ABSTRACT Antenatal daily ingestion of pomegranate juice (POM), compared to placebo, in women with pregnancies diagnosed with intrauterine growth restriction (IUGR) relates to changes in the micro-structural organization within the anterior and posterior limbs of the internal capsule and functional connectivity within the visual network of the offspring. What is unknown is whether or not the effects on the growth-restricted fetus are due to POM-induced improved placental function or due to the transfer of POM phytochemicals to the fetus in utero. We tested the hypothesis that maternal ingestion of POM in a pregnancy with IUGR yields juice metabolites in the fetal circulation, improves placental function, both, or neither. We conducted a randomized, blinded, placebo-controlled-trial of daily antenatal ingestion of eight ounces (240 ml) of pomegranate juice, or color-matched placebo juice, starting the week between 24-34 weeks’ gestation IUGR, diagnosed by < 10% ultrasound-estimated fetal weight (clinicaltrials.gov:NCT00788866). Eighty women enrolled had two metabolites of POM measured in maternal and cord blood at delivery, and newborn outcomes and placental structure and function were assessed. Dimethyl-ellagic-acid glucuronide and urolithin A strongly correlated between maternal and fetal blood, with a linear regression of 1.56 + 0.77 x and R2 = 0.88. There were no significant differences in mode of delivery, birthweight, Apgar scores, or immediate clinical status of the newborn in the POM versus placebo groups. There were no differences between the two groups for placental weight, pathology, histology, immunocytochemistry, or protein expression analyses. We conclude that POM metabolites pass from the maternal to the fetal circulation across the placenta and are thus available to influence brain connectivity. POM does not improve placental structure or function in IUGR that is established prior to POM use.
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