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

• Published in: American journal of obstetrics and gynecology 2017-03, Vol.216 (3), p.302.e1-302.e8
• Main Authors: Lo, Jamie O., MD, Schabel, Matthias C., PhD, Roberts, Victoria H.J., PhD, Wang, Xiaojie, PhD, Lewandowski, Katherine S., BS, Grant, Kathleen A., PhD, Frias, Antonio E., MD, Kroenke, Christopher D., PhD
• Format: Article
• Language: English
• Subjects: alcohol; Animals; Ethanol - adverse effects; Female; Fetal Development - drug effects; Fetus - drug effects; Fetus - metabolism; imaging; Macaca mulatta; Magnetic Resonance Imaging; Models, Animal; nonhuman primate; Obstetrics and Gynecology; Oxygen - metabolism; oxygenation; Placental Circulation - drug effects; Placental Circulation - physiology; placental perfusion; Pregnancy; Pregnancy Trimester, First; Ultrasonography, Prenatal
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2017.01.016

Background 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 that links altered placental function to impaired fetal development remain areas of active research. Objective Recently, we developed magnetic resonance imaging techniques in nonhuman primates to characterize placental blood oxygenation through measurements of T 2 * and perfusion using dynamic contrast-enhanced magnetic resonance imaging. 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 self-administer orally either 1.5 g/kg/d of a 4% ethanol solution (equivalent to 6 drinks/d) or an isocaloric control fluid from preconception until gestational day 60 (term is G168). All animals underwent Doppler ultrasound scanning followed by magnetic resonance imaging that consisted of T 2 * and dynamic contrast-enhanced measurements. Doppler ultrasound scanning was used to measure uterine artery and umbilical vein velocimetry and diameter to calculate uterine artery volume blood flow and placental volume blood flow. After noninvasive imaging, animals underwent cesarean delivery for placenta collection and fetal necropsy at gestational day 110 (n=6) or 135 (n=6). Results Fetal weight and biparietal diameter were significantly smaller in ethanol-exposed animals compared with control animals at gestational day 110. By Doppler ultrasound scanning, placental volume blood flow was significantly lower ( P =.04) at gestational day 110 in ethanol-exposed vs control animals. A significant reduction in placental blood flow was evident by dynamic contrast-enhanced magnetic resonance imaging. As we demonstrated recently, T 2 * values vary throughout the placenta and reveal gradients in blood deoxyhemoglobin concentration that range from highly oxygenated blood (long T 2 * ) proximal to spiral arteries to highly deoxygenated blood (short T 2 * ). Distributions of T2 *throughout the placenta show significant global reduction in T 2 * (and hence high blood deoxyhemoglobin concentration) in ethanol-exposed vs control animals at gestational day 110 ( P =.02). Fetal brain measurements indicated