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Levothyroxine for subclinical hypothyroidism during pregnancy: an updated systematic review and meta-analysis of randomized controlled trials

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Abstract

Purpose

We aimed to perform a systematic review and meta-analysis addressing the efficacy of levothyroxine therapy in pregnant women with subclinical hypothyroidism considering most recent evidence and subgroups of interest for clinical practice.

Methods

PubMed, Embase, and Cochrane Central were searched from inception for randomized controlled trials (RCTs) comparing levothyroxine with placebo or no intervention in pregnant women with subclinical hypothyroidism. We used a random-effects model and conducted subgroup analyses based on thyroid peroxidase antibody status, thyroid stimulating hormone levels, fertility treatment, and recurrent miscarriage.

Results

We included 11 RCTs comprising 2,749 pregnant women with subclinical hypothyroidism. Patients treated with levothyroxine (1,439; 52.3%) had significantly lower risk of pregnancy loss (risk ratio 0.69; 95% confidence interval 0.52–0.91; p < 0.01; 6 studies). However, there was no significant association between levothyroxine and live birth (risk ratio 1.01; 95% confidence interval 0.99–1.03; p = 0.29; 8 studies). No statistically significant interaction was observed across subgroups (p > 0.05).

Conclusion

Levothyroxine replacement therapy for subclinical hypothyroidism during pregnancy may decrease pregnancy loss when early prescribed. Nevertheless, further investigation is needed in patients with thyroid stimulating hormone above four milliunits per liter, especially when associated with recurrent miscarriage or infertility.

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Authors and Affiliations

  1. Department of Medicine, Barão de Mauá University Center, Ribeirão Preto, SP, Brazil

    Henrique Provinciatto

  2. Department of Medicine, University Potiguar (UnP), Natal, RN, Brazil

    Marcus Vinicius Barbosa Moreira

  3. Department of Medicine, State University of Pará (UEPA), Belém, PA, Brazil

    Gabriel Rezende Neves

  4. Department of Medicine, Federal University of Juiz de Fora (UFJF), Juiz de Fora, MG, Brazil

    Lucas Rezende De Freitas & Henrique Costa Mitsui

  5. Department of Medicine, University of São Paulo Medical School (USP), São Paulo, SP, Brazil

    Julio Min Fei Zhang

  6. Department of Obstetrics, Paulista School of Medicine, Federal University of São Paulo (EPM-UNIFESP), Rua Belchior de Azevedo, 156 Apto. 111 Torre Vitoria, São Paulo, SP, 05089-030, Brazil

    Edward Araujo Júnior

  7. Discipline of Woman Health, Municipal University of São Caetano do Sul (USCS), São Caetano do Sul, SP, Brazil

    Edward Araujo Júnior

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  1. Henrique Provinciatto
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  2. Marcus Vinicius Barbosa Moreira
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  4. Lucas Rezende De Freitas
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Henrique Provinciatto, Marcus Vinicius Barbosa Moreira and Gabriel Rezende Neves. The first draft of the manuscript was written by Henrique Costa Mitsui, Julio Min Fei Zhang and Edward Araujo Júnior and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Edward Araujo Júnior.

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Provinciatto, H., Moreira, M.V.B., Neves, G.R. et al. Levothyroxine for subclinical hypothyroidism during pregnancy: an updated systematic review and meta-analysis of randomized controlled trials. Arch Gynecol Obstet 309, 2387–2393 (2024). https://doi.org/10.1007/s00404-024-07512-3

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