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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, Author(s): Eun-Young Choi 1, Han Eol Jeong 1,2, Yunha Noh 1,2, Ahhyung Choi 1, Dong Keon Yon 3,4, Jung Yeol Han 5, Ji-Hee Sung 6, Seung-Ah Choe 7, Ju-Young Shin [...]

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 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., Author(s): Yunha Noh 1, Hyesung Lee 1,2, Ahhyung Choi 1, Jun Soo Kwon 3,4,5, Seung-Ah Choe 6, Jungmi Chae 7, Dong-Sook Kim 7,*, Ju-Young Shin 1,2,8,* Introduction Anxiety, insomnia, and [...]

Information gap in drug labeling among countries create challenges in therapeutic use of drugs. We aimed to evaluate the consistency of drug interaction information in drug labels among five countries. The study drugs were chosen from the commonly approved drug list in the US, UK, China, Japan, and Korea. The degree of agreement of drug interaction data was evaluated by kappa coefficient. Thirty‐eight drugs were evaluated, and moderate degree of agreement was observed among all countries' labeling (κ = 0.43, 95% confidence interval (CI) = 0.41–0.46). The degree of agreement was the highest for the UK and Korea (κ = 0.71, 95% CI = 0.67–0.75) and the lowest for the UK and Japan (κ = 0.02, 95% CI = 0.00–0.04). Information regarding drug interactions listed in the studied drug labels was not in high agreement. International standardization of drug labeling is required to ensure safe drug therapy. [ABSTRACT FROM AUTHOR]

Objectives: This study explored predictors of coronavirus disease 2019 (COVID-19) booster hesitancy among fully vaccinated young adults and parental COVID-19 vaccine hesitancy for their children., Methods: This cross-sectional study administered an online survey from December 2 to December 20, 2021. We enrolled participants aged 18-49 years, for whom ≥2 weeks had passed after their initial COVID-19 vaccination. We estimated odds ratios (ORs) with 95% confidence intervals (CIs) using multivariate logistic regression to evaluate factors associated with booster/vaccine hesitancy., Results: Among the 2,993 participants, 48.8% showed hesitancy (wait and see: 40.2%; definitely not: 8.7%). Booster hesitancy was more common among women (OR, 1.25; 95% CI, 1.05 to 1.50), younger people (OR, 1.44; 95% CI, 1.17 to 1.77), those with a lower education level (OR, 2.05; 95% CI, 1.10 to 3.82), those who received the mRNA-1273 vaccine type (OR, 2.01; 95% CI, 1.65 to 2.45), and those who experienced serious adverse events following previous COVID-19 vaccination (OR, 2.03; 95% CI, 1.47 to 2.80). The main reasons for booster hesitancy were concerns about safety (54.1%) and doubts about efficacy (29.8%). Among the 1,020 respondents with children aged <18 years, 65.8% were hesitant to vaccinate their children against COVID-19; hesitancy was associated with younger parental age, education level, the type of vaccine the parent received, and a history of COVID-19 infection., Conclusions: Concerns about the efficacy and safety of COVID-19 vaccines were the major barrier to booster acceptance. The initial COVID-19 vaccine type (mRNA-1273), young age, gender (women), a low education level, and adverse events after the first COVID-19 vaccine were key predictors of booster hesitancy.