Association Between Smoking and Hypertension in Pregnancy Among Japanese Women: A Meta-analysis of Birth Cohort Studies in the Japan Birth Cohort Consortium (JBiCC) and JECS.

BACKGROUND: Recent literature suggest the effect of maternal smoking on risk of hypertensive disorders in pregnancy (HDP) and preeclampsia may differ by ethnicity; however, studies on Asians are limited. METHODS: We investigated the association of maternal smoking with HDP and preeclampsia using a common analysis protocol to analyze the association in six birth cohorts participating in a Japanese consortium of birth cohorts (JBiCC). Results were compared with-published results from cohorts not included in this consortium, and, where possible, we produced a meta-analysis including these studies. RESULTS: Meta-analysis of four cohort studies including 28,219 participants produced an odds ratio (OR) of 1.24 (95% confidence interval [CI], 0.88-1.87) for the effect of smoking beyond early pregnancy compared to women who did not smoke during pregnancy. These results combined with those from the Japan Environment and Children's Study (JECS) yielded an OR of 1.19 (95% CI, 1.00-1.43, P = 0.056). Meta-analysis results for categories of smoking volume were insignificant, but when combined with JECS yielded an OR of 0.86 (95% CI, 0.65-1.12) for smoking 1-4 cigarettes, 1.25 (95% CI, 0.98-1.60) for smoking 5-9 cigarettes, and 1.27 (95% CI, 1.04-1.54) for smoking 10 or more cigarettes per day. All effects were insignificant for preeclampsia. CONCLUSION: Our results suggest that the protective effects of smoking longer and smoking more on HDP and preeclampsia repeatedly observed among Europeans and North Americans likely do not hold for the Japanese.

Sex differences in neurodevelopmental trajectories in children with different levels of autistic traits.

AIM: Little is known about early manifestations of autism spectrum disorders (ASD) in females, including those who may be overlooked by the current diagnostic criteria. We longitudinally explored sex differences in the trajectories of cognitive and motor functions and adaptive behaviors in children with different levels of autistic traits. METHODS: The participants were 824 children from the Hamamatsu Birth Cohort for Mothers and Children (HBC Study), Japan, who were classified into three autistic trait groups-low, moderate, and high-based on the Social Responsiveness Scale-Second Edition. Cognitive and motor functions were measured at seven time-points from 0.5 to 3.5 years of age using the Mullen Scales of Early Learning. Adaptive behaviors were measured at five time-points from 2.7 to 9 years of age using the Vineland Adaptive Behavior Scales-Second Edition. Trajectories were depicted using latent growth curve modeling. RESULTS: Sex-specific trajectories were observed in the high-autistic-trait group, with only males showing a temporary decline in expressive language around the age of 2 years and a slight improvement thereafter. They also showed a slight improvement around 3 years in the adaptive behavior communication domain but a gradual downward trend later. Females in the high-autistic-trait group showed no distinct manifestation before the age of 3 years but showed a downward trend after 3.5 years in the adaptive behavior communication domain. CONCLUSION: Females and males with higher autistic traits than their same-sex peers, independent of clinical diagnosis, may have different phenotypes in certain neurodevelopmental domains during infancy and early childhood.

Early temperament as a predictor of language skills at 40 months.

BACKGROUND: Mastering language involves the development of expressive and receptive skills among children. While it has been speculated that early temperament plays a role in the acquisition of language, the actual mechanism has not yet been explored. We investigated whether temperament at 18 months predicted expressive or receptive language skills at 40 months. METHODS: A representative sample of 901 children and their mothers who were enrolled and followed-up longitudinally in the Hamamatsu Birth Cohort for Mothers and Children study was included in the analysis. Child temperament was measured at 18 months using the Japanese version of the Early Childhood Behavior Questionnaire. Expressive and receptive language skills were measured at 40 months using the Mullen Scales of Early Learning. RESULTS: The multiple regression analysis, adjusting for potential confounders, suggested that higher motor activation (fidgeting) at 18 months was associated with lower expressive and receptive language skills at 40 months. Higher perceptual sensitivity was associated with higher expressive and receptive language skills at 40 months. CONCLUSIONS: Specific temperament at 18 months of age predicted the development of the child's expressive and receptive language skills at 40 months.

