NICHD Stillbirth Research Consortium: Research on Advanced Diagnostics and Management of All Pregnancies to Prevent Stillbirth (ROADMAPS)
| Registry | NCT07745101, acronym ROADMAPS |
|---|---|
| Status | Not yet recruiting |
| Study type | Observational |
| Enrollment | 7000 (Estimated) |
| Sponsor | RTI International (Other); collaborators: Old Dominion University, University of Utah, Columbia University, University of California, San Diego, Oregon Health and Science University, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) |
| Conditions | Stillbirth |
| Dates | start 2026-08-01 (estimated), primary completion 2030-07-31 (estimated), completion 2030-07-31 (estimated), first posted 2026-08-04, last updated 2026-08-04 |
| Locations | 5 sites in United States |
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All trials for Stillbirth
The primary objective of the Stillbirth Research Consortium (SBRC) longitudinal cohort study is to develop and evaluate a robust multivariable prediction model to identify pregnancies at <14 weeks gestation that are at increased risk of stillbirth or fetal growth restriction (FGR), often reflecting underlying placental dysfunction.
Secondary objectives include:
* To evaluate placental pathology among cases and selected controls using standardized Amsterdam criteria.
* To identify key aspects of perinatal nutrition contributing to placental dysfunction
* To determine relationships between maternal biomarkers, placental pathology and energetics, with the goal of identifying biomarkers predictive of placental dysfunction
* To develop a risk stratification model for pregnancies complicated by decreased fetal movements (DFM)
In the United States, stillbirth defined as fetal death at or beyond 20 weeks' gestation affects approximately 5.48/1,000 births, or 1 in 180 pregnancies, a rate that surpasses many other high-resource countries, highlighting major opportunities for improvement and prevention. Prevention of stillbirth in the United States requires improved risk stratification to identify pregnancies at highest risk. Unfortunately, commonly used pre-pregnancy risk factors such as parity, advanced maternal age, and body mass index are poor predictors of stillbirth and explain only a small proportion of stillbirth risk. Critical gaps in stillbirth risk stratification hamper efforts to accurately identify at-risk pregnancies early enough to enable effective interventions and ultimately reduce stillbirth and those on the path to stillbirth.
FGR is frequently a manifestation of underlying placental dysfunction and one of the strongest known risk factors for stillbirth, with a stillbirth rate of 1.5% (two-fold increased risk). FGR, defined as a fetus that fails to reach its growth potential, is difficult to diagnose. The term small for gestational age, defined as estimated or actual birthweight below the 10th percentile, is often used interchangeably with FGR, although it does not distinguish between constitutionally small fetuses and those affected by pathologic growth restriction.
Early onset FGR is well recognized as a major risk factor for stillbirth, yet nearly half of FGR fetuses are not detected antenatally. The development of abnormal fetal umbilical artery (UA) Doppler indices differentiates between constitutionally small fetuses and those with increased risk of stillbirth. Estimated fetal weight below the 3rd percentile has been associated with a further increased risk of adverse perinatal outcome irrespective of Doppler indices (3-fold risk over 3rd to 5th percentile, and 4- to 7-fold risk over 5th to 10th percentile).
To address the need for more timely identification of pregnancies at risk for stillbirth or FGR, we will conduct a longitudinal prospective cohort study to develop a prediction model to identify pregnancies at <14 weeks gestation with increased risk of stillbirth or severe FGR. We will use the Hadlock nomogram to define birthweight percentile since we seek to identify at-risk pregnancies prenatally.
Placental Dysfunction
Placental dysfunction is a central biological pathway underlying both FGR and many stillbirths. It reflects the inability of the placenta to meet the metabolic demands of a growing fetus. However, placental dysfunction is heterogenous and difficult to diagnose during an ongoing pregnancy. Post delivery, placental dysfunction can be identified following a complete pathologic evaluation, using standardized pathologic criteria, including maternal vascular malperfusion (MVM), fetal vascular malperfusion (FVM), inflammatory villitis of unknown etiology (VUE) or acute chorioamnionitis (ACA) patterns of injury, or as Massive Perivillous Fibrin Deposition/Maternal Floor Infarction (MPVFD/MFI) as defined by the Amsterdam Workshop Guidelines.
