28: First trimester alcohol exposure alters placental perfusion and fetal oxygen availability affecting fetal growth and development in a non-human primate model

Abstract

Objective-Prenatal alcohol exposure leads to impaired fetal growth, brain development, and stillbirth. Placental impairment likely contributes to these adverse outcomes, but the mechanisms and specific vasoactive effects of alcohol linking altered placental function to impaired fetal development remain areas of active research. Recently, we developed MRI techniques in nonhuman primates to characterize placental blood oxygenation through measurements of T 2 *, and perfusion using dynamic contrast-enhanced (DCE) MRI. The objective of this study was to evaluate the effects of first trimester alcohol exposure on macaque placental function and to characterize fetal brain development, in vivo.Study Design-Timed-pregnant Rhesus macaques (n=12) were divided into 2 groups: control (n=6) and ethanol exposed (n=6). Animals were trained to orally self-administer either 1.5g/kg/day of a 4% ethanol solution (equivalent to 6 drinks/day) or an isocaloric control fluid from pre-conception until gestational day 60 (G60, term is G168). All underwent Doppler ultrasound (D-US) followed by MRI consisting of T 2 * and DCE measurements. D-US was used to measure uterine artery (Uta) and umbilical vein velocimetry and diameter to calculate Uta volume Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.The authors report no conflicts of interest.Presented orally at the 37 th Society of Maternal Fetal Medicine Annual Meetings in Las Vegas, Nevada, January 23-28 th , 2017Reprints will not be available. HHS Public Access Author Manuscript Author Manuscript Author ManuscriptAuthor Manuscript blood flow (cQuta) and placental volume blood flow (cQuv). After non-invasive imaging, animals underwent C-section delivery for placenta collection and fetal necropsy at G110 (n=6) or G135 (n=6).Results-Fetal weight and biparietal diameter were significantly smaller in ethanol exposed compared to controls at G110. By D-US, cQuta was decreased (p=0.1) and cQuv was significantly lower (p=0.04) at both G110 and G135 in ethanol exposed versus control animals. A significant reduction in placental blood flow was evident by DCE-MRI. As we demonstrated recently, T 2 * values vary throughout the placenta, and reveal gradients in blood deoxyhemoglobin concentration ranging from highly oxygenated blood (long T 2 *) proximal to spiral arteries to highly deoxygenated blood (short T 2 *). Distributions of T 2 * throughout the placenta show significant global reduction in T 2 * (and hence high blood deoxyhemoglobin concentration) in ethanol exposed vs. control at G110 (p=0.02). Fetal brain measurements indicated impaired grow...