First-trimester plasma tocopherols are associated with risk of miscarriage in rural Bangladesh

Background: Tocopherols were discovered for their role in animal reproduction, but little is known about the contribution of deficiencies of vitamin E to human pregnancy loss. Objective: We sought to determine whether higher first-trimester concentrations of alpha-tocopherol and gamma-tocopherol were associated with reduced odds of miscarriage (pregnancy losses <24 wk of gestation) in women in rural Bangladesh. Design: A case-cohort study in 1605 pregnant Bangladeshi women [median (IQR) gestational age: 10 wk (8-13 wk)] who participated in a placebo-controlled vitamin A or beta-carotene supplementation trial was done to assess ORs of miscarriage in women with low a-tocopherol (<12.0 mu mol/L) and gamma-tocopherol (<0.81 mu mol/L; upper tertile cutoff of the gamma-tocopherol distribution in women who did not miscarry). Results: In all women, plasma alpha- and gamma-tocopherol concentrations were low [median (IQR): 10.04 mu mol/L (8.07-12.35 mu mol/L) and 0.66 mu mol/L, (0.50-0.95 mu mol/L), respectively]. In a logistic regression analysis that was adjusted for cholesterol and the other tocopherol, low alpha-tocopherol was associated with an OR of 1.83 (95% CI: 1.04, 3.20), whereas a low gamma-tocopherol concentration was associated with an OR of 0.62 (95% CI: 0.41, 0.93) for miscarriage. Subgroup analyses revealed that opposing ORs were evident only in women with BMI (in kg/m(2)) >= 18.5 and serum ferritin concentration <= 150 mu g/L, although low BMI and elevated ferritin conferred stronger risk of miscarriage. Conclusions: In pregnant women in rural Bangladesh, low plasma alpha-tocopherol was associated with increased risk of miscarriage, and low gamma-tocopherol was associated with decreased risk of miscarriage. Maternal vitamin E status in the first trimester may influence risk of early pregnancy loss.