A Meta-Analysis of Pregnancy Outcomes With Levothyroxine Treatment in Euthyroid Women With Thyroid Autoimmunity

Context: Thyroid autoimmunity (TAI), the most common cause of (sub)clinical hypothyroidism, is associated with adverse pregnancy outcomes. The benefits of levothyroxine (LT4) intervention in women with TAI remain controversial. Objective: The purpose of this analysis is to determine the effect of LT4 on pregnancy outcomes in euthyroid women with TAI. Data sources: Databases were searched up to May 2019. Study selection: Randomized controlled trails (RCTs) and retrospective studies that reported effects of LT4 administration on pregnancy outcomes in euthyroid women with TAI were screened. Data extraction: Quality assessment and data extraction were conducted independently by 2 researchers. Conflicts were settled by a third researcher. Data synthesis: Six trials comprising 2249 women were included. Overall, no beneficial effect on pregnancy outcomes was observed with LT4 supplementation. For women with individualized initial LT4 dosages, the risk of miscarriage decreased (relative risk [RR] 0.62, 95% CI: 0.41-0.93, I-2 = 28%); there was no difference among women with fixed LT4 dosages (RR 0.96, 95% CI: 0.74-1.24, I-2 = 0%). Women who initiated LT4 treatment in early pregnancy had a significantly lower preterm birth rate (RR 0.54, 95% CI: 0.31-0.92, I-2 = 0%) than those who received no treatment or placebo. No improvement was observed among women who initiated treatment before conception (RR 1.14, 95% CI: 0.71-1.84, I-2 = 0%). Conclusion: No definitive evidence showed improvement of pregnancy outcomes with LT4 supplementation in euthyroid women with TAI. However, therapeutic strategies, especially dosages and initial times of intervention, may be of great importance. Additional large RCTs are needed in the future.