Levothyroxine Treatment Among Pregnant Women and Risk of Seizure in Children: A Population-Based Cohort Study

Grace Mengqin Ge, Kenneth K. C. Man, Edmund C. L. Cheung, Patrick Ip, Wing Cheong Leung, Annie W. C. Kung, Ching-Lung Cheung and Ian C. K. Wong ()
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Grace Mengqin Ge: The University of Hong Kong
Kenneth K. C. Man: The University of Hong Kong
Edmund C. L. Cheung: The University of Hong Kong
Patrick Ip: The University of Hong Kong
Wing Cheong Leung: Kwong Wah Hospital
Annie W. C. Kung: The University of Hong Kong
Ching-Lung Cheung: The University of Hong Kong
Ian C. K. Wong: The University of Hong Kong

Drug Safety, 2023, vol. 46, issue 11, No 7, 1149-1159

Abstract: Abstract Introduction and Objective The risk of seizure in offspring following prenatal exposure to levothyroxine is not well investigated. This study aimed to evaluate the association between levothyroxine treatment among pregnant women and the risk of seizure in their offspring. Methods This population-based cohort study included all pregnant women who delivered a live birth between January 2001 to January 2018, with a follow-up to December 2020, using data from the Hong Kong Clinical Data Analysis and Reporting System. Propensity score fine-stratification weighted hazard ratios (wHR) with 95% confidence intervals (CIs) were presented to assess the association between maternal levothyroxine use during pregnancy and seizures in children. Results Among 528,343 included mother–child pairs, 3044 children were prenatally exposed to levothyroxine at any time during the pregnancy period. A significantly increased risk of seizure was observed in children of the prenatally exposed group compared with the prenatally unexposed group (wHR 1.12, 95% CI 1.02–1.22). An increased risk of seizure was observed when comparing the prenatally exposed group with euthyroid mothers who had no history of thyroid-related diagnosis or prescriptions (wHR 1.12, 95% CI 1.02–1.23). However, no significant difference was observed between the prenatally exposed group and those previously exposed to levothyroxine but had stopped during pregnancy (wHR 0.97, 95% CI 0.66–1.44). No significant difference was observed in the sibling-matched analysis either (wHR 1.23, 95% CI 0.76–2.01). Conclusion The observed increased risk of seizure in children born from mothers exposed to levothyroxine during pregnancy might be due to residual confounding by maternal thyroid disease. The findings support the current guidelines on the safe use of levothyroxine treatment during pregnancy.

Date: 2023
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DOI: 10.1007/s40264-023-01352-x

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