SWI/SNF complex prevents lineage reversion and induces temporal patterning in neural stem cells.

Members of the SWI/SNF chromatin-remodeling complex are among the most frequently mutated genes in human cancer, but how they suppress tumorigenesis is currently unclear. Here, we use Drosophila neuroblasts to demonstrate that the SWI/SNF component Osa (ARID1) prevents tumorigenesis by ensuring correct lineage progression in stem cell lineages. We show that Osa induces a transcriptional program in the transit-amplifying population that initiates temporal patterning, limits self-renewal, and prevents dedifferentiation. We identify the Prdm protein Hamlet as a key component of this program. Hamlet is directly induced by Osa and regulates the progression of progenitors through distinct transcriptional states to limit the number of transit-amplifying divisions. Our data provide a mechanistic explanation for the widespread tumor suppressor activity of SWI/SNF. Because the Hamlet homologs Evi1 and Prdm16 are frequently mutated in cancer, this mechanism could well be conserved in human stem cell lineages. PAPERCLIP:

The association between sleep and empathy in young preschoolers: A population study.

Sleep is vital for children's early socio-emotional development, particularly empathy. This study aimed to explore the associations between sleep and empathy in young preschoolers. A sample of 23,259 preschoolers (4.3 ± 0.3 years) at the entry year of preschool was recruited as part of the Shanghai Children's Health, Education and Lifestyle Evaluation-Preschool (SCHEDULE-P) study. Caregivers reported on child sleep, affective empathy, and cognitive empathy through the Children's Sleep Habits Questionnaire and the Griffith Empathy Measure. Ordinary least-square regression and quantile regression were performed for the associations between sleep and empathy. Sex differences were also investigated. Night sleep duration was negatively associated with affective empathy (ß = -0.35, p < 0.001), and positively associated with cognitive empathy (ß = 0.41, p < 0.001). Longer nap duration was associated with higher affective empathy (ß = 0.28, p < 0.001). Sleep disturbances were positively associated with affective empathy (ß = 0.04, p < 0.001) and negatively associated with cognitive empathy (ß = -0.09, p < 0.001). These associations were generally stronger in children at higher empathy quantiles and also those at the 10th cognitive empathy quantile. The associations between sleep and affective empathy were mainly contributed by girls, and were more common in boys in terms of cognitive empathy, particularly at the 10th and the 30th quantiles. In conclusion, longer night sleep duration and fewer sleep disturbances are associated with a more mature empathy pattern in young preschoolers. The associations are more prominent in children at the higher end of the empathy spectrum, and vary by sex. These findings highlight the importance to promote sleep health in young children for optimal socio-emotional development.

GWAS-identified variants to allergic disease and early environmental exposure in Chinese schoolchildren with allergic rhinitis induced by house dust mite.

BACKGROUND: There is growing evidence that environmental exposure in early life is associated with the development of childhood allergic rhinitis. OBJECTIVE: To investigate whether polymorphisms in previously published genome wide association studies (GWAS) allergic disease loci are associated with childhood house dust mite-induced allergic rhinitis (HDM-AR) and interaction effects of genetic and environmental factors on it. METHODS: 156 cases diagnosed by HDM-AR and 173 controls were enrolled. Potential confounders were analyzed by using Logistic regression. Twenty-one single nucleotide polymorphisms (SNPs) of GWAS-related allergic diseases including EMSY-LRRC32, IL18R1, IL18RAP, IL13, IL4, HLA region, KIF3A were genopyped and analyzed using the improved multiplex ligation detection reaction (imLDR) technique in all the subjects. RESULTS: Only IL18R1_rs2287037 was associated with HDM-AR in children. After adjusting for several likely confounders, the protective TT genotype of IL18R1_rs2287037 was found in the population analyzed with the fittest recessive model. (adjusted odds ratio [aOR]: 0.44; 95% confidence interval [CI]: 0.21-0.95). The rs2287037_ TT might interact with early-life exclusive breastfeeding in the first 4 months (aOR: 0.33; 95%CI: 014-0.97) or full-term birth (aOR: 0.45; 95%CI: 0.19-0.95) exposure to decrease the risk of HDM-AR. CONCLUSIONS: These data suggest that IL18R1 polymorphism may play a role in controlling risk to HDM-AR and underline the importance of early environmental exposure into studies of genetic risk factors.

