Autoimmune disorders reported following COVID-19 vaccination: A disproportionality analysis using the WHO database.

PURPOSE: Owing to adverse event following immunization (AEFI) related to autoimmune disorders and coronavirus disease 2019 (COVID-19) vaccines sharing common biological mechanisms, identifying the risk of AEFIs associated with COVID-19 vaccines remains a critical unmet need. We aimed to assess the potential safety signals for 16 AEFIs and explore co-reported adverse events (AEs) and drugs using the global database of the World Health Organization, VigiBase. METHODS: We assessed the occurrence of 16 AEFIs following COVID-19 vaccination through the Standardized MedDRA Queries group "Immune-mediated/Autoimmune Disorders" from MedDRA and performed a disproportionality analysis using reporting odds ratio (ROR) and information component (IC) with 95% confidence intervals (CIs). RESULTS: We identified 25,219 events associated with COVID-19 vaccines in VigiBase. Although rare, we detected four potential safety signals related to autoimmune disorders following COVID-19 vaccination, including ankylosing spondylitis or psoriatic arthritis (ROR 1.86; 95% CI 1.53-2.27), inflammatory bowel disease (ROR 1.77; 95% CI 1.60-1.96), polymyalgia rheumatica (ROR 1.42; 95% CI 1.30-1.55), and thyroiditis (ROR 1.40; 95% CI 1.30-1.50), with positive IC025 values. The top co-reported AEs were musculoskeletal disorders, and immunosuppressants were the most representative co-reported drugs. CONCLUSION: In addressing the imperative to comprehend AEFI related to autoimmune disorders following COVID-19 vaccination, our study identified four potential safety signals. Thus, our research underscores the importance of proactive safety monitoring for the identification of the four AEFIs following COVID-19 vaccination, considering the associated advantages.

Safety of BNT162b2 mRNA COVID-19 vaccine in children with chronic kidney disease: a national population study from South Korea.

BACKGROUND: In South Korea, COVID-19 vaccination has been recommended to adolescents aged 12 - 17 since October, 2021. We aimed to assess the rate of adverse events following COVID-19 vaccination in adolescents with chronic kidney disease (CKD) in South Korea, using national cohort data. METHODS: We retrieved the clinical information of adolescents 12 - 17 years old from the Korea Disease Control and Prevention Agency-COVID19-National Health Insurance Service (K-COV-N) database, to calculate incidence rates of purpura and other hemorrhagic conditions, Guillain-Barré syndrome (GBS), Kawasaki disease/multisystem inflammatory syndrome in children (MIS-C), myocarditis and/or pericarditis, and anaphylaxis in adolescents with CKD, after BNT162b2 vaccination. RESULTS: Among the 2306 adolescents with CKD, 62.7% (n = 1446) had received the BNT-162b2 vaccine. GBS, Kawasaki disease/MIS-C, and anaphylaxis or anaphylactic shock did not occur during the observation period. Purpura and hemorrhagic conditions were more frequent in the unvaccinated group (7/860 vs. 1/1446), while myocarditis/pericarditis was observed only in the vaccinated group (0/860 vs. 1/1446). Adjusted odds ratio for any of the two adverse events was lower in vaccinated adolescents than in the unvaccinated group which did not reach statistical significance (adjusted odds ratio = 0.14, 95% confidence interval: 0.02, 1.16, P = 0.068). CONCLUSIONS: In this national cohort study of adolescents with CKD in South Korea, we observed no evidence of increased risk of adverse events following BNT162b2 vaccination. Our finding offers insights into the safety of COVID-19 vaccines, empowering adolescent patients with CKD and their caregivers to make informed decisions.

Safety of COVID-19 Vaccination During Pregnancy and Lactation: A VigiBase Analysis.