Elevated risk of attention deficit hyperactivity disorder (ADHD) in Japanese children with higher genetic susceptibility to ADHD with a birth weight under 2000 g.

BACKGROUND: Both genetic and pre- and perinatal factors, including birth weight, have been implicated in the onset of attention deficit hyperactivity disorder (ADHD) traits among children. This study aimed to elucidate to what extent the genetic risk of ADHD moderates the association between birth weight and ADHD traits among Japanese children. METHODS: We conducted a longitudinal birth cohort study (Hamamatsu Birth Cohort for Mother and Children Study) to investigate the association of genetic risk for ADHD and low birth weight with ADHD traits among Japanese children. Out of 1258 children, we included 796 who completed follow-ups at 8 to 9 years of age. Birth weight was categorized as <2000 g, 2000-2499 g, and ≥2500 g. Polygenic risk score for ADHD was generated using the summary data of a large-scale genome-wide association study. The Rating Scale IV (ADHD-RS) assessed ADHD traits (inattention and hyperactivity/impulsivity) based on parental reports. Following previous studies, sex, birth order of the child, gestational age at birth, mother's age at delivery, educational attainment, pre-pregnancy body mass index, pre-pregnancy or during pregnancy smoking status, alcohol consumption during pregnancy, father's age, education, and annual family income were considered as covariates. Multivariable negative binomial regression was applied to evaluate the association between birth weight and ADHD traits, while adjusting for potential covariates. The interaction term between birth weight categories and binary polygenic risk was added to the model. RESULTS: Birth weight of 2000-2499 g was not associated with ADHD traits. Birth weight under 2000 g was significantly associated with both inattention and hyperactivity. When accounting for higher and lower genetic risk for ADHD, only those with higher genetic risk and birth weight < 2000 g were associated with inattention (rate ratio [RR] 1.56, 95% CI 1.07-2.27) and hyperactivity (RR 1.87, 95% CI 1.14-3.06). CONCLUSIONS: Birth weight under 2000 g, together with the genetic risk of ADHD, contributes to higher levels of ADHD traits among Japanese children aged 8 to 9 years. The suggested association between low birth weight and ADHD is confined to children with a genetic susceptibility to ADHD, indicating the relevance of genetic-environmental interactions in the etiology.

Altered growth trajectory in children born to mothers with gestational diabetes mellitus and preeclampsia.

PURPOSE: Gestational diabetes mellitus (GDM) and preeclampsia are leading causes of mortality and morbidity in mothers and children. High childhood body mass index (BMI) is among their myriad of negative outcomes. However, little is known about the trajectory of the child BMI exposed to GDM and co-occurring preeclampsia from early to mid-childhood. This study examined the independent and joint impact of GDM and preeclampsia on childhood BMI trajectory. METHODS: A population-based sample of 356 mothers were recruited from OB/GYN clinics in New York. Their children were then followed annually from 18 to 72 months. Maternal GDM and preeclampsia status were obtained from medical records. Child BMI was calculated based on their height and weight at annual visits. RESULTS: Hierarchical Linear Modeling was used to evaluate the trajectories of child BMI exposed to GDM and preeclampsia. BMI trajectory by GDM decreased (t ratio = - 2.24, [Formula: see text]0.45, 95% CI - 0.05-0.95, p = 0.07), but the trajectory by preeclampsia increased over time (t ratio = 3.153,[Formula: see text]0.65, 95% CI 0.11-1.18, p = 0.002). Moreover, there was a significant interaction between the two (t ratio = -2.24, [Formula: see text]- 1.244, 95% CI 0.15-2.33, p = 0.02), such that the BMI of children born to mothers with both GDM and preeclampsia showed consistent increases over time. CONCLUSIONS: GDM and preeclampsia could be used as a marker for childhood obesity risk and the identification of a high-risk group, providing potential early intervention. These findings highlight the importance of managing obstetric complications, as an effective method of child obesity prevention.

Neurodevelopmental Trajectory During Infancy and Diagnosis of Autism Spectrum Disorder as an Outcome at 32 Months of Age.

