Predicting Placental Pathologies by Ultrasound Imaging

Completed

Interventions: Diagnostic Test: Comprehensive Doppler Ultrasound of the Placenta
Other: Verasonics Ultrasound scanner (ultra-sensitive Doppler imaging)

Brief 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.

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.

Recruitment & Eligibility

Inclusion Criteria

Not provided

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

Arm && Interventions

Group	Intervention	Description
Normal pregnancy	Verasonics Ultrasound scanner (ultra-sensitive Doppler imaging)	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.
Intrauterine Growth Restriction	Comprehensive Doppler Ultrasound of the Placenta	Pregnant women carrying a fetus identified with intrauterine growth restriction during the third trimester (\>28 weeks gestation)
Normal pregnancy	Comprehensive Doppler Ultrasound of the Placenta	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.
Intrauterine Growth Restriction	Verasonics Ultrasound scanner (ultra-sensitive Doppler imaging)	Pregnant women carrying a fetus identified with intrauterine growth restriction during the third trimester (\>28 weeks gestation)

Primary Outcome Measures

Name	Time	Method
Number of Participants With Uterine Artery Indices Completed	Gestational age of 34-36 weeks	Measured by Doppler and 3D microvessel imaging, used to calculate outcomes 3-5
Number of Patients With Umbilical Artery Indices Completed	Gestational Age of 34-36 weeks	Measured by Doppler and 3D microvessel imaging, used to calculate outcomes 3-5
Systolic(S)/Diastolic(D) Ratio	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)
Resistance Index (RI)	Gestational Age of 34-36 weeks	Resistance index (RI) = (systolic velocity - diastolic velocity / systolic velocity)
Pulsatility Index (PI)	Gestational age of 34-36 weeks	Pulsatility index (PI) = (systolic velocity - diastolic velocity / mean velocity)
Number of Participants With Placental Pathology Indicating Chronic Villitis	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 Outcome Measures

Name	Time	Method
Gestational Age at Birth	Gestational age up to 42 weeks	The gestational age in weeks of when the baby was delivered.
Preterm Labor	Gestational age up to 37 weeks	Pregnancy that delivered prior to 37 weeks gestational age
Birth Weight of Infant	Gestational age up to 42 weeks	Weight of infant at time of birth