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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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 Summary:

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
Sponsor: Washington University School of Medicine

Current Primary Outcome: 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)


Original Primary Outcome:

  • CNS injury at term by MR Imaging [ Time Frame: 24 months ]
  • Neurodevelopmental delay at 18-24 months MDI and PDI by Bayley Scale of Infant Development (BSID III) (> 2SD from the norm, score ≤ 70) [ Time Frame: 24 months ]


Current Secondary Outcome:

  • Placental morphology: weight and size [ Time Frame: At birth ]
  • Gestational age at delivery [ Time Frame: At birth ]
  • Birth weight [ Time Frame: At birth ]
  • Ellagic acid levels from cord blood [ Time Frame: To discharge ]
  • Dubowitz neurologic exam at term [ Time Frame: To discharge ]
  • Time to full oral feeds [ Time Frame: To discharge ]
  • ROP [ Time Frame: To discharge ]
  • NEC [ Time Frame: To discharge ]
  • Length of ventilatory support [ Time Frame: To discharge ]
  • Time to discharge [ Time Frame: To discharge ]
  • Placental micrography: number of villi, vasculature, collagen content [ Time Frame: At birth ]
  • Placental immunohistochemistry: proliferation, apoptosis and differentiation [ Time Frame: At birth ]
  • Placental: immunoassays: HSP90, lipid hydroperoxide, nitrotyrosine assay, paraoxonase 1 expression, superoxide dismutases [ Time Frame: At birth ]
  • Placental RNA microarray [ Time Frame: At birth ]
  • Umbilical cord gases [ Time Frame: At birth ]
  • Pregnancy complications: preeclampsia [ Time Frame: At birth ]
  • Neonatal wellbeing: APGAR scores, need for resuscitation [ Time Frame: At birth ]


Original Secondary Outcome:

  • Placental weight [ Time Frame: To discharge ]
  • Gestation [ Time Frame: To discharge ]
  • Birth weight [ Time Frame: To discharge ]
  • Ellagic acid levels from cord blood [ Time Frame: To discharge ]
  • Dubowitz neurologic exam at term [ Time Frame: To discharge ]
  • Time to full oral feeds [ Time Frame: To discharge ]
  • ROP [ Time Frame: To discharge ]
  • NEC [ Time Frame: To discharge ]
  • Length of ventilatory support [ Time Frame: To discharge ]
  • Time to discharge [ Time Frame: To discharge ]


Information By: Washington University School of Medicine

Dates:
Date Received: November 10, 2008
Date Started: December 2008
Date Completion:
Last Updated: October 16, 2014
Last Verified: October 2014