EFFECT OF DIETARY FOLIC-ACID LEVELS AND GESTATIONAL ETHANOL-CONSUMPTION ON TISSUE FOLATE CONTENTS AND RAT FETAL DEVELOPMENT

It has been shown that folate deficiency potentiates the teratogenicity/embryotoxicity of ethanol. In this study the degree of folate deficiency in exacerbating ethanol's teratogenic/embryotoxic potential was assessed. Four levels of folate were tested. Female rats were deprived of folate for three weeks to lower their folate stores. They were then divided into four groups and fed diets containing 0.05, 0.20, 0.50, or 2.00 mg folic acid/kg diet (1% succinylsulfathiazole). After two weeks they were mated and were continued on their respective diets during pregnancy. On day 11, ethanol (5 g/kg body weight in two divided doses four hrs apart) was administered to half of the rats in each group intragastrically. The other half of the rats that served as controls were given isocaloric sucrose in the same manner. Food intakes were similar in all groups. Rats were killed on day 21. Folate levels were determined in six tissues: maternal liver and plasma, placenta, fetal liver, brain and plasma. Folate deficient, ethanol-treated groups produced less viable fetuses that were correlated with tissue folate levels (L. casei procedure), which, in turn, correlated with folate levels in the diets. There is a relationship between the degree of folate deficiency and the ethanol's adverse effect: the more severe the folate deficiency the more potent the teratogenic/embryotoxic effect of ethanol. The numbers of dead and resorbed fetuses expressed as a percentage of total implants were (ethanol vs control): 0.05 mg folate/kg diet, 38.9 vs 18.9; 0.20 mg/kg, 23.1 vs 6.8; 0.50 mg/kg, 16.7 vs 8.4. But when rats were fed sufficient folic acid (2 mg/kg diet), ethanol treatment had no effect on fetal outcome. These observations strongly suggest that maternal folate deficiency may play an important role in the fetal alcohol syndrome.