title: Marginal biotin deficiency during normal pregnancy.
abstract: BACKGROUND
  Biotin deficiency is teratogenic in several mammalian species. Approximately 50% of pregnant women have an abnormally increased urinary excretion of 3-hydroxyisovaleric acid (3-HIA), which probably reflects decreased activity of the biotin-dependent enzyme methylcrotonyl-CoA carboxylase. However, increased 3-HIA excretion could result from pregnancy per se (eg, from an effect of pregnancy on renal handling of organic acids).
  
  
  OBJECTIVE
  We tested the hypothesis that biotin supplementation significantly decreases 3-HIA excretion in pregnant women with abnormally increased 3-HIA excretion.
  
  
  METHODS
  Twenty-six pregnant women with increased 3-HIA excretion were studied in a randomized, placebo-controlled trial; 10 women were studied during early pregnancy (6-17 wk gestation) and 16 women during late pregnancy (21-37 wk gestation). Urine samples were collected before and after 14 d of supplementation with 300 microg (1.2 micromol) biotin/d or placebo.
  
  
  RESULTS
  In the early-pregnancy group, 3-HIA excretion decreased (P < 0.006) by 11.7 +/- 3.6 mmol/mol creatinine (mean +/- SEM) in the 5 women who received biotin supplements, whereas 3-HIA excretion increased by 1.6 +/- 0.6 mmol/mol creatinine in the 5 women who received placebo. In the late-pregnancy group, 3-HIA excretion decreased (P < 0.002) by 7.1 +/- 1.2 mmol/mol creatinine in the 8 women who received biotin supplements, whereas 3-HIA excretion increased by 0.9 +/- 1.8 mmol/mol creatinine in the 8 women who received placebo.
  
  
  CONCLUSIONS
  This study provides evidence that the increased excretion of 3-HIA seen frequently in normal pregnancy reflects reduced biotin status. The conclusion that marginal biotin deficiency occurs frequently in the first trimester further raises concern about potential human teratogenicity.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, 72205, USA. mockdonaldm@uams.edu
authors.forename: Donald M
authors.initials: DM
authors.lastname: Mock
authors.forename: J Gerald
authors.initials: JG
authors.lastname: Quirk
authors.forename: Nell I
authors.initials: NI
authors.lastname: Mock
mesh_terms: D000328:Adult; D001710:Biotin / Q000172:deficiency* / Q000627:therapeutic use; D003677:Deficiency Diseases / Q000188:drug therapy / Q000652:urine; D005260:Female; D006801:Humans; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy / Q000652:urine; D014631:Valerates / Q000652:urine*
chemical_list: D014631:Valerates; C004961:beta-hydroxyisovaleric acid; D001710:Biotin