Predicting Placental Pathologies by Ultrasound Imaging

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

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.

Study Overview

• Status: Completed
• Conditions: Intrauterine Growth Restriction; IUGR; Villitis
• Intervention / Treatment: Diagnostic test: Comprehensive Doppler Ultrasound of the Placenta; Other: Verasonics Ultrasound scanner (ultra-sensitive Doppler imaging)

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

• Study Contact: Name: Maureen A Lemens, BSN; Phone Number: 507-293-1487; Email: lemens.maureen@mayo.edu
• Study Contact Backup: Name: Emily N Smith, BSN; Phone Number: 507-266-4813; Email: smith.emily3@mayo.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited from women obtaining prenatal care in the obstetrics clinic at Mayo Clinic in Rochester, Minnesota. This study will consist of two cohorts: 1) women diagnosed with intrauterine growth restriction (IUGR) and 2) women having uncomplicated pregnancies. Forty women will be enrolled after being diagnosed with IUGR. Based on prior clinical data it is expected that 50% will have a VUE diagnosis. Another cohort of 20 women having uncomplicated pregnancies will also be enrolled, matched for fetal sex and gestational age at ultrasound.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Intrauterine Growth Restriction; Pregnant women carrying a fetus identified with intrauterine growth restriction during the third trimester (>28 weeks gestation)	Diagnostic test: Comprehensive Doppler Ultrasound of the Placenta; 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.; Other: Verasonics Ultrasound scanner (ultra-sensitive Doppler imaging); 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.
Normal pregnancy; Pregnant women identified with an uncomplicated pregnancy during the third trimester (>28 weeks), matched for fetal sex and gestational age with women enrolled in the IUGR group.	Diagnostic test: Comprehensive Doppler Ultrasound of the Placenta; 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.; Other: Verasonics Ultrasound scanner (ultra-sensitive Doppler imaging); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Uterine artery indices	Measured by Doppler and 3D microvessel imaging, used to calculate outcomes 3-5	34-36 weeks
Umbilical artery indices	Measured by Doppler and 3D microvessel imaging, used to calculate outcomes 3-5	34-36 weeks
Systolic(S)/diastolic(D) ratio	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)	34-36 weeks
Resistance index (RI)	Resistance index (RI) = (systolic velocity - diastolic velocity / systolic velocity)	34-36 weeks
Pulsatility index (PI)	Pulsatility index (PI) = (systolic velocity - diastolic velocity / mean velocity)	34-36 weeks
Placental pathology	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.	up to 42 weeks

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Study Chair: Elizabeth Ann L Enninga, PhD, Mayo Clinic; Principal Investigator: Mauro Schenone, MD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2020
• Primary Completion (Actual): July 31, 2023
• Study Completion (Actual): October 31, 2023

Study Registration Dates

• First Submitted: July 23, 2020
• First Submitted That Met QC Criteria: August 5, 2020
• First Posted (Actual): August 10, 2020

Study Record Updates

• Last Update Posted (Actual): November 28, 2023
• Last Update Submitted That Met QC Criteria: November 26, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Fetal Diseases; Pregnancy Complications; Growth Disorders; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Fetal Growth Retardation
• Other Study ID Numbers: 20-000991

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No