Fetal intrauterine growth restriction remains a risk for later adverse neurodevelopmental outcome with no current therapeutic options to protect the newborn brain. Pomegranate juice is rich in natural polyphenols, which in animal experimental work provide neonatal neuroprotection following maternal ingestion. Two randomized double blind controlled trials were conducted at Barnes-Jewish Hospital, St Louis and Brigham and Womens Hospital, Boston between 2012-2020 enrolling infants were: 1)fetal diagnosis of IUGR defined by estimated fetal weight < 10th percentile for gestational age by Hadlock growth curves; 2) 24–34 weeks’ gestation. Mothers were randomized to receive 8oz of pomegranate juice or a control beverage matched for color and caloric content. All infants received magnetic resonance imaging after delivery or at term equivalence for evaluation of any brain abnormality by a systemic scoring system (Kidokoro scoring) read by a neuroradiologist blinded to group. A meta-analysis of all data was undertaken given the high similarity in trial design and value of combining independent data sets. One hundred and eighty women were randomized with mean maternal age 28 years (IQR 22-33 years), 50% black with recruitment at 30 weeks gestation (IQR 28-32). Women received median 20 days of juice supplementation (IQR 8-34 days). For intention-to-treat analysis, the treatment arms did not differ, however infants whose mothers received maternal pomegranate juice showed lower rates of white matter injury on neonatal magnetic resonance imaging (White matter injury: Pomegranate juice odds ratio 0.43; 95% CI: 0.28-0.65, p< 0.0001). There were no differences noted in infant growth or brain growth on MRI. Maternal pomegranate juice, a potent antioxidant, administered in pregnancies complicated by fetal intrauterine growth restriction resulted in a significant reduction in the risk of neonatal cerebral white matter injury, which is known to be associated with adverse neurodevelopmental outcome.View Large Image Figure ViewerDownload Hi-res image Download (PPT)