Background: Compared with singletons, a twin pregnancy is associated with a larger thyroid hormone demand and an increased stimulation of gestational thyroid function due to higher concentrations of human chorionic gonadotropin. However, such effects have been sparsely quantified. The aim of this study was to evaluate thyroid function and thyroid function test abnormalities in twin pregnancies during early and late pregnancy compared with singletons. Methods: We included 1208 twin pregnancies and 46,834 singleton pregnancies with thyroid function tests available. Thyroid function test abnormalities were defined using population-based reference ranges. The analyses were adjusted for potential confounders including maternal age and body mass index. Results: Compared with singletons, a twin pregnancy was associated with a lower thyrotropin (TSH) (β = -0.46 [95% confidence interval, CI -0.49 to -0.44], p < 0.001) and a higher free thyroxine (fT4) (β = 0.91 [CI 0.69-1.16], p < 0.001) during early pregnancy. During late pregnancy, a twin pregnancy was associated with a higher TSH (β = 0.35 [CI 0.29-0.42], p < 0.001) while fT4 did not differ (β = -0.11 [CI -0.22 to 0.01], p = 0.065). During early pregnancy, a twin pregnancy was associated with a higher risk of overt hyperthyroidism (odds ratio, OR = 7.49 [CI 6.02-9.33], p < 0.001), subclinical hyperthyroidism (OR = 5.26 [CI 4.17-6.64], p < 0.001), and isolated hypothyroxinemia (OR = 1.89 [CI 1.43-2.49], p < 0.001), but with a lower risk of subclinical hypothyroidism (OR = 0.27 [CI 0.13-0.54], p < 0.001). In late pregnancy, a twin pregnancy was associated with a higher risk of subclinical hypothyroidism (OR = 4.05 [CI 3.21-5.11], p < 0.001), isolated hypothyroxinemia (OR = 1.48 [CI 1.04-2.10], p = 0.028), and subclinical hyperthyroidism (OR = 1.76 [CI 1.27-2.43], p < 0.001). Conclusions: During early pregnancy, a twin pregnancy was associated with a higher thyroid function and a higher risk of (subclinical) hyperthyroidism, as well as a higher risk of isolated hypothyroxinemia. During late pregnancy, a twin pregnancy was associated with a higher TSH concentration and a higher risk of subclinical hypothyroidism, as well as a persistently higher risk of isolated hypothyroxinemia and subclinical hyperthyroidism. The study was approved by Chinese Clinical Trial Registry (registration no. ChiCTR1800014394).
Keywords: TSH; dysfunction; fT4; thyroid; twin pregnancy.