Rational design and optimization of synthetic gene switches for controlling cell-fate decisions in pluripotent stem cells.

Advances in synthetic biology have enabled robust control of cell behavior by using tunable genetic circuits to regulate gene expression in a ligand-dependent manner. Such circuits can be used to direct the differentiation of pluripotent stem cells (PSCs) towards desired cell types, but rational design of synthetic gene circuits in PSCs is challenging due to the variable intracellular environment. Here, we provide a framework for implementing synthetic gene switches in PSCs based on combinations of tunable transcriptional, structural, and posttranslational elements that can be engineered as required, using the vanillic acid-controlled transcriptional activator (VanA) as a model system. We further show that the VanA system can be multiplexed with the well-established reverse tetracycline-controlled transcriptional activator (rtTA) system to enable independent control of the expression of different transcription factors in human induced PSCs in order to enhance lineage specification towards early pancreatic progenitors. This work represents a first step towards standardizing the design and construction of synthetic gene switches for building robust gene-regulatory networks to guide stem cell differentiation towards a desired cell fate.

Cohort Profile: The Shanghai Sleep Birth Cohort Study.

BACKGROUND: Sleep disturbances in women occur frequently throughout pregnancy. Previous studies have demonstrated that the increasing incidence of physiological and psychological illness is concurrent with increasing sleep deprivation and poor sleep quality in adults and children. OBJECTIVES: The Shanghai Sleep Birth Cohort Study (SSBCS) was established to examine the effect of sleep disturbances during the third trimester on emotional regulation of mothers; to assess the effect of maternal sleep during pregnancy on the growth and development of children; and to explore the influence of children's sleep characteristics on physical and social-emotional development. POPULATION: The study was conducted in the Renji Hospital in Pudong New District, Shanghai from May 2012 to July 2013. Women and their newborns who met the inclusion criteria and agreed to participate in this study were recruited to the SSBCS. METHODS: The follow-up visits for children were conducted at the age of 42 days, 3, 6, 9, 12, 18, and 24 months, and 3, 4, and 6 years. Data on demographic factors, physical examination, sleep assessment, developmental and psychiatric assessment, diet records, and biological samples were collected throughout the study. PRELIMINARY RESULTS: A total of 277 pregnant women were recruited to the study; the response rate was 64.3%. 37.9% of the pregnant women had poor sleep quality and 12.0% suffered from depression. Infant sleep patterns changed during the first year of life, but most sleep characteristics showed little variation from 6 to 12 months. CONCLUSIONS: The SSBCS is an on-going prospective cohort study with follow-up to 6 years. The detailed data on demographic factors, sleep assessment, physical examinations, neurodevelopmental and psychiatric assessment, diet records, and biological samples make this research platform an important resource for examining the potential effects of sleep characteristics on both maternal and child health.

Combined effects of weight change trajectories and eating behaviors on childhood adiposity status: A birth cohort study.

Previous studies have suggested that infant rapid weight change can be associated with an increased weight later in life. However, the weight change trajectory in early life over time and which childhood lifestyle behaviors may modify the risk of rapid weight change have not been characterized. Using our ongoing birth cohort study, we have addressed these issues. Nine follow-up time points (birth, 3, 6, 9, 12, 18, 24, 36, and 48 months) were used to calculate the change between two adjacent weight-for-age z-scores (WAZ-change), and then WAZ-change trajectories were defined via group-based trajectory modeling. The solitary, independent and combined effects of WAZ-change trajectories and each lifestyle factor (eating behaviors, physical activity, media exposure time and total sleep duration) on childhood adiposity measures at age 4 years were determined using multivariate regression analysis. Overall, 84 (38%) children had a steady growth trajectory from birth to 4 years, while the other 137 (62%) children had an early infancy rapid growth trajectory, particularly in the first three months. Compared to children with steady growth, children with early infancy rapid growth had a significantly higher body mass index, waist circumference, and subcutaneous fat. Moreover, weight change trajectory and three eating behaviors (i.e. food responsiveness, satiety responsiveness and food fussiness), not only had independent effects, but also combined (synergistic) effects on the majority of adiposity measures. Our results extend the current literature and provide a potentially valuable model to aid clinicians and health professionals in designing early-life interventions targeting specific populations, specific ages and specific lifestyle behaviors to prevent childhood overweight/obesity.