BACKGROUND: Little is known about the extent to which neurodevelopmental trajectories in infancy predict a later diagnosis of autism spectrum disorder (ASD). METHODS: We investigated the association between the neurodevelopmental trajectory classes identified using a latent class growth analysis and the distal clinical outcome. Participants included 952 infants from the Hamamatsu Birth Cohort for Mothers and Children (HBC study). Neurodevelopment was measured using the Mullen Scales of Early Learning, which contains five subscales (gross motor, fine motor, visual reception, receptive language, and expressive language), at seven time points from 1 to 24 months of age. ASD was diagnosed in 3.1% of the children at 32 months of age. The clinical outcome was included in our analysis model. RESULTS: Five neurodevelopmental classes were identified: high normal (11.5%), normal (49.2%), low normal (21.2%), delayed (14.1%), and markedly delayed (4.0%). The probability of a diagnosis of ASD in the markedly delayed class was highest (32.6%) when compared with the other classes. The probabilities of receiving a diagnosis of ASD in the delayed and low normal classes were 6.4% and 4.0%, respectively, whereas the probabilities in the normal and high normal classes were both 0%. CONCLUSIONS: A diagnosis of ASD may be predicted by the neurodevelopmental trajectories during infancy, which can be evaluated both routinely and objectively in clinical settings. In this representative population, children diagnosed with ASD showed early signs in neurodevelopmental domains during the first 2 years of life.

Reliability and validity of the Japan Ijime Scale and estimated prevalence of bullying among fourth through ninth graders: A large-scale school-based survey.

AIM: The present study aimed at developing a novel scale, the Japan Ijime Scale (JaIS), to measure bullying in Japan with substantial reliability and validity, with which we estimated the prevalence of bullying among children and adolescents of school age. METHODS: The JaIS is a self-report questionnaire and consists of three parts: subscales measuring victimization and witnessing, and an item measuring perpetration. To test the reliability and validity of the two subscales, the authors analyzed responses to the JaIS from 2334 school students (Grades 4-9) in six elementary and three junior high schools in a middle-sized industrial city in central Japan, using exploratory factor analysis, item response theory, and examination of the external validity of the items. The prevalence of bullying victimization, witnessing, and perpetration was estimated. RESULTS: Item response theory models revealed that both the Victimization and Witness subscales have sufficient discrimination power and measurement precision, and the external validity of each scale has been confirmed. Using the JaIS, we found that 35.8% of students had been victims of bullying every 2-3 months (27.6% were solely victims and 8.3% were bully/victims), 32.8% had witnessed some type of bullying act, and 11.8% had perpetrated some type of bullying (3.5% as perpetrators, and 8.3% as bully/victims). CONCLUSION: The JaIS is a reliable and valid measure. Using this scale, we found a high prevalence of bullying victimization in Japanese schools.

Does maternal postpartum depression affect children's developmental outcomes?

AIM: The etiology of maternal postpartum depression (PPD) remains inconclusive, and there is no consensus concerning whether maternal PPD affects children's developmental outcomes. Consequently, in this literature review, we examined whether maternal PPD affects children's physical, neuromotor, language and general cognitive development. METHODS: We conducted an electronic search using PubMed to select case-control and cohort studies that addressed maternal depression, depressive episodes or depressive symptoms among postpartum (within 6 months) women. We omitted studies that focused on a specific population (e.g. preterm infants). RESULTS: The methodological problems of prior studies indicate that their findings must be interpreted with caution. Insufficient and or inconsistent evidence has supported associations between maternal PPD and children's developmental trajectories. Nevertheless, some key studies have revealed findings that require further analysis, including the associations between maternal PPD and children's stunted growth/being underweight in developed countries, the slight delay in children's fine motor development, and in children's language development. CONCLUSION: Although several studies have investigated the longstanding effects of maternal PPD on children's physical and neurodevelopment, no conclusive evidence has elucidated a relationship between maternal PPD and all four domains of child development - physical, neuromotor, language and general cognitive ability. Therefore, large-scale, longitudinal studies with a long-term follow-up period - extending to school age and beyond - are needed. Moreover, confounding factors should be carefully considered. Specifically, household income, parental education, breastfeeding, bonding/attachment and paternal mental health may be associated with maternal mental health and children's neurodevelopment.

Influence of in utero exposure to maternal depression and natural disaster-related stress on infant temperament at 6 months: The children of Superstorm Sandy.