BACKGROUND: There is limited evidence on the safety of coronavirus disease 2019 (COVID-19) vaccination during pregnancy and lactation. Thus, we aimed to evaluate the association between COVID-19 vaccination during pregnancy and lactation and reporting risk of adverse pregnancy or lactation outcomes. METHODS: Using VigiBase, we performed a disproportionality analysis with case/non case design. Cases were defined based on the Standardized MedDRA Queries (SMQs) of "pregnancy and neonatal topics" and non-cases were defined as all other adverse events. We included all reports with COVID-19 vaccines as the suspected cause. Using the full database as the comparators, reporting odds ratios (RORs) with 95% confidence intervals (CIs) were estimated by logistic regression while adjusting for maternal age. Infants' age and sex were additionally adjusted in analyzing the risk of COVID-19 vaccination during lactation. RESULTS: We identified 10,266 and 6,474 reports with the SMQ of "pregnancy and neonatal topics" associated with COVID-19 vaccines during pregnancy and lactation, respectively. No significant RORs of adverse pregnancy outcomes associated with COVID-19 vaccines during pregnancy were observed; however, "functional lactation disorders" showed significant disproportionality during lactation with adjusted ROR of 1.48 (95% CI, 1.21-1.79). Further analysis that analyzed "functional lactation disorders" at a preferred term level, showed higher ROR in mastitis (2.76 [95% CI, 1.45-5.27]). CONCLUSION: Overall, we did not observe a positive association between COVID-19 vaccination during pregnancy and risk of reporting adverse pregnancy outcomes. However, we found a significant disproportionate reporting association between COVID-19 vaccination during lactation and "functional lactation disorders", specifically mastitis. Continuous surveillance is warranted to confirm the safety of COVID-19 vaccine during pregnancy and lactation.

Adverse Events Following COVID-19 Vaccination in Adolescents: Insights From Pharmacovigilance Study of VigiBase.

BACKGROUND: During coronavirus disease 2019 (COVID-19) pandemic, several COVID-19 vaccines were licensed with fast-track procedures. Although these vaccines have demonstrated high immunogenicity, there has been concerns on the serious adverse events (AEs) following COVID-19 vaccination among adolescents. We aimed to analyze comparative safety of COVID-19 vaccination in adolescents. METHODS: In this pharmacovigilance study, we performed a disproportionality analysis using VigiBase, the World Health Organization's global individual case safety report (ICSR) database. To compare serious AEs reported following COVID-19 vaccines vs. all other vaccines in adolescents aged 12-17 years, ICSRs following any vaccines on adolescents aged 12-17 years were included, defining cases as reports with the AEs of interest, with all other AEs as non-cases. The AEs of interest were myocarditis/pericarditis, multisystem inflammatory syndrome/Kawasaki disease (MIS/KD), anaphylaxis, Guillain-Barré syndrome (GBS), and immune thrombocytopenia (ITP). We conducted a disproportionality analysis to estimate reporting odds ratio (ROR) with 95% confidence interval (CI) for each AE of interest, adjusted for sex by using logistic regression. RESULTS: Of 99,735 AE reports after vaccination in adolescents, 80,018 reports were from COVID-19 vaccinated adolescents (52.9% females; 56.3% America). The AEs of interest were predominantly reported as serious AE (76.1%) with mRNA vaccines (99.4%). Generally, higher reporting odds for the AEs were identified following COVID-19 vaccination in adolescents; myocarditis/pericarditis (2,829 reports for the COVID-19 vaccine vs. 35 for all other vaccines, adjusted ROR [aROR], 19.61; 95% CI, 14.05-27.39), and MIS/KD (104 vs. 6, aROR, 4.33; 95% CI, 1.89-9.88). The reporting odds for anaphylaxis (515 vs. 165, aROR, 0.86; 95% CI, 0.72-1.02), GBS (94 vs. 40, aROR, 0.64; 95% CI, 0.44-0.92) and ITP (52 vs. 12, aROR, 1.12; 95% CI, 0.59-2.09) were not significantly higher following COVID-19 vaccination. CONCLUSION: In this study, there were disproportionate reporting of immune-related AEs following COVID-19 vaccination. While awaiting definitive evidence, there is a need to closely monitor for any signs of immune-related AEs following COVID-19 vaccination among adolescents.

Social Inequities in the Survival of Liver Cancer: A Nationwide Cohort Study in Korea, 2007-2017.

