Arachidonic acid-derived dihydroxy fatty acids in neonatal cord blood relate symptoms of autism spectrum disorders and social adaptive functioning: Hamamatsu Birth Cohort for Mothers and Children (HBC Study).

AIM: Autism spectrum disorder (ASD) is associated with abnormal lipid metabolism, such as a high total ratio of omega-6 to omega-3 in polyunsaturated fatty acids (PUFAs). PUFAs are metabolized to epoxy fatty acids by cytochrome P450 (CYP); then, dihydroxy fatty acid is produced by soluble epoxide hydrolase. This study examined the association between PUFA metabolites in the cord blood and ASD symptoms and adaptive functioning in children. METHODS: This prospective cohort study utilized cord blood to quantify PUFA metabolites of the CYP pathway. The Autism Diagnostic Observation Schedule (ADOS-2) and Vineland Adaptive Behaviors Scales, Second Edition (VABS-II) were used to assess subsequent ASD symptoms and adaptive functioning in children at 6 years. The analysis included 200 children and their mothers. RESULTS: Arachidonic acid-derived diols, 11,12-diHETrE was found to impact ASD symptom severity on the ADOS-2-calibrated severity scores and impairment in the socialization domain as assessed by the VABS-II (P = 0.0003; P = 0.004, respectively). High levels of 11,12-diHETrE impact social affect in ASD symptoms (P = 0.002), while low levels of 8,9-diHETrE impact repetitive/restrictive behavior (P = 0.003). Notably, there was specificity in the association between diHETrE and ASD symptoms, especially in girls. CONCLUSION: These findings suggest that the dynamics of diHETrE during the fetal period is important in the developmental trajectory of children after birth. Given that the role of diol metabolites in neurodevelopment in vivo is completely uncharacterized, the results of this study provide important insight into the role of diHETrE and ASD pathophysiology.

Reliability of the Two-dimensional Mood Scale for self-reported mood assessment by older adults with dementia.

The purpose of this study was to evaluate the reliability of the Two-dimensional Mood Scale (TDMS) for mood assessment among older adults with dementia. The study included 100 elderly patients with dementia admitted to two hospitals. For each mood state measured by the TDMS, the intraclass correlation coefficient of agreement (ICCagreement) was calculated to evaluate test-retest reliability. Scores corresponding to the minimal detectable change (MDC) in each mood state at the individual level (MDCind) was also calculated to evaluate measurement error, while McDonald's omega was calculated to evaluate internal consistency. The TDMS ICC was 0.54 for vitality, 0.74 for stability, 0.70 for pleasure, and 0.55 for arousal. The MDCind was 6.89 for vitality, 5.88 for stability, 9.96 for pleasure, and 4.11 for arousal. McDonald's omega ranged from 0.60 to 0.84. The TDMS has generally acceptable reliability for the self-assessment of mood states by older adults with dementia.

Baloxavir Marboxil for Prophylaxis against Influenza in Household Contacts.

