Research On Advanced Diagnostics and Management of All Pregnancies to Prevent Stillbirth (ROADMAPS) (ROADMAPS)
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)
Studienübersicht
Status
Bedingungen
Detaillierte Beschreibung
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.
Studientyp
Einschreibung (Geschätzt)
Kontakte und Standorte
Studienkontakt
- Name: Carla Bann, PhD
- Telefonnummer: 919-485-2773
- E-Mail: cmb@rti.org
Studieren Sie die Kontaktsicherung
- Name: Elizabeth McClure, PhD
- Telefonnummer: 919-316-3773
- E-Mail: mcclure@rti.org
Studienorte
-
-
California
-
San Diego, California, Vereinigte Staaten, 92093
- University of California Center for Stillbirth Prevention
-
Kontakt:
- Mana Parast, MD, PhD
- Telefonnummer: 858-534-8631
- E-Mail: mparast@health.ucsd.edu
-
Hauptermittler:
- Mana Parast, MD, PhD
-
-
New York
-
New York, New York, Vereinigte Staaten, 10027
- The Collaborative Action for Research to End Stillbirth (CARES) Research Center at Columbia University
-
Hauptermittler:
- Uma Reddy, MD, MPH
-
Kontakt:
- Uma Reddy, MD, MPH
- Telefonnummer: 240-401-3605
- E-Mail: uma.reddy@yale.edu
-
Hauptermittler:
- Xiao Xu, PhD
-
-
Oregon
-
Portland, Oregon, Vereinigte Staaten, 97239
- Oregon Health & Science University
-
Kontakt:
- Karen Gibbins, MD, MSCI
- Telefonnummer: 503-494-2101
- E-Mail: gibbins@ohsu.edu
-
Hauptermittler:
- Karen Gibbins, MD, MSCI
-
-
Utah
-
Salt Lake City, Utah, Vereinigte Staaten, 84112
- University of Utah
-
Kontakt:
- Robert Silver, MD
- Telefonnummer: 801-581-8425
- E-Mail: bob.silver@hsc.utah.edu
-
Hauptermittler:
- Robert Silver, MD
-
-
Virginia
-
Norfolk, Virginia, Vereinigte Staaten, 23529
- Old Dominion University
-
Kontakt:
- George Saade, MD
- Telefonnummer: 757-446-5257
- E-Mail: saadegr@odu.edu
-
-
Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
- Erwachsene
- Älterer Erwachsener
Akzeptiert gesunde Freiwillige
Probenahmeverfahren
Studienpopulation
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.
Beschreibung
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
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
Kohorten und Interventionen
Gruppe / Kohorte |
|---|
|
Early Pregnancy Cohort
|
|
Late Pregnancy Cohort
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
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.
Zeitfenster: 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:
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
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Stillbirth
Zeitfenster: Delivery
|
Stillbirth among all births
|
Delivery
|
|
Fetal growth restriction (FGR)
Zeitfenster: Delivery
|
Fetal growth restriction <10%ile with at least one of the following criteria:
|
Delivery
|
|
Neonatal mortality
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: Delivery
|
Classification of cause of stillbirth using published classification system
|
Delivery
|
|
Apgar score
Zeitfenster: Delivery
|
Among fetal growth restriction (<10th%ile) infants, 5-minute Apgar score
|
Delivery
|
|
Neurologic injury
Zeitfenster: Birth to 7 days
|
Evidence of neurologic injury among infants with severe FGR
|
Birth to 7 days
|
|
Hypoxic-ischemic encephalopathy (HIE)
Zeitfenster: Birth to 7 days
|
HIE based on the Sarnat examination among infants with severe fetal growth restriction.
|
Birth to 7 days
|
|
Intraventricular hemorrhage
Zeitfenster: delivery
|
Diagnosis of intraventricular hemorrhage among infants with severe fetal growth restricition.
|
delivery
|
|
Hypotension
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: Birth to 7 days
|
Neonatal seizures among infants with severe fetal growth restriction
|
Birth to 7 days
|
|
Gestational age at delivery
Zeitfenster: 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)
Zeitfenster: Birth to day 28
|
Number days admitted to the NICU among infants with severe fetal growth restriction
|
Birth to day 28
|
|
Neonatal mortality
Zeitfenster: Birth to 28 days post-delivery
|
Neonaal death (<=28 days) among infants with severe fetal growth restriction.
|
Birth to 28 days post-delivery
|
Mitarbeiter und Ermittler
Sponsor
Mitarbeiter
Ermittler
- Hauptermittler: Elizabeth McClure, PhD, RTI International
Publikationen und hilfreiche Links
Allgemeine Veröffentlichungen
- Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc Behav. 1983 Dec;24(4):385-96. No abstract available.