BACKGROUND: To analyze the effects of socioeconomic status (type of insurance and income level) and cancer stage on the survival of patients with liver cancer in Korea. METHODS: A retrospective cohort study was constructed using data from the Healthcare Big Data Platform project in Korea between January 1, 2007, and December 31, 2017. A total of 143,511 patients in Korea diagnosed with liver cancer (International Classification of Diseases, 10th Revision [ICD-10] codes C22, C220, and C221) were followed for an average of 11 years. Of these, 110,443 died. The patient's insurance type and income level were used as indicators of socioeconomic status. Unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a Cox proportional hazards regression model to analyze the relationship between the effects of sex, age, and cancer stage at first diagnosis (Surveillance, Epidemiology, and the End Results; SEER), type of insurance, and income level on the survival of patients with liver cancer. The interactive effects of the type of insurance, income level, and cancer stage on liver cancer death were also analyzed. RESULTS: The lowest income group (medical aid) showed a higher risk for mortality (HR (95% CI); 1.37 (1.27-1.47) for all patients, 1.44 (1.32-1.57) for men, and 1.16 (1.01-1.34) for women) compared to the highest income group (1-6) among liver cancer (ICD-10 code C22) patients. The risk of liver cancer death was also higher in the lowest income group with a distant cancer stage (SEER = 7) diagnosis than for any other group. CONCLUSION: Liver cancer patients with lower socioeconomic status and more severe cancer stages were at greater risk of death. Reducing social inequalities is needed to improve mortality rates among patients in lower social class groups who present with advanced cancer.

Neonatal and maternal adverse outcomes and exposure to nonsteroidal anti-inflammatory drugs during early pregnancy in South Korea: A nationwide cohort study.

BACKGROUND: Existing data on the use of nonsteroidal anti-inflammatory drugs (NSAIDs) during late pregnancy is well established, providing assurance. However, the use of NSAIDs during early pregnancy remains inconclusive owing to conflicting findings on adverse neonatal outcomes as well as the limited data on adverse maternal outcomes. Therefore, we sought to investigate whether early prenatal exposure to NSAIDs was associated with neonatal and maternal adverse outcomes. METHODS AND FINDINGS: We conducted a nationwide, population-based cohort study using Korea's National Health Insurance Service (NHIS) database with a mother-offspring cohort constructed and validated by the NHIS to include all live births in women aged 18 to 44 years between 2010 and 2018. We defined exposure to NSAIDs as at least two records of NSAID prescriptions during early pregnancy (first 90 days of pregnancy for congenital malformations and first 19 weeks for nonmalformation outcomes) and compared against three distinct referent groups of (1) unexposed, no NSAID prescription during the 3 months before pregnancy start to end of early pregnancy; (2) acetaminophen-exposed, at least two acetaminophen prescriptions during early pregnancy (i.e., active comparator); and (3) past users, at least two NSAID prescriptions before the start of pregnancy but no relevant prescriptions during pregnancy. Outcomes of interest were adverse birth outcomes of major congenital malformations and low birth weight and adverse maternal outcomes of antepartum hemorrhage and oligohydramnios. We estimated relative risks (RRs) with 95% CIs using generalized linear models within a propensity score (PS) fine stratification weighted cohort that accounted for various potential confounders of maternal sociodemographic characteristics, comorbidities, co-medication use, and general markers of burden of illness. Of 1.8 million pregnancies in the PS weighted analyses, exposure to NSAIDs during early pregnancy was associated with slightly increased risks for neonatal outcomes of major congenital malformations (PS-adjusted RR, 1.14 [CI, 1.10 to 1.18]) and low birth weight (1.29 [1.25 to 1.33]), and for maternal outcome of oligohydramnios (1.09 [1.01 to 1.19]) but not antepartum hemorrhage (1.05 [0.99 to 1.12]). The risks of overall congenital malformations, low birth weight, and oligohydramnios remained significantly elevated despite comparing NSAIDs against acetaminophen or past users. Risks of adverse neonatal and maternal outcomes were higher with cyclooxygenase-2 selective inhibitors or use of NSAIDs for more than 10 days, whereas generally similar effects were observed across the three most frequently used individual NSAIDs. Point estimates were largely consistent across all sensitivity analyses, including the sibling-matched analysis. Main limitations of this study are residual confounding by indication and from unmeasured factors. CONCLUSIONS: This large-scale, nationwide cohort study found that exposure to NSAIDs during early pregnancy was associated with slightly higher risks of neonatal and maternal adverse outcomes. Clinicians should therefore carefully weigh the benefits of prescribing NSAIDs in early pregnancy against its modest, but possible, risk of neonatal and maternal outcomes, where if possible, consider prescribing nonselective NSAIDs for <10 days, along with continued careful monitoring for any safety signals.

Chromosomal Abnormality, fetal/neonatal Death and Socioeconomic Status: A Prospective Cohort Study.

