A Causality Assessment Framework for COVID-19 Vaccines and Adverse Events at the COVID-19 Vaccine Safety Research Center

During the coronavirus disease 2019 (COVID-19) pandemic, conclusively evaluating possible associations between COVID-19 vaccines and potential adverse events was of critical importance. The National Academy of Medicine of Korea established the COVID-19 Vaccine Safety Research Center (CoVaSC) with support from the Korea Disease Control and Prevention Agency to investigate the scientific relationship between COVID-19 vaccines and suspected adverse events. Although determining whether the COVID-19 vaccine was responsible for any suspected adverse event necessitated a systematic approach, traditional causal inference theories, such as Hill's criteria, encountered certain limitations and criticisms. To facilitate a systematic and evidence-based evaluation, the United States Institute of Medicine, at the request of the Centers for Disease Control and Prevention, offered a detailed causality assessment framework in 2012, which was updated in the recent report by the National Academies of Sciences, Engineering, and Medicine (NASEM) in 2024.This framework, based on a weight-of-evidence approach, allows the independent evaluation of both epidemiological and mechanistic evidence, culminating in a comprehensive conclusion about causality. Epidemiological evidence derived from population studies is categorized into four levels—high, moderate, limited, or insufficient—while mechanistic evidence, primarily from biological and clinical studies in animals and individuals, is classified as strong, intermediate, weak, or lacking. The committee then synthesizes these two types of evidence to draw a conclusion about the causal relationship, which can be described as “convincingly supports” (“evidence established” in the 2024 NASEM report), “favors acceptance,” “favors rejection,” or “inadequate to accept or reject.” The CoVaSC has established an independent committee to conduct causality assessments using the weightof-evidence framework, specifically for evaluating the causality of adverse events associated with COVID-19 vaccines. The aim of this study is to provide an overview of the weight-ofevidence framework and to detail the considerations involved in its practical application in the CoVaSC.

Socioeconomic Factors and Abortive Outcomes of Clinical Pregnancy After Embryo Transfer in the Setting of Universal Health Insurance Coverage of IVF

Background@#In vitro fertilization-embryo transfer (IVF-ET), an expensive option for infertile couples, started to be fully covered by the National Health Insurance (NHI) from October 2017 in South Korea. We investigated the association between woman’s socioeconomic status (SES) and abortive outcomes in pregnancies after IVF-ET in the setting of universal coverage of the treatment. @*Methods@#Using the NHI database in South Korea, we conducted a retrospective cohort study of all women who achieved clinical pregnancy after ET between October 2017 and February 2019. A total of 44,038 clinical pregnancy episodes of 29,847 women who underwent ET were analyzed. We used employment status, income in percentiles, and living in the Seoul capital area as indicators of SES. Relative risks (RRs) for abortive pregnancy outcomes were calculated for each socioeconomic stratum, using log-binomial regression models included woman’s age, body mass index, fasting blood glucose, fresh ET, month of ET, and history of smoking. @*Results@#While most pregnancy outcomes were live births (n = 30,783, 69.9%), 11,215 (25.5%) cycles ended with abortion or early pregnancy loss, 1,779 (4.0%) cycles were ectopic pregnancy, 45 (0.1%) were coded as molar pregnancy, and 224 (0.5%) were fetal death in utero or stillbirth. The risk of overall abortive outcomes was higher when a woman was unemployed (adjusted RR, 1.08; 95% confidence interval [CI], 1.05–1.11) or living in a nonSeoul capital area (1.11; 95% CI, 1.08–1.14). The association between relative income level and abortive outcomes was close to null. Living outside Seoul capital area was associated with the greater risk of abortive outcomes especially in younger women. @*Conclusion@#Unemployment and living in non-capital areas were associated with a higher risk of abortive outcomes among pregnancies after ET, even in the setting of universal coverage of IVF-ET. This suggests potential impact of socioeconomic position on the IVF-ET pregnancy.

Women's Employment in Industries and Risk of Preeclampsia and Gestational Diabetes: A National Population Study of Republic of Korea

