Results of Levothyroxine Treatment in Pregnant Women with Recurrent Pregnancy Losses with Subclinical Hypothyroidism or Anti-TPO Antibody Positivity

Methodology and Objectives of the Analysis

A previous meta-analysis published in 2019 had already demonstrated the benefits of thyroxine supplementation in women with subclinical hypothyroidism and TPOAb positivity in terms of improving pregnancy outcomes. However, it did not specifically consider the population of women with recurrent pregnancy losses (RPL), who are a subgroup with greater psychological burden and higher risk of adverse pregnancy outcomes, such as stillbirth, miscarriage, placental abruption, uterine infections, and the need for cesarean sections. The objective of this recently published work was to comprehensively evaluate the effects of levothyroxine on pregnancy outcomes and thyroid function in women with RPL and subclinical hypothyroidism or TPOAb positivity.

The authors conducted a literature review of studies published up to June 2022 in English or Chinese. They looked for randomized controlled trials and cohort studies comparing pregnancy outcomes in women with RPL and subclinical hypothyroidism or TPOAb positivity who were treated or not treated with levothyroxine. Out of 345 studies, they included 15 in the meta-analysis (8 cohort and 7 randomized controlled studies) totaling 1911 women (981 treated with levothyroxine and 930 without levothyroxine). The size of the combined effect was expressed as relative risk (RR) with a 95% confidence interval (CI). They also conducted a sensitivity analysis.

Findings

In patients with RPL and TPOAb positivity, levothyroxine treatment, according to combined data, was associated with a 52% reduction in the risk of preterm birth (RR 0.48; 95% CI 0.32–0.72), a 41% reduction in the risk of miscarriage (RR 0.59; 95% CI 0.44–0.79), a 56% reduction in the risk of premature rupture of membranes (RR 0.44; 95% CI 0.29–0.66), and a 67% reduction in the risk of intrauterine growth retardation (RR 0.33; 95% CI 0.12–0.89). There was no influence of levothyroxine administration on the risk of ectopic pregnancy, 1 and 5-minute Apgar scores, chances of conception, or birth weight.

In women with RPL who had subclinical hypothyroidism, levothyroxine administration was associated with a 20% increase in the chance of live birth (RR 1.20; 95% CI 1.01–1.42) and a 35% reduction in the risk of miscarriage (RR 0.65; 95% CI 0.44–0.97). One study also showed a higher chance of conception with levothyroxine treatment (RR 4.68; 95% CI 3.28–6.69). In these women, levothyroxine administration did not influence the risk of preterm birth, premature rupture of membranes, ectopic pregnancy, or neonatal birth weight.

Levothyroxine treatment significantly reduced levels of thyroid-stimulating hormone (TSH; weighted mean difference [WMD] −0.23; 95% CI −0.31 to −0.16) and TPO (WMD −23.48; 95% CI −27.50 to −19.47). Levothyroxine treatment did not significantly affect T4 levels.

Conclusion

Levothyroxine improves pregnancy outcomes in women with a history of recurrent pregnancy losses and subclinical hypothyroidism or TPOAb positivity. The authors suggest that further studies should be conducted to verify this finding in more detail.

(zza)

Source: Yu M., Long Y., Wang Y. et al. Effect of levothyroxine on the pregnancy outcomes in recurrent pregnancy loss women with subclinical hypothyroidism and thyroperoxidase antibody positivity: a systematic review and meta-analysis. J Matern Fetal Neonatal Med 2023 Dec; 36 (2): 2233039, doi: 10.1080/14767058.2023.2233039.