Heat- and alcohol-induced neural tube defects: interactions with folate in a golden hamster model

Maternal hyperthermia or ethanol each can induce fetal neural tube defects (NTD) following exposures on the 8th day of gestation in golden hamsters. To explore the relationship between NTD and varying doses of either heat or ethanol, timed pregnant golden hamsters were exposed to various doses of either 25% ethanol, or heat in an incubator at 39.5 degrees C on the morning of the 8th day of gestation. Two doses of 0.015 ml/g body weight of 25% ethanol 4 h apart resulted in a 44% incidence of NTD when fetuses were examined on day 13. Single doses of 25% ethanol (either 0.015 or 0.0075 ml/g) resulted in very low incidences of NTD that were not significantly different from zero. A 50-min exposure to heat resulted in a 35% incidence of NTD. A shorter exposure (44 min) resulted in a 23% incidence, and a longer exposure (56 min) resulted in a 68% incidence of NTD. A 0.0075 ml/g dose of 25% ethanol, followed by these same durations of heat, resulted in incidences of NTD that were not significantly different from heat alone. In order to determine what effect folate supplementation might have on ethanol- or heat-induced NTD, osmotic pumps filled with either folate or saline were placed subcutaneously in pregnant hamsters on the 6th day of gestation. Animals were then exposed to ethanol or heat on the morning of day 8. No significant protection from NTD was evident among fetuses from mothers supplemented with folate despite significant elevations in their red cell folate levels on day 8 of gestation.