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Background Intrahepatic cholestasis of pregnancy (ICP) is the most common obstetric liver disorder and is associated with an increased risk of iatrogenic preterm birth and adverse infant outcomes. Hence, there are several plausible pathways through which ICP could affect offspring neurodevelopment. However, to the best of our knowledge, no studies have investigated these associations. Thus, we aimed to determine whether ICP is associated with offspring neurodevelopmental conditions. Methods and findings In this Swedish register-based cohort study, we included singleton non-adopted children born in Sweden between the 1st of January 1987 and the 31st of December 2010, who were resident in Sweden >5 years, with no missing covariate information, which we followed until the 31st of December 2016. Maternal ICP diagnosis and the date of the initial diagnosis during pregnancy were obtained from the National Patient Register. Offspring diagnoses of attention deficit/hyperactivity disorder (ADHD), autism, or intellectual disability were obtained from the National Patient Register, and the dispensation of ADHD medications were obtained from the Prescribed Drug Register. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression while controlling for observed confounders and unobserved confounders shared among full siblings and maternal full cousins. A total of 2,375,856 children were included in the study; 81.6% of them were of Nordic origin, and 51.4% were male. Of these, 10,378 (0.44%) were exposed to ICP. During a median of 18 years follow-up (interquartile range 11 to 24), 143,746 (6.05%) of children were diagnosed with a neurodevelopmental condition. After adjusting for child's sex, birth year, birth month, maternal age, highest parental education level, maternal birth country, birth order, maternal psychiatric history, ICP was associated with increased odds of offspring neurodevelopmental conditions (OR 1.22, 95% CI 1.13 to 1.31), particularly among those exposed to early-onset ICP (OR 2.38, 95% CI 1.71 to 3.30) as compared to ICP diagnosed after reaching term ([greater than or equal to]37 weeks of gestation) (OR 1.08, 95% CI 0.97 to 1.20). The findings of early-onset ICP were consistent in family-based analyses. Within-family comparisons of full maternal cousins yielded an OR of 2.99 (95% CI 1.48 to 6.04), and comparisons of full siblings showed an OR of 1.92 (95% CI 0.92 to 4.02), though the latter was less precise. The findings were consistent across specific neurodevelopmental conditions and different analytical approaches. The primary limitations of this study included its observational design, the absence of data on ICP therapeutics, and the lack of bile acid measures. Conclusions In this study, we observed that exposure to ICP during gestation is associated with an increased likelihood of neurodevelopmental conditions in offspring, particularly in cases of early-onset ICP. Further studies are warranted to better understand the role of early-ICP in offspring neurodevelopment., Author(s): Shuyun Chen 1,*, Viktor H. Ahlqvist 1,*, Hugo Sjöqvist 1, Olof Stephansson 2,3, Cecilia Magnusson 1,4, Christina Dalman 1,4, Håkan Karlsson 5, Brian K. Lee 1,6,7, Renee M. Gardner [...]

Objective: Exercise is increasingly used as adjunct treatment for alcohol use disorder (AUD). Evidence suggests that moderate-to-high-intensity exercise can ameliorate cravings. We explored the potential mediating effects of changes in mood states in the relationship between exercise intensity and alcohol cravings. Method: Secondary analyses of a nested single-arm trial within a randomized controlled trial (FitForChange). In total, 117 sedentary adults (68.4% female, M = 52 ± 12 years) with clinician diagnosed (Diagnostic and Statistical Manual of Mental Disorders, fifth edition) AUD and indications of craving (Desire for Alcohol Questionnaire) completed a 12-min submaximal cardiorespiratory fitness test on a cycle ergometer. Assessments of craving, mood states (POMS), and state anxiety (STAI-Y1) were taken immediately before, after, and 30 min after exercise. Ratings of perceived exertion (RPE) were included as indirect measures of exercise intensity. The med4way command in Stata was used to explore mediating and interaction effects of improvements in total mood disturbance (TMD) and state anxiety. Results: Improvements in mood and anxiety did not mediate the effect of higher exercise intensity on reductions in alcohol craving. A significant reference interaction was found between "hard" (or greater) exertion and anxiety improvements (β = −1.06, 95% CI [−1.50, −0.61]). Participants whose anxiety reduced during exercise had two times higher odds of reduced cravings when exercising at a higher intensity than participants whose anxiety worsened (OR = 2.04, 95% CI [1.12, 3.72]). Conclusions: Reductions in anxiety may partly explain the positive effect of higher exercise intensity on alcohol cravings. The findings are preliminary and require replication in future studies. Public Health Significance Statement: Alcohol use disorder (AUD) is prevalent and associated with poor somatic and psychiatric health. Exercise interventions are shown to reduce cravings for alcohol in those with AUD, but the underlying mechanisms are unclear. This study found that decreases in state anxiety in those reporting higher exercise intensity were associated with reductions in postexercise alcohol cravings. Findings can inform future exercise-based interventions for AUD. [ABSTRACT FROM AUTHOR]