The splicing co-factor Barricade/Tat-SF1 is required for cell cycle and lineage progression in Drosophila neural stem cells.

Stem cells need to balance self-renewal and differentiation for correct tissue development and homeostasis. Defects in this balance can lead to developmental defects or tumor formation. In recent years, mRNA splicing has emerged as an important mechanism regulating cell fate decisions. Here we address the role of the evolutionarily conserved splicing co-factor Barricade (Barc)/Tat-SF1/CUS2 in Drosophila neural stem cell (neuroblast) lineage formation. We show that Barc is required for the generation of neurons during Drosophila brain development by ensuring correct neural progenitor proliferation and differentiation. Barc associates with components of the U2 small nuclear ribonucleoprotein (snRNP) complex, and its depletion causes alternative splicing in the form of intron retention in a subset of genes. Using bioinformatics analysis and a cell culture-based splicing assay, we found that Barc-dependent introns share three major traits: they are short, GC rich and have weak 3' splice sites. Our results show that Barc, together with the U2 snRNP complex, plays an important role in regulating neural stem cell lineage progression during brain development and facilitates correct splicing of a subset of introns.

Association of number of siblings, birth order, and thinness in 3- to 12-year-old children: a population-based cross-sectional study in Shanghai, China.

BACKGROUND: Sibship size and structure have a significant association with overweight and obesity in children, but the relationship with thinness has not been fully studied and understood, especially in Asia. This study evaluated the associations among number of siblings, birth order, and childhood thinness and investigated the association of number of younger or older siblings with childhood thinness. METHODS: In this study, we performed a population-based cross-sectional study among 84,075 3- to 12-year-old children in Shanghai using multistage stratified cluster random sampling. We defined grades 1, 2, and 3 thinness according to the body mass index cutoff points set by the International Obesity Task Force and used multinomial logistic regression models to estimate the odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: Compared with only children, for boys, children with two or more siblings were more likely to suffer from grade 2 (OR = 1.29, 95% CI 1.02, 1.64) and grade 3 thinness (OR = 1.60, 95% CI 1.07, 2.40); and the youngest child faced a higher risk of grade 2 (OR = 1.44, 95% CI 1.09, 1.90) and grade 3 thinness (OR = 1.53, 95% CI 1.01, 2.33). For girls, children with one sibling were more likely to suffer from grade 1 thinness (OR = 1.22, 95% CI 1.05, 1.42); the oldest child, middle child, and youngest child faced a higher risk of grade 1 (OR = 1.42, 95% CI 1.09, 1.84), grade 2 (OR = 1.26, 95% CI 1.03, 1.54), and grade 1 thinness (OR = 1.87, 95% CI 1.21, 2.88) respectively. There was no statistically significant relationship, however, between a larger number of younger or older siblings and childhood thinness. CONCLUSIONS: Regardless of sex, having either siblings or a higher birth order was positively associated with childhood thinness. The present study has suggested that future interventions to prevent childhood thinness should consider family background as an important factor, especially in multi-child-families.

De novo truncating variant in NSD2gene leading to atypical Wolf-Hirschhorn syndrome phenotype.