OBJECTIVES: To assess the risk gradient of chromosomal abnormalities and fetal or neonatal death across a socioeconomic spectrum of pregnant women. METHODS: We used the data from the Korean Prenatal Diagnosis Study (KPDS), which included singleton pregnancies who were candidates for fetal aneuploidy screening enrolled from the Seoul Capital Area from December 2016 to April 2018. We analyzed chromosomal abnormalities which were diagnosed pre- or postnatally, and fetal or neonatal death. The highest level of education among the women and the average monthly household income were used as proxies for socioeconomic status. RESULTS: Among the 6,715 women, the majority of were 30-39 years old and university graduates, with a reported household income higher than the national median. Chromosomal abnormalities occurred in 45 women (6.7 per 1,000). Fetal or neonatal death occurred in 70 (11.3 per 1,000), excluding pregnancies affected by chromosomal abnormality diagnosis. The adjusted odds ratio for chromosomal abnormalities was higher when household income was < 4,484 USD per month. For fetal or neonatal death, the risk estimates for lower education and lower household income were generally positive but remained imprecise. CONCLUSION: We observed some evidence of an inverse association between the risk of fetal chromosomal abnormality and level of household income in a prospective cohort of pregnant women. Interventions to reduce socioeconomic disparities in perinatal health should focus on those with a low household income.

Trend of Women's Health Research in Korea, 2012-2020: Topic and Text Network Analysis.

BACKGROUND: With the epidemiological transition, sociodemographic changes and differential lifetime experiences of women, women's health research improves knowledge of diverse health issues and the impact of policies. To explore the initiatives of women's health research in Korea, the present study examined the trends and topics of research on women's health funded by the government. METHODS: We searched all research projects on women's health funded by the government between 2012 and 2020 in Korea using the National Science & Technology Information Service database. We reviewed all the titles and abstract of the projects and examined the research trends by year. Content analysis was performed using both deductive and inductive approaches. Text network analysis and visualization by topic were conducted for keywords with a minimum of 10 occurrences in the title and abstract. RESULTS: Total number and funding amount of research projects on women's health in 2020 increased by 2.4 and 2.2 times over 2012 levels, respectively. The Ministry of Health and Welfare and the Ministry of Food and Drug Safety funded 20.9% of all projects. The majority of the topics (59.8%) addressed breast and gynecological cancers. Those on sexual and reproductive health accounted for 16.7%, with steep growth in the number (6.1 times) and funding (11.1 times) over 2012 levels. The topic analysis presented a more complex keyword network in 2020 than in 2012; however, the keywords frequently used in 2020 were similar to those of 2012. CONCLUSION: Women's health research projects have been growing in number and funding, with limited diversity in topics. Diversifying the topics and focusing on issues beyond the breast and pregnancy would be needed to reflect the complete life course of women. Institutionalization of diverse communication channels with various interest groups for women's health would be needed to better understand women's health needs from a public health perspective.

Widening Social Inequalities in Cancer Mortality of Children Under 5 Years in Korea.

BACKGROUND: To investigate the effect of parental social class on cancer mortality in children under 5 in Korea, two birth cohorts were constructed by linking national birth data to under-5 death data from the Statistics Korea for 1995-1999 (3,323,613 births) and 2010-2014 (2,297,876 births). METHODS: The Cox proportional hazards model adjusted for covariates was used in this study. RESULTS: Social inequalities of under-5 cancer mortality risk in paternal education and paternal employment status were greater in 2010-2014 than in 1995-1999. The gap of hazard ratio (HR) of under-5 cancer mortality between lower (high school or below) and higher (university or higher) paternal education increased from 1.23 (95% confidence interval, 1.041.46) in 1995-1999 to 1.45 (1.11-1.97) in 2010-2014; the gap of HR between parents engaged in manual work and non-manual work increased from 1.32 (1.12-1.56) in 1995-1999 to 1.45 (1.12-1.89) in 2010-2014 for fathers, and from 1.18 (0.7-1.98) to 1.69 (1.03-2.79) for mothers. When the parental social class was lower, the risk of under-5 cancer mortality was higher in not only adverse but normal births. CONCLUSION: Social inequalities must be addressed to reduce the disparity in cancer mortality of children under 5 years old.

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 non-Seoul 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.

