Maternal alcohol consumption in pregnancy enhances arterial stiffness and alters vasodilator function that varies between vascular beds in fetal sheep

The Journal of Physiology (Impact Factor: 5.04). 04/2014; 592(12). DOI: 10.1113/jphysiol.2013.262873


While the impact of alcohol consumption by pregnant women on fetal neurodevelopment has received much attention, the effects on the cardiovascular system are not well understood. We hypothesised that repeated exposure to alcohol (ethanol) in utero would alter fetal arterial reactivity and wall stiffness, key mechanisms leading to cardiovascular disease in adulthood. Ethanol (0.75 g per kg body weight) was infused intravenously into ewes over one hour daily for 39 days in late pregnancy (days 95–133 of pregnancy, term ∼147 days). Maternal and fetal plasma ethanol concentrations at the end of the hour were ∼115 mg dL−1, and then declined to apparent zero over 8 h. At necropsy (day 134), fetal body weight and fetal brain-body weight ratio were not affected by alcohol infusion. Small arteries (250–300 μm outside diameter) from coronary, renal, mesenteric, femoral (psoas) and cerebral beds were isolated. Endothelium-dependent vasodilation sensitivity was reduced 10-fold in coronary resistance arteries, associated with a reduction in endothelial nitric oxide synthase mRNA (P = 0.008). Conversely, vasodilation sensitivity was enhanced 10-fold in mesenteric and renal resistance arteries. Arterial stiffness was markedly increased (P = 0.0001) in all five vascular beds associated with an increase in elastic modulus and, in cerebral vessels, with an increase in collagen Iα mRNA. Thus, we show for the first time that fetal arteries undergo marked and regionally variable adaptations as a consequence of repeated alcohol exposure. These alcohol-induced vascular effects occurred in the apparent absence of fetal physical abnormalities or fetal growth restriction.This article is protected by copyright. All rights reserved

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    ABSTRACT: Background Clubfoot is associated with maternal cigarette smoking in several studies, but it is not clear if this association is confined to women who smoke throughout the at-risk period. Maternal alcohol and coffee drinking have not been well studied in relation to clubfoot.Methods The present study used data from a population-based case–control study of clubfoot conducted in Massachusetts, New York, and North Carolina from 2007 to 2011. Mothers of 646 isolated clubfoot cases and 2037 controls were interviewed about pregnancy events and exposures, including the timing and frequency of cigarette smoking, alcohol intake, and coffee drinking.ResultsMore mothers of cases than controls reported smoking during early pregnancy (28.9% vs. 19.1%). Of women who smoked when they became pregnant, those who quit in the month after a first missed period had a 40% increase in clubfoot risk and those who continued to smoke during the next 3 months had more than a doubling in risk, after controlling for demographic factors, parity, obesity, and specific medication exposures. Adjusted odds ratios for women who drank >3 servings of alcohol or coffee per day throughout early pregnancy were 2.38 and 1.77, respectively, but the numbers of exposed women were small and odds ratios were unstable.Conclusions Clubfoot risk appears to be increased for offspring of women who smoke cigarettes, particularly those who continue smoking after pregnancy is recognisable, regardless of amount. For alcohol and coffee drinkers, suggested increased risks were only observed in higher levels of intake.
    Paediatric and Perinatal Epidemiology 12/2014; 29(1). DOI:10.1111/ppe.12163 · 3.13 Impact Factor