Maternal Subclinical Hypothyroidism, Thyroid Autoimmunity, and the Risk of Miscarriage: A Prospective Cohort Study

Background: Increasing data suggest that subclinical hypothyroidism (SCH) and thyroid autoimmunity (TAI) are associated with adverse pregnancy outcomes, but there are limited data on the association of these conditions in early pregnancy with subsequent miscarriage. Methods: In this prospective cohort study, we screened 3315 women at low risk for thyroid dysfunction at four to eight weeks' gestation from iodine-sufficient areas of China between January 2012 and September 2012. Thyrotropin (TSH), free thyroxine (fT4), and the autoantibodies thyroid-peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) were measured. Based on these results, women were divided into four groups for comparison: euthyroidism (ET), isolated SCH, isolated TAI (positive TPOAb or/and TgAb), and SCH with TAI (SCH+TAI). The SCH group was stratified into two subgroups (SCH 1 and SCH 2) on the basis of the level of TSH (2.5 <= TSH<5.22 or 5.22 <= TSH<10 respectively). Accordingly, the SCH+TAI group was also stratified into two subgroups (SCH+TAI 1 and SCH+TAI 2). The outcome of interest was miscarriage, defined as spontaneous pregnancy loss prior to 20 weeks. Results: Compared to women with ET, the risk of miscarriage was significantly higher among women with SCH 2 (7.1% vs. 2.2%, aOR 3.40 [CI 1.62-7.15]; p=0.002), isolated TAI (5.7% vs. 2.2%, aOR 2.71 [CI 1.43-5.12]; p=0.003), SCH+TAI 1 (10.0% vs. 2.2%, aOR 4.96 [CI 2.76-8.90]; p=0.000), and SCH+TAI 2 (15.2% vs. 2.2%, aOR 9.56 [CI 3.76-24.28]; p=0.000). The gestational ages of 110 women at miscarriage were lower among women with subclinical thyroid abnormalities compared to ET (11.13 +/- 3.21 weeks with subclinical thyroid abnormalities vs. 9.33 +/- 1.71 weeks with ET; p=0.024). In parallel with the higher TSH levels, there were earlier gestation ages at miscarriage between subgroups of SCH and SCH+TAI (SCH 1 vs. SCH 2: 10.79 +/- 1.77 vs. 9.70 +/- 1.47 weeks, p=0.039; SCH+TAI 1 vs. SCH+TAI 2: 9.59 +/- 1.97 vs. 8.88 +/- 1.24 weeks, p=0.031). Conclusions: Women with SCH and TAI are at an increased risk of miscarriage between four and eight gestational weeks. Women with a combination of SCH and TAI were found to have the highest risk and earlier gestational ages of miscarriage.