Impact of Maternal Pomegranate Juice on Brain Injury in Infants With Intrauterine Growth Restriction (IUGR)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- CNS injury at term by MR Imaging
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- Double (Care Provider, Investigator)
入排标准
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •Major congenital abnormalities
- •Known fetal chromosomal disorder
- •Maternal illicit drug use
- •Maternal IV and Hepatitis C infection
- •Premature rupture of membranes
结局指标
主要结局
CNS injury at term by MR Imaging
时间窗: 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)
次要结局
- Placental RNA microarray(At birth)
- Placental immunohistochemistry: proliferation, apoptosis and differentiation(At birth)
- Placental morphology: weight and size(At birth)
- Birth weight(At birth)
- Umbilical cord gases(At birth)
- Time to discharge(To discharge)
- Placental: immunoassays: HSP90, lipid hydroperoxide, nitrotyrosine assay, paraoxonase 1 expression, superoxide dismutases(At birth)
- Pregnancy complications: preeclampsia(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)
- 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)
研究者
Methodius Tuuli, MD, MPH
Assistant Professor
Washington University Early Recognition Center