BACKGROUND: Baloxavir marboxil (baloxavir) is a polymerase acidic protein (PA) endonuclease inhibitor with clinical efficacy in the treatment of uncomplicated influenza, including in outpatients at increased risk for complications. The postexposure prophylactic efficacy of baloxavir in the household setting is unclear. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial to evaluate the postexposure prophylactic efficacy of baloxavir in household contacts of index patients with confirmed influenza during the 2018-2019 season in Japan. The participants were assigned in a 1:1 ratio to receive either a single dose of baloxavir or placebo. The primary end point was clinical influenza, as confirmed by reverse-transcriptase-polymerase-chain-reaction testing, over a period of 10 days. The occurrence of baloxavir-selected PA substitutions associated with reduced susceptibility was assessed. RESULTS: A total of 752 household contacts of 545 index patients were randomly assigned to receive baloxavir or placebo. Among the index patients, 95.6% had influenza A virus infection, 73.6% were younger than 12 years of age, and 52.7% received baloxavir. Among the participants who could be evaluated (374 in the baloxavir group and 375 in the placebo group), the percentage in whom clinical influenza developed was significantly lower in the baloxavir group than in the placebo group (1.9% vs. 13.6%) (adjusted risk ratio, 0.14; 95% confidence interval [CI], 0.06 to 0.30; P<0.001). Baloxavir was effective in high-risk, pediatric, and unvaccinated subgroups of participants. The risk of influenza infection, regardless of symptoms, was lower with baloxavir than with placebo (adjusted risk ratio, 0.43; 95% CI, 0.32 to 0.58). The incidence of adverse events was similar in the two groups (22.2% in the baloxavir group and 20.5% in the placebo group). In the baloxavir group, the viral PA substitutions I38T/M or E23K were detected in 10 (2.7%) and 5 (1.3%) participants, respectively. No transmission of these variants from baloxavir-treated index patients to participants in the placebo group was detected; however, several instances of transmission to participants in the baloxavir group could not be ruled out. CONCLUSIONS: Single-dose baloxavir showed significant postexposure prophylactic efficacy in preventing influenza in household contacts of patients with influenza. (Funded by Shionogi; Japan Primary Registries Network number, JapicCTI-184180.).

Effect of a novel nasal oxytocin spray with enhanced bioavailability on autism: a randomized trial.

Although intranasal oxytocin is expected to be a novel therapy for the core symptoms of autism spectrum disorder, which has currently no approved medication, the efficacy of repeated administrations was inconsistent, suggesting that the optimal dose for a single administration of oxytocin is not optimal for repeated administration. The current double-blind, placebo-controlled, multicentre, crossover trial (ClinicalTrials.gov Identifier: NCT03466671) was aimed to test the effect of TTA-121, a new formulation of intranasal oxytocin spray with an enhanced bioavailability (3.6 times higher than Syntocinon® spray, as assessed by area under the concentration-time curve in rabbit brains), which enabled us to test a wide range of multiple doses, on autism spectrum disorder core symptoms and to determine the dose-response relationship. Four-week administrations of TTA-121, at low dose once per day (3 U/day), low dose twice per day (6 U/day), high dose once per day (10 U/day), or high dose twice per day (20 U/day), and 4-week placebo were administered in a crossover manner. The primary outcome was the mean difference in the reciprocity score (range: 0-14, higher values represent worse outcomes) on the Autism Diagnostic Observation Schedule between the baseline and end point of each administration period. This trial with two administration periods and eight groups was conducted at seven university hospitals in Japan, enrolling adult males with high-functioning autism spectrum disorder. Enrolment began from June 2018 and ended December 2019. Follow-up ended March 2020. Of 109 males with high-functioning autism spectrum disorder who were randomized, 103 completed the trial. The smallest P-value, judged as the dose-response relationship, was the contrast with the peak at TTA-121 6 U/day, with inverted U-shape for both the full analysis set (P = 0.182) and per protocol set (P = 0.073). The Autism Diagnostic Observation Schedule reciprocity score, the primary outcome, was reduced in the TTA-121 6 U/day administration period compared with the placebo (full analysis set: P = 0.118, mean difference = -0.5; 95% CI: -1.1 to 0.1; per protocol set: P = 0.012, mean difference = -0.8; 95% CI: -1.3 to -0.2). The per protocol set was the analysis target population, consisting of all full analysis set participants except those who deviated from the protocol. Most dropouts from the full analysis set to the per protocol set occurred because of poor adherence to the test drug (9 of 12 in the first period and 8 of 15 in the second period). None of the secondary clinical and behavioural outcomes were significantly improved with the TTA-121 compared with the placebo in the full analysis set. A novel intranasal spray of oxytocin with enhanced bioavailability enabled us to test a wide range of multiple doses, revealing an inverted U-shape dose-response curve, with the peak at a dose that was lower than expected from previous studies. The efficacy of TTA-121 shown in the current exploratory study should be verified in a future large-scale, parallel-group trial.

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.

Baloxavir safety and clinical and virologic outcomes in influenza virus-infected pediatric patients by age group: age-based pooled analysis of two pediatric studies conducted in Japan.

