Table 2 Abnormal Gestational Biology
Overarching Goal: To understand the mechanisms contributing to preterm birth and stillbirth, with emphasis upon infectious, genetic, and environmental factors, abnormal placental vascular development, and early gestational events | |||||
|---|---|---|---|---|---|
| Â | Milestones* | Â | |||
Output | Post-Conference (by 2010) | Short-Term (by 2012) | Intermediate (by 2015) | Long-Term (beyond 2015) | Success Metrics |
A. Determine causes and differential susceptibility to infection, and maternalrfetal immune response associated with PTB and SB utilizing high-dimensional systems biology approaches | 1. Identify existing cohorts to characterize the pregnancy "biome" | 2. Treat existing known infectious causes of PTB/SB 2. Establish cohort to characterize pregnancy "biome" 3. Characterize human vaginal microbiome | 5. Identify polymorphisms and immunoregulatory genes associated with PTB/SB 6. Utilize systems biology to identify non-invasive biomarkers for PTB/SB 7. Study vaginal and cervical mucosal immunity and the biology of the microbial flora | 8. Validate models to assess intervention strategies 9. Study short-and long-term conseguences of inflammation on fetal origin of adult disease and neurodevelopmental outcome | • Cost-effective interventions to reduce morbidity/mortality associated with inflammation- induced prematurity |
B. Determine causes of vascular mal-adaptation resulting in abnormal uteroplacental perfusion, fetal growth restriction and abruption associated PTB and SB utilizing high-dimensional systems biology approaches | 1. Increase grant RFAs by national and international research funding agencies | 2. Study origins of spiral artery adaptation 3. Study genetic and environmental influences on vasculopathy 4. Develop models for vascular pathology, including endometrial modifications | 5. Develop cost-effective interventions to promote normal placentation | 6. Study short-and long-term conseguences on fetal origin of adult disease and neurodevelopmental outcomes | • Cost-effective interventions to reduce morbidity/mortality associated with vascular associated prematurity linked to abnormal uteroplacental vasculature |
C. Determine if preconceptual and/or antenatal micronutrient exposure contributes to PTB/SB | 1. Systematic review of available evidence | 2. Cohort studies to confirm associations | 3. RCTs of micronutrient support or environmental modification 4. Assess translational feasibility | 5. Specific trials for LMICs | • Identification of cost-effective micronutrient interventions to reduce PTB/SB |