This study examined the effects of in utero exposure to maternal depression and Superstorm Sandy, a hurricane that hit metropolitan New York in 2012, on infant temperament at 6 months. Temperament was assessed using the Infant Behavior Questionnaire-Revised. Maternal depression was measured by the Edinburgh Postnatal Depression Scale. The main effects and the interaction of maternal depression and Sandy exposure on infant temperament were examined using a multivariable generalized linear model. Results show that prenatal maternal depression was associated with lower emotion regulation and greater distress. Stratification and interaction analyses suggested that the adverse effects of prenatal maternal depression on problematic temperament were amplified by in utero Sandy exposure. This study underscores the importance of providing prenatal screening and treatment for maternal depression during pregnancy while also identifying high-risk families who may have suffered from disaster-related traumas to provide necessary services. As the frequency of natural disasters may increase due to climate change, it is important to understand the consequences of in utero stress on child development and to formulate plans for early identification.

El estudio examinó los efectos del estar expuesto in-utero a la depresión materna y a la Gran Tormenta Sandy, un huracán que afectó el área metropolitana de Nueva York en 2012, sobre el temperamento del infante a los 6 meses. Se evaluó el temperamento usando el Revisado Cuestionario de Conducta del Infante. La depresión materna fue medida por medio de la Escala de Depresión Posnatal de Edinburgh. Los principales efectos y la interacción de la depresión materna y el estar expuesto a Sandy sobre el temperamento del infante se examinaron usando el Modelo Lineal General de Variables Múltiples. Los resultados muestran que la depresión materna prenatal se asoció con una más baja regulación de la emoción y una mayor angustia. Los análisis de estratificación e interacción sugirieron que los efectos adversos de la depresión materna prenatal sobre el temperamento problemático se ampliaron por el hecho de haber estado expuesto a Sandy in-utero. El estudio subraya la importancia de proveer examen y tratamiento prenatal para la depresión materna durante el embarazo, mientras simultáneamente se identifican las familias bajo alto riesgo que pudieran haber sufrido de traumas relacionados con desastres con el fin de proveer los servicios necesarios. Ya que la frecuencia de desastres naturales pudiera aumentar debido a los cambios climáticos, es importante comprender las consecuencias que el estrés in-utero tiene sobre el desarrollo del niño y formular planes para la temprana identificación.

Cette étude a examiné les effets de l'exposition à la dépression maternelle et à la grande tempête Sandy in-utero sur le tempérament du bébé à 6 mois, la tempête Sandy ayant été un cyclone ayant frappé la ville de New York aux Etats-Unis en 2012. Le tempérament a été évalué en utilisant le Questionnaire Révisé du Comportement du Nourrisson. La dépression maternelle a été mesurée au moyen d'Echelle de Dépression Postnatale d'Edinburgh. Les principaux effets et l'interaction de la dépression maternelle et l'exposition à Sandy sur le tempérament du bébé ont été examinés en utilisant un Modèle Général de Linéarité (MGL). Les résultats montrent que la dépression maternelle prénatale est liée à une émotion-régulation moindre et à une plus grande détresse. Les analyses de stratification et d'interaction suggèrent que les effets adverses de la dépression maternelle prénatale sur un tempérament problématique ont été amplifiés par l'exposition à Sandy in-utero. Cette étude souligne l'importance qu'il y a d'offrir un dépistage et un traitement pour la dépression maternelle durant la grossesse, tout en identifiant simultanément les familles à haut risque qui peuvent avoir souffert de traumatismes liés à des désastres naturels de façon à offrir des services nécessaires. Comme la fréquence des catastrophes naturelles peut augmenter avec le changement climatique il est important de comprendre les conséquences du stress in-utero sur le développement de l'enfant et de formuler des plans d'identification précoce.

Birth Cohort Consortium of Asia: Current and Future Perspectives.

BACKGROUND: The environmental health of children is one of the great global health concerns. Exposures in utero and throughout development can have major consequences on later health. However, environmental risks or disease burdens vary from region to region. Birth cohort studies are ideal for investigating different environmental risks. METHODS: The principal investigators of three birth cohorts in Asia including the Taiwan Birth Panel Study (TBPS), the Mothers and Children's Environmental Health Study (MOCEH), and the Hokkaido Study on Environment and Children' Health (Hokkaido Study) coestablished the Birth Cohort Consortium of Asia (BiCCA) in 2011. Through a series of five PI meetings, the enrolment criteria, aim of the consortium, and a first-phase inventory were confirmed. RESULTS: To date, 23 birth cohorts have been established in 10 Asian countries, consisting of approximately 70,000 study subjects in the BiCCA. This article provides the study framework, environmental exposure and health outcome assessments, as well as maternal and infant characteristics of the participating cohorts. CONCLUSIONS: The BiCCA provides a unique and reliable source of birth cohort information in Asian countries. Further scientific cooperation is ongoing to identify specific regional environmental threats and improve the health of children in Asia.