BACKGROUND: Anti-influenza treatment is important for children and is recommended in many countries. This study assessed safety, clinical, and virologic outcomes of baloxavir marboxil (baloxavir) treatment in children based on age and influenza virus type/subtype. METHODS: This was a post hoc pooled analysis of two open-label non-controlled studies of a single weight-based oral dose of baloxavir (day 1) in influenza virus-infected Japanese patients aged < 6 years (n = 56) and ≥ 6 to < 12 years (n = 81). Safety, time to illness alleviation (TTIA), time to resolution of fever (TTRF), recurrence of influenza illness symptoms and fever (after day 4), virus titer, and outcomes by polymerase acidic protein variants at position I38 (PA/I38X) were evaluated. RESULTS: Adverse events were reported in 39.0 and 39.5% of patients < 6 years and ≥ 6 to < 12 years, respectively. Median (95% confidence interval) TTIA was 43.2 (36.3-68.4) and 45.4 (38.9-61.0) hours, and TTRF was 32.2 (26.8-37.8) and 20.7 (19.2-23.8) hours, for patients < 6 years and ≥ 6 to < 12 years, respectively. Symptom and fever recurrence was more common in patients < 6 years with influenza B (54.5 and 50.0%, respectively) compared with older patients (0 and 25.0%, respectively). Virus titers declined (day 2) for both age groups. Transient virus titer increase and PA/I38X-variants were more common for patients < 6 years. CONCLUSIONS: The safety and effectiveness of single-dose baloxavir were observed in children across all age groups and influenza virus types. Higher rates of fever recurrence and transient virus titer increase were observed in children < 6 years. TRIAL REGISTRATION: Japan Pharmaceutical Information Center Clinical Trials Information JapicCTI-163,417 (registered 02 November 2016) and JapicCTI-173,811 (registered 15 December 2017).

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.

Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents.

BACKGROUND: Baloxavir marboxil is a selective inhibitor of influenza cap-dependent endonuclease. It has shown therapeutic activity in preclinical models of influenza A and B virus infections, including strains resistant to current antiviral agents. METHODS: We conducted two randomized, double-blind, controlled trials involving otherwise healthy outpatients with acute uncomplicated influenza. After a dose-ranging (10 to 40 mg) placebo-controlled trial, we undertook a placebo- and oseltamivir-controlled trial of single, weight-based doses of baloxavir (40 or 80 mg) in patients 12 to 64 years of age during the 2016-2017 season. The dose of oseltamivir was 75 mg twice daily for 5 days. The primary efficacy end point was the time to alleviation of influenza symptoms in the intention-to-treat infected population. RESULTS: In the phase 2 trial, the median time to alleviation of influenza symptoms was 23.4 to 28.2 hours shorter in the baloxavir groups than in the placebo group (P<0.05). In the phase 3 trial, the intention-to-treat infected population included 1064 patients; 84.8 to 88.1% of patients in each group had influenza A(H3N2) infection. The median time to alleviation of symptoms was 53.7 hours (95% confidence interval [CI], 49.5 to 58.5) with baloxavir, as compared with 80.2 hours (95% CI, 72.6 to 87.1) with placebo (P<0.001). The time to alleviation of symptoms was similar with baloxavir and oseltamivir. Baloxavir was associated with greater reductions in viral load 1 day after initiation of the regimen than placebo or oseltamivir. Adverse events were reported in 20.7% of baloxavir recipients, 24.6% of placebo recipients, and 24.8% of oseltamivir recipients. The emergence of polymerase acidic protein variants with I38T/M/F substitutions conferring reduced susceptibility to baloxavir occurred in 2.2% and 9.7% of baloxavir recipients in the phase 2 trial and phase 3 trial, respectively. CONCLUSIONS: Single-dose baloxavir was without evident safety concerns, was superior to placebo in alleviating influenza symptoms, and was superior to both oseltamivir and placebo in reducing the viral load 1 day after initiation of the trial regimen in patients with uncomplicated influenza. Evidence for the development of decreased susceptibility to baloxavir after treatment was also observed. (Funded by Shionogi; JapicCTI number, 153090, and CAPSTONE-1 ClinicalTrials.gov number, NCT02954354 .).

