Childhood neurodevelopmental disorders and maternal diabetes: A population-based cohort study.

AIM: To assess the risk of a wide spectrum of neurodevelopmental disorders (NDDs) in offspring of mothers with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and gestational diabetes mellitus (GDM). METHOD: This retrospective cohort study included 877 233 singletons born between 2004 and 2008 in Taiwan. Children were followed up to 2015 for diagnoses of NDDs, including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), developmental delay, intellectual disability, cerebral palsy, and epilepsy/infantile spasms using health insurance claims data. We performed Cox regression models to estimate the relative risks of NDDs associated with maternal diabetes. Covariates included parental age, year of birth, child sex, family income, urbanization level, hypertensive disorder, and preterm delivery status. RESULTS: In utero there were 338 (0.04%) children exposed to T1DM, 8749 (1.00%) to T2DM, and 90 200 (10.28%) to GDM. The effect of T1DM on NDDs was the largest, followed by T2DM, then GDM. T1DM was associated with an increased risk of developmental delay, intellectual disability, and epilepsy/intellectual spasms in offspring. T2DM was associated with an increased risk of ASD, ADHD, developmental delay, intellectual disability, cerebral palsy, and epilepsy/intellectual spasms. GDM was associated with an increased risk of ASD, ADHD, and developmental delay. INTERPRETATION: Maternal diabetes during pregnancy, including T1DM, T2DM, and GDM, is associated with an increased risk of some NDDs in offspring.

Sex differences in the diagnosis of autism spectrum disorder and effects of comorbid mental retardation and attention-deficit hyperactivity disorder.

BACKGROUND/PURPOSE: The association between sex and diagnostic behavior of autism spectrum disorder (ASD), and the effects of comorbid mental retardation (MR) and attention-deficit hyperactivity disorder (ADHD), were explored. METHODS: Based on the Taiwan Longitudinal Health Insurance Database (LHID)-2000 and data from 1996 through 2008, the cumulative incidence of ASD over time was compared between the sexes (both cohorts n = 38,117) using the log-rank test. The effects of comorbid MR and ADHD on the incidence of ASD were evaluated using Cox proportional hazard regression analysis. The age at first diagnosis of ASD in the two sexes was compared using the independent-sample t-test. RESULTS: The incidence was higher in males than in females (0.0007 vs. 0.0002) across ages. Comorbid MR or ADHD increased the incidence of ASD in both sexes; comorbid MR or ADHD also decreased the male to female hazard ratio of ASD, with no significant differences in the incidence density of ASD between sexes. ADHD delayed diagnosis in both sexes (males: 6.61 vs 5.10, p < 0.0001; females: 6.83 vs 4.69, p = 0.0037). CONCLUSION: The general concept of a higher incidence of ASD among males was noted in this study of a Taiwanese population, but disappeared in those with comorbid MR or ADHD, indicating unique vulnerabilities to MR/ADHD or under-identification of high-functioning females with ASD in childhood. Increasing the diagnostic sensitivity of ASD in those with comorbid ADHD is important due to a delayed diagnostic age in this group.

Association of rosacea with depression and anxiety: A systematic review and meta-analysis.

BACKGROUND: Rosacea is associated with several comorbidities, but its relationship with psychiatric disorders remains controversial. We aimed to investigate the association of rosacea with depression and anxiety. METHODS: A systematic review was performed of relevant observational studies in the PubMed, Web of Science, Embase, and Wanfang databases from inception to June 8, 2021. The inclusion criteria for eligible studies were observational studies comparing the incidence or prevalence of depression or anxiety between patients with rosacea and individuals without rosacea. We conducted meta-analyses with a random-effects model. The main outcome was pooled analysis of prevalence or incidence of depression and anxiety in patients with rosacea. RESULTS: We included nine studies with 101,114,209 patients with rosacea. A pooled analysis from cross-sectional and case-control studies revealed that patients with rosacea were significantly more likely to have depression (crude odds ratio [OR], 2.855; 95% confidence interval [CI], 1.258-6.481) and anxiety (crude OR, 2.373; 95% CI, 1.448-3.888) than matched controls; however, adjusted ORs showed no significant association. Furthermore, the meta-analysis from cohort studies indicated that patients with rosacea have significantly higher risks of developing depression (adjusted incidence rate ratio [IRR], 2.443; 95% CI, 1.603-3.723) and anxiety (adjusted IRR, 2.181; 95% CI, 1.660-2.864). LIMITATIONS: Data for a subgroup analysis based on different demographic factors were insufficient. CONCLUSIONS: Current findings provide more evidence that rosacea is significantly associated with depression and anxiety, and rosacea may predispose patients to develop depression and anxiety. Clinicians should be aware of the psychological aspects of rosacea.

Childhood neurodevelopmental disorders and maternal hypertensive disorder of pregnancy.

