At present, there are few data applicable to humans on the risks of intermittent alcohol use (binge drinking) in pregnancy. Such information is urgently needed by medical professionals counseling pregnant women, but for both ethical and practical reasons cannot be obtained from human studies. An alternate primate model is necessary. A recent pilot project demonstrating a binge model for fetal alcohol syndrome in the pigtailed macaque (Macaca nemestrina) found severe teratogenic effects in the animal exposed to 4.1 g/kg of ethanol once per week from mid-first trimester to term. Moderate effects were found in one of two animals exposed to 2.5 g/kg of ethanol over the same gestational period. In this study 39 additional females and their resultant infants will be evaluated. When added to the pilot project infants, there will be 6 groups of 7 animals each exposed to 0, 0.3, 0.6, 1.2, 2.5, or 4.1 g/kg of ethanol once/week throughout gestation. The mothers will be given the ethanol by gavage weekly from the first week after conception to term. Maternal weight gain, dietary intake and general health will be closely monitored. Serum ethanol degradation curves will be obtained after each dosage and after parturition. The infants will be observed for 6 months. Physical examinations for major and minor malformations at birth and at 6 months will be recorded. Roentgenograms and photographs will be obtained. A standardized battery of developmental and psychological tests will be applied. A complete autopsy at 6 months with extensive neuroanatomic and neurochemical studies will be done. The study will provide much needed information on variation in ethanol metabolism throughout pregnancy and when non-pregnant as well as on the dose-response curve for each physical, behavioral and neuroanatomic-neurochemical characteristic of the infant that is affected by periodic exposure to alcohol during gestation.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA005616-04
Application #
3109023
Study Section
Alcohol Biomedical Research Review Committee (ALCB)
Project Start
1982-09-29
Project End
1986-11-30
Budget Start
1985-09-01
Budget End
1986-11-30
Support Year
4
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Bonthius, D J; Bonthius, N E; Napper, R M et al. (1996) Purkinje cell deficits in nonhuman primates following weekly exposure to ethanol during gestation. Teratology 53:230-6
Astley, S J; Weinberger, E; Shaw, D W et al. (1995) Magnetic resonance imaging and spectroscopy in fetal ethanol exposed Macaca nemestrina. Neurotoxicol Teratol 17:523-30
Clarren, S K; Astley, S J (1992) Pregnancy outcomes after weekly oral administration of ethanol during gestation in the pig-tailed macaque: comparing early gestational exposure to full gestational exposure. Teratology 45:1-9
Clarren, S K; Astley, S J; Gunderson, V M et al. (1992) Cognitive and behavioral deficits in nonhuman primates associated with very early embryonic binge exposures to ethanol. J Pediatr 121:789-96
Siebert, J R; Astley, S J; Clarren, S K (1991) Holoprosencephaly in a fetal macaque (Macaca nemestrina) following weekly exposure to ethanol. Teratology 44:29-36
Clarren, S K; Astley, S J; Bowden, D M et al. (1990) Neuroanatomic and neurochemical abnormalities in nonhuman primate infants exposed to weekly doses of ethanol during gestation. Alcohol Clin Exp Res 14:674-83
Clarren, S K; Astley, S J; Bowden, D M (1988) Physical anomalies and developmental delays in nonhuman primate infants exposed to weekly doses of ethanol during gestation. Teratology 37:561-9
Sheller, B; Clarren, S K; Astley, S J et al. (1988) Morphometric analysis of Macaca nemestrina exposed to ethanol during gestation. Teratology 38:411-7
Clarren, S K; Bowden, D M; Astley, S J (1987) Pregnancy outcomes after weekly oral administration of ethanol during gestation in the pig-tailed macaque (Macaca nemestrina). Teratology 35:345-54