A Nationwide Survey of mRNA COVID-19 Vaccinee's Experiences on Adverse Events and Its Associated Factors.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) vaccines have been distributed worldwide under emergency use authorization, the real-world safety profiles of mRNA vaccines still need to be clearly defined. We aimed to identify the overall incidence and factors associated with adverse events (AEs) following mRNA COVID-19 vaccination. METHODS: We conducted web-based survey from December 2 to 10 in 2021 with a 2,849 nationwide sampled panel. Study participants were individuals who had elapsed at least two-weeks after completing two dosing schedules of COVID-19 vaccination aged between 18-49 years. We weighted the participants to represent the Korean population. The outcome was the overall incidence of AEs following mRNA COVID-19 vaccination and associated factors. We estimated the weighted odds ratios (ORs) using multivariable logistic regression models to identify the factors associated with AEs. RESULTS: Of the 2,849 participants (median [interquartile range] age, 35 [27-42] years; 51.6% male), 90.8% (n = 2,582) for the first dose and 88.7% (n = 2,849) for the second dose reported AEs, and 3.3% and 4.3% reported severe AEs, respectively. Occurrence of AEs was more prevalent in mRNA-1273 (OR, 2.06; 95% confidence interval [CI], 1.59-2.67 vs. BNT162b2), female sex (1.88; 1.52-2.32), and those with dermatologic diseases (2.51; 1.32-4.77). History of serious allergic reactions (1.96; 1.06-3.64) and anticoagulant medication use (4.72; 1.92-11.6) were associated with severe AEs. CONCLUSION: Approximately 90% of participants reported AEs following mRNA COVID-19 vaccination. Substantial factors, including vaccine type (mRNA-1273), female sex, and dermatologic diseases were associated with AEs. Our findings could aid policymakers in establishing vaccination strategies tailored to those potentially susceptible to AEs.

Effectiveness and Safety of COVID-19 Vaccination During Preconceptional and Preclinical Pregnancy Period: A National Population Study.

BACKGROUND: We aimed to assess the risk of maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and early abortive outcomes after the association between coronavirus disease 2019 (COVID-19) vaccination during the preconceptional period and preclinical pregnancy, which are likely to be inadvertent vaccination. METHODS: We used data from the Korea Disease Control and Prevention Agency-COVID19-National Health Insurance Service cohort from December 2020 to December 2021. The vaccinated pregnant women were matched to unvaccinated pregnant controls at a 1:4 ratio. The risks of SARS-CoV-2 infection and intensive care unit (ICU) admission within 14 days of infection were analyzed to assess its effectiveness. For safety measures, the adjusted relative risks (aRRs) of early abortive outcomes for the first COVID-19 vaccination during the preconceptional and preclinical periods were calculated considering covariates. We compared the risk of early abortion between mRNA and viral vector vaccines. RESULTS: The overall COVID-19 vaccination rates during the preconceptional period and preclinical pregnancy were 3.1% (6,662/215,211) and 2.6% (5,702/215,211), respectively. The cumulative incidence of ICU admission within 14 days of SARS-CoV-2 infection was 6/100,000 in the unvaccinated group, whereas there were no ICU admissions in the vaccinated groups. The risks of early abortive outcomes were not significantly different between the preconceptional vaccination group and the unvaccinated group (aRR, 1.04; 95% confidence interval [CI],0.99-1.10) or between preclinical pregnancy vaccination and their matched controls (1.02; 95% CI, 0.96-1.08). mRNA and viral vector vaccines have shown similar risks for early abortive outcomes and miscarriages. CONCLUSION: Our findings have provided compelling evidence regarding the effectiveness and safety of COVID-19 vaccination prior to and during early pregnancy. Further research is required to extend the safety and efficacy profiles of COVID-19 vaccines to pregnant women and their babies.

Age at menarche of adolescent girls and the neighbourhood socioeconomic status of their school area.

