Pregnancy-induced alterations in mitochondrial function in euthyroid pregnant women and pregnant women with subclinical hypothyroidism; relation to adverse outcome

Abstract

Background: It is well documented that overt hypothyroidism is associated with adverse pregnancy outcomes, but studies of subclinical hypothyroidism have demonstrated conflicting results. Objective: Thyroid hormones are known to regulate mitochondrial function, and the aim of this study was to examine the possible relationship of subclinical hypothyroidism and mitochondrial dysfunction to adverse pregnancy outcomes in pregnant women. Methods: Women in their third trimester of pregnancy (n = 113) who did not receive thyroid medication were included in this cross-sectional study. All participants were interviewed, and their thyroid status was determined. All participants had concentrations of thyroid hormones (fT4 and tT3) within the reference range. In addition to thyroid status, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were measured by flow cytometry. To establish a reference range of MMP and ROS, a group of euthyroid, nonpregnant women were used as euthyroid controls. Adverse pregnancy outcome was defined as preterm delivery, preeclampsia, placental abruption, Apgar score <7 points 1 minute after birth, or postpartum hemorrhage. Results: The prevalence of subclinical hypothyroidism among pregnant women was 17% (n = 19), and the number of overall adverse pregnancy outcomes was increased (p = 0.02) compared with that in euthyroid pregnant women. Preeclampsia, poor Apgar score, and postpartum hemorrhage were more frequent in the subclinical hypothyroidism group than in the euthyroid group (p = 0.04, p = 0.001 and p = 0.03, respectively), and more women showed prolonged gestation and gave birth later than 41 weeks of gestation than in the euthyroid group (p = 0.04). Compared with euthyroid, nonpregnant controls, a physiological upregulation of mitochondrial function was observed in euthyroid pregnant women. This was impaired in pregnant women with subclinical hypothyroidism. Compared with euthyroid, nonpregnant controls, pregnant women had increased ROS regardless of their thyroid status. Conclusion: We speculate that the unfavorable effects on mitochondrial function in women with subclinical hypothyroidism may be associated with higher prevalence of adverse pregnancy outcomes.

Keywords

• Subclinical hypothyroidism
• Pregnancy outcome
• Mitochondrial dysfunction
• Mitochondrial membrane potential
• Reactive oxygen species