Effects of Maternal L-glutamine Supplementation on Fetus to Mitigate Teratogenic Effects of Alcohol
Women who drink alcohol during pregnancy are at high risk of giving birth to children with physical, behavioral or cognitive developmental problems called Fetal Alcohol Spectrum Disorders (FASD). Prenatal alcohol exposure is known to be associated with fetal growth restriction, disturbances in amino acid bioavailability, and alterations in fetal hemodynamics, blood flow and oxidative stress. Alterations in these parameters can persist into adolescence and low birth weight can lead to altered fetal development and programming, which can have lifelong consequences. Glutamine has been associated with fetal nitrogen and carbon metabolism, synthesis of the cellular anti-oxidant glutathione, apoptosis suppression, serving as a precursor for the synthesis of other amino acids, and increases in protein synthesis. Glutamine has been used clinically as a nutrient supplement in low birth weight infants. Therefore, it is hypothesized that repeated third trimester-equivalent maternal alcohol exposure in the sheep model decreases the bioavailability of amino acids, hampers fetal body growth, alters maternal-fetal hemodynamics, hampers uterine blood flow, alters fetal blood flow, increases cerebellar oxidative stress and that maternal L-glutamine supplementation may attenuate these negative developmental effects of prenatal alcohol exposure.
Maternal alcohol exposure during the third trimester-equivalent period in the sheep model significantly reduced fetal body weight, height, crown-rump length and thoracic girth, and maternal glutamine supplementation successfully improved these fetal growth parameters in the alcohol+glutamine group. Maternal alcohol exposure during the third trimester-equivalent period resulted in significant reduction in glutamine and glutamine related amino acids bioavailability in maternal and fetal plasma as well as in the fetal amniotic and allantoic fluid. Maternal glutamine supplementation improved the bioavailability and efficacy of amino acids in the maternal and fetal compartment. This study also revealed that maternal alcohol exposure resulted in maternal acidemia, maternal hypercapnea, maternal hypoxemia as well as fetal acidemia and fetal hypercapnea, but not fetal hypoxemia. Maternal alcohol exposure during this period led to an increase in fetal mean arterial pressure, alterations in fetal brain blood flow and fetal cerebellar oxidative stress. Maternal alcohol exposure during the third trimester-equivalent period resulted in a more than 40% reduction in uterine artery blood flow. Maternal glutamine supplementation during the third trimester-equivalent period successfully attenuated the incidences of alcohol-induced maternal hypercapnea, fetal acidemia, alterations in fetal brain blood flow and improved the fetal cerebellar endogenous antioxidant status. Collectively these results signify that maternal glutamine supplementation mitigates negative developmental effects of prenatal alcohol exposure.