- Cox JL, Holden JM, Sagovsky R. Detection of postnatal depression. Development of the 10-item Edinburgh Postnatal Depression Scale. Br J Psychiatry. 1987 Jun;150:782-6. doi: 10.1192/bjp.150.6.782.
- Azpurua H, Funai EF, Coraluzzi LM, Doherty LF, Sasson IE, Kliman M, Kliman HJ. Determination of placental weight using two-dimensional sonography and volumetric mathematic modeling. Am J Perinatol. 2010 Feb;27(2):151-5. doi: 10.1055/s-0029-1234034. Epub 2009 Aug 3.
- Khong TY, Mooney EE, Ariel I, Balmus NC, Boyd TK, Brundler MA, Derricott H, Evans MJ, Faye-Petersen OM, Gillan JE, Heazell AE, Heller DS, Jacques SM, Keating S, Kelehan P, Maes A, McKay EM, Morgan TK, Nikkels PG, Parks WT, Redline RW, Scheimberg I, Schoots MH, Sebire NJ, Timmer A, Turowski G, van der Voorn JP, van Lijnschoten I, Gordijn SJ. Sampling and Definitions of Placental Lesions: Amsterdam Placental Workshop Group Consensus Statement. Arch Pathol Lab Med. 2016 Jul;140(7):698-713. doi: 10.5858/arpa.2015-0225-CC. Epub 2016 May 25.
- Caradeux J, Martinez-Portilla RJ, Basuki TR, Kiserud T, Figueras F. Risk of fetal death in growth-restricted fetuses with umbilical and/or ductus venosus absent or reversed end-diastolic velocities before 34 weeks of gestation: a systematic review and meta-analysis. Am J Obstet Gynecol. 2018 Feb;218(2S):S774-S782.e21. doi: 10.1016/j.ajog.2017.11.566. Epub 2017 Dec 9.
- Riley RD, Ensor J, Snell KIE, Harrell FE Jr, Martin GP, Reitsma JB, Moons KGM, Collins G, van Smeden M. Calculating the sample size required for developing a clinical prediction model. BMJ. 2020 Mar 18;368:m441. doi: 10.1136/bmj.m441. No abstract available.
- Steyerberg EW, Harrell FE Jr. Prediction models need appropriate internal, internal-external, and external validation. J Clin Epidemiol. 2016 Jan;69:245-7. doi: 10.1016/j.jclinepi.2015.04.005. Epub 2015 Apr 18. No abstract available.
- Society for Maternal-Fetal Medicine (SMFM). Electronic address: pubs@smfm.org; Martins JG, Biggio JR, Abuhamad A. Society for Maternal-Fetal Medicine Consult Series #52: Diagnosis and management of fetal growth restriction: (Replaces Clinical Guideline Number 3, April 2012). Am J Obstet Gynecol. 2020 Oct;223(4):B2-B17. doi: 10.1016/j.ajog.2020.05.010. Epub 2020 May 12.
- Marshall NE, Abrams B, Barbour LA, Catalano P, Christian P, Friedman JE, Hay WW Jr, Hernandez TL, Krebs NF, Oken E, Purnell JQ, Roberts JM, Soltani H, Wallace J, Thornburg KL. The importance of nutrition in pregnancy and lactation: lifelong consequences. Am J Obstet Gynecol. 2022 May;226(5):607-632. doi: 10.1016/j.ajog.2021.12.035. Epub 2021 Dec 27.
- Zimet, G. D., Dahlem, N. W., Zimet, S. G. & Farley, G. K. (1988). The Multidimensional Scale of Perceived Social Support. Journal of Personality Assessment, 52, 30-41.