Background@#Some working conditions may pose a higher physical or psychological demand to pregnant women leading to increased risks of pregnancy complications. @*Objectives@#We assessed the association of woman's employment status and the industrial classification with obstetric complications. @*Methods@#We conducted a national population study using the National Health Information Service database of Republic of Korea. Our analysis encompassed 1,316,310 women who experienced first-order live births in 2010–2019. We collected data on the employment status and the industrial classification of women, as well as their diagnoses of preeclampsia (PE) and gestational diabetes mellitus (GDM) classified as A1 (well controlled by diet) or A2 (requiring medication). We calculated odds ratios (aORs) of complications per employment, and each industrial classification was adjusted for individual risk factors. @*Results@#Most (64.7%) were in employment during pregnancy. Manufacturing (16.4%) and the health and social (16.2%) work represented the most prevalent industries. The health and social work exhibited a higher risk of PE (aOR = 1.11, 95% confidence interval [CI]: 1.03–1.21), while the manufacturing industry demonstrated a higher risk of class A2 GDM (1.20, 95% CI: 1.03–1.41) than financial intermediation. When analyzing both classes of GDM, women who worked in public administration and defense/social security showed higher risk of class A1 GDM (1.04, 95% CI: 1.01, 1.07). When comparing high-risk industries with nonemployment, the health and social work showed a comparable risk of PE (1.02, 95% CI: 0.97, 1.07). @*Conclusion@#Employment was associated with overall lower risks of obstetric complications. Health and social service work can counteract the healthy worker effect in relation to PE. This highlights the importance of further elucidating specific occupational risk factors within the high-risk industries.

Relationship between personal care products usage and triclosan exposure: the second Korean National Environmental Health Survey (KoNEHS 2012–2014)

BACKGROUND: We aimed to find the exposure level of triclosan (TCS), a known endocrine disruptor, related to the use of personal care products using a nationally representative data of the general population in Korea. METHODS: This study included data of 6288 adults aged 19 years and older (2692 men, 3596 women), based on the Second Korean National Environmental Health Survey (KoNEHS 2012–2014). The data were divided according to gender. The frequency and proportion of each variable were determined by dividing participants into two groups based on the top 75th percentile concentration of urinary TCS (male: 1.096 μg/g creatinine, female: 1.329 μg/g creatinine). Odds ratios (ORs) were calculated using logistic regression analysis for the high TCS exposure and low TCS exposure groups. RESULTS: Overall, the proportion of participants using personal care products was higher in women than in men. There was a significantly higher proportion of participants in the high TCS exposure group with younger age, higher education and income levels and with more frequent use of fragrance products, hair care products, body cleansers, cosmetics, and antimicrobial agents. In both men and women, ORs tended to increase with increased frequency of use of hair care products, body cleansers, and cosmetics before and after adjustment. CONCLUSIONS: Our findings demonstrate that as the frequency of use of personal care products increases, urine TCS concentration increases. Because TCS is a well-known endocrine disruptor, further studies are needed and explore other health effects with exposure to TCS in general population in Korea. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40557-019-0283-y) contains supplementary material, which is available to authorized users.

Female non-smokers' environmental tobacco smoking exposure by public transportation mode

BACKGROUND: This study aimed to analyze environmental tobacco smoking exposure in female nonsmokers by public transportation mode using representative data of Koreans. METHODS: Data from the Second Korean National Environmental Health Survey (2012–2014) were analyzed. Urine cotinine was analyzed by public transport behavior, secondhand smoke exposure, socioeconomic factors, and health-related factors. Participants were 1322 adult females; those with the top 75% urine cotinine concentrations were assigned to the high exposure group. A logistic regression analysis was performed considering appropriate weights and stratification according to the sample design of the Second Korean National Environmental Health Survey. RESULTS: The geometric mean of urine cotinine concentrations differed according to public transportation modes: subway (1.66 μg/g creatinine) bus (1.77 μg/g creatinine), and taxi (1.94 μg/g creatinine). The odds ratio [OR] was calculated for the high exposure group. The OR of the taxi (2.39; 95% confidence interval, 1.00–5.69) was statistically significantly higher than the subway value (reference), and marginally significant after adjusted with life style, sociodemographic factors and involuntary smoking frequency (2.42, 95% confidence interval, 0.97–6.04). CONCLUSIONS: The odds ratio of passengers who mainly used taxis was marginally significantly higher than those of passengers who used subways and buses after adjusted with life style and sociodemographic factors. Implementation of supplementary measures and further studies on exposure to environmental tobacco smoking in taxis are warranted.

