Conflicting indicators of biotin status from a cross-sectional study of normal pregnancy

Objective: To assess biotin nutritional status during normal human gestation. Methods: Urine samples were obtained in a cross-sectional design from 16 women in early pregnancy (17 +/- 1 weeks, mean +/- 1 SD) and from 13 women in late pregnancy (36 +/- 1 weeks). The urinary excretion of biotin, two metabolites bisnorbiotin (BNB) and biotin sulfoxide (BSO), and the organic acid 3-hydroxyisovaleric acid (3-HIA) were measured by HPLC/avidin-binding assay and GC/MS, respectively. Excretion rates were expressed as concentration ratios to urinary creatinine. Results: In both early and late pregnancy, 3-HIA excretion was increased compared to controls (p < 0.0001), suggesting decreased activity of a biotin-dependent enzyme caused by tissue biotin depletion. In early pregnancy, urinary excretion of biotin was normal; in late pregnancy, excretion was increased (p < 0.0002), suggesting biotin status was not decreased. In late pregnancy, urinary excretion of BNB and BSO were increased (p < 0.009). Conclusion: The apparent conflict in the indices of biotin status is not explained by this study but could be resolved by two alternate explanations: 1) pregnancy caused an impairment of renal reclamation of biotin, BNB, and BSO leading to a paradoxical increase in biotin excretion. 2) Pregnancy caused metabolic or renal effects that increased 3-HIA excretion nonspecifically; hence, the increased 3-HIA excretion did not reflect biotin deficiency. We speculate that some of the women studied were marginally biotin deficient and that renal wasting and accelerated breakdown of biotin contributed to the deficiency.