- Zhou MS, Hasson RE, Baylin A, Leung CW. Associations between Diet Quality and Allostatic Load in US Adults: Findings from the National Health and Nutrition Examination Survey, 2015-2018. J Acad Nutr Diet. 2022 Dec;122(12):2207-2217. doi: 10.1016/j.jand.2022.05.001. Epub 2022 May 6.
- Silver RM, Reddy U. Stillbirth: we can do better. Am J Obstet Gynecol. 2024 Aug;231(2):152-165. doi: 10.1016/j.ajog.2024.05.042. Epub 2024 May 23.
- Kawakita T, Diab YH, Onishi K, Saade G. Nutrition Pattern and Adverse Pregnancy Outcomes in Nulliparous Individuals: A Cluster Analysis. Am J Perinatol. 2026 May;43(7):955-962. doi: 10.1055/a-2712-5518. Epub 2025 Sep 29.
- Jack-Roberts C, Maples P, Kalkan B, Edwards K, Gilboa E, Djuraev I, Zou S, Hoepner L, Fordjour L, Lee WC, Kral J, Dalloul M, Jiang X. Gestational diabetes status and dietary intake modify maternal and cord blood allostatic load markers. BMJ Open Diabetes Res Care. 2020 Oct;8(1):e001468. doi: 10.1136/bmjdrc-2020-001468.
- International Stillbirth Alliance Collaborative for Improving Classification of Perinatal Deaths; Flenady V, Wojcieszek AM, Ellwood D, Leisher SH, Erwich JJHM, Draper ES, McClure EM, Reinebrant HE, Oats J, McCowan L, Kent AL, Gardener G, Gordon A, Tudehope D, Siassakos D, Storey C, Zuccollo J, Dahlstrom JE, Gold KJ, Gordijn S, Pettersson K, Masson V, Pattinson R, Gardosi J, Khong TY, Froen JF, Silver RM. Classification of causes and associated conditions for stillbirths and neonatal deaths. Semin Fetal Neonatal Med. 2017 Jun;22(3):176-185. doi: 10.1016/j.siny.2017.02.009. Epub 2017 Mar 9.
- Howell A, Thilaganathan B, Margelyte R, Burden C, Cheng V, Sandall J, Viner M, Brigante L, Anumba D, Winter C, Harlev-Lam B, Draycott T, Judge A, Lenguerrand E; Tommy's National Centre for Maternity Improvement. Why current risk factor-based approaches fall short in predicting stillbirth: a national cohort study of nulliparous women in England. BMC Med. 2026 Jan 22;24(1):94. doi: 10.1186/s12916-025-04598-7.
- Ego A, Monier I, Skaare K, Zeitlin J. Antenatal detection of fetal growth restriction and risk of stillbirth: population-based case-control study. Ultrasound Obstet Gynecol. 2020 May;55(5):613-620. doi: 10.1002/uog.20414.
- Committee on Genetics. ACOG Committee Opinion No. 383: Evaluation of stillbirths and neonatal deaths. Obstet Gynecol. 2007 Oct;110(4):963-6. doi: 10.1097/01.AOG.0000263934.51252.e0.
- Billioux, A., Verlander, K., Anthony, S., & Alley, D. (2017). Standardized screening for health-related social needs in clinical settings: The Accountable Health Communities Screening Tool. National Academy of Medicine Perspectives, 1-9.
- Arleo EK, Troiano RN, da Silva R, Greenbaum D, Kliman HJ. Utilizing two-dimensional ultrasound to develop normative curves for estimated placental volume. Am J Perinatol. 2014 Sep;31(8):683-8. doi: 10.1055/s-0033-1357265. Epub 2013 Oct 9.
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Geschätzt)
Primärer Abschluss (Geschätzt)
Studienabschluss (Geschätzt)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Urogenitale Erkrankungen
- Pathologische Prozesse
- Weibliche Urogenitalerkrankungen und Schwangerschaftskomplikationen
- Schwangerschaftskomplikationen
- Tod
- Fötale Krankheiten
- Wachstumsstörungen
- Fötaler Tod
- Angeborene, erbliche und neonatale Krankheiten und Anomalien
- Pathologische Zustände, Anzeichen und Symptome
- Fötale Wachstumsverzögerung
- Totgeburt
Andere Studien-ID-Nummern
- SBRC ROADMAPS
- UM2HD119552 (US NIH Stipendium/Vertrag)
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .