title: Daily ethanol exposure during late ovine pregnancy: physiological effects in the mother and fetus in the apparent absence of overt fetal cerebral dysmorphology.
abstract: High levels of ethanol (EtOH) consumption during pregnancy adversely affect fetal development; however, the effects of lower levels of exposure are less clear. Our objectives were to assess the effects of daily EtOH exposure (3.8 USA standard drinks) on fetal-maternal physiological variables and the fetal brain, particularly white matter. Pregnant ewes received daily intravenous infusions of EtOH (0.75 g/kg maternal body wt over 1 h, 8 fetuses) or saline (8 fetuses) from 95 to 133 days of gestational age (DGA; term ∼145 DGA). Maternal and fetal arterial blood was sampled at 131-133 DGA. At necropsy (134 DGA) fetal brains were collected for analysis. Maternal and fetal plasma EtOH concentrations reached similar maximal concentration (∼0.11 g/dl) and declined at the same rate. EtOH infusions produced mild reductions in fetal arterial oxygenation but there were no changes in maternal oxygenation, maternal and fetal Pa(CO(2)), or in fetal mean arterial pressure or heart rate. Following EtOH infusions, plasma lactate levels were elevated in ewes and fetuses, but arterial pH fell only in ewes. Fetal body and brain weights were similar between groups. In three of eight EtOH-exposed fetuses there were small subarachnoid hemorrhages in the cerebrum and cerebellum associated with focal cortical neuronal death and gliosis. Overall, there was no evidence of cystic lesions, inflammation, increased apoptosis, or white matter injury. We conclude that daily EtOH exposure during the third trimester-equivalent of ovine pregnancy has modest physiological effects on the fetus and no gross effects on fetal white matter development.
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Victoria, Australia.
authors.forename: Kelly
authors.initials: K
authors.lastname: Kenna
authors.forename: Robert
authors.initials: R
authors.lastname: De Matteo
authors.forename: Takushi
authors.initials: T
authors.lastname: Hanita
authors.forename: Sandra
authors.initials: S
authors.lastname: Rees
authors.forename: Foula
authors.initials: F
authors.lastname: Sozo
authors.forename: Victoria
authors.initials: V
authors.lastname: Stokes
authors.forename: David
authors.initials: D
authors.lastname: Walker
authors.forename: Alan
authors.initials: A
authors.lastname: Bocking
authors.forename: James
authors.initials: J
authors.lastname: Brien
authors.forename: Richard
authors.initials: R
authors.lastname: Harding
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000196:embryology / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000502:physiology*; D005865:Gestational Age; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D015994:Incidence; D007262:Infusions, Intravenous; D007773:Lactates / Q000097:blood; D023421:Models, Animal; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects / Q000502:physiology*; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology; D012756:Sheep; D013345:Subarachnoid Hemorrhage / Q000139:chemically induced / Q000453:epidemiology
chemical_list: D007773:Lactates; D000431:Ethanol