Maternal Prenatal Infections and Biliary Atresia in Offspring.

Importance: Investigations into the association of antepartum maternal infections with the pathogenesis of biliary atresia (BA) in human offspring are insufficient. Objective: To examine the association between prenatal infections in mothers and the development of BA in their offspring. Design, Setting, and Participants: This population-based case-control study obtained administrative data from the Taiwan National Health Insurance Research Database with linkage to the Taiwan Maternal and Child Health Database, capturing demographic and medical information on nearly all 23 million of the Taiwan population. The cohort comprised 2 905 978 singleton live births among mother-infant dyads between January 1, 2004, and December 31, 2020, in Taiwan. The case group of infants with BA was identified from use of International Classification of Diseases diagnostic codes for BA and subsequent Kasai procedure or liver transplant. The control group was randomly selected from infants without BA, representing approximately 1 in 1000 study population. Data analyses were performed from May 1 to October 31, 2023. Exposure: Prenatal maternal infections, including intestinal infection, influenza, upper airway infection, pneumonia, soft-tissue infection, and genitourinary tract infection. Main Outcomes and Measures: The main outcome was exposure to prenatal maternal infections. Inverse probability weighting analysis was performed by building a logistic regression model to estimate the probability of the exposure observed for a particular infant and using the estimated probability as a weight in subsequent analyses. The weighted odds ratio (OR) estimated by logistic regressions was then used to assess the risk of BA in offspring after prenatal maternal infections. Results: Among the mother-infant dyads included, 447 infants with BA were cases (232 females [51.9%]) and 2912 infants without BA were controls (1514 males [52.0%]). The mean (SD) maternal age at childbirth was 30.7 (4.9) years. Offspring exposed to prenatal intestinal infection (weighted OR, 1.46; 95% CI, 1.17-1.82) and genitourinary tract infection (weighted OR, 1.22; 95% CI, 1.05-1.41) in mothers exhibited a significantly higher risk of BA. Furthermore, maternal intestinal infection (weighted OR, 6.05; 95% CI, 3.80-9.63) and genitourinary tract infection (weighted OR, 1.55; 95% CI, 1.13-2.11) that occurred during the third trimester were associated with an increased risk of BA in offspring. Conclusions and Relevance: Results of this case-control study indicate an association between prenatal intestinal infection and genitourinary tract infection in mothers and BA occurrence in their offspring. Further studies are warranted to explore the underlying mechanisms of this association.

ZNF582 hypermethylation as a prognostic biomarker for malignant transformation of oral lesions.

OBJECTIVES: This hospital-based cohort study evaluated whether ZNF582 and PAX1 methylation levels at baseline can be used as biomarkers to identify lesions with a high potential for malignant transformation in patients with normal mucosa and oral potentially malignant disorders. PATIENTS AND METHODS: We recruited 171 adult patients with normal mucosa and oral potentially malignant disorders in 2012-2014. They were followed until 2017. Outcomes, including advanced histopathological findings and oral cancer occurrence, were obtained from medical charts, the Taiwan Cancer Registry, and cause-of-death data. Kaplan-Meier analysis and Cox proportional hazards regression models were used to examine the association of ZNF582 and PAX1 methylation levels at baseline with subsequent outcome occurrences. RESULTS: After 260,192 days of follow-up, 11 cases of oral cancer and 4 cases of advanced histopathological progression occurred. Patients with higher ZNF582 and PAX1 methylation levels at baseline had a higher incidence of disease progression. After adjustment for all studied factors using Cox proportional hazards regression models, ZNF582m level (adjusted hazard ratio, 11.41; 95% CI, 2.05-63.36; p = 0.005) was the only significant and independent predictor of disease progression. CONCLUSIONS: ZNF582 hypermethylation can be an effective and noninvasive biomarker for identifying oral lesions with a high potential for malignant transformation.

Association of interferon-based therapy with risk of autoimmune diseases in patients with chronic hepatitis C virus infection: A population-based Taiwanese cohort study.

