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

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.

Risk of Adverse Events and Delirium after COVID-19 Vaccination in Patients Living with Dementia.

OBJECTIVES: The aim of this study was to compare incidences of adverse events of special interest (AESI) and delirium in 3 cohorts: after COVID-19 vaccination, prepandemic, and SARS-CoV-2 polymerase chain reaction (PCR) test positive. DESIGN: This is a population-based cohort study using electronic medical records linked with vaccination records in Hong Kong. SETTING AND PARTICIPANTS: A total of 17,449 older people with dementia received at least 1 dose of CoronaVac (n = 14,719) or BNT162b2 (n = 2730) between February 23, 2021, and March 31, 2022. Moreover, 43,396 prepandemic and 3592 SARS-CoV-2 test positive patients were also included in this study. METHODS: The incidences of AESI and delirium up to 28 days after vaccination in the vaccinated dementia cohort were compared with the prepandemic and SARS-CoV-2 test positive dementia cohorts by calculating incidence rate ratios (IRRs). Patients who received multiple doses were followed up separately for each dose, up to the third dose. RESULTS: We did not detect an increased risk of delirium and most AESI following vaccination compared to the prepandemic period and those tested positive for SARS-CoV-2. No AESI group nor delirium incidence exceeded 10 per 1000 person-days in vaccinated individuals. CONCLUSIONS AND IMPLICATIONS: The findings provide evidence for the safe use of COVID-19 vaccines in older patients with dementia. In the short run, benefit appears to outweigh the harm due to vaccine; however, longer follow-up should be continued to identify remote adverse events.

Global trends in the consumption of benzodiazepines and Z-drugs in 67 countries and regions from 2008 to 2018: a sales data analysis.

STUDY OBJECTIVES: To investigate the trends in the consumption of benzodiazepines (BZDs) and Z-drugs at global, regional, and national levels from 2008 to 2018, across 67 countries and regions. METHODS: This cross-sectional descriptive study investigated the consumption of BZDs and Z-drugs analyzed by global pharmaceutical sales data from the IQVIA-Multinational Integrated Data Analysis System database between 2008 and 2018. Consumption was measured in defined daily dose (DDD) per 1000 inhabitants per day (DDD/TID). The global, regional, and national trends were estimated using linear mixed models. Additional analyses were conducted by grouping countries by income level. The association between consumption and Gross Domestic Product (GDP) and the prevalence of different medical conditions was explored in univariable linear models. RESULTS: BZD consumption decreased annually by -1.88% (95% CI: -2.27%, -1.48%), and Z-drugs increased by + 3.28% (+2.55%, +4.01%). In 2008, the top ten countries for BZD and Z-drug consumption were all European, ranging from 63.69 to 128.24 DDD/TID. Very low levels were found in Russia, Kuwait, United Arab Emirates, Saudi Arabia, French West Africa, and the Philippines, with DDD/TID < 1. The consumption in high-income countries was much higher than in middle-income countries. The results showed that increased consumption of BZDs and Z-drugs was statistically associated (p < 0.05) with higher GDP and increased prevalence of anxiety, self-harm, neurological disorders, chronic respiratory diseases, cardiovascular diseases, and cancers. CONCLUSIONS: Distinct differences in consumption and trends of BZDs and Z-drugs were found across different countries and regions. Further exploration is needed to understand the association and safety of the use of BZDs and Z-drugs in patients with comorbidities.

Association of maternal levothyroxine use during pregnancy with offspring birth and neurodevelopmental outcomes: a population-based cohort study.

BACKGROUND: The influence of maternal levothyroxine treatment during pregnancy remains unclear. This study aimed to evaluate the associations of maternal levothyroxine treatment during pregnancy with the birth and neurodevelopmental outcomes in offspring. METHODS: This population-based cohort study was conducted among pregnant women using the Hong Kong Clinical Data Analysis and Reporting System. Mother-child pairs in Hong Kong from 2001 to 2015 were included and children were followed up till 2020. We defined the exposure group as mothers who were exposed to levothyroxine during pregnancy. Preterm birth and small for gestational age (SGA) were included as birth outcomes. Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) were included as neurodevelopmental outcomes. Odds ratios (OR) or hazard ratios (HRs) with a 95% confidence interval (CI) were evaluated to assess the association of gestational levothyroxine use with offspring birth and neurodevelopmental outcomes respectively, using propensity score fine-stratification weighting and a Cox proportional hazards regression model. RESULTS: Among 422,156 mother-child pairs, 2125 children were born from mothers exposed to levothyroxine during pregnancy. A significantly increased risk of preterm birth was observed in children with maternal levothyroxine exposure during pregnancy, when compared to mothers who had no history of thyroid-related diagnoses or prescriptions (weighted OR [wOR]: 1.22, 95% CI: 1.07, 1.39). Similarly, an increased risk of preterm birth was found among children of gestational levothyroxine users, when compared to children of mothers who had used levothyroxine before but stopped during pregnancy (wOR: 2.16, 95% CI: 1.09, 4.25). Sensitivity analysis, by excluding mothers exposed to psychotropic or antiepileptic medications before or during pregnancy, also indicated a similar increased risk of preterm birth regarding the gestational use of levothyroxine (wOR: 1.26, 95% CI: 1.10, 1.45). No significant association was observed for the risk of SGA, ADHD, and ASD. CONCLUSIONS: There is no evidence that gestational use of levothyroxine is associated with SGA, ADHD, or ASD in offspring. Gestational levothyroxine treatment is associated with a higher risk of preterm birth. Such risk might be confounded by the underlying maternal thyroid disease itself, however, we cannot completely exclude the possible effect of gestational L-T4 treatment on offspring preterm birth. Our findings provided support to the current guidelines on the cautious use of levothyroxine treatment during pregnancy.