Zinc finger protein 804A (ZNF804A) and verbal deficits in individuals with autism.

BACKGROUND: In a genome-wide association study of autism, zinc finger protein 804A (ZNF804A) single nucleotide polymorphisms (SNPs) were found to be nominally associated in verbally deficient individuals with autism. Zinc finger protein 804A copy number variations (CNVs) have also been observed in individuals with autism. In addition, ZNF804A is known to be involved in theory of mind (ToM) tasks, and ToM deficits are deemed responsible for the communication and social challenges faced by individuals with autism. We hypothesized that ZNF804A could be a risk gene for autism. METHODS: We examined the genetic association and CNVs of ZNF804A in 841 families in which 1 or more members had autism. We compared the expression of ZNF804A in the postmortem brains of individuals with autism (n = 8) and controls (n = 13). We also assessed in vitro the effect of ZNF804A silencing on the expression of several genes known to be involved in verbal efficiency and social cognition. RESULTS: We found that rs7603001 was nominally associated with autism (p = 0.018). The association was stronger (p = 0.008) in the families of individuals with autism who were verbally deficient (n = 761 families). We observed ZNF804A CNVs in 7 verbally deficient boys with autism. In ZNF804A knockdown cells, the expression of synaptosomal-associated protein, 25kDa (SNAP25) was reduced compared with controls (p = 0.009). The expression of ZNF804A (p = 0.009) and SNAP25 (p = 0.009) were reduced in the anterior cingulate gyrus (ACG) of individuals with autism. There was a strong positive correlation between the expression of ZNF804A and SNAP25 in the ACG (p < 0.001). LIMITATIONS: Study limitations include our small sample size of postmortem brains. CONCLUSION: Our results suggest that ZNF804A could be a potential candidate gene mediating the intermediate phenotypes associated with verbal traits in individuals with autism.

Comparison between placental gene expression of 11ß-hydroxysteroid dehydrogenases and infantile growth at 10 months of age.

AIM: The local expression of two isoenzymes of 11ß-hydroxysteroid dehydrogenase, type 1 (11ßHSD-1) and type 2 (11ßHSD-2), regulates the access of glucocorticoid hormones to their target cells. Reports on the association between the placental expression of 11ßHSD and infantile growth are limited. The aim of the present study was to investigate if the placental gene expression of 11ßHSD affects infantile growth at 10 months of age. METHODS: Placentas and umbilical venous cord blood were obtained from 42 singleton cases of cesarean deliveries between 31 and 40 weeks of gestation at Hamamatsu University Hospital between March 2009 and June 2010. The gene expression of both 11ßHSD-1 and 11ßHSD-2 was measured by quantitative reverse transcription polymerase chain reaction. Adiponectin and leptin levels in umbilical cord blood were measured using enzyme-linked immunoassay. RESULTS: 11ßHSD-1 and 11ßHSD-2 gene expression in human placentas did not correlate with bodyweight or the ponderal index (PI) at 10 months of age, whereas the gene expression of 11ßHSD-1, but not 11ßHSD-2, correlated with birthweight as well as PI at birth. Adiponectin levels in umbilical cord blood significantly correlated with the placental gene expression of 11ßHSD-1 as well as bodyweight and PI at 10 months of age, although no direct correlation was observed between them. CONCLUSION: No direct correlation was observed between the placental gene expression of 11ßHSD and infantile growth at 10 months of age. However, the placental gene expression of 11ßHSD-1 may be indirectly connected with infantile growth via adiponectin-associated metabolic regulation represented by adiponectin levels in umbilical cord blood.

Interleukin-23 levels in umbilical cord blood are associated with neurodevelopmental trajectories in infancy.

