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Lack of beneficiary effect of levothyroxine therapy of pregnant women with subclinical hypothyroidism in terms of neurodevelopment of their offspring

  • Maternal-Fetal Medicine
  • Published:
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Abstract

Purpose

Despite the beneficial effects of levothyroxine (LT4) therapy on pregnancy outcomes of women with subclinical hypothyroidism (SCH), its impact on the developmental status of offspring remains unclear. We aimed to assess the effects of LT4 therapy on the neurodevelopment of infants of SCH women in the first 3 years of life.

Methods

A follow-up study was conducted on children born to SCH pregnant women who had participated in a single-blind randomized clinical trial (Tehran Thyroid and Pregnancy Study). In this follow-up study, 357 children of SCH mothers were randomly assigned to SCH + LT4 (treated with LT4 after the first prenatal visit and throughout pregnancy) and SCH-LT4 groups. Children born of euthyroid TPOAb-women served as the control group (n = 737). The neurodevelopment status of children was assessed in five domains (communication, gross motor, fine motor, problem-solving, and social–personal domains) using the Ages and Stages Questionnaires (ASQ) at the age of 3 years.

Results

Pairwise comparisons of ASQ domains between euthyroid, SCH + LT4, and SCH-LT4 groups show no statistically significant difference between groups in the total score [median 25–75 total score: 265 (240–280); 270 (245–285); and 265 (245–285); P-value = 0.2, respectively]. The reanalyzing data using the TSH cutoff value of 4.0 mIU/L indicated no significant difference between groups in the score of ASQ in each domain or total score with TSH levels < 4.0 mIU/L, however, a statistically significant difference in the median score of the gross motor was observed between those SCH + LT4 with baseline TSH values ≥ 4.0 mIU/L and SCH-LT4 [60 (55–60) vs. 57.5 (50–60); P = 0.01].

Conclusions

Our study does not support the beneficiary effect of LT4 therapy for SCH pregnant women in terms of the neurological development of their offspring in the first three years of life.

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Data availability

The data that support the findings of this study are available from the corresponding author upon request.

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Acknowledgements

The authors wish to acknowledge Ms. Niloofar Shiva for her critical editing of the English grammar and syntax of the manuscript.

Funding

This work was financially supported by the Research Institute for Endocrine Sciences.

Author information

Authors and Affiliations

  1. Department of Midwifery, Varamin-Pishva Branch, Islamic Azad University, Tehran, Iran/, Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran

    Sima Nazarpour

  2. Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, 24 Parvaneh, Yaman Street, Velenjak, P.O.Box: 19395-4763, Tehran, 1985717413, Islamic Republic of Iran

    Fahimeh Ramezani Tehrani

  3. Pediatric Neurorehabilitation Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Islamic Republic of Iran

    Firoozeh Sajedi

  4. Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran

    Maryam Rahmati

  5. Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran

    Razieh Bidhendi Yarandi

  6. Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran

    Fereidoun Azizi

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Contributions

All authors contributed significantly to the work, meet the criteria for authorship, provided a critical review of the manuscript and approved the final version. Dr. SN conceptualized and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript. Prof. FRT conceptualized and designed the study, coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content. Dr. FS designed the data collection instruments, collected data, and reviewed and revised the manuscript. Dr. MR carried out the initial analyses, and reviewed and revised the manuscript. Dr. BY carried out the initial analyses, and reviewed and revised the manuscript. Prof. FA contributed to the study design, execution and manuscript drafting. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Fahimeh Ramezani Tehrani.

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Conflict of interest

The authors declare that they have no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Ethical approval

This study was approved by the ethics committee of the Research Institute of Endocrine Sciences (RIES) (Approval code numbers for study: IR.SBMU.ENDOCRINE.REC.1395.300). This article does not contain any studies with animals performed by any of the authors. Informed consent was obtained from all parents of the children participants included in the study.

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Nazarpour, S., Ramezani Tehrani, F., Sajedi, F. et al. Lack of beneficiary effect of levothyroxine therapy of pregnant women with subclinical hypothyroidism in terms of neurodevelopment of their offspring. Arch Gynecol Obstet 309, 975–985 (2024). https://doi.org/10.1007/s00404-023-06954-5

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