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.

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 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.

FIGURE 1

Urinary excretion of 3-hydroxyisovaleric acid (3-HIA) in pregnant women before and after supplementation with 1.2 μmol biotin/d (top; n = 13) or a placebo (bottom; n = 13) for 14 d. Women were studied either early (n = 5 per subgroup) or late (n = 8 per subgroup) in pregnancy. The normal range (white box) was calculated as the 10th–90th percentiles of 3-HIA excretion for a population of 21 nonpregnant women.

FIGURE 2

Urinary excretion of biotin in pregnant women before and after supplementation with 1.2 μmol biotin/d (top; n = 13) or a placebo (bottom; n = 13) for 14 d. The groups (early and late pregnancy) are the same as those described in the legend to Figure 1. The normal range (white box) was calculated as the 10th–90th percentiles of biotin excretion for a population of 23 nonpregnant women.

FIGURE 3

Urinary excretion of 3-hydroxyisovaleric acid (3-HIA) and biotin in 5 nonpregnant control women before and after supplementation with 1.2 μmol biotin/d for 14 d. For 3-HIA excretion, the normal range (white box) was calculated as the 10th–90th percentiles for a population of 21 nonpregnant women. For biotin excretion, the normal range (white box) was calculated as the 10th–90th percentiles for a population of 23 nonpregnant women.