PURPOSE: To assess the association between abnormal timing of menarche among adolescent girls and neighbourhood socioeconomic status of their school area. MATERIALS AND METHODS: Our analysis included 187,024 girls aged 15-18 years from the Korea Youth Risk Behaviour Web-Based Survey (KYRBS) from 2007 to 2015. Early and late menarche were defined as menarche before 11 years and no menarche by age 14 years, respectively. The deprivation index values for the areas where the schools were located were used as an indicator of neighbourhood socioeconomic status based on the 2005 national census data. We calculated odds ratios (OR) for early and late menarche using a multinomial logistic regression model. Covariates included body mass index, parental education, single or stepparents, siblings, household wealth, year of birth, survey year, and urbanisation. RESULTS: Mean age at menarche was 12 years. The overall proportions of early and late menarche were 11.3% and 3.3%, respectively. When divided into four quartile groups based on the socioeconomic deprivation index, 11.3% of girls in the most deprived quartile and 10.6% in the least deprived area showed early menarche. The prevalence of late menarche did not differ across the deprivation index quartiles of school area. Attendance at schools located in highly deprived areas was associated with up to 10% higher risk of early menarche. This positive association was not evident for late menarche. CONCLUSION: Among contemporary Korean girls, socioeconomic deprivation of the school area was associated with earlier puberty. This finding highlights the potential role of the socioeconomic environment of schools in women's lifetime health.

First-trimester exposure to benzodiazepines and risk of congenital malformations in offspring: A population-based cohort study in South Korea.

BACKGROUND: Benzodiazepines are frequently prescribed during pregnancy; however, evidence about possible teratogenicity is equivocal. We aimed to evaluate the association between first-trimester benzodiazepine use and the risk of major congenital malformations. METHODS AND FINDINGS: Using Korea's nationwide healthcare database, we conducted a population-based cohort study of women who gave birth during 2011 to 2018 and their live-born infants. The exposure was defined as one or more benzodiazepine prescriptions during the first trimester. We determined the relative risks (RRs) and confidence intervals (CIs) of overall congenital malformations and 12 types of organ-specific malformations. Infants were followed from birth to death or 31 December 2019, whichever came first (up to 8 years of age). Propensity score fine stratification was employed to control for 45 potential confounders. Among a total of 3,094,227 pregnancies, 40,846 (1.3%) were exposed to benzodiazepines during the first trimester (mean [SD] age, 32.4 [4.1] years). The absolute risk of overall malformations was 65.3 per 1,000 pregnancies exposed to benzodiazepines versus 51.4 per 1,000 unexposed pregnancies. The adjusted RR was 1.09 (95% CI 1.05 to 1.13, p < 0.001) for overall malformations and 1.15 (1.10 to 1.21, p < 0.001) for heart defects. Based on mean daily lorazepam-equivalent doses, the adjusted RRs for overall malformations and heart defects were 1.05 (0.99 to 1.12, p = 0.077) and 1.12 (1.04 to 1.21, p = 0.004) for <1 mg/day and 1.26 (1.17 to 1.36, p < 0.001) and 1.31 (1.19 to 1.45, p < 0.001) for >2.5 mg/day doses, respectively, suggesting a dose-response relationship. A small but significant increase in risk for overall and heart defects was detected with several specific agents (range of adjusted RRs: 1.08 to 2.43). The findings were robust across all sensitivity analyses, and negative control analyses revealed a null association. Study limitations include possible exposure misclassification, residual confounding, and restriction to live births. CONCLUSIONS: In this large nationwide cohort study, we found that first-trimester benzodiazepine exposure was associated with a small increased risk of overall malformations and heart defects, particularly at the higher daily dose. The absolute risks and population attributable fractions were modest. The benefits of benzodiazepines for their major indications must be considered despite the potential risks; if their use is necessary, the lowest effective dosage should be prescribed to minimize the risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT04856436.

Child mortality of twins and singletons among late preterm and term birth: a study of national linked birth and under-five mortality data of Korea.

Twins involve a higher risk of perinatal complications compared to singletons. We compared the risk of under five mortality between twins and singletons among late preterm and term births. The national birth data of South Korea pertaining to the years 2010-2014 linked with the mortality record of children aged under 5 years in 2010-2019 was analyzed. The final study population was 2,199,632 singletons and 62,351 twins. We conducted a survival analysis of under-five mortality with adjustment for neonatal and familial factors. Overall under-five mortality rates during the study period were 3.6 and 2.0 for twins and singletons, respectively. Although the unadjusted overall under-five mortality was higher in twins (hazard ratio [HR] = 1.80, 95% confidence interval [CI]: 1.57, 2.06, overall risk), twin birth was associated with comparable or lower risk (HR = 0.70, 95% CI: 0.58, 0.85, overall; 0.70, 95% CI: 0.56, 0.87, excluding neonatal mortality; 0.59, 95% CI: 0.40, 0.86, excluding infant mortality) after controlling for both neonatal and familial factors. Twins born at a gestational age of 34-35 weeks showed a generally lower risk of under-five mortality than their singleton counterparts, regardless of model specification.Conclusion: Among late preterm and term birth, under-5-year mortalities for twins were lower than singleton births when adjusted for neonatal and familial risk factors. This highlights the differential implication of gestational age at birth between twin and singleton in the child mortality.