Background: Interferon in combination with ribavirin has been the standard of care for chronic hepatitis C virus infection (HCV) for the past few decades. However, its effect on the risk of autoimmune diseases (ADs) among patients with HCV infection remains unclear. We assessed the potential association between interferon-based therapy (IBT) and AD risk in patients with HCV infection. Methods: This retrospective cohort study identified patients diagnosed with HCV infection between January 1, 2006, and December 31, 2015, from Taiwan's National Health Insurance Research Database. In total, 16,029 patients with HCV infection who received IBT and 141,214 patients with HCV infection who did not receive IBT were included. Both cohorts were followed up to assess the development of ADs. Hazard ratios (HRs) were calculated using the Cox proportional hazards regression model, which was adjusted for potential confounders. Results: The median follow-up period for IBT and non-IBT users was 4.53 and 3.34 years, respectively. No significant difference in the risk of overall ADs (adjusted HR [aHR]: 0.96, 95% confidence interval [CI]: 0.81-1.14) or systemic ADs (aHR: 0.88, 95% CI: 0.71-1.10) was noted during the study period. However, a slight increase in the risk of organ-specific ADs was noted among IBT users (incidence rate ratio: 1.33, 95% CI: 1.02-1.72). Furthermore, analysis of AD subgroups revealed a significant increase in the risks of Graves' disease (aHR: 6.06, 95% CI: 1.27-28.8) and Hashimoto's thyroiditis (aHR 1.49, 95% CI 1.01-2.21) among IBT users. Conclusions: IBT use increases the risk of autoimmune thyroid diseases (Hashimoto's thyroiditis and Graves' disease) in patients with HCV infection to a greater extent than non-IBT use.

Quality of life and cognitive assessment in healthy older Asian people with early and moderate chronic kidney disease: The NAHSIT 2013-2016 and validation study.

BACKGROUND: Taiwan has the highest prevalence of chronic kidney disease (CKD). Impaired cognition and quality of life are significant phenomena in the late stages of CKD. We sought to obtain an overview and the attributable effect of impaired glomerular filtration on multiple domains in cognition and dimensions of quality of life for community-based healthy older adults in Taiwan. METHODS: The study was derived from the Nutrition and Health Survey in Taiwan (NAHSIT) 2013-2016, a nationwide cross-sectional study conducted to sample healthy, community-based older adults aged ≥65 years in Taiwan. Participants were categorized into four CKD groups: CKD stage 1, stage 2, stages 3a and 3b, and stages 4-5. The Mini-Mental State Examination (MMSE) and the QoL questionnaire derived from the 12-item Short Form Health Survey (SF-12) were measured. Generalized linear mixed models (GLMMs) and principal component regressions were employed for the analysis and validation, respectively. RESULTS: Participants with moderate CKD (stages 3a and 3b) showed deficits in global MMSE, domain orientation to time, calculation, complex commands, and role-physical and vitality in QoL questionnaires. In GLMMs, impaired eGFR per 30 mL/min/1.73 m² was associated with lower global MMSE scores (ß = -0.807, standard error [SE] = 0.235, P = 0.0007), domain orientation to time (ß = -0.155, SE = 0.047, P = 0.0011), calculation (ß = -0.338, SE = 0.109, P = 0.0020), complex commands (ß = -0.156, SE = 0.079, P = 0.0494), and role-physical (ß = -2.219, SE = 0.779, P = 0.0046) dimensions of QoL. CONCLUSIONS: Elderly Han Chinese adults with moderately impaired renal filtration could manifest cognitive deficits in orientation to time, calculation, and impaired quality of life in physical role functioning.

Effects of socioeconomic status on the control of hypertension in patients <65 and ≥65 years of age in Taiwan: a nationwide cross-sectional study.

OBJECTIVE: Implementation of National Health Insurance in 1995 improved the control of hypertension due to comprehensive coverage of medical costs for all residents in Taiwan. However, the role of individual socioeconomic status (iSES), namely, education and personal income, in awareness, treatmen, and control of blood pressure, has not been well studied in Taiwan. DESIGN: A nationwide cross-sectional survey was executed in this study. SETTING: A systematic, multistage sampling scheme from a nationwide cohort in Taiwan was adopted to select adult participants. Hypertension was defined as blood pressure ≥ 140/90 mm Hg or the use of antihypertensive medications. PARTICIPANTS: A total of 4599 subjects completed door-to-door household interviews and physical examinations. PRIMARY AND SECONDARY OUTCOME MEASURES: A summing z score of iSES was constructed by two domains of the iSES, namely, income and education, through which participants were classified into three SES levels. Logistic regression models were used to assess associations of awareness, treatment, and control in younger (<65 years) and older (≥65 years) participants with hypertension. RESULTS: Younger people in the highest tertile of iSES were less likely to be aware of their hypertension (OR: 0.48, 95% CI: 0.37 to 0.64, p<0.0001) or to have it treated (OR: 0.49, 95% CI 0.37 to 0.64, p<0.0001) but more likely to have their hypertension controlled (OR: 1.52, 95% CI 1.19 to 1.94, p=0.0009). We did not detect an association in people aged >65 years. CONCLUSION: Health education to improve awareness and treatment of hypertension should focus on younger people with higher iSES in Taiwan.