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Research On Advanced Diagnostics and Management of All Pregnancies to Prevent Stillbirth (ROADMAPS) (ROADMAPS)

29 de julho de 2026 atualizado por: Elizabeth McClure, RTI International

NICHD Stillbirth Research Consortium: Research on Advanced Diagnostics and Management of All Pregnancies to Prevent Stillbirth (ROADMAPS)

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)

Visão geral do estudo

Status

Ainda não está recrutando

Condições

Natimorto

Descrição detalhada

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.

Tipo de estudo

Observacional

Inscrição (Estimado)

7000

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Contato de estudo

Nome: Carla Bann, PhD
Número de telefone: 919-485-2773
E-mail: cmb@rti.org

Estude backup de contato

Nome: Elizabeth McClure, PhD
Número de telefone: 919-316-3773
E-mail: mcclure@rti.org

Locais de estudo

Estados Unidos
- California
  - San Diego, California, Estados Unidos, 92093
    - University of California Center for Stillbirth Prevention
    - Contato:
      
      Mana Parast, MD, PhD
      
      Número de telefone: 858-534-8631
      
      E-mail: mparast@health.ucsd.edu
    - Investigador principal:
      
      Mana Parast, MD, PhD
- New York
  - New York, New York, Estados Unidos, 10027
    - The Collaborative Action for Research to End Stillbirth (CARES) Research Center at Columbia University
    - Investigador principal:
      
      Uma Reddy, MD, MPH
    - Contato:
      
      Uma Reddy, MD, MPH
      
      Número de telefone: 240-401-3605
      
      E-mail: uma.reddy@yale.edu
    - Investigador principal:
      
      Xiao Xu, PhD
- Oregon
  - Portland, Oregon, Estados Unidos, 97239
    - Oregon Health & Science University
    - Contato:
      
      Karen Gibbins, MD, MSCI
      
      Número de telefone: 503-494-2101
      
      E-mail: gibbins@ohsu.edu
    - Investigador principal:
      
      Karen Gibbins, MD, MSCI
- Utah
  - Salt Lake City, Utah, Estados Unidos, 84112
    - University of Utah
    - Contato:
      
      Robert Silver, MD
      
      Número de telefone: 801-581-8425
      
      E-mail: bob.silver@hsc.utah.edu
    - Investigador principal:
      
      Robert Silver, MD
- Virginia
  - Norfolk, Virginia, Estados Unidos, 23529
    - Old Dominion University
    - Contato:
      
      George Saade, MD
      
      Número de telefone: 757-446-5257
      
      E-mail: saadegr@odu.edu

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

Adulto
Adulto mais velho

Aceita Voluntários Saudáveis

Sim

Método de amostragem

Amostra de Probabilidade

População do estudo

The study population for the primary objective will include pregnant individuals who are screened and enrolled between 12.0 and 13.6 weeks of gestation at participating clinical sites ("Early Pregnancy Cohort"). Individuals may also be screened and enrolled at later gestational ages greater than or equal to 28 weeks gestation to address the secondary objectives of the project, including DFM, and FGR and relationship to perinatal nutrition and allostatic load ("Late Pregnancy Cohort").

This study will collect discarded neonatal cord blood post-delivery and will request access to neonatal medical record charts using appropriate HIPAA Authorization. We will also collect paternal saliva samples, when possible, after obtaining consent from the father.

Descrição

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

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

Número de grupos/coortes

Coortes e Intervenções

Grupo / Coorte
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

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado	Descrição da medida	Prazo
The primary outcome is a composite outcome of stillbirth or severe placental dysfunction, defined as the occurrence of birth at or beyond 20.0 weeks of gestation. Prazo: 7 days post delivery	Stillbirth, Fetal Growth Restriction (FGR) or Neonatal Mortality <7 days among births at ≥20.0 weeks' gestation meeting one or more of the following: Stillbirth among births at >20.0 weeks' gestation FGR defined as: FGR < 3rd percentile FGR 3 - <10th percentile with at least one of the following criteria: Umbilical artery Doppler > 95th percentile for either systolic/diastolic ratio (S/D), pulsatility index (PI), or resistance index (RI) Oligohydramnios Non-reassuring fetal heart rate or biophysical profile - Neonatal death less than or equal to 7 days, excluding non-medical causes Primary outcome Time Frame: Birth through 7-days post delivery	7 days post delivery

Medidas de resultados secundários

Medida de resultado	Descrição da medida	Prazo
Stillbirth Prazo: Delivery	Stillbirth among all births	Delivery
Fetal growth restriction (FGR) Prazo: Delivery	Fetal growth restriction <10%ile with at least one of the following criteria: Umbilical artery Doppler > 95th percentile for either systolic/diastolic ratio (S/D), pulsatility index (PI), or resistance index (RI) Oligohydramnios Non-reassuring fetal heart rate or biophysical profile	Delivery
Neonatal mortality Prazo: Up to 7 days after delivery	Early neonatal mortality among live births	Up to 7 days after delivery
Placental dysfunction among stillbirths, fetal growth restriction and neonatal deaths Prazo: Delivery	Placental dysfunction will be defined using the Amsterdam Criteria including the following characteristics: Maternal vascular malperfusion (MVM), fetal vascular malperfusion (FVM), VUE, or MPVFD/MFI; other important findings associated with placental insufficiency; and/or cord abnormalities associated with placental insufficiency	Delivery
Cause of stillbirth Prazo: Delivery	Classification of cause of stillbirth using published classification system	Delivery
Apgar score Prazo: Delivery	Among fetal growth restriction (<10th%ile) infants, 5-minute Apgar score	Delivery
Neurologic injury Prazo: Birth to 7 days	Evidence of neurologic injury among infants with severe FGR	Birth to 7 days
Hypoxic-ischemic encephalopathy (HIE) Prazo: Birth to 7 days	HIE based on the Sarnat examination among infants with severe fetal growth restriction.	Birth to 7 days
Intraventricular hemorrhage Prazo: delivery	Diagnosis of intraventricular hemorrhage among infants with severe fetal growth restricition.	delivery
Hypotension Prazo: Birth to 7 days	Hypotension requiring vasopressor or inotrope for cardiovascular support among infants with severe fetal growth restriction	Birth to 7 days
Cord arterial blood gas Prazo: Birth to 7 days	Cord arterial blood gas demonstrating pH <7.0 or base excess > 12 mEq/L among infants with severe fetal growth restriction	Birth to 7 days
Seizures Prazo: Birth to 7 days	Neonatal seizures among infants with severe fetal growth restriction	Birth to 7 days
Gestational age at delivery Prazo: Delivery	Estimated gestational age at delivery based on early ultrasound among infants with severe fetal growth restriction.	Delivery
Days admitted to the Neonatal Intensive Care Unit (NICU) Prazo: Birth to day 28	Number days admitted to the NICU among infants with severe fetal growth restriction	Birth to day 28
Neonatal mortality Prazo: Birth to 28 days post-delivery	Neonaal death (<=28 days) among infants with severe fetal growth restriction.	Birth to 28 days post-delivery

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

RTI International

Colaboradores

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

University of California, San Diego

Columbia University

Oregon Health and Science University

University of Utah

Old Dominion University

Investigadores

Investigador principal: Elizabeth McClure, PhD, RTI International

Publicações e links úteis

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Publicações Gerais

Links úteis

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Estimado)

1 de agosto de 2026

Conclusão Primária (Estimado)

31 de julho de 2030

Conclusão do estudo (Estimado)