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

Abstract

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. We sought to determine whether higher first-trimester concentrations of α-tocopherol and γ-tocopherol were associated with reduced odds of miscarriage (pregnancy losses <24 wk of gestation) in women in rural Bangladesh. 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 β-carotene-supplementation trial was done to assess ORs of miscarriage in women with low α-tocopherol (<12.0 μmol/L) and γ-tocopherol (<0.81 μmol/L; upper tertile cutoff of the γ-tocopherol distribution in women who did not miscarry). In all women, plasma α- and γ-tocopherol concentrations were low [median (IQR): 10.04 μmol/L (8.07-12.35 μmol/L) and 0.66 μmol/L (0.50-0.95 μmol/L), respectively]. In a logistic regression analysis that was adjusted for cholesterol and the other tocopherol, low α-tocopherol was associated with an OR of 1.83 (95% CI: 1.04, 3.20), whereas a low γ-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 μg/L, although low BMI and elevated ferritin conferred stronger risk of miscarriage. In pregnant women in rural Bangladesh, low plasma α-tocopherol was associated with increased risk of miscarriage, and low γ-tocopherol was associated with decreased risk of miscarriage. Maternal vitamin E status in the first trimester may influence risk of early pregnancy loss. The JiVitA-1 study, from which data for this report were derived, was registered at clinicaltrials.gov as NCT00198822.