Pregnancy outcomes after weekly oral administration of ethanol during gestation in the pig-tailed macaque: comparing early gestational exposure to full gestational exposure.
An oral dose of 1.8 g/kg ethanol given once per week throughout gestation to gravid pig-tailed macaques (Macaca nemestrina) has been established previously as teratogenic. This study was designed to use this nonhuman primate model to mimic a common problematic human circumstance in which women intermittently abuse alcohol into early pregnancy, realize that they are in fact pregnant, and then want to know the chance that the conceptus is harmed. In order to evaluate this situation, gravid macaques were assigned to one of four dosing cohorts. Animals were given the 1.8 gm/kg dose of ethanol once per week for the first 3, 6, or 24 weeks (full gestation) of pregnancy. Control animals received an isocaloric, isovolemic sucrose solution once per week for 24 weeks. The pregnancies were carefully monitored and the infants were comprehensively evaluated for the first 24 months of life. This paper describes the pregnancies while subsequent papers will describe the infants. Peak plasma ethanol levels ranged from 175 to 250 mg/dl. Weekly maternal exposure to this intoxicating dose of ethanol, starting early in pregnancy, did not influence risk of pregnancy failure during the first 30 days of gestation but appeared to be associated with an increased risk of abortion occurring between gestational days 30 and 160. Of the pregnancies that were successfully carried to full term, the potentially teratogenic dose of ethanol did not alter pregnancy outcome in any clinically significant way.
Clarren
S K
SK
Department of Pediatrics, University of Washington, Seattle 98195.
Astley
S J
SJ
D000022:Abortion, Spontaneous / Q000139:chemically induced; D000818:Animals; D015331:Cohort Studies; D004334:Drug Administration Schedule; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005865:Gestational Age; D006339:Heart Rate / Q000187:drug effects; D008254:Macaca nemestrina; D008297:Male; D011247:Pregnancy; D011256:Pregnancy Outcome; D011897:Random Allocation; D013723:Teratogens / Q000633:toxicity*; D013997:Time Factors; D015430:Weight Gain / Q000187:drug effects
D013723:Teratogens; D000431:Ethanol