for disproportionately affected populations during pregnancy and up to one year postpartum?
• • What is/are the knowledge, attitudes, and beliefs toward COVID-19 testing and COVID-19 vaccination among pregnant and postpartum persons? What factors may lead to pregnant/postpartum persons with chronic medical or mental/behavioral health conditions approaching COVID-19 testing different than non-pregnant persons with these conditions?

• • What are the challenges, barriers, and/or opportunities to improve trust and facilitate COVID-19 testing and vaccine uptake, such as access to high quality information?
  • What dissemination and implementation strategies can be used to improve COVID-19 testing uptake and vaccine acceptance?
• Area 4: Develop an integrated understanding of pregnancy-related and pregnancy-associated morbidity and MM causes, related to COVID-19.
  • What are the factors contributing to disparities related to maternal morbidity and mortality? How do they interface with those contributing to disparities in COVID-19 during pregnancy and postpartum?
  • Are there predictors or other risk factors that increase susceptibility and severity of COVID-19 thereby disproportionately affecting pregnant persons across race and ethnicity?
  • How can novel predictive analytics be used to identify and mitigate health risks during pregnancy in this and future pandemics?

To accelerate research, NIH encourages investigatorsto leverage ongoing significant investments made on domestic resources, cohorts, and research infrastructure studying pregnant persons, or studies examining SRD that could be expanded to include a focus on pregnancy and COVID-19. Some examples of currently funded projects that may be leveraged include:

• The NICHD Maternal-Fetal Medicine Units Network Gestational Research Assessments for COVID-19 (GRAVID) study includes a registry of approximately 20,000 pregnant persons and is focused on maternal cardiac, neurologic, pulmonary outcomes in COVID-19+ pregnant persons.
• The NIAID Mother-Child Pairs Studies conduct phenotyping and deep immune phenotyping in cohorts of pregnant persons and mother infant-pairs.
• The Healthy Brain and Child Development Study HEALthy Brain and Child Development (HBCD) Study Phase I. A subset of the grantees are examining the effects of the COVID-19 pandemic on pregnant and postpartum persons and birth outcomes for their children.Across all awards, data are expected from 3,000+ individuals.

SRD can be assessed directly (e.g., indexes of residential segregation, unequal treatment in healthcare settings, etc.) or through self-reported experiences of study participants.

Administrative supplements must be within the scope of the project that is already supported. Urgent competitive revisionsallow the expansion of the scope of the parent award to address the urgent needs identified in this NOSI. Clinical trials are allowed. Foreign institutions may not apply, and foreign components are not allowed. Supplements for a project that will be carried out by collaborating investigators as part of a larger network (e.g., the Maternal-Fetal Medicine Units) may submit a single, combined application through the coordinating center or equivalent entity. The applicant must be able to collect or obtain COVID-19 related data from pregnant or postpartum persons and/or conduct coordination of study sites that manage such projects. Applicants must demonstrate how the additional NIH funding will advance science and/or medicine above their current funding level.

Application and Submission Information

Applications in response to this NOSI must be submitted using the following targeted funding opportunities or subsequent re-issued equivalents:

• PA-18-935- Urgent Competitive Revision to Existing NIH Grants and Cooperative Agreements (Urgent Supplement - Clinical Trial Optional) is intended to provide funds for NIH grantees applying to expand the scope of their active grant.
• PA-20-272 - Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
• The funding instrument, or activity code, will be the same as the parent award.

When developing applications in response to this NOSI, all instructions in the SF424 (R&R) Application Guide, PA-20-272, and PA-18-935 must be followed, with the following additions:

• The Research Strategy section of the application is limited to 6 pages and should include the following information:
  • Discussion of the scientific rationale and relevance of the COVID-19 pandemic for pregnant and up to one year postpartum persons
  • For multi-site studies:
    • Discussion of how sites will coordinate, harmonize, and submit data as a collective across study sites
    • Plans for managing and dispersing funds to participating sites
  • Common data elements (CDEs) proposed (applicants are strongly encouraged to use the NIH resources listed in the Data Harmonization section below), description of instruments, and description of any other measures proposed for data collection
  • Proposed timeline
• For funding consideration, applicants must include NOT-OD-21-071 (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