BACKGROUND: Wolf-Hirschhorn syndrome (WHS) is a contiguous gene syndrome caused by partial 4p deletion highly variable in size in individual patients. The core WHS phenotype is defined by the association of growth delay, typical facial characteristics, intellectual disability and seizures. The WHS critical region (WHSCR) has been narrowed down and NSD2 falls within this 200 kb region. Only four patients with NSD2 variants have been documented with phenotypic features in detail. CASE PRESENTATION: Herein, we report the case of a 12-year-old boy with developmental delay. He had dysmorphic facial features including wide-spaced eyes, prominent nasal bridge continuing to forehead, abnormal teething and micrognathia. He also had mild clinodactyly of both hands. Using whole-exome sequencing, we identified a pathogenic mutation in NSD2 [c.4029_4030insAA, p.Glu1344Lysfs*49] isolated from peripheral blood DNA. Sanger confirmation of this variant revealed it as a de novo truncating variant in the family. CONCLUSION: Here, we reported a boy with de novo truncating variant in NSD2 with atypical clinical features comparing with 4p16.3 deletion related WHS. Our finding further supported the pathogenesis of truncating variants in NSD2 and delineated the possible symptom spectrum caused by these variants.

Social-Emotional Functioning Explains the Effects of Physical Activity on Academic Performance among Chinese Primary School Students: A Mediation Analysis.

OBJECTIVE: To examine the mediating effects of socioemotional and behavioral functioning in the association between physical activity and academic achievement in Chinese children. STUDY DESIGN: Chinese children (n = 17 318; aged 6-11 years) from the Shanghai Children's Health, Education and Lifestyle Evaluation study in 2014 were the source of data. Children reported the time spent in moderate-to-vigorous physical activities (MVPA) during weekdays and weekends. Parents rated their children's socioemotional and behavioral difficulties. Head teachers rated the academic performance of each student. A mediation analysis with multiple mediators was performed to test the mediation effects of 5 socioemotional and behavioral variables (emotional problems, conduct problems, hyperactivity and inattention, peer relationship, and prosocial behaviors) in the association between MVPA and academic achievement, adjusting for demographic and health-related variables. RESULTS: Results revealed that MVPA was positively associated with academic performance (b = 0.78; SE = .01; P < .001). Conduct problems, hyperactivity and inattention, and peer problems showed significant mediating effects in the association between MVPA and academic achievement, with hyperactivity and inattention being the strongest mediator (b = 0.38; SE = 0.04; P < .001) accounting for 49% of the total effect. CONCLUSIONS: This study provides evidence that MVPA is associated with fewer socioemotional difficulties, which, in turn, is associated with better academic achievement. Promoting physical activity among school-aged children may benefit their overall development.

Pox neuro control of cell lineages that give rise to larval poly-innervated external sensory organs in Drosophila.

The Pox neuro (Poxn) gene of Drosophila plays a crucial role in the development of poly-innervated external sensory (p-es) organs. However, how Poxn exerts this role has remained elusive. In this study, we have analyzed the cell lineages of all larval p-es organs, namely of the kölbchen, papilla 6, and hair 3. Surprisingly, these lineages are distinct from any previously reported cell lineages of sensory organs. Unlike the well-established lineage of mono-innervated external sensory (m-es) organs and a previously proposed model of the p-es lineage, we demonstrate that all wild-type p-es lineages exhibit the following features: the secondary precursor, pIIa, gives rise to all three support cells-socket, shaft, and sheath, whereas the other secondary precursor, pIIb, is neuronal and gives rise to all neurons. We further show that in one of the p-es lineages, that of papilla 6, one cell undergoes apoptosis. By contrast in Poxn null mutants, all p-es lineages have a reduced number of cells and their pattern of cell divisions is changed to that of an m-es organ, with the exception of a lineage in a minority of mutant kölbchen that retains a second bipolar neuron. Indeed, the role of Poxn in p-es lineages is consistent with the specification of the developmental potential of secondary precursors and the regulation of cell division but not apoptosis.

Drosophila neural stem cells in brain development and tumor formation.

