Levothyroxine in euthyroid pregnant women with thyroid peroxidase antibody: a systematic review and meta-analysis of randomized controlled trials

Abstract Objective: Thyroid peroxidase antibody (TPOAb) is a prevalent condition amongst women of reproductive age and has been associated with adverse pregnancy outcomes. However, there is currently no proven treatment for euthyroid pregnant women with TPOAb. Therefore, we aimed to investigate the efficacy of levothyroxine treatment in this population. Methods: We searched PubMed, Embase and Cochrane Central from inception to or randomized controlled trials (RCTs) comparing levothyroxine with placebo or no treatment in euthyroid pregnant women who were positive for TPOAb. Our main outcomes were miscarriage, preterm birth, and live birth. We performed subgroup analysis based on recurrent pregnancy loss (RPL). Results: We included 8 RCTs comprising 1,645 pregnant women, of whom 814 (49.5%) were randomized to receive levothyroxine. Pregnant women treated with levothyroxine had significantly lower miscarriages (RR 0.78; 95% CI 0.63-0.98; p=0.035). No significant difference was found regarding pre-term birth (RR 0.78; 95% CI 0.55-1.13; p=0.189) and live birth (RR 1.05; 95% CI 0.99-1.12; p=0.097). Our subgroup analysis demonstrated a significant interaction (p=0.048) between patients with RPL (RR 1.21; 95% CI 1.03-1.42; p=0.023) and no RPL (RR 1.00; 95% CI 0.92-1.09; p=0.922). Conclusion: Levothyroxine reduced miscarriage in pregnant women with TPOAb and improved live birth rate when associated with RPL. Our subgroup analysis also provides evidence that levothyroxine may have a higher benefit for patients with a history of RPL. PROSPERO Registry: CRD42023410433