Early Pregnancy loss (EPL), defined as a pregnancy loss occurring up to 20 weeks gestation, is a very common pregnancy complication, occurring in 12-15% of clinically recognized pregnancies, with increased prevalence associated with increasing maternal age. The use of highly sensitive hCG assays allows the detection of pregnancy earlier in gestation than the time of clinical recognition, and gives an even higher estimated loss of 50-70% of conceptions prior to the second trimester. To achieve a successful pregnancy, a series of strict embryonic and maternal conditions must be met, that include high quality embryos, favorable conditions for embryo implantation, receptive maternal endometrium and optimal uterine environment to sustain the conceptus to term. In addition, maternal immune tolerance and hormonal factors play a critical role. While approximately half of all cases of EPL appear to be due to embryonic aneuploidy, very little is known about the physiologic and pathophysiologic processes that underlie non-aneuploid EPL. As a result, there is also a lack of understanding for the underlying causes of recurrent pregnancy loss (RPL). This NOSI seeks to address these critical knowledge gaps by encouraging basic, translational and clinical studies on biological processes that may uncover potential etiologies of EPL and RPL. This includes research to understand implantation mechanistically and identify a range of key factors, involved in implantation and placentation that are important for early pregnancy establishment, including abnormalities that contribute to sporadic EPL and recurrent pregnancy loss.
This notice applies to due dates on or after September 8, 2022 and subsequent receipt dates through September 8, 2025.
NOT-HD-22-026
Example research topics that may elucidate sex and/or gender differences in AD/ADRD risk, development, progression, diagnosis, clinical presentation, and outcomes include, but are not limited to, the following:
- Sex and/or gender differences in longevity, survival bias, and comorbidities
- Life course factors (e.g., early life adversity, place of birth, neurodevelopment, educational experiences, reproductive history, occupational careers, caregiving responsibilities, etc.)
- Complex interactions among sociocultural, behavioral, psychological, neural systems, and biological processes and their responses to the sociocultural and physical environments, and the timing, level, and duration of exposures
- Cohort differences related to social and behavioral factors (e.g., caregiver-child interactions, changes in family structure, fertility, educational attainment, labor force participation, occupational characteristics (e.g., job control, cognitive demands, etc.)) and health behaviors (e.g., tobacco use) which may shape AD/ADRD trends
- Intersectional approaches which consider sex and gender differences among racial and ethnic minority, socioeconomically disadvantaged, underserved rural, and sexual and gender minority (SGM) populations. SGM populations include, but are not limited to, individuals who identify as lesbian, gay, bisexual, asexual, transgender, two-spirit, queer, and/or intersex as well as other individuals whose sexual orientation, gender identity or expression, or reproductive development is characterized by non-binary constructs of sexual orientation, gender, and/or sex
- Structural gender inequalities (e.g., barriers to access healthcare services and high-quality care) that impact AD/ADRD outcomes
- Sex-specific risk factors (e.g., oophorectomy; menopause, including role of hot flashes and sleep disturbances; pregnancy, including preeclampsia and gestational diabetes; androgen-deprivation therapy; and testosterone loss) across the lifespan that may impact AD/ADRD outcomes
- Sex and gender differences in AD/ADRD risk factors common to both sexes (e.g., cardiovascular disease, diabetes, education, hearing loss, depression, etc.)
- Sex differences in immune responses related to risk of AD/ADRD
- Role of hormone changes and/or therapy on brain function (e.g., metabolism) and risk for AD/ADRD and how these may interact with other factors (e.g., sleep)
- Sex differences in genetic risk factors for AD/ADRD (e.g., APOE, x-linked, common variants, autosomal dominant mutations)
- Sex and gender differences in the clinical detection, diagnosis, management, and treatment of AD/ADRD