The Effect of Prenatal Alcohol Exposure on Fetal Growth and Cardiovascular Parameters in a Baboon Model of Pregnancy

Abstract

Prenatal alcohol exposure often results in an array of fetal developmental abnormalities termed fetal alcohol spectrum disorders (FASDs). Despite the high prevalence of FASDs, the pathophysiology of fetal damage by alcohol remains poorly understood. One of the major obstacles in studying fetal development in response to alcohol exposure is the inability to standardize the amount, pattern of alcohol consumption, and peak blood alcohol levels in pregnant mothers. In the present study, we used Doppler ultrasonography to assess fetal growth and cardiovascular parameters in response to alcohol exposure in pregnant baboons. Baboons were subjected to gastric alcohol infusion 3 times during the second trimester equivalent to human pregnancy, with maternal blood alcohol levels reaching 80 mg/dL within 30 to 60 minutes following alcohol infusion. The control group received a drink that was isocaloric to the alcohol-containing one. Doppler ultrasonography was used for longitudinal assessment of fetal biometric parameters and fetal cardiovascular indices. Fetal abdominal and head circumferences, but not femur length, were significantly decreased in alcohol-exposed fetuses near term. Peak systolic velocity of anterior and middle cerebral arteries decreased during episodes of alcohol intoxication, but there was no difference in Doppler indices between groups near term. Acute alcohol intoxication affected fetal cerebral blood flow independent of changes in the fetal cardiac output. Unlike fetal growth parameters, changes in vascular indices did not persist over gestation. In summary, alcohol effects on fetal growth and on fetal vascular function have different time courses.

Proteomic Analysis of Baboon Cerebral Artery Reveals Potential Pathways of Damage by Prenatal Alcohol Exposure*

“…In addition, changes in brain vessel proteome were described in Alzheimer's disease mice (6). A growing body of evidence strongly suggests that the cerebral circulation is a critical target of prenatal alcohol exposure (7)(8)(9)(10)(11). The current work represents the first documentation of proteome changes in fetal cerebral arteries following prenatal alcohol exposure.…”

“…Alcohol-driven alteration in cerebrovascular function is associated with long-lasting effects on fetal development. Our recent study utilizing Doppler sonography on pregnant baboons shows that alterations in fetal cerebral artery indices in instances of maternal alcohol consumption during the period equivalent to the second trimester of human pregnancy precedes morphometric developmental delays in alcohol-exposed fetuses (11). In an ovine model, larger alterations in fetal cerebral blood flow in the presence of alcohol were linked to the severity of subsequent neuronal loss (7).…”

Prenatal Alcohol Exposure, Anesthesia, and Fetal Loss in Baboon Model of Pregnancy

“…In this regard, standardized alcohol exposure during timed pregnancy in animal models has been widely used as an alternative [29, 30, 31]. Nonhuman primates (including baboons) are often utilized in various studies that involve anesthesia [32, 33, 34] or alcohol consumption [35, 36], including studies on anesthesia or alcohol exposure during pregnancy [18, 19, 22, 37]. Appropriately for this study, baboon reproductive physiology is similar to humans [38].…”

“…Fetal outcome and maternal vital sign under anesthesia records were available from baboons that underwent anesthesia during a study on the consequences of prenatal alcohol exposure to the fetal cerebral artery as described [18, 19]. In particular, dams were subjected to either alcohol or control infusion procedures at 90 d, 100 d, and 110 d of gestation (dGA).…”

“…In the present study, we used a retrospective analysis of pregnancy outcome records and vital sign monitoring during anesthesia from pregnant baboons that underwent anesthesia during a study focusing on the consequences of prenatal alcohol exposure to the fetal cerebral artery [18, 19]. Baboons were first sedated with ketamine, then deep anesthesia was achieved and maintained with isoflurane.…”