Our previous study, which aimed to understand the early neurodevelopmental trajectories of children with and without neurodevelopmental disorders, identified five classes of early neurodevelopmental trajectories, categorized as high normal, normal, low normal, delayed, and markedly delayed. This investigation involved measurement using the Mullen Scale of Early Learning in a representative sample of Japanese infants followed up from the age of 0 to 2 years (Nishimura et al., 2016). In the present study, we investigated the potential association between cytokine concentrations in umbilical cord serum with any of the five classes of neurodevelopmental trajectories previously assigned, as follows: high normal (N = 85, 13.0%), normal (N = 322, 49.1%), low normal (N = 137, 20.9%), delayed (N = 87, 13.3%), and markedly delayed (N = 25, 3.8%) in infancy. Decreased interleukin (IL)-23 levels in the cord blood were associated with the markedly delayed class, independent of potential confounders (odds ratio, 0.44; 95%confidence interval: 0.26-0.73). Furthermore, IL-23 levels decreased as the developmental trajectory became more delayed, demonstrating that IL-23 plays an important role in development, and is useful for predicting the developmental trajectory at birth.

Fine Motor Skills, a Surrogate of Motor Planning Ability, at Age 2 Predict Social Skills at Age 6.

OBJECTIVES: Motor planning is the cognitive process of planning necessary steps for achieving a purposeful movement and is specifically reflected through object manipulation. This study aimed to investigate whether fine motor skills, a surrogate of the motor planning ability of object manipulation, in early childhood are associated with later social skills, in a general-population birth cohort. METHODS: A total of 913 children, participating in the Hamamatsu Birth Cohort for Mothers and Children, were enrolled. Social skills were measured using the Vineland Adaptive Behavior Scales-II, Socialization domain, at age 6 years. Fine motor skills were measured using the Mullen Scales of Early Learning at 14, 24, and 32 months. The associations between fine motor skills at ages 14, 24, and 32 months and social skills at age 6 years were tested separately through multivariable linear regression after adjusting for covariates, including gross motor and language skills at the contemporaneous age, autistic symptoms at age 6 years, and demographic factors. RESULTS: Fine motor skills at 24 and 32 months were significantly associated with social skills at age 6 years (at 24 months: nonstandardized regression coefficient = 1.38 [95% CI, 0.50-2.26], p = 0.002; at 32 months: 1.47 [0.56-2.38], p = 0.001). CONCLUSION: Fine motor skills in early childhood predicted social skills at age 6 years, indicating an association between the complex motor planning ability of object manipulation and later social skills. Children who demonstrate fine motor delay at as early an age as 2 years should be closely monitored by child professionals.

The Population-Attributable Fractions of Small-for-Gestational-Age Births: Results from the Japan Birth Cohort Consortium.

A fetal growth restriction is related to adverse child outcomes. We investigated risk ratios and population-attributable fractions (PAF) of small-for-gestational-age (SGA) infants in the Japanese population. Among 28,838 infants from five ongoing prospective birth cohort studies under the Japan Birth Cohort Consortium, two-stage individual-participant data meta-analyses were conducted to calculate risk ratios and PAFs for SGA in advanced maternal age, pre-pregnancy underweight, and smoking and alcohol consumption during pregnancy. Risk ratio was calculated using modified Poisson analyses with robust variance and PAF was calculated in each cohort, following common analyses protocols. Then, results from each cohort study were combined by meta-analyses using random-effects models to obtain the overall estimate for the Japanese population. In this meta-analysis, an increased risk (risk ratio, [95% confidence interval of SGA]) was significantly associated with pre-pregnancy underweight (1.72 [1.42-2.09]), gestational weight gain (1.95 [1.61-2.38]), and continued smoking during pregnancy (1.59 [1.01-2.50]). PAF of underweight, inadequate gestational weight gain, and continued smoking during pregnancy was 10.0% [4.6-15.1%], 31.4% [22.1-39.6%], and 3.2% [-4.8-10.5%], respectively. In conclusion, maternal weight status was a major contributor to SGA births in Japan. Improving maternal weight status should be prioritized to prevent fetal growth restriction.

Cultural diversity in physical diseases among patients with mental illnesses.

