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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: The successful implementation and interpretation of machine learning (ML) models in epidemiological studies can be challenging without an extensive programming background. We provide a didactic example of machine learning for risk prediction in this study by determining whether early life factors could be useful for predicting adolescent psychopathology., Methods: In total, 9643 adolescents ages 9-10 from the Adolescent Brain and Cognitive Development (ABCD) Study were included in ML analysis to predict high Child Behavior Checklist (CBCL) scores (i.e., t-scores ≥ 60). ML models were constructed using a series of predictor combinations (prenatal, family history, sociodemographic) across 5 different algorithms. We assessed ML performance through sensitivity, specificity, F1-score, and area under the curve (AUC) metrics., Results: A total of 1267 adolescents (13.1 %) were found to have high CBCL scores. The best performing algorithms were elastic net and gradient boosted trees. The best performing elastic net models included prenatal and family history factors (Sensitivity 0.654, Specificity 0.713; AUC 0.742, F1-score 0.401) and prenatal, family, history, and sociodemographic factors (Sensitivity 0.668, Specificity 0.704; AUC 0.745, F1-score 0.402). Across all 5 ML algorithms, family history factors (e.g., either parent had nervous breakdowns, trouble holding jobs/fights/police encounters, and counseling for mental issues) and sociodemographic covariates (e.g., maternal age, child's sex, caregiver income and caregiver education) tended to be better predictors of adolescent psychopathology. The most important prenatal predictors were unplanned pregnancy, birth complications, and pregnancy complications., Conclusion: Our results suggest that inclusion of prenatal, family history, and sociodemographic factors in ML models can generate moderately accurate predictions of adolescent psychopathology. Issues associated with model overfitting, hyperparameter tuning, and system seed setting should be considered throughout model training, testing, and validation. Future early risk predictions models may improve with the inclusion of additional relevant covariates., Competing Interests: The authors declare no potential conflicts of interest., (© 2024 The Authors. Published by Elsevier Inc.)

Living kidney donors have been regarded as those people having earned the healthiest status level after having undergone scrutiny. Although one's post-donation GFR is expected to fall to 50% of their pre-donation value, it is well documented that there is a compensatory increase in GFR which subsequently reaches approximately 60-70% of the donor's pre-donation value. Data regarding gout/hyperuricemia in living kidney donors has remained scarce until now. This study involved kidney donors enrolled within the years 2000 to 2017, where those who were selected to be matched to those in group of case cohort by age, year of index date, gender and co-morbidity were considered as the control cohort. During the 17-year study period 2,716 participants were enrolled. Results revealed that kidney donors experienced a risk of new onset gout/ hyperuricemia (adjusted HR = 1.73; 95%CI = 1.27, 2.36), and new onset CKD (adjusted HR = 6.7; 95% CI = 4.4, 10.21) were found to be higher in kidney donors. Our findings suggest that people after kidney donation are significantly associated with a higher risk of new onset gout/hyperuricemia. Clinical professionals therefore need to be cautious of new onset gouy/hyperuricemia after donation surgery., (© 2024. The Author(s).)