Markers of Oxidative Stress and Systemic Vasoconstriction in Pregnant Women Drinking ≥48 g of Alcohol per Day

Abstract

Background-The precise pathway by which alcohol causes the characteristic features of fetal alcohol spectrum disorders (FASD) is unknown. Proposed mechanisms for fetal injury from maternal alcohol use include cellular damage from oxidative stress and impaired fetal oxygenation related to maternal systemic vasoconstriction. Our objective was to compare levels of urinary markers of oxidative stress and systemic vasoconstriction between women consuming large amounts of alcohol during pregnancy and women who did not drink alcohol during pregnancy.

Vascular effects of maternal alcohol consumption

“…We will first review the effects of alcohol on the prostanoid system that is activated during pregnancy. In one study, pregnant women who were consuming Ն48 g alcohol per day and those who abstained were studied and no significant differences in levels of urine 8-isoprostane F 2␣ (oxidative stress marker), 2,3-dinor-6-ketoprostaglandin F 1␣ (a vasodilator metabolite of prostaglandin I 2 ), and 11-dehydro-thromboxane B 2 (a vasoconstrictor metabolite of thromboxane A 2 ) were detected, and the authors concluded against a significant role for eicosanoid markers of oxidative stress (79). In contrast, an earlier study conducted in drinking pregnant women who consumed higher amounts of alcohol (5-to 20-yr history of alcohol abuse; consumption, ϳ140 -840 g/wk during first half of gestation or beyond) showed the ratio of the urinary combined prostacyclin metabolites (vasodilator) and thromboxane B 2 (vasoconstrictor) to be significantly lower compared with that in the controls (101).…”

“…Next, we will discuss oxygen free radicals as redox balance impairment produces vasoconstriction. Substantial evidence exists to demonstrate maternal alcohol exposure increases oxidative stress markers in the fetus (11), fetoplacental compartment (40), maternal ovine uterine artery endothelial cells (69), etc., via multiple mechanisms that are discussed in other excellent review articles (9,11,27), whereas there is a paucity of human clinical studies especially in pregnant women (79). Another paracrine factor that is critical in gestational adaptations is NO.…”

Maternal Alcohol Use During Pregnancy Causes Systemic Oxidation of the Glutathione Redox System

“…In utero alcohol exposure causes increased oxidant stress in the exposed offspring in multiple organs in a variety of animal models (Devi et al, 1993; Gauthier et al, 2005; Henderson et al, 1999; Rathinam et al, 2006). However, for the alcohol-consuming pregnant female, controversy remains whether alcohol-induced maternal systemic oxidative stress contributes to the adverse outcomes of the alcohol-exposed newborn (Cohen-Kerem and Koren, 2003; Signore et al, 2008). …”

Metabolomics and fetal alcohol spectrum disorder

“…Other possible mechanisms whereby alcohol exerts its influence includes the effects it has on cell division, cell death, and the composition and fluidity of cell membranes. More attention in recent years has pointed towards oxidative stress as a major factor in the severity of FASD, in addition to impaired fetal oxygenation related to maternal systemic vasoconstriction (Signore et al 2008). However, in one study (Signore et al 2008), the authors found no differences in the oxidative stress marker 8-isoprostane F2␣, or the prostaglandin metabolites 2,3-dinor-6-keto-prostaglandin F1␣ and 11-dehydrothromboxane B2, in the urine of mothers who consumed alcohol during pregnancy compared with those who abstained.…”

“…More attention in recent years has pointed towards oxidative stress as a major factor in the severity of FASD, in addition to impaired fetal oxygenation related to maternal systemic vasoconstriction (Signore et al 2008). However, in one study (Signore et al 2008), the authors found no differences in the oxidative stress marker 8-isoprostane F2␣, or the prostaglandin metabolites 2,3-dinor-6-keto-prostaglandin F1␣ and 11-dehydrothromboxane B2, in the urine of mothers who consumed alcohol during pregnancy compared with those who abstained. This either suggests that these are not the ideal biomarkers to test for maternal drinking in general, or for the potential for FASD, or that oxidative stress and (or) reduced oxygen supply to the fetus is not a major cause of FASD.…”