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.

Open-label study of the safety, pharmacokinetics, and effectiveness of a 2 mg/kg dose of baloxavir marboxil 2% granules in children <20 kg with influenza.

INTRODUCTION: Baloxavir marboxil is an oral anti-influenza drug with demonstrated safety and efficacy in pediatric patients when a 2% granules formulation is administered at 1 mg/kg. This study assessed safety, effectiveness, and pharmacokinetics of a higher dose (2 mg/kg) of baloxavir marboxil 2% granules in pediatric patients weighing <20 kg. METHODS: This multicenter, open-label, noncontrolled study was conducted at 15 sites in Japan (January 2019-March 2020; JapicCTI-194577). Patients aged <12 years with confirmed influenza received a single oral dose of baloxavir marboxil at 2 mg/kg if body weight was <10 kg or 20 mg if ≥ 10 to <20 kg. Safety, pharmacokinetics, effectiveness (time to illness alleviation [TTIA] of influenza; time to resolution of fever; virus titer), and polymerase acidic protein (PA) substituted viruses were assessed over 22 days. RESULTS: 45 patients, all aged ≤6 years, were enrolled. Adverse events were reported in 24 (53.3%) patients, most commonly nasopharyngitis, diarrhea, and upper respiratory tract infection. Median (95% confidence interval [CI]) TTIA was 37.8 (27.5-46.7) hours; median (95% CI) time to resolution of fever was 22.0 (20.2-28.6) hours. A >4 log decrease in mean viral titer occurred at day 2 and a subsequent temporary 1-2 log increase in patients with influenza A(H3N2) and B. Treatment-emergent PA/I38X-substituted virus was detected in 16/39 (41.0%) patients, but no prolonged TTIA or time to resolution of fever was associated with its presence. CONCLUSIONS: Baloxavir granules administered at 2 mg/kg in children <20 kg were well tolerated, with symptom alleviation similar to 1 mg/kg.

Treatment-Emergent Influenza Variant Viruses With Reduced Baloxavir Susceptibility: Impact on Clinical and Virologic Outcomes in Uncomplicated Influenza.

BACKGROUND: Single-dose baloxavir rapidly reduces influenza virus titers and symptoms in patients with uncomplicated influenza, but viruses with reduced in vitro susceptibility due to amino acid substitutions at position 38 of polymerase acidic protein (PA/I38X) sometimes emerge. METHODS: We evaluated the kinetics, risk factors, and effects on clinical and virologic outcomes of emergence of PA/I38X-substituted viruses. RESULTS: Viruses containing PA/I38X substitutions were identified 3-9 days after baloxavir treatment in 9.7% (36/370) of patients, of whom 85.3% had transient virus titer rises. Median time to sustained cessation of infectious virus detection was 192, 48, and 96 hours in the baloxavir recipients with PA/I38X-substituted viruses, without PA/I38X-substituted viruses, and placebo recipients, respectively. The corresponding median times to alleviation of symptoms were 63.1, 51.0, and 80.2 hours, respectively. After day 5, symptom increases occurred in 11.5%, 8.0%, and 13.0%, respectively, and in 8.9% of oseltamivir recipients. Variant virus emergence was associated with lower baseline neutralizing antibody titers. CONCLUSIONS: The emergence of viruses with PA/I38X substitutions following baloxavir treatment was associated with transient rises in infectious virus titers, prolongation of virus detectability, initial delay in symptom alleviation, and uncommonly with symptom rebound. The potential transmissibility of PA/I38X-substituted viruses requires careful study. CLINICAL TRIAL REGISTRATION: NCT02954354.

Baloxavir Marboxil in Japanese Pediatric Patients With Influenza: Safety and Clinical and Virologic Outcomes.