Short-term and long-term outcomes of trichorionic triplet pregnancies with expectant management.

INTRODUCTION: Reproductive endocrinologists recommend selective multifetal pregnancy reduction (MFPR) to save at least one or two babies, because triplet pregnancy is known to increase the risk of miscarriage and preterm delivery. However, recently improved obstetric and neonatal care may affect pregnancy outcomes differently in triplet pregnancies, which could alter practice. We compared the maternal, perinatal, and long-term outcomes of triplet pregnancies managed expectantly with those of pregnancies reduced to twins. MATERIAL AND METHODS: In this retrospective cohort study, we reviewed the clinical records of 552 trichorionic triplet pregnancies for obstetric, perinatal, and neurodevelopmental outcomes, which consisted of the expectant management (EM) group (n = 225) and MFPR group (n = 327), in Seoul National University Hospital and CHA Bundang Medical Center from January 2006 to December 2018. Neuromotor development was evaluated using the Korean-Ages and Stages Questionnaire, Bayley-III tests, and/or Gross Motor Function Measure. The two groups were compared for the following outcomes: (1) nonviable pregnancy loss before 23 weeks, (2) preterm birth before 32 weeks of gestation, (3) fetal and neonatal survival and (4) long-term neurodevelopmental outcomes. RESULTS: There were no differences in maternal age, body mass index, nulliparity or previous preterm birth between the two groups. The risk of nonviable pregnancy loss was lower in the EM group than that in the MFPR group (2 [0.9%] vs 21 [6.4%], p = 0.001). The risk of preterm delivery before 34 weeks of gestation was lower in the MFPR group (adjusted odds ratios [aOR] = 0.47, 95% confidence interval [CI] 0.30-0.73, p = 0.001). The survival rate of neonates until discharge (644 [95.4%] vs 572 [87.5], p < 0.001) and the rate of pregnancies with at least one survivor (220 [97.8%] vs 301 [92.0], p = 0.002) were higher in the EM group than those in the MFPR group. In the MFPR group, the risk of developmental delay (aOR = 2.89, 95% CI 1.38-6.02, p = 0.005) was higher. CONCLUSIONS: In trichorionic triplet pregnancies, the possibility of EM to improve survival and reduce the risk of developmental delay has been shown.

Alcohol use during pregnancy: findings from a gender-based violence survey in Mongolia.

This study aimed to explore the risk factors for alcohol use during pregnancy in Mongolia, wherein high-risk alcohol use is prevalent. We analyzed nationwide data from the Gender-Based Violence (GBV) Survey of Mongolia conducted in 2017. We conducted an analysis restricted to 2714 women who had given birth within 5 years of the survey and who had responded to questions about their health-related behaviors during pregnancy. We assessed the association between alcohol use during pregnancy and pregnancy-related factors, including maternal age, educational attainment, history of abortion, smoking during pregnancy, unintended pregnancy, prior experience of sexual and physical violence, physical violence during pregnancy, and current binge drinking while also considering their residential region. Alcohol use during pregnancy was reported in 5.4% of the participating women. Unintended pregnancy for women (OR = 1.95, 95% confidence interval [CI]: 1.60, 2.38), abortion history (1.89, 95% CI: 1.60, 2.24), smoking during pregnancy (8.30, 95% CI: 6.60, 10.43), physical violence during pregnancy (2.22, 95% CI: 1.75, 2.81), and being a binge drinker (6.05, 95% CI: 3.63, 10.10) were associated with higher odds of alcohol use during pregnancy. Associations with maternal age, marital status, higher education, or multiparity were not evident. Our finding provides knowledge of risk factors for alcohol drinking among pregnant women and evidence for another harm of gender-based violence. This would contribute to the development of effective strategies for preventing antenatal exposure to alcohol in Mongolia.

Occupational radiation exposure and cancer incidence in a cohort of diagnostic medical radiation workers in South Korea.

