Predicting Placental Pathologies by Ultrasound Imaging

Intrauterine Growth Restriction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04506970
• Other study ID #: 20-000991
• Status: Completed
• Start date: September 27, 2020
• Est. completion date: October 31, 2023

Study information

• Verified date: November 2023
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: October 31, 2023
• Est. primary completion date: July 31, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Fetal Growth Retardation
• Intrauterine Growth Restriction
• IUGR
• Villitis

Intervention

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.

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Uterine artery indices	Measured by Doppler and 3D microvessel imaging, used to calculate outcomes 3-5	34-36 weeks
Primary	Umbilical artery indices	Measured by Doppler and 3D microvessel imaging, used to calculate outcomes 3-5	34-36 weeks
Primary	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
Primary	Resistance index (RI)	Resistance index (RI) = (systolic velocity - diastolic velocity / systolic velocity)	34-36 weeks
Primary	Pulsatility index (PI)	Pulsatility index (PI) = (systolic velocity - diastolic velocity / mean velocity)	34-36 weeks
Primary	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

External Links

•   Mayo Clinic Clinical Trials