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Original Research Communication |
1 From the Departments of Biochemistry and Molecular Biology and of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR (DMM and NM), and the Department of Obstetrics, Gynecology, and Reproductive Medicine, State University of New York, Stony Brook, Health Sciences Center (JGQ).
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.
Design: 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 µg (1.2 µmol) 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.
Key Words: Pregnancy • teratogenicity • biotin deficiency • 3-hydroxyisovaleric acid • women
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