OBJECTIVES: We investigated the association between protracted low-dose ionising radiation and the risk of cancer in medical radiation workers, the largest group of workers with occupational radiation exposures. METHODS: Data of all South Korean diagnostic medical radiation workers enrolled at the National Dose Registry during 1996-2011 were merged with the death and cancer incidence data until 31 December 2017. SIRs, relative risks and excess relative risks (ERRs) for cancer were calculated to quantify the radiation dose-response relationship using Poisson regression models. RESULTS: A total of 3392 first primary cancer cases were identified among 93 920 diagnostic medical radiation workers. The mean cumulative badge dose in the cohort was 7.20 mSv. The ERRs for solid cancer with a 5-year lag and haematopoietic cancers with a 2-year lag for all workers were 0.15 per 100 mGy (95% CI -0.20 to 0.51) and 0.09 per 100 mGy (95% CI -2.02 to 2.20), respectively. The ERRs for cancers did not significantly vary by job title, different lag years or after excluding thyroid and lung cancers. Sensitivity analyses restricted to workers employed for at least 1 year, or who were employed in or after 1996, or who had exposure to a cumulative badge dose of 1 mSv or more showed similar results. CONCLUSIONS: Occupational radiation doses were not significantly associated with cancer incidence among South Korean diagnostic medical radiation workers. However, cautious interpretation of ERRs is needed due to the limitations of short follow-up and low cumulative radiation doses.

Harmful alcohol use among mothers of under-five child: findings from the Panel Study on Korean Children.

BACKGROUND: Harmful alcohol use in young mothers as a primary caregiver has a profound impact on their own health and interaction with the child. We studied the epidemiology of harmful alcohol use among Korean mothers and their partners of under-five children. METHODS: We used a longitudinal data of 2,150 Korean mothers of the Panel Study on Korean Children (PSKC). We assessed temporal trend and risk factors for harmful alcohol use in mothers using generalized estimating equation (GEE) model. To estimate the impact of maternal harmful alcohol use on the child, the association between neurodevelopment of the child measured by the Korean-Ages & Stages Questionnaire (K-ASQ) and maternal harmful alcohol use was analyzed using GEE and generalized linear mixed model. We included mother's age, education, preterm, year of the survey and time-varying covariates (including maternal working status, monthly household income, plan for additional childbirth, psychological stress related with childcare, current smoking, and partner's harmful alcohol use) in the model. RESULTS: Mean age of mothers at the baseline was 31.3 years. Annual prevalence of harmful alcohol use increased from 0.7% in the 1st year to 2.6% in the 4th year (P for linear trend < 0.001). Prevalence of harmful alcohol use increased by 48% per year among the mothers (adjusted odds ratio (OR) = 1.48, 95% confidence interval (CI): 1.22, 1.78). Lower education than college or university graduation was associated with higher odds of harmful alcohol use (2.52, 95% CI: 1.43, 4.45). Current smoking (7.44, 95% CI: 3.00, 18.45), harmful use of alcohol of partner (2.66, 95% CI: 1.57, 4.49) were associated with higher risk of harmful alcohol use in mothers. The association between low K-ASQ score and maternal harmful alcohol use was toward positive which did not reach statistical significance. CONCLUSIONS: In a cohort of Korean mothers participating in the PKSC, risk of harmful alcohol use increases over time and is associated with harmful alcohol use of their partners. We suggest an approach targeting both parents can be more effective in controlling the harmful alcohol use of mothers.

Trend of Antibiotic Use in Children with Acute Otitis Media in Korea.

Public interventions have shown to optimize the use of antibiotics in children with acute otitis media (AOM). In this study, we describe the AOM-related antibiotic use among children in South Korea using national cohort data. We retrieved the Health Insurance Review & Assessment Service data to construct a national cohort of children aged 0-6 years who had been diagnosed with AOM between 2012 and 2018. Of 25,212,264 children included, the antibiotic prescription has increased for amoxicillin/amoxicillin-clavulanate from 56.1% in 2012 to 61.8% in 2018. Prescription has decreased for cephalosporin (35.1% in 2012 to 31.8% in 2018) and macrolide (8.7% in 2012 to 6.4% in 2018). National cohort data have shown an increased trend in AOM-related aminopenicillin prescription and downward trend cephalosporin and macrolide use in South Korea. A multi-faceted approach is required to control the antimicrobial resistance at a population level.