Key Points: Question: Does acetaminophen use during pregnancy increase children's risk of neurodevelopmental disorders? Findings: In this population-based study, models without sibling controls identified marginally increased risks of autism and attention-deficit/hyperactivity disorder (ADHD) associated with acetaminophen use during pregnancy. However, analyses of matched full sibling pairs found no evidence of increased risk of autism (hazard ratio, 0.98), ADHD (hazard ratio, 0.98), or intellectual disability (hazard ratio, 1.01) associated with acetaminophen use. Meaning: Acetaminophen use during pregnancy was not associated with children's risk of autism, ADHD, or intellectual disability in sibling control analyses. This suggests that associations observed in other models may have been attributable to confounding. Importance: Several studies suggest that acetaminophen (paracetamol) use during pregnancy may increase risk of neurodevelopmental disorders in children. If true, this would have substantial implications for management of pain and fever during pregnancy. Objective: To examine the associations of acetaminophen use during pregnancy with children's risk of autism, attention-deficit/hyperactivity disorder (ADHD), and intellectual disability. Design, Setting, and Participants: This nationwide cohort study with sibling control analysis included a population-based sample of 2 480 797 children born in 1995 to 2019 in Sweden, with follow-up through December 31, 2021. Exposure: Use of acetaminophen during pregnancy prospectively recorded from antenatal and prescription records. Main Outcomes and Measures: Autism, ADHD, and intellectual disability based on International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes in health registers. Results: In total, 185 909 children (7.49%) were exposed to acetaminophen during pregnancy. Crude absolute risks at 10 years of age for those not exposed vs those exposed to acetaminophen were 1.33% vs 1.53% for autism, 2.46% vs 2.87% for ADHD, and 0.70% vs 0.82% for intellectual disability. In models without sibling control, ever-use vs no use of acetaminophen during pregnancy was associated with marginally increased risk of autism (hazard ratio [HR], 1.05 [95% CI, 1.02-1.08]; risk difference [RD] at 10 years of age, 0.09% [95% CI, −0.01% to 0.20%]), ADHD (HR, 1.07 [95% CI, 1.05-1.10]; RD, 0.21% [95% CI, 0.08%-0.34%]), and intellectual disability (HR, 1.05 [95% CI, 1.00-1.10]; RD, 0.04% [95% CI, −0.04% to 0.12%]). To address unobserved confounding, matched full sibling pairs were also analyzed. Sibling control analyses found no evidence that acetaminophen use during pregnancy was associated with autism (HR, 0.98 [95% CI, 0.93-1.04]; RD, 0.02% [95% CI, −0.14% to 0.18%]), ADHD (HR, 0.98 [95% CI, 0.94-1.02]; RD, −0.02% [95% CI, −0.21% to 0.15%]), or intellectual disability (HR, 1.01 [95% CI, 0.92-1.10]; RD, 0% [95% CI, −0.10% to 0.13%]). Similarly, there was no evidence of a dose-response pattern in sibling control analyses. For example, for autism, compared with no use of acetaminophen, persons with low (<25th percentile), medium (25th-75th percentile), and high (>75th percentile) mean daily acetaminophen use had HRs of 0.85, 0.96, and 0.88, respectively. Conclusions and Relevance: Acetaminophen use during pregnancy was not associated with children's risk of autism, ADHD, or intellectual disability in sibling control analysis. This suggests that associations observed in other models may have been attributable to familial confounding. This nationwide cohort study with sibling control analysis examines the association of acetaminophen use during pregnancy with children's risk of autism, ADHD, and intellectual disability. [ABSTRACT FROM AUTHOR]

