Clinical trial NCT02749851: Placenta Imaging Project
Official title: Functional Imaging of Human Placenta by MRI
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: High Risk Pregnancy
Keywords: pregnancy
growth restriction
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2016-04-25
Enrollment: 379
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 52
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Women who plan to deliver at OHSU or University of Utah hospitals and live within the areas served by those medical facilities.

Brief summary: The purpose of this study is to test the application of newly generated magnetic resonance imaging (MRI) protocols for the assessment of placental perfusion in human subjects. The primary objective is to validate and establish the utility of placental MRI in pregnant women. The study will be entirely MRI-technology based with collection of placental tissue at the time of infant delivery for later correlative studies.

Detailed description: The placenta provides all the nutrition from a pregnant mother to a developing fetus. A placenta that functions normally is needed to ensure normal fetal growth and development. Unfortunately, the placenta is the least understood human organ even though it is involved in all pregnancy complications. The placenta is so poorly understood because our current methods to look at it during pregnancy, like ultrasound, do not provide enough information about placental growth and function.

This study will help provide information about:

* How the placenta grows and develops during pregnancy
* How the placenta delivers nutrients, like oxygen to the developing fetus
* If placental function using new advanced imaging tools can predict pregnancy complications like fetal growth restriction, stillbirth, preeclampsia and preterm labor

This study will explore how blood flow to the placenta affects placental growth, fetal growth, and oxygen delivery to the fetus. Blood flow to the placenta may determine how the placenta supports fetal growth and development. Having a way to measure placental function during pregnancy may provide a way to understand normal pregnancies but importantly also identify pregnancies at increased risk for pregnancy complications.

Additionally we want to have an ancillary intrauterine growth restriction (IUGR) arm; the objective of this ancillary study is to test the sensitivity of the placental MRI protocol in women with confirmed cases of IUGR in the third trimester.

Eligibility criteria: Pregnant women will be recruited based on inclusion criteria for 3 subject groups:

1. Non-smokers with low risk for placental insufficiency
2. Smokers
3. Non-smokers who are at a high risk for adverse outcomes based on prior clinical history.

Inclusion criteria: Pregnant women fulfilling inclusion criteria, and not meeting exclusion criteria, will be invited to participate in this study.

Inclusion criteria for all groups:

1. Maternal age over 18 years and able to give informed consent
2. Pregnant patient, as defined by positive pregnancy test for elevated β-human chorionic gonadotropin (HCG) and certain menstrual history, or early ultrasound, identified prior to 14 weeks of gestation

Inclusion criteria for low risk group:

1. No history of a second or third trimester loss
2. No history of fetal growth restriction

Inclusion criteria for high risk group:

1. History of pregnancy complicated by placental insufficiency in a previous singleton pregnancy (i.e. severe preeclampsia requiring preterm delivery, preterm delivery due to placenta insufficiency (eg. fetal growth restriction (FGR), oligohydramnios, abnormal umbilical artery Doppler's, abnormal antenatal testing), FGR \<10% delivered at term; stillbirth attributed to placental cause, regardless of gestational age
2. Not currently a smoker
3. Pregnancy at risk for placental insufficiency due to clinical concerns (eg. chronic hypertension)
4. Spontaneous preterm birth \<34 weeks

Exclusion criteria: These criteria will exclude women whose medications, personality traits or obstetric conditions could confound their ability to complete a 1 hour MRI scan.

1. Individuals with intellectual disability or who are incarcerated
2. Multiple gestation
3. Major fetal anomalies known to be associated with abnormal growth (i.e. major congenital heart defect, gastroschisis)
4. Current maternal history of alcohol or illicit drug use
5. Current medical problems requiring chronic treatment:

   * Cancer
   * Active liver disease (acute hepatitis, chronic active hepatitis, persistently abnormal liver enzymes)
   * Chronic pulmonary disease including asthma requiring regular use of medication
6. Prior history of claustrophobia
7. Metal implants
8. Increased aneuploidy risk based on ultrasound findings or genetic testing

Primary outcomes:
measure: Placental perfusion (Units of measure: ml/min) measured at 3 time points across gestation.
timeFrame: Change from 16, 24, and 32 weeks gestation
measure: Optimal cutoff values of placental MRI for placenta mediated adverse outcomes using receiver operating characteristics (ROC)
timeFrame: Change from 16, 24, and 32 weeks gestation
measure: Composite of placenta-mediated adverse pregnancy outcomes
timeFrame: 39 weeks gestation
Secondary outcomes:
measure: Composite of Placenta histologic outcomes
timeFrame: 39 weeks gestation
measure: Diagnosis of preeclampsia using standard clinical criteria
timeFrame: 39 weeks gestation
measure: Small for gestational age fetus at 3% and 5%
timeFrame: 39 weeks gestation
measure: Gestational age at delivery prior to 37 weeks gestation.
timeFrame: 37 weeks gestation
Other outcomes:
Locations:
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: Oregon Health and Science University
name: Antonio Frias, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schabel MC, Roberts VHJ, Gibbins KJ, Rincon M, Gaffney JE, Streblow AD, Wright AM, Lo JO, Park B, Kroenke CD, Szczotka K, Blue NR, Page JM, Harvey K, Varner MW, Silver RM, Frias AE. Quantitative longitudinal T2* mapping for assessing placental function and association with adverse pregnancy outcomes across gestation. PLoS One. 2022 Jul 19;17(7):e0270360. doi: 10.1371/journal.pone.0270360. eCollection 2022.