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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intrauterine Growth Restriction | Pregnant women carrying a fetus identified with intrauterine growth restriction during the third trimester (>28 weeks gestation) |
| |
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Uterine Artery Indices Completed | Measured by Doppler and 3D microvessel imaging, used to calculate outcomes 3-5 | Gestational age of 34-36 weeks |
| Number of Patients With Umbilical Artery Indices Completed | Measured by Doppler and 3D microvessel imaging, used to calculate outcomes 3-5 | Gestational Age of 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) | Gestational Age of 34-36 weeks |
| Resistance Index (RI) | Resistance index (RI) = (systolic velocity - diastolic velocity / systolic velocity) | Gestational Age of 34-36 weeks |
| Pulsatility Index (PI) | Pulsatility index (PI) = (systolic velocity - diastolic velocity / mean velocity) | Gestational age of 34-36 weeks |
| Number of Participants With Placental Pathology Indicating Chronic Villitis | 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. | Gestational age up to 42 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Gestational Age at Birth | The gestational age in weeks of when the baby was delivered. | Gestational age up to 42 weeks |
| Preterm Labor | Pregnancy that delivered prior to 37 weeks gestational age |
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Inclusion Criteria for IUGR study cohort:
Inclusion Criteria for control cohort:
Exclusion Criteria:
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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.
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| Name | Affiliation | Role |
|---|---|---|
| Mauro Schenone, MD | Mayo Clinic | Principal Investigator |
| Elizabeth Ann L Enninga, PhD | Mayo Clinic | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic | Rochester | Minnesota | 55905 | United States |
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| Label | URL |
|---|---|
| Mayo Clinic Clinical Trials | View source |
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Enrollment from September 2020 through March 2023
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| ID | Title | Description |
|---|---|---|
| FG000 | Intrauterine Growth Restriction | Pregnant women carrying a fetus identified with intrauterine growth restriction during the third trimester (>28 weeks gestation) 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. 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. |
| FG001 | 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. 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. 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Intrauterine Growth Restriction | Pregnant women carrying a fetus identified with intrauterine growth restriction during the third trimester (>28 weeks gestation) 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. 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Uterine Artery Indices Completed | Measured by Doppler and 3D microvessel imaging, used to calculate outcomes 3-5 | Posted | Count of Participants | Participants | Gestational age of 34-36 weeks |
|
From enrollment during the third trimester (> 28 weeks gestation) till the mother gives birth. Max reporting period is from Gestational age of 28 weeks to 42 weeks, a maximum of 14 weeks.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Intrauterine Growth Restriction | Pregnant women carrying a fetus identified with intrauterine growth restriction during the third trimester (>28 weeks gestation) 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. 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. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mauro Schenone | Mayo Clinic | 5072840210 | schenone.mauro@mayo.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 6, 2023 | Dec 20, 2023 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D005317 | Fetal Growth Retardation |
| ID | Term |
|---|---|
| D005315 | Fetal Diseases |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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| 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. |
|
| Gestational age up to 37 weeks |
| Birth Weight of Infant | Weight of infant at time of birth | Gestational age up to 42 weeks |
| BG001 | 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. 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. 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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Gravidity | Mean | Standard Deviation | Pregnancies |
|
| Maternal BMI at ultrasound | Mean | Standard Deviation | kg/m^2 |
|
| Smoking | Smoking status collected at baseline. Potential risk factor for pregnancy. | Count of Participants | Participants |
|
| Hypertension | Count of Participants | Participants |
|
| Preeclampsia | Count of Participants | Participants |
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| Gestational Diabetes | Count of Participants | Participants |
|
| Hypothyroidism | Count of Participants | Participants |
|
| OG001 | 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. 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. 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. |
|
|
| Primary | Number of Patients With Umbilical Artery Indices Completed | Measured by Doppler and 3D microvessel imaging, used to calculate outcomes 3-5 | Posted | Count of Participants | Participants | Gestational Age of 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) | Posted | Mean | Standard Deviation | ratio | Gestational Age of 34-36 weeks |
|
|
|
| Primary | Resistance Index (RI) | Resistance index (RI) = (systolic velocity - diastolic velocity / systolic velocity) | Posted | Mean | Standard Deviation | Ratio | Gestational Age of 34-36 weeks |
|
|
|
| Primary | Pulsatility Index (PI) | Pulsatility index (PI) = (systolic velocity - diastolic velocity / mean velocity) | Posted | Mean | Standard Deviation | Ratio | Gestational age of 34-36 weeks |
|
|
|
| Primary | Number of Participants With Placental Pathology Indicating Chronic Villitis | 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. | Posted | Count of Participants | Participants | Gestational age up to 42 weeks |
|
|
|
| Secondary | Gestational Age at Birth | The gestational age in weeks of when the baby was delivered. | Posted | Mean | Standard Deviation | Weeks | Gestational age up to 42 weeks |
|
|
|
| Secondary | Preterm Labor | Pregnancy that delivered prior to 37 weeks gestational age | Posted | Count of Participants | Participants | Gestational age up to 37 weeks |
|
|
|
| Secondary | Birth Weight of Infant | Weight of infant at time of birth | Posted | Mean | Standard Deviation | Grams | Gestational age up to 42 weeks |
|
|
|
| 0 |
| 40 |
| 0 |
| 40 |
| 0 |
| 40 |
| EG001 | 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. 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. 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. | 0 | 20 | 0 | 20 | 0 | 20 |
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| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D006130 | Growth Disorders |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |