Impact of Maternal Pomegranate Juice on Brain Injury in Infants With Intrauterine Growth Restriction (IUGR)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 80
- Locations
- 1
- Primary Endpoint
- CNS injury at term by MR Imaging
Study Overview
Brief Summary
Infants with intrauterine growth restriction are known to be at increased risk for long term neurodevelopmental delay into adulthood. The main mechanism for this is likely decreased blood flow to the brain secondary to altered placental blood flow. Antioxidants may serve to protect the developing brain from this process. Animal studies have shown that pomegranate juice protects the fetal brain from injury in a model of stroke. This clinical trial is intended to evaluate if giving mothers pomegranate juice during the last several weeks of pregnancy can help protect intrauterine growth restricted babies' brains.
Detailed Description
This study is divided into two separate phases.
Phase I evaluated if the antioxidants produced from pomegranate juice cross the placenta in normal healthy pregnancies. Twenty women were enrolled, 10 who will take 8 oz of pomegranate juice daily and then 10 others who will take 8 oz of placebo juice without pomegranate daily. Blood samples were first collected from the woman at the time enrollment and then from both the woman and the cord blood at the time of delivery. These blood samples were analyzed to measure the levels of antioxidant metabolites from the pomegranate juice. This phase was deigned to confirm placental transfer of antioxidant pomegranate metabolites. The results confirmed placenta transfer of pomegranate metabolites. Further, placental tissues from 12 patients (4 in the pomegranate group and 8 in the control group) were collected for analysis of oxidative stress. The preliminary in vivo results were extended to oxidative stress and cell death assays in vitro. Placental explants and cultured primary human trophoblasts were exposed to pomegranate juice or glucose (control) under defined oxygen tensions and chemical stimuli. We found decreased oxidative stress in term human placentas from women who labored after prenatal ingestion of pomegranate juice compared with apple juice as control. Moreover, pomegranate juice reduced in vitro oxidative stress, apoptosis, and global cell death in term villous explants and primary trophoblast cultures exposed to hypoxia, the hypoxia mimetic cobalt chloride, and the kinase inhibitor staurosporine. Punicalagin, but not ellagic acid, both prominent polyphenols in pomegranate juice, reduced oxidative stress and stimulus-induced apoptosis in cultured syncytiotrophoblasts.
Phase II focuses on pregnancies with intrauterine growth restriction. If they meet entry criteria, then woman will be enrolled and randomized into 1 of 2 groups.
Treatment group: Expecting mothers in this group will start a daily regimen of 8 oz glass of pomegranate juice. They will keep a daily diary documenting their compliance. They will continue this daily intake up until delivery of their infant.
Placebo group: These women will start a daily regimen of an 8 oz of pomegranate free juice placebo that matches taste, calories, and appearance to regular pomegranate juice but lacks polyphenols. They will also keep a diary of daily intake to help ensure compliance similar to the treatment group. They too will continue to take the placebos up until the time they deliver.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Prevention
- Masking
- Double (Care Provider, Investigator)
Eligibility Criteria
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Inclusion Criteria:
- •Healthy expecting mothers two weeks from their expected due dates
- •No evidence of IUGR
- •No evidence of fetal problems
- •Inclusion Criteria:
- •Expecting mother with a fetal diagnosis of intrauterine growth restriction (IUGR) defined by estimated fetal weight <10th percentile for gestational age
- •24 - 34 weeks gestation
Exclusion Criteria
- •Major congenital abnormalities
- •Known fetal chromosomal disorder
- •Maternal illicit drug use
- •Maternal IV and Hepatitis C infection
- •Premature rupture of membranes
Arms & Interventions
Pomegranate juice
This arm with receive 8oz of pomegranate juice per day.
Intervention: Pomegranate Juice (Dietary Supplement)
Placebo
This group will take 8oz of placebo juice that lacks pomegranate daily
Intervention: Placebo (Dietary Supplement)
Outcomes
Primary Outcomes
CNS injury at term by MR Imaging
Time Frame: 36 - 41 weeks (post delivery)
1. Qualitative MRI injury- white matter injury (WMI) and gray matter injury (GMI) 2. Brain Metrics on MR imaging 3. Diffusion- apparent diffusion coefficient (ADC) and fractional anisotropy (FA) 4. Spectroscopy- lactate and NAA levels in the basal ganglia 5. Advanced MRI development indices - brain volumes, surface based morphology (SBM, folding indices)
Secondary Outcomes
- Time to discharge(To discharge)
- Placental morphology: weight and size(At birth)
- Birth weight(At birth)
- Placental immunohistochemistry: proliferation, apoptosis and differentiation(At birth)
- Placental RNA microarray(At birth)
- Umbilical cord gases(At birth)
- Placental: immunoassays: HSP90, lipid hydroperoxide, nitrotyrosine assay, paraoxonase 1 expression, superoxide dismutases(At birth)
- Gestational age at delivery(At birth)
- Time to full oral feeds(To discharge)
- NEC(To discharge)
- Ellagic acid levels from cord blood(To discharge)
- Dubowitz neurologic exam at term(To discharge)
- ROP(To discharge)
- Pregnancy complications: preeclampsia(At birth)
- Length of ventilatory support(To discharge)
- Placental micrography: number of villi, vasculature, collagen content(At birth)
- Neonatal wellbeing: APGAR scores, need for resuscitation(At birth)
Investigators
Methodius Tuuli, MD, MPH
Assistant Professor
Washington University Early Recognition Center