Increased excretion of 3-hydroxyisovaleric acid provides evidence of biotin deficiency during pregnancy

In animals, subclinical biotin deficiency causes increased fetal malformations and mortality. We examined biotin nutritional status during pregnancy by measuring urinary excretion of biotin, bisnorbiotin (BNB), and 3-hydroxyisovaleric acid (3-HIA). Increased excretion of BNB, a biotin metabolite, is an indicator of increased biotin breakdown. Increased excretion of 3-HIA, an organic acid, reflects a decrease in biotin at the tissue level. In a cross-sectional design, we obtained untimed urine samples from women during either early (17±1 wk, n=13) or late (36±1 wk, n=13) pregnancy. 3-HIA (μmol/mg creatinine) was increased in both early and late pregnancy relative to control urine obtained from nonpregnant women (p<0.0001 by an unpaired t-test). Urinary biotin excretion (nmol/mg creatinine) was normal early and increased late in pregnancy (p<0.004). BNB (nmol/mg creatinine) was also normal early and increased late in pregnancy (p<0.003). The conflict between increased 3-HIA and normal/increased biotin suggests two alternate explanations: 1) Pregnancy causes a decrease in renal reclamation of organic acids, leading to an increase in 3-HIA excretion that does not reflect biotin deficiency. 2) Pregnancy causes an impairment of renal reclamation of biotin. leading to a paradoxical increase in urinary biotin. We speculate that these women were biotin deficient and that increased biotin breakdown contributed to the deficiency. Determination of the effect of biotin supplementation during pregnancy on 3-HIA excretion may provide a resolution 10 the conflict.