OBJECTIVE: People with psychiatric diseases have a severely increased risk for physical morbidity and premature death from physical diseases. The aims of the study were to investigate the occurrence of cardiovascular diseases (CVD), diabetes (DM) and obesity in schizophrenia and depression in three different geographical areas - Asia (Japan), Africa (Nigeria) and Western Europe (Switzerland, Germany and Denmark) - and to search for possible transcultural differences in these correlations, which would also reflect the differences between low-income areas in Africa (Nigeria) and high-income areas in Europe and Japan. METHOD: Patients with International Classification of Diseases (ICD-10) F2 diseases (schizophrenia spectrum disorders) and F3 diseases (affective disorders) admitted to one Nigerian, one Japanese, two Swiss, two German and six Danish centres during 1 year were included. Physical diseases in accordance with ICD-10 were also registered. Psychiatric and physical comorbidity were calculated and standardized rate ratio incidences of background populations were our primary measures. RESULTS: Incidence rate ratios were increased for both CVD, DM and overweight in both F2 and F3 in all cultures (Western Europe, Nigeria and Japan) within the same ranges (however, the Japanese results should be interpreted conservatively owing to the limited sample size). Overweight among the mentally ill were marked in Nigeria. A parallelism of the incidence of overweight, CVD and diabetes with the occurrence in background populations was seen and was most marked in overweight. CONCLUSIONS: Overweight, CVD and DM were increased in schizophrenia spectrum disorders and affective disorders in all three cultures investigated (Western Europe, Nigeria and Japan). Lifestyle diseases were also seen in Nigeria and Japan. The results from this study indicate that cultural background might be seen as an important factor in dealing with lifestyle diseases among people with a severe mental illness, as it is in the general population.

Screen Time at Age 1 Year and Communication and Problem-Solving Developmental Delay at 2 and 4 Years.

Importance: Whether some domains of child development are specifically associated with screen time and whether the association continues with age remain unknown. Objective: To examine the association between screen time exposure among children aged 1 year and 5 domains of developmental delay (communication, gross motor, fine motor, problem-solving, and personal and social skills) at age 2 and 4 years. Design, Participants, and Setting: This cohort study was conducted under the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Pregnant women at 50 obstetric clinics and hospitals in the Miyagi and Iwate prefectures in Japan were recruited into the study between July 2013 and March 2017. The information was collected prospectively, and 7097 mother-child pairs were included in the analysis. Data analysis was performed on March 20, 2023. Exposure: Four categories of screen time exposure were identified for children aged 1 year (<1, 1 to <2, 2 to <4, or ≥4 h/d). Main Outcomes and Measures: Developmental delays in the 5 domains for children aged 2 and 4 years were assessed using the Japanese version of the Ages & Stages Questionnaires, Third Edition. Each domain ranged from 0 to 60 points. Developmental delay was defined if the total score for each domain was less than 2 SDs from its mean score. Results: Of the 7097 children in this study, 3674 were boys (51.8%) and 3423 were girls (48.2%). With regard to screen time exposure per day, 3440 children (48.5%) had less than 1 hour, 2095 (29.5%) had 1 to less than 2 hours, 1272 (17.9%) had 2 to less than 4 hours, and 290 (4.1%) had 4 or more hours. Children's screen time was associated with a higher risk of developmental delay at age 2 years in the communication (odds ratio [OR], 1.61 [95% CI, 1.23-2.10] for 1 to <2 h/d; 2.04 [1.52-2.74] for 2 to <4 h/d; 4.78 [3.24-7.06] for ≥4 vs <1 h/d), fine motor (1.74 [1.09-2.79] for ≥4 vs <1 h/d), problem-solving (1.40 [1.02-1.92] for 2 to <4 h/d; 2.67 [1.72-4.14] for ≥4 vs <1 h/d), and personal and social skills (2.10 [1.39-3.18] for ≥4 vs <1 h/d) domains. Regarding risk of developmental delay at age 4 years, associations were identified in the communication (OR, 1.64 [95% CI, 1.20-2.25] for 2 to <4 h/d; 2.68 [1.68-4.27] for ≥4 vs <1 h/d) and problem-solving (1.91 [1.17-3.14] for ≥4 vs <1 h/d) domains. Conclusions and Relevance: In this study, greater screen time for children aged 1 year was associated with developmental delays in communication and problem-solving at ages 2 and 4 years. These findings suggest that domains of developmental delay should be considered separately in future discussions on screen time and child development.

Socioeconomic and education-based inequality in suspected developmental delays among Nepalese children: a subnational level assessment.

