Clinical trial NCT04394910: Impact of Antioxidant Juice Intake on Brain Injury and Placental Pathology in Infants With Intrauterine Growth Restriction (IUGR)
Official title: Impact of Antioxidant Juice Intake on Brain Injury and Placental Pathology in Infants With Intrauterine Growth Restriction (IUGR)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Intrauterine Growth Restriction
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: University of California, Los Angeles
name: POM Wonderful LLC
First posted: 2020-05-20
Enrollment: 103
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Infants diagnosed with intrauterine growth restriction are at increased risk for brain injury in the neonatal period, and eventually increased risk for adverse long-term neurodevelopmental outcomes. This kind of growth restriction is often caused by long-term placental insufficiency leading to chronic lack of oxygen in the brain during development. Pomegranate juice is one of the highest polyphenol-containing dietary supplements commercially available. Previous studies have shown that pomegranate-derived polyphenols are potent neuroprotective antioxidants with no proven side effects. The investigators hypothesize that maternal dietary supplementation with pomegranate juice during the last trimester of pregnancy will reduce the effects of exogenous stimuli contributing to placental insufficiency, and will enhance brain growth and development in the IUGR population.

Detailed description: The current study seeks to investigate the impact of maternal dietary supplementation with pomegranate juice on placental morphology and on subsequent newborn brain development and function. A total of 99 consenting women carrying fetuses with a diagnosis of intrauterine growth restriction (IUGR) in the third trimester were randomized to one of two arms.

Treatment Group: Expecting mothers in this group will be randomized to consume 8oz of pomegranate juice daily. Participants will keep a daily diary documenting compliance with the regimen. Participants will continue daily intake until delivery.

Placebo group: Expecting mothers will be randomized to consume an 8oz of pomegranate free juice placebo that matches taste, calories, and appearance to regular pomegranate juice but lacks polyphenols. Participants will keep a diary of daily intake to help ensure compliance similar to the treatment group. Participants will continue to placebo until delivery.

Both groups: Maternal blood and urine samples will be collected prior to starting the juice regimen in order to establish baseline metabolite status. For the first 84 mothers enrolled, a fetal MRI was scheduled prior to beginning the juice regimen. Phase I participants will undergo two fetal echocardiograms: one before starting the juice regimen, and a second two weeks into the juice regimen to establish the safety of high polyphenol intake on fetal heart development. All women will be contacted on a weekly basis to assess compliance. At the time of delivery, maternal blood and urine, and cord blood will be collected and sent for analysis to test for the presence of dimethylellagic acid glucuronide (DMEAG) and urolithin A glucuronide (UAG), polyphenic components of pomegranate juice. Placental material will be sent for formal pathological exam.

If clinically stable, MRI will be undertaken without sedation at term equivalent (38-41 weeks CGA). Infants will undergo testing of cognitive, gross and fine motor, and speech skills at around 2 years of age.

Eligibility criteria: Inclusion Criteria:

- Expecting mother with a fetal diagnosis of less than 5th percentile on the Doubilet fetal growth curve

Exclusion Criteria:

* Multiple congenital abnormalities
* Known fetal chromosomal disorder
* Maternal illicit drug or alcohol intake

Primary outcomes:
measure: Infant brain injury assessed on term-equivalent brain magnetic resonance image (MRI) using the Kidokoro injury scoring system.
timeFrame: One time occurrence at birth or term-equivalent age if infant is born preterm.
measure: Total and regional infant brain volumes assessed on term equivalent brain MRI using MANTiS.
timeFrame: One time occurrence at birth or term-equivalent age if infant is born preterm.
measure: Diffusion tensor imaging measures of fractional anisotropy (FA), and mean (MD), radial (RD), and axial (AD) diffusivity from infant term equivalent brain MRI.
timeFrame: One time occurrence at birth or term-equivalent age if infant is born preterm.
Secondary outcomes:
measure: Cognitive, motor, and language neurodevelopment scores on the Bayley III exam.
timeFrame: The Bayley III exam will be administered at a one-time visit scheduled between 18-36 months.
measure: Maternal compliance with juice regimen.
timeFrame: Comparison of one pre-juice regimen UA and DMEAG concentration measurement (ng/mL) to one post-juice regimen blood and urine concentration measurement (ng/mL) collected at the time of delivery.
Other outcomes:
measure: Placental weight.
timeFrame: The placenta will be weighed as part of routine pathology exam within 1-3 days of delivery.
measure: Incidence of pre-eclampsia.
timeFrame: The electronic medical record will be reviewed within 1 week of delivery.
measure: Gestational age at delivery.
timeFrame: The electronic medical record will be reviewed within 1 week of delivery.
measure: Incidence of resuscitation at delivery.
timeFrame: The electronic medical record will be reviewed within 1 week of delivery.
measure: Cord gas characteristics.
timeFrame: The electronic medical record will be reviewed within 1 week of delivery.
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Terrie E Inder, MD, MBChB
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ross MM, Cherkerzian S, Mikulis ND, Turner D, Robinson J, Inder TE, Matthews LG. A randomized controlled trial investigating the impact of maternal dietary supplementation with pomegranate juice on brain injury in infants with IUGR. Sci Rep. 2021 Feb 11;11(1):3569. doi: 10.1038/s41598-021-82144-0.