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Completed

NCT Number: NCT04506970

Predicting Placental Pathologies by Ultrasound Imaging

Intrauterine growth restriction (IUGR) is caused when the placenta cannot provide enough nutrients to allow normal growth of the fetus during pregnancy. It is unclear why IUGR happens, but an increase in inflammatory T cells in the placenta known as villitis of unknown etiology (VUE) is observed in many IUGR infants. The investigators aim to develop ultrasound methods for diagnosing VUE to understand it's role in IUGR.

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Key information

About this study

Intrauterine growth restriction (IUGR) occurs in 3-10% of all pregnancies and is associated with significant morbidity and mortality during pregnancy, after birth and throughout the child's lifespan. IUGR is caused by the inability of the placental vasculature to provide enough oxygen and nutrients to support the fetus; yet, the mechanisms leading to disruption of placental vasculature are unknown. The placenta of ~50% of IUGR fetuses are infiltrated with inflammatory cells, specifically maternal T cells, which destroy placental blood vessels that support the fetus. This infiltration of T cells is known as villitis of unknown etiology (VUE). The diagnosis of VUE is problematic because it occurs without clinical signs and symptoms of maternal (or fetal) distress and puts the fetus at significant risk of demise. Additionally, VUE commonly recurs in subsequent pregnancies putting future offspring at risk. Yet, the exact prevalence of VUE and its significance in IUGR pathogenesis and outcomes are poorly understood as VUE is only diagnosed after the infant is outside the womb. Therefore, the study aims to recognize risk factors and cellular mechanisms associated with VUE and develop methods for diagnosing and treating VUE in utero, in order to improve infant health.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

for IUGR study cohort:

  • Pregnancy > 28 weeks gestation
  • Diagnosis of Intrauterine Growth Restriction (IUGR) before admission for labor and delivery
  • Weight > 110 lbs (50 kg)
  • Ability to understand and provide written informed consent

Inclusion criteria

for control cohort:

  • Pregnancy > 28 weeks gestation
  • No known pregnancy complications at prenatal obstetrical visit (+/- 1 week gestational age of matched subject in IUGR cohort)
  • Weight > 110 lbs (50 kg)
  • Ability to understand and provide written informed consent

Exclusion criteria

  • Known immunodeficiency or pregnancy complication (i.e. preeclampsia or gestational diabetes)
  • Known autoimmune disease (e.g., rheumatoid arthritis or systemic lupus erythematosus) or chronic hypertension
  • Chronic, active viral infections, including HIV-1/2, HTLV-1/2, Hepatitis B or C
  • Solid organ or transplant recipient
  • Current smokers (tobacco exposure within 30 days of registration)
  • Conceptions from assisted reproductive technology (prior Clomid use is allowed)
  • Multiple gestation
  • Ruptured membranes
  • Pregnancy <28 weeks gestation
  • Not planning on delivering at Mayo Clinic

Treatment and study plan

Comprehensive Doppler Ultrasound of the Placenta

Diagnostic Test

Ultrasound measures to be collected include uterine artery (UtA) and umbilical artery (UA), systolic/diastolic (S/D) ratio, resistance index (RI), pulsatility index (PI) and presence of early diastolic notch.

Verasonics Ultrasound scanner (ultra-sensitive Doppler imaging)

Other

In addition, a Verasonics ultrasound scanner will be used for ultra-sensitive Doppler imaging. Data will be collected on vessel density, periphery-to-center vessel density ratio (VDR) and microvessel morphology.

Primary outcomes

  1. Number of Participants With Uterine Artery Indices Completed

    Time frame: Gestational age of 34-36 weeks

    Measured by Doppler and 3D microvessel imaging, used to calculate outcomes 3-5

  2. Number of Patients With Umbilical Artery Indices Completed

    Time frame: Gestational Age of 34-36 weeks

    Measured by Doppler and 3D microvessel imaging, used to calculate outcomes 3-5

  3. Systolic(S)/Diastolic(D) Ratio

    Time frame: Gestational Age of 34-36 weeks

    S = Systolic peak (max velocity); Maximum velocity during contraction of the fetal heart.

    D = End-diastolic flow; Continuing forward flow in the umbilical artery during the relaxation phase of the heartbeat.

    S/D ratio = (systolic / diastolic ratio)

  4. Resistance Index (RI)

    Time frame: Gestational Age of 34-36 weeks

    Resistance index (RI) = (systolic velocity - diastolic velocity / systolic velocity)

  5. Pulsatility Index (PI)

    Time frame: Gestational age of 34-36 weeks

    Pulsatility index (PI) = (systolic velocity - diastolic velocity / mean velocity)

  6. Number of Participants With Placental Pathology Indicating Chronic Villitis

    Time frame: Gestational age up to 42 weeks

    Using the Amsterdam criteria, following delivery, placentae will be histologically examined for placental villitis (presence of maternal T cells) and graded by severity. High grade involves greater than 10 villi while low grade affects fewer than 10 villi.

Secondary outcomes

  1. Gestational Age at Birth

    Time frame: Gestational age up to 42 weeks

    The gestational age in weeks of when the baby was delivered.

  2. Preterm Labor

    Time frame: Gestational age up to 37 weeks

    Pregnancy that delivered prior to 37 weeks gestational age

  3. Birth Weight of Infant

    Time frame: Gestational age up to 42 weeks

    Weight of infant at time of birth

Sponsors and collaborators

Lead sponsor

Mayo Clinic

Other

Registry information

Official study title

Predicting Placental Pathologies by Ultrasound Imaging of the Human Placenta During Gestation

Important dates

Study start
2020
Primary completion
2023
Study completion
2023
First posted
Aug 10, 2020
Registry last updated
Oct 10, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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