AIM: To examine the association of maternal chronic hypertension and pregnancy-induced hypertension (PIH)/preeclampsia with childhood neurodevelopmental disorders (NDDs) in a large-scale population-based cohort. METHOD: We conducted a linked Taiwan National Health Insurance Research Database cohort study of children born between 2004 and 2008 (n=877 233). Diagnoses of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), developmental delay, intellectual disability, cerebral palsy (CP), and epilepsy/infantile spasms were identified from birth to the end of 2015. Cox proportional hazards models were fitted with adjustment for potential confounders to estimate the effect of maternal hypertensive disorder of pregnancy on childhood outcomes. RESULTS: Compared with the offspring of unexposed mothers, offspring of mothers with chronic hypertension or PIH/preeclampsia exhibited increased risk of developing a wide spectrum of NDDs. Chronic hypertension was associated with increased risks of ADHD (hazard ratio 1.22, 95% confidence interval [CI] 1.13-1.​31), developmental delay (1.29, 1.21-1.38), intellectual disability (1.67, 1.43-1.95), CP (1.45, 1.14-1.85), and epilepsy/infantile spasms (1.31, 1.10-1.56) in the offspring, whereas PIH/preeclampsia was associated with increased risks of ASD (1.27, 1.12-1.43), ADHD (1.23, 1.17-1.29), developmental delay (1.29, 1.24-1.35), intellectual disability (1.53, 1.37-1.71), CP (1.44, 1.22-1.70), and epilepsy/infantile spasms (1.36, 1.22-1.52) in the offspring after adjustment for potential confounders. The co-occurrence of maternal diabetes, preterm deliveries, or fetal growth restriction further increased the risk. INTERPRETATION: Chronic hypertension or PIH/preeclampsia seems to be sufficient to increase the risk of childhood NDDs. What this paper adds Children exposed to maternal hypertensive disorders have a higher cumulative incidence of neurodevelopmental disorders (NDDs) than unexposed children. Chronic hypertension or pregnancy-induced hypertension/preeclampsia seems to be sufficient to increase the risk of childhood NDDs. Co-occurrence of maternal diabetes, preterm deliveries, or fetal growth restriction further increases the risk.

Parental Socioeconomic Status and Autism Spectrum Disorder in Offspring: A Population-Based Cohort Study in Taiwan.

Studies from the United States have shown increasing incidence of autism spectrum disorder (ASD) with increasing socioeconomic status (SES), whereas in Scandinavian countries, no such relation was identified. We investigated how ASD risk in offspring varied according to parental SES in Taiwan, where there is universal health care. Through linking birth reporting data and data from Taiwan's national health insurance program, we studied 706,111 singleton births from 2004 to 2007 and followed them until 2015. Parental SES was determined by monthly salary at the time of childbirth, and child neuropsychiatric outcomes were defined using International Classification of Diseases codes. We identified 7,323 ASD cases and 7,438 intellectual disability (ID) cases; 17% of ASD cases had co-occurring ID. In multivariable Cox regression analysis, higher SES was independently associated with higher risk of ASD after we took into account urbanization levels, child sex, parental age, and other covariates. By contrast, higher SES was independently associated with lower risk of ID. Besides the SES disparity in ASD case ascertainment and in the access to health care, findings from Taiwan suggest that other social, environmental, biological, and immunological factors linked with parental SES levels may contribute to the positive relation of SES and ASD risk.

Plasma oxytocin levels in major depressive and bipolar II disorders.

Oxytocin may play a role in mood regulation. Research has shown the plasma oxytocin level of patients with bipolar I disorder (BD I) during a manic episode was significantly higher than that of BD I patients of other statuses, and also that of healthy subjects. However, whether or not a difference in the level of oxytocin exists between patients with major depressive disorder (MDD) and those with BD II is unclear. This study aimed to investigate the plasma oxytocin levels in MDD and BD II patients in a depressive episode. 119 healthy controls, 135 BD II patients, and 97 MDD patients were enrolled. All of the BD II and MDD patients were drug-naïve, with baseline depressive status 17-item Hamilton Depression Rating Scale scores >15. The plasma oxytocin level of the BD II patients was significantly higher than that of the MDD patients and controls at baseline. After treatment, the plasma oxytocin level of the BD II patients increased significantly; however, in the MDD group, the oxytocin level decreased slightly after treatment. Our findings suggested more significant plasma oxytocin dysregulation in the patients in the BD II group than in the MDD patients and controls, both before and after treatment.

The effect of lower body stabilization and different writing tools on writing biomechanics in children with cerebral palsy.

A high percentage of children with cerebral palsy (CP) have difficulty keeping up with the handwriting demands at school. Previous studies have addressed the effects of proper sitting and writing tool on writing performance, but less on body biomechanics. The aim of this study was to investigate the influence of lower body stabilization and pencil design on body biomechanics in children with CP. Fourteen children (12.31±4.13 years old) with CP were recruited for this study. A crossover repeated measures design was employed, with two independent variables: lower body stabilization (with/without) and pencil (regular/assigned grip height/biaxial). The writing task was to trace the Archimedean spiral mazes. Electromyography (EMG) of the upper extremity, the wrist flexion/extension movements, and the whole body photography were recorded to quantify the changes in posture and upper extremity biomechanics. Two-way repeated measures ANOVA was used for statistical analysis. No significant main effects were revealed in the EMG and wrist kinematics. The lower body stabilization significantly decreased the trunk lateral and forward deviations, and the visual focus-vertical angle. The biaxial pencil and the assigned grip height design significantly decreased the head, shoulder, trunk, and pelvic deviations compared with the regular design. The results indicated that the lower body positioning was effective in improving the trunk posture. A pencil with an assigned grip height or with a biaxial design could improve head, shoulder, trunk and pelvic alignment, but did not influence the muscle exertion of the upper extremity. This study could provide guidelines for parents, teachers and clinicians regarding the selection of writing tools and the knowledge of proper positioning for the children with handwriting difficulties. Further analyses can focus on the design, modification and clinical application of assitive sitting and writing devices for the use in children with handwriting difficulties.