BACKGROUND: We assessed the safety and effectiveness of baloxavir marboxil administration in Japanese children with influenza. METHODS: This open-label study administered 1 weight-adjusted dose of baloxavir to 107 children aged 1-11 years with laboratory-confirmed, febrile influenza virus infection of ≤48 hours duration. RESULTS: Adverse events (AEs) were reported in 34.6% of patients, most commonly vomiting (7.5%); no serious AEs or AEs causing discontinuation occurred. The median time to alleviation of influenza illness was 44.6 hours (95% confidence interval, 38.9-62.5 hours), to resolution of fever was 21.4 hours, and to sustained cessation of infectious viral shedding was 24.0 hours. However, viruses with amino acid substitutions in the viral polymerase acidic protein at position I38 (PA/I38T/M) emerged in 18 of 77 (23.4%) patients. Emergence was associated with longer infectious virus detectability (median time, 180.0 hours) and time to illness alleviation (median, 79.6 vs 42.8 hours in patients without PA/I38T/M-substituted viruses). Among patients with PA/I38T/M-substituted virus emergence, those with baseline hemagglutinin inhibition (HAI) antibody titer <40 experienced delay in time to illness alleviation (median, 85.4 vs 56.0 hours in patients with higher baseline HAI antibody titer). CONCLUSIONS: A single, oral dose of baloxavir marboxil was well tolerated and rapidly reduced viral titers, but the common emergence of PA/I38T/M-substituted viruses warrants consideration of alternative dosing regimens in young children. CLINICAL TRIALS REGISTRATION: Japan Pharmaceutical Information Center Clinical Trials Information (Japic CTI-163417).

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.

Factors affecting the performance of activities of daily living in patients with advanced cancer undergoing inpatient rehabilitation: results from a retrospective observational study.

[Purpose] Many clinicians believe that rehabilitation for patients with advanced cancer is futile. We determined factors affecting the performance of activities of daily living in patients with advanced cancer based on age, gender, marital status, living arrangement, rehabilitation intensity, type of cancer, impairment, metastasis, and active cancer treatment. [Participants and Methods] We assessed the Barthel Index to evaluate the performance of activities of daily living. Of the 120 adult patients with cancer who underwent inpatient rehabilitation, we analyzed the Barthel Index scores, consisting of 10 items, and reviewed the clinical characteristics from the medical records of 48 patients who completed supportive or palliative rehabilitation according to Dietz and showed an increased or maintained total Barthel Index score at final evaluation. [Results] The median total Barthel Index score increased from 45 (5-95) to 72.5 (5-100); the rehabilitation intensity was 320 (40-1,240) minutes. The analytical results showed that the increase of total Barthel Index score was positively associated with rehabilitation intensity (ß=0.350) and negatively associated with the initial grooming score (ß=-0.277). [Conclusion] Adequate rehabilitation positively affects performance of activities of daily living, especially in patients with advanced cancer who lost their grooming ability at the onset of rehabilitation. Importantly, rehabilitation may be beneficial for patients with advanced cancer.

Use of a multilayer perceptron to create a prediction model for dressing independence in a small sample at a single facility.

[Purpose] This study aimed to assess the accuracy of a prediction model for dressing independence created with a multilayer perceptron in a small sample at a single facility. [Participants and Methods] This retrospective observational study included 82 first-stroke patients. The prediction models for dressing independence at hospital discharge were created using a multilayer perceptron, logistic regression, and a decision tree, and compared for predictive accuracy. Age, dressing performance, trunk function, visuospatial perception, balance, and cognitive function at admission were used as variables. [Results] The area under the receiver operating characteristic curve, classification accuracy, sensitivity, specificity, positive-predictive value, and negative-predictive value for training data were highest with the multilayer perceptron model. Cochran's Q and multiple comparison tests revealed a significant difference between logistic regression and multilayer perceptron models. Testing of data in 10-fold cross-validation yielded the same results, except for sensitivity. [Conclusion] The present study suggested that higher accuracy could be expected with a multilayer perceptron than with logistic regression and a decision tree when creating a prediction model for independence of activities of daily living in a small sample of stroke patients.