Objective: To investigate the associations between low education and risk of mental disorders, substance use disorders and self‐harm in different age‐groups. Methods: All subjects in Stockholm born between 1931 and 1990 were linked to their own or their parent's highest education in 2000 and followed‐up for these disorders in health care registers 2001–2016. Subjects were stratified into four age‐groups: 10–18, 19–27, 28–50, and 51–70 years. Hazard Ratios with 95% Confidence Intervals (CIs) were estimated with Cox proportional hazard models. Results: Low education increased the risk of substance use disorders and self‐harm in all age‐groups. Males aged 10–18 with low education had increased risks of ADHD and conduct disorders, and females a decreased risk of anorexia, bulimia and autism. Those aged 19–27 years had increased risks of anxiety and depression, and those aged 28–50 had increased risks of all mental disorders except anorexia and bulimia in males with Hazard Ratios ranging from 1.2 (95% CIs 1.0–1.3) for bipolar disorder to 5.4 (95% CIs 5.1–5.7) for drug use disorder. Females aged 51–70 years had increased risks of schizophrenia and autism. Conclusion: Low education is associated with risk of most mental disorders, substance use disorders and self‐harm in all age‐groups, but especially among those aged 28–50 years. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether patients with clozapine treatment are at an increased risk of a more severe COVID‐19 infection as compared with patients on other antipsychotic drugs. Methods: In this register‐based cohort study, all residents (age 18 or older) in the Stockholm Region with a psychotic disorder diagnosis and antipsychotic treatment were included (N = 8 233) and followed from 1 March 2020 to 14 January 2021. The exposure was defined as clozapine treatment and the outcome measures (indicating a more severe COVID‐19 infection) were: inpatient care, care within intensive care unit or death due to COVID‐19 infection. Differences in outcome rates between exposed (n = 966) and unexposed (other antipsychotics; n = 7 267) were examined using Cox proportional hazards models and expressed as hazard ratios (HR) with 95% confidence intervals (CI). Results: No statistically significant differences in outcome rates were found between the two groups of patients after adjusting for age, sex and residence in retirement homes. The adjusted HR for the exposed compared to the unexposed was 0.96 (95% CI: 0.54, 1.70) for inpatient care; 1.69 (0.48, 5.93) for care in intensive care unit (ICU); and 0.86 (0.26, 2.80) for death. Regarding inpatient care, additional adjusting for country of birth, living in socioeconomically vulnerable areas, number of care visits during the previous year, and comorbid medical illnesses did not alter the results. Conclusions: Our results may add support to the present guidelines, recommending sustained clozapine treatment during the current COVID‐19 pandemic with careful monitoring and readiness to alter drug doses as needed. [ABSTRACT FROM AUTHOR]

Objective: To determine whether parenthood among 25‐ to 44‐year‐olds is associated with a lower suicide rate in men and women in Sweden, and whether this is explained by selection into parenthood. Methods: In total, 1,582,360 Swedish women and men, born between 1967 and 1985, and childless at their 25th birthday, were followed from 1992 to 2011. All data originated from linkage to national Swedish registers. Cox regression models were used with time‐varying parenthood status to estimate adjusted hazard ratios and 95% confidence intervals (aHR;CI) for suicide. Results: Having one, two, three or more children was associated with 64%, 79% and 78% lower suicide rate, respectively, compared with having no children, in models with basic adjustments. When a wide range of indicators of selection into parenthood were taken into account, the suicide rate was 58% lower in parents with one child and 70% lower in parents with two or more children compared with childless individuals (aHR 0.42 [95% CI 0.36‐0.48]; 0.30 [95% CI 0.25‐0.35]; 0.30 [95% CI 0.21‐0.42]). In fathers with one, two, three or more children suicide rate was 54%, 64% and 59% lower, respectively, compared with non‐fathers whereas in mothers was 70%, 83% and 93% lower, respectively, compared with non‐mothers. Conclusion: Parenthood among 25‐to 44‐year‐olds is associated with a lower suicide risk in both men and women but to a larger extent among women, and particularly in parents with two or more children. Although selection into parenthood is possible, a protective effect of parenthood on suicide is likely in both men and women. [ABSTRACT FROM AUTHOR]

Background: It has been hypothesised that refugees have an increased risk of suicide.Aims: To investigate whether risk of suicide is higher among refugees compared with non-refugee migrants from the same areas of origin and with the Swedish-born population, and to examine whether suicide rates among migrants converge to the Swedish-born population over time.Method: A population-based cohort design using linked national registers to follow 1 457 898 people born between 1 January 1970 and 31 December 1984, classified by migrant status as refugees, non-refugee migrants or Swedish-born. Participants were followed from their 16th birthday or date of arrival in Sweden until death, emigration or 31 December 2015, whichever came first. Cox regression models estimated adjusted hazard ratios for suicide by migrant status, controlling for age, gender, region of origin and income.Results: There were no significant differences in suicide risk between refugee and non-refugee migrants (hazard ratio 1.28, 95% CI 0.93-1.76) and both groups had a lower risk of suicide than Swedish born. During their first 5 years in Sweden no migrants died by suicide; however, after 21-31 years their suicide risk was equivalent to the Swedish-born population (hazard ratio 0.94, 95% CI 0.79-1.22). After adjustment for income this risk was significantly lower for migrants than the Swedish-born population.Conclusions: Being a refugee was not an additional risk factor for suicide. Our findings regarding temporal changes in suicide risk suggest that acculturation and socioeconomic deprivation may account for a convergence of suicide risk between migrants and the host population over time.Declaration Of Interest: None. [ABSTRACT FROM AUTHOR]