Despite advances in placental pathology, there are currently no validated biomarkers that can reliably identify placental dysfunction during pregnancy. The placenta generates and utilizes considerable energy to support its own function consuming half of the oxygen and nutrients supplied to the pregnant uterus. Measurement of trophoblast energetics in vitro post-delivery allows assessment into placental "health" and ability to support the fetus.
To address the need for more timely identification of pregnancies at risk for stillbirth and FGR, we will utilize innovative placental imaging and biomarkers to examine early indicators of placental dysfunction before 14 weeks' gestation and their association with stillbirth and severe FGR (Secondary Objective).
Perinatal Nutrition
Perinatal nutrition is a potentially modifiable factor that influences placental function and pregnancy outcomes. Higher diet quality has been associated with lower allostatic load, while suboptimal perinatal nutrition is associated with stillbirth and adverse pregnancy outcomes. Nutritional status is critical for the health of the pregnant individual, placental function, and developing offspring. By understanding the role of nutrition in pregnancy outcomes, we will be able to better identify high-risk individuals and potential interventions.
Decreased Fetal Movements
DFM are generally assessed as part of standard care; however, assessment and management vary widely, and evidence regarding their predictive value is inconsistent. Within this cohort, we will collect standardized data on fetal movements and evaluate their association with adverse outcomes. These data will be used to develop a risk stratification framework and inform best practices for the clinical management of DFM.
Together, achieving these objectives will provide a better understanding of these factors will provide robust information to inform clinical practice to improve birth outcomes in the United States.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Early Pregnancy Cohort | * 18 years or older * Gestational age at enrollment: Between 12.0 and 13.6 weeks of gestation * Pregnant individuals receiving care at participating clinical sites with intent of delivering at study hospital * Consent to participate in study procedures through 6 weeks postpartum | ||
| Late Pregnancy Cohort | * 18 years or older * Gestational age at enrollment: greater than or equal to 28.0 weeks gestational age * Clinical indications of risk (FGR <10th percentile or report of decreased fetal movement) * Pregnant individual receiving care at participating clinical sites with intent of delivering at study hospital * Consent to participate in study procedures through 6 weeks postpartum |
Sex: Female, ages: 18 Years to any, accepts healthy volunteers
Early Pregnancy Cohort Inclusion Criteria * 18 years of age * Gestational age at enrollment: Between 12.0 and 13.6 weeks of gestation * Pregnant individuals receiving care at participating clinical sites with intent of delivering at study hospital * Consent to participate in study procedures through 6 weeks postpartum Late Pregnancy Cohort * 18 years or older * Gestational age at enrollment: greater than or equal to 28.0 weeks gestational age * Clinical indications of risk FGR <10th percentile or report of decreased fetal movement) * Pregnant individual receiving care at participating clinical sites with intent of delivering at study hospital * Consent to participate in study procedures through 6 weeks postpartum Exclusion Criteria: * Evidence of fetal genetic anomaly or major structural malformation * Known fetal aneuploidy based on chorionic villus sampling * Positive cell-free fetal DNA screening for aneuploidy * Multifetal gestation * Less than 18 years of age * Not fluent in either English or Spanish
| Facility | City | Country | Status |
|---|---|---|---|
| University of California Center for Stillbirth Prevention | San Diego, California | United States | |
| The Collaborative Action for Research to End Stillbirth (CARES) Research Center at Columbia University | New York, New York | United States | |
| Oregon Health & Science University | Portland, Oregon | United States | |
| University of Utah | Salt Lake City, Utah | United States | |
| Old Dominion University | Norfolk, Virginia | United States |
NIH grants: UM2HD119552