Impact of Maternal Pomegranate Juice on Brain Injury in Infants With Intrauterine Growth Restriction (IUGR)
Impact of Maternal Pomegranate Juice on Brain Injury in Infants With Intrauterine Growth Restriction (IUGR)
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.
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.

 Both groups: All women will be followed up on a weekly basis to assess compliance. A detailed
 diet history will be collected from the women at the time of enrollment, midway through the
 3rd trimester and at the time of delivery. Furthermore, all women will have a detailed social
 history collected at the time of enrollment. Upon delivery, cord blood will be collected and
 sent for ellagic acid, a polyphenic component. All placental material will be sent for formal
 pathological exam and analyzed for markers of placental injury.

 If clinically stable, the infants will receive MRI evaluations to evaluate for possible brain
 injury.
Phase I:

 Inclusion Criteria:

 -  Healthy expecting mothers two weeks from their expected due dates

 -  No evidence of IUGR

 -  No evidence of fetal problems

 Phase II:

 Inclusion Criteria:

 1. Expecting mother with a fetal diagnosis of intrauterine growth restriction (IUGR)
 defined by estimated fetal weight <10th percentile for gestational age

 2. 24 - 34 weeks gestation

 Exclusion Criteria:

 1. Major congenital abnormalities

 2. Known fetal chromosomal disorder

 3. Maternal illicit drug use

 4. Maternal IV and Hepatitis C infection

 5. Premature rupture of membranes