• The award project period of the submission must not exceed one year. A single extension not to exceed 18 months may be requested to complete the proposed work. Requests for second no-cost extensions will be considered on a case-by case-basis only.
• Project budgets up to $2,000,000 (Total Costs) will be considered. Applicants considering budget requests greater than $2,00,0000 totaldirect costs are strongly encouraged to consult with funding IC program staff prior to submitting the supplement request. The budgets should be commensurate with the number of sites, subjects, and complexity of the study proposed. The proposed budget must reflect the actual needs of the proposed project.
• The parent award must be active when the supplement application is submitted (i.e., within the originally reviewed and approved project period), regardless of the time remaining on the current project.
• Applications may be submitted on a rolling basis beginning on March 5, 2021, with a submission date of April 14, 2021 (by 5:00 PM local time of the applicant organization). This NOSI expires on April 21, 2021. Applications received after April 14, 2021 by the designated time will not be considered.
• All applications (including those for multi-project activity codes) must be submitted electronically using a single-project application form package
• Investigators planning to submit an application in response to the NOSI are strongly encouraged to contact the program officers of the parent award to discuss the proposed project in the context of the parent award.
• The process for Streamlined Submissions using the eRA Commons cannot be used for this initiative.
• Period of performance extensions to be considered on a case-by-case basis.
• Awardees must submit milestone progress reports.
• Applicants proposing a project that will be carried out by network collaborating investigators funded through multiple awards may submit a single application on behalf of participating network parent project investigators through the coordinating center or equivalent entity.

Data Harmonization

To maximize comparisons across datasets or studies and facilitate data integration and collaboration where appropriate to study aims, researchers funded through this NOSI are strongly encouraged to use the following data resources below. Researchers addressing COVID-19 questions, whether population-based or for clinical research, are strongly encouraged to consider these COVID-19 specific survey item repositories and select existing survey items or protocol modules currently being fielded where they address questions of interest. Existing COVID-19 survey items are publicly available through two NIH-supported platforms: the NIH Public Health Emergency and Disaster Research Response (DR2) [https://dr2.nlm.nih.gov/] and the PhenX Toolkit [https://www.phenxtoolkit.org/index.php]. Investigators are strongly encouraged to use these data resources. In particular, the use of the collections detailed below is strongly encouraged where applicable:

• NICHD Promoting Data Harmonization to Accelerate COVID-19 Pregnancy Research, which encompasses a collective contribution of NIH extramural and intramural investigators from the relevant research community (see list of contributors on page 4 of the referenced document).
• Data Harmonization for SDoH, COVID-19, mental health, and other relevant measures via the PhenX Toolkit: Investigators involved in human-subject studies are strongly encouraged to employ a common set of tools and resources that will promote the collection of comparable data on SDoH and mental health across studies. In particular, human-subject studies should incorporate SDoH measures from the Core and Specialty collections that are available in the Social Determinants of Health Collection of the PhenX Toolkit (https://www.phenxtoolkit.org/collections/view/6) and the Psychosocial and Mental Health toolkit (https://www.phenxtoolkit.org/sub-collections/view/34)

Review Process

Each IC will conduct administrative reviews of applications that will then be prioritized by NIH staff on the NIH Maternal Mortality Task Force. Applications for competitive revisions will be evaluated for scientific and technical merit by an appropriate internal review panel convened by staff of the NIH awarding component.

Criteria:

Priority will be given to projects that incorporate SRD and community-identified needs and perspectives in populations disproportionately affected by MM/SMM. NIH staff will review the following:

• Does the work proposed address one or more of the goals as defined earlier in this notice (NOT-OD-21-071)?
• Will the proposal address pregnancy-related and pregnancy-associated morbidity/MM in one or more high risk populations based on race/ethnicity, age, or geographic region?
• Does the application address SRD in the context of COVID-19, pregnancy, and maternal outcomes?
• Is the project designed to advance our understanding of the mechanisms, interventions, or risk profiles of pregnancy-related and pregnancy-associated morbidity/MM in the U.S.?
• Does the application propose to address the psychosocial risk factors and outcomes from COVID-19 during pregnancy and up to one year postpartum? If not, is there strong justification for addressing other related research questions?
• Is the work proposed within the scope of the active parent award (for administrative supplements)?
• Is the parent award progressing satisfactorily/according to planned timeline and milestones?
• Is the proposed project technically feasible within the budget and funding period?
• Is the overall strategy, methodology, and analyses proposed in the application well-reasoned and appropriate to accomplish the activities in the proposed project period?

Budget and Period of Support

NIH staff will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications nonresponsive to terms of this NOSI will be withdrawn from consideration for this initiative.

Inquiries

Please direct inquiries to:

IMPROVEinitiative@od.nih.gov