Relationship between dietary factors and bisphenol a exposure: the second Korean National Environmental Health Survey (KoNEHS 2012–2014)

BACKGROUND: This study was aimed at finding out the exposure level of bisphenol A (BPA), a well-known endocrine disruptor, in relation to dietary factors using a data representing the Korean general population. METHODS: This study was performed on 5402 adults aged 19 years and older based on the Second Korean National Environmental Health Survey (KoNEHS 2012–2014). The data analyzed urinary BPA concentration in relation to socio-demographic variables, health behavior-related variables, and dietary factor-related variables. Odds ratio (OR) was calculated through a logistic regression analysis after dividing the participants into high BPA exposure group and low BPA exposure group based on the top 75 percentile concentration. The logistic regression analysis was carried out considering the appropriate sample weight, stratification, and clustering of the second KoNEHS sample design. RESULTS: The group drinking bottled water at home and the group using zip-top bags/plastic bags showed significantly higher urinary BPA concentration in female. OR tends to increase as the intake frequency of frozen food increased and OR of frozen food consumption of more than once a week was 1.48 (95% confidence interval (CI) 1.02–2.24) for male and the group drinking bottled water showed significantly higher OR of 1.45 (95% CI 1.06–2.17) after adjusting the related factors for female. CONCLUSIONS: BPA levels were high in female using bottled water and in male consuming frozen food, and therefore bottled water and frozen food need to be avoided to reduce BPA levels.

The association between long working hours and hearing impairment in noise unexposed workers: data from the 5th Korea National Health and Nutrition Examination Survey (KNHANES 2010–2012)

BACKGROUND: This study is aimed at finding out the relationship between long working hours, one of major job stress elements, and hearing impairment in unexposed workers to occupational and environmental noise. METHODS: This study was performed on 1628 regular, full-time wage workers between the age of 25-64 who indicated in the survey of having no experience of exposure to noise, normal otoscopic findings, and not suffering from diabetes based on the data from the fifth Korea National Health and Nutrition Examination Survey (KNHANES 2010–2012). The average working hours per week was categorized into 40 h and lower group, more than 40 to 48 h group, more than 48 to 60 h group, and more than 60 h group. The groups were defined as suffering from low or high frequencies hearing impairment if the average hearing threshold for 0.5, 1, 2 kHz or 3, 4, 6 kHz in both ears exceeds 25 dB based on the pure tone audiometry. The association between average weekly working hours and hearing impairment was analyzed using logistic regression after gender stratification. RESULTS: The prevalences of low and high frequencies hearing impairment in male workers were 4.3 and 28.6 %, respectively, which were much higher than female’s prevalence of 2.7 and 11.1 %. For male workers, no significant association was found between average weekly working hours and low and high frequencies hearing impairment. For female workers, odds ratios (OR) of low and high frequencies hearing impairment were 4.22 (95 % confidence interval (CI) 1.09–16.27) and 4.49 (95 % CI 1.73–11.67), respectively, after controlling for several related factors, such as, age, Body Mass Index (BMI), socio-economic status, health-related behavioral, and occupational characteristics variables, in the final model in the group working more than 60 h compared to the group working 40 h and lower. In addition, a dose-response relationship was observed that ORs of low and high frequencies hearing impairment were increased according to increasing average weekly working hours. CONCLUSIONS: The association between long working hours and hearing impairment in both low and high frequencies was significant in Korean female workers with a dose-response relationship. Therefore, the law to change the culture of long working hours should be enacted in order to protect the workers’ health and improve the quality of life in Korean workers.

The relationship between night work and involuntary weight change: data from the fifth Korea National Health and Nutrition Examination Survey (KNHANES 2010–2012)

BACKGROUND: Previous studies on the association between shift or night work and weight change have been focused on finding the risk of weight gain caused by shift or night work. In this study, we aimed to reveal the risk of weight gain and weight loss associated with night work by using a nationwide representative data. METHODS: This study was performed on 1605 full-time wage workers between the age of 20 and 69 based on the fifth Korea National Health and Nutrition Examination Survey (KNHANES 2010–2012). The association between night work and involuntary weight change in the previous year was divided into the categories of weight gain and weight loss and studied with modifications in socio-demographic variables, health behavior-related variables, and occupational characteristic variables. RESULTS: The participants working in night work accounted for 10.6 % of total study participants (male; 11.9 %, female 7.4 %). Workers who worked more than 48 hours per week on average accounted for 41.6 % of the total study participants (male; 46.3 %, female 29.1 %). Odds ratio (OR) of weight loss associated with night work in male workers was 0.34 (95 % confidence interval (CI) 0.16–0.76) after controlling for several related factors. OR of weight loss associated with night work in female workers with long working hours was 1.95 (95 % CI 0.47–80.86) and that of weight gain was 2.83 (95 % CI 0.12–69.83) after adjusting associated factors. CONCLUSIONS: In this cross-sectional study with national representative sample, night work may lower the risk of weight loss in male workers and induce weight change (weight loss or weight gain) in female workers with long working hours. Therefore, future studies with cohort study design for night workers are needed to reveal the mechanisms and health effects of weight change associated with night work and establish proper management solutions with health and labor policies for Korean night workers.