Maternal pomegranate juice intake and brain structure and function in infants with intrauterine growth restriction: A randomized controlled pilot study

Abstract

Polyphenol-rich pomegranate juice has been shown to have benefit as a neuroprotectant in animal models of neonatal hypoxic-ischemia. No published studies have investigated maternal polyphenol administration as a potential neuroprotectant in at-risk newborns, such as those with intrauterine growth restriction (IUGR). This was a randomized, placebo-controlled, double-blind pilot study to investigate the impact of maternal pomegranate juice intake in pregnancies with IUGR, on newborn brain structure and function at term-equivalent age (TEA). Mothers with IUGR at 24–34 weeks’ gestation were recruited from Barnes-Jewish Hospital obstetrical clinic. Consented mothers were randomized to treatment (8 oz. pomegranate juice) or placebo (8 oz. polyphenol-free juice) and continued to take juice daily from enrollment until delivery (mean 20.1 and 27.1 days, respectively). Infants underwent brain MRI at TEA (36–41 weeks’ gestation). Brain measures were compared between groups including: brain injury score, brain metrics, brain volumes, diffusion tensor imaging and resting state functional connectivity. Statistical analyses were undertaken as modified intention-to-treat (including randomized participants who received their allocated intervention and whose infants received brain MRI) and per-protocol (including participants who strictly adhered to the protocol, based on metabolite status). Seventy-seven mothers were randomized to treatment (n = 40) or placebo (n = 37). Of these, 28 and 27 infants, respectively, underwent term-equivalent MRI. There were no group differences in brain injury, metrics or volumes. However, treatment subjects displayed reduced diffusivity within the anterior and posterior limbs of the internal capsule compared with placebo. Resting state functional connectivity demonstrated increased correlation and covariance within several networks in treatment subjects, with alterations most apparent in the visual network in per-protocol analyses. Direct effects on health were not found. In conclusion, maternal pomegranate juice intake in pregnancies with known IUGR was associated with altered white matter organization and functional connectivity in the infant brain, suggesting differences in brain structure and function following in utero pomegranate juice exposure, warranting continued investigation. Clinical trial registration. NCT00788866 , registered November 11, 2008, initial participant enrollment August 21, 2012.

Grape Seed Extract Polyphenols Improve Resistance Artery Function in Pregnant eNOS–/– Mice

“…However, a wide variety of dietary sources of natural antioxidants, including polyphenols, is underexplored and investigation of their effects in pregnancy is currently a key research area. A recent randomized controlled pilot study has shown potential neuroprotective effects of maternal pomegranate juice supplementation, which is also rich in antioxidants and bioactive polyphenols, in FGR newborns at risk for hypoxic-ischemic injury (Matthews et al, 2019). A double−blind randomized controlled trial using EGCG as an intervention in pregnant women with gestational diabetes mellitus, reported therapeutic effects of this natural catechin-rich compound for both maternal and neonatal complications, such as improved low-birthweight and lower number of infants with hypoglycemia (Zhang et al, 2017).…”

“…Trials aimed at improving pregnancy outcomes in other high-risk groups have shown benefits with the use of supplements containing high levels of polyphenols. Maternal administration of a catechin-rich dietary supplement (epigallocatechin 3-gallate, EGCG), has been demonstrated to improve both maternal and neonatal outcomes in pregnancies affected by gestational diabetes mellitus, including neonatal weight at birth ( Zhang et al, 2017 ), and data from a recent randomized placebo-controlled, double-blind pilot study ( Matthews et al, 2019 ), have provided preliminary evidence of in utero neuroprotective effects of polyphenol-rich pomegranate juice, in newborns from FGR pregnancies. These approaches may be of benefit in hypertensive pregnancies, though data are currently lacking.…”

Gender-Related and Hemispheric Effects in Cortical Thickness-Based Hemispheric Brain Morphological Network

“…On the other hand, diffusion tensor imaging (DTI) and functional magnetic resonance imaging MRI (fMRI) have been commonly used for constructing the individual brain networks connected by way of the axonal pathways (in DTI) or coupled changes of brain functional activations (in fMRI), respectively [ 3 , 4 ]. The brain structural covariance network partly reflects the patterns of brain white matter-based physical connectivity [ 5 – 7 ], coordinated oscillations in BOLD signal changes across the whole brain during the resting status (so-called resting state functional connectivity) [ 8 , 9 ], and coordinated brain development and maturation [ 1 , 10 , 11 ]. For the construction of brain network, the sMRI could be preferred to fMRI or DTI because of its advantages in terms of easy access, high signal-to-noise ratio, and relative insensitivity to artifacts.…”

A randomized controlled trial investigating the impact of maternal dietary supplementation with pomegranate juice on brain injury in infants with IUGR

“…Pomegranate juice is one of the highest polyphenol-containing, commercially available dietary supplements with particularly potent antioxidant capacity due to high bioavailability of biologically active compounds like flavonoids, ellagic acid and ellagitannins. These properties have led to increasing interest in its potential role in the prevention of chronic diseases associated with oxidative stress, such as cardiovascular diseases, cancer, diabetes and neurodegenerative diseases [16][17][18][19][20][21] , although until recently, no studies have examined the effects of prenatal pomegranate juice consumption in humans 22 .…”

“…We recently reported differences in white matter microstructure and resting state connectivity within visual networks in IUGR infants born to mothers who consumed pomegranate juice compared to placebo 22 , representing to the best of our knowledge the only study of prenatal pomegranate juice exposure and the developing human brain. In the current study we sought to continue to explore the neuroprotectant potential of pomegranate juice by further investigating associations between pomegranate juice consumption and neonatal brain injury, volumes and white matter microstructure in a second site involving IUGR pregnancies presenting at a major tertiary hospital in Boston, MA.…”