Failure to meet early childhood developmental milestones leads to difficulty in schooling and social functioning. Evidence on the inequality in the burden of developmental delays across population groups, and identification of potential risk factors for suspected developmental delays (SDD) among younger children, are essential for designing appropriate policies and programs. This study explored the level of socioeconomic and maternal education-based inequality in the prevalence of SDD among Nepalese children at subnational level and identified potential risk factors. Individual-level data from the 2019 Nepal Multiple Indicator Cluster Survey was used to estimate the prevalence of SDD among children aged 3-4 years. Regression-based slope index of inequality (SII) and relative index of inequality were used to measure the magnitude of inequality, in terms of household socioeconomic status (SES) and mother's education, in the prevalence of SDD. In addition, a multilevel logistic regression model was used to identify potential risk factors for SDD. The national prevalence of SDD was found to be 34.8%, with relatively higher prevalence among children from rural areas (40.0%) and those from Karnali Province (45.0%) followed by Madhesh province (44.2%), and Sudhurpashchim Province (40.1%). The prevalence of SDD was 32 percentage points higher (SII: -0.32) among children from the poorest households compared to their rich counterparts at the national level. At the subnational level, such inequality was found to be highest in Lumbini Province (SII = -0.47) followed by Karnali Province (SII = -0.37), and Bagmati Province (SII = -0.37). The prevalence of SDD was 36 percentage points higher (SII: -0.36) among children whose mother had no formal education compared to children of higher educated mothers. The magnitude of education-based absolute inequality in SDD was highest in Lumbini Province (SII = -0.44). Multilevel logistic regression model identified lower levels of mother's education, disadvantaged SES and childhood stunting as significant risk factors for SDD. One in each three children in Nepal may experience SDD, with relatively higher prevalence among children from rural areas. Subnational level variation in prevalence, and socioeconomic and education-based inequality in SDD highlight the urgent need for province-specific tailored interventions to promote early childhood development in Nepal.

Autism symptoms, functional impairments, and gaze fixation measured using an eye-tracker in 6-year-old children.

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder clinically characterized by abnormalities in eye contact during social exchanges. We aimed to clarify whether the amount of gaze fixation, measured at the age of 6 years using Gazefinder, which is an established eye-tracking device, is associated with ASD symptoms and functioning. Methods: The current study included 742 participants from the Hamamatsu Birth Cohort Study. Autistic symptoms were evaluated according to the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2), and the functioning of the participating children in real life was assessed using the Japanese version of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II). The Gazefinder system was used for gaze fixation rates; two areas of interest (eyes and mouth) were defined in a talking movie clip, and eye gaze positions were calculated through corneal reflection techniques. Results: The participants had an average age of 6.06 ± 0.14 years (males: 384; 52%). According to ADOS, 617 (83%) children were assessed as having none/mild ASD and 51 (7%) as severe. The average VABS-II scores were approximately 100 (standard deviation = 12). A higher gaze fixation rate on the eyes was associated with a significantly lower likelihood of the child being assigned to the severe ADOS group after controlling for covariates (odds ratio [OR], 0.02; 95% confidence interval [CI], 0.002-0.38). The gaze fixation rate on the mouth was not associated with ASD symptoms. A higher gaze fixation rate on the mouth was associated with a significantly lower likelihood of the child being assigned to the low score group in VABS-II socialization after controlling for covariates (OR, 0.18; 95% CI, 0.04-0.85). The gaze fixation rate on the eyes was not associated with functioning. Conclusion: We found that children with low gaze fixation rates on the eyes were likely to have more ASD symptoms, and children with low gaze fixation rates on the mouth were likely to demonstrate poorer functioning in socialization. Hence, preschool children could be independently assessed in the general population for clinically relevant endophenotypes predictive of ASD symptoms and functional impairments.

The association between screen time and genetic risks for neurodevelopmental disorders in children.

Whether longer screen time in infancy increases risk of neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and ADHD has long been debated, but no causal relationship between the two remains has been established. Using ongoing longitudinal cohort data, we found that in children 24 to 40 months of age, the genetic risk of ASD was associated with longer screen time and that of ADHD with an increase in screen time over time. These data suggest that prolonged screen time may not be a cause of the genetic risk for NDD, but an early sign of NDDs.