62 Purpose: In the ICR mouse, maternal biotin deficiency during gestation results in specific fetal malformations (cleft palate, micrognathia, microglossia, and limb hypoplasia). However, the relationships of maternal and fetal biotin status to the incidence of fetal malformations have not been fully elucidated. Description: We sought to determine the effect of various egg-white diets (0, 1, 1.3, 2, 3, 5, 10, and 25%) on (a) the incidence of fetal malformations, (b) maternal biotin status assessed by the urinary excretion rate of 3-hydroxyisovaleric acid (3HIA, an organic acid that arises from the decreased activity of the biotin-dependent enzyme methylcrotonyl-CoA carboxylase), and (c) fetal biotin status as assessed by hepatic biotin and carboxylase activities at gestational day 17. Results: The incidence of fetal malformations increased as maternal and fetal biotin status decreased (Figure). The effect of diet was significant by ANOVA at p < 0.0001 for each malformation. Increasing egg white was associated with increased excretion rates of 3HIA, providing strong evidence that the egg-white diets caused maternal biotin status to decrease. Analysis of maternal and fetal livers from gestational day 17 confirmed an incremental reduction in maternal and fetal biotin status as the percentage of dietary egg-white increased. Conclusion: These data are consistent with the hypothesis that maternal biotin deficiency during gestation induces fetal biotin deficiency, which in turn results in an increased incidence of fetal malformations.FIG