Neuroblasts, the neural stem cells in Drosophila, generate the complex neural structure of the central nervous system. Significant progress has been made in understanding the mechanisms regulating the self-renewal, proliferation, and differentiation in Drosophila neuroblast lineages. Deregulation of these mechanisms can lead to severe developmental defects and the formation of malignant brain tumors. Here, the authors review the molecular genetics of Drosophila neuroblasts and discuss some recent advances in stem cell and cancer biology using this model system.

The relation among sleep duration, homework burden, and sleep hygiene in chinese school-aged children.

Insufficient sleep in school-aged children is common in modern society, with homework burden being a potential risk factor. The aim of this article is to explore the effect of sleep hygiene on the association between homework and sleep duration. Children filled out the Chinese version of the Adolescent Sleep Hygiene Scale, and parents filled out a sociodemographic questionnaire. The final sample included 363 boys and 371 girls with a mean age of 10.82 ± 0.38 years. Children with more homework went to bed later and slept less. Better sleep hygiene was associated with earlier bedtimes and longer sleep duration. Findings suggest that homework burden had a larger effect on sleep duration than sleep hygiene. Fifth-grade children in Shanghai have an excessive homework burden, which overwrites the benefit of sleep hygiene on sleep duration.

Daytime sleep duration during infancy as an indicator for cognitive development at school age: a prospective cohort study.

STUDY OBJECTIVES: The reduction in daytime sleep during early life is considered one of the indicators of the maturation of sleep patterns, which is closely associated with cognitive development. The current study aims to analyze the relationships between daytime sleep duration (DSD) during infancy and cognitive development at 6 and 10 years. METHODS: The study included 262 mothers with their newborns from the Shanghai Sleep Birth Cohort Study, spanning 11 follow-ups from 42 days to 10 years. Sleep parameters were assessed using parent-reported questionnaires at each follow-up, and cognitive development was evaluated with the Wechsler Intelligence Scale for Children, fourth edition at 6 and 10 years. RESULTS: Two distinct DSD trajectories in early childhood were identified: "typical DSD" (66.7%) and "infancy excessive DSD" (33.3%). Children in the "infancy excessive DSD" trajectory exhibited lower working memory scores than those in the "typical DSD" trajectory at 6 years (mean difference = 5.90, 95% confidence interval [1.83, 9.96], P = .005) and 10 years (mean difference = 4.37, 95% confidence interval [0.26, 8.48], P = .037). Additional analysis in a relatively homogeneous sample consistently showed correlations between DSD trajectories and working memory performance. No consistent significant differences were found in other domains of cognitive development. CONCLUSIONS: Excessive daytime sleep during infancy may serve as an early indicator for poor working memory at school age. These findings raise concerns about the long-term cognitive development of infants with excessive DSD. CITATION: Lin J, Jiang Y, Xiao X, et al. Daytime sleep duration during infancy as an indicator for cognitive development at school age: a prospective cohort study. J Clin Sleep Med. 2024;20(7):1069-1077.

Insufficient Sleep is Associated With Increasing Trends in Adolescent Suicidal Behaviors.

PURPOSE: Youth suicide has been increasing and became a public health concern worldwide. Identifying insufficient sleep as the potential risk factor is critical to reducing suicide risk and increasing trends. This study aimed to determine whether insufficient sleep is associated with increasing trends in suicidal behaviors and disparities by sex, age, and race/ethnicity among school adolescents. METHODS: The present study used biennial data from the US nationally representative Youth Risk Behavior Survey from 2007 to 2019. Joinpoint regression models were used to estimate biennial percent changes (BPCs) and average BPCs (ABPCs) of suicidal behaviors by sleep duration. Logistic regression models were used to examine the association between insufficient sleep and suicidal behaviors. RESULTS: Of 73,356 adolescent students included (mean [standard deviation] age, 16.11 [1.23] years), 50.03% were female. Suicidal ideation and suicide plan among insufficient sleep group increased from 2007 to 2019 (BPC = 2.88% [95% confidence interval {CI}: 1.65%, 4.13%]; BPC = 3.42% [95% CI: 2.09%, 4.77%]), but were nonsignificant among sufficient sleep group. Trends in suicidal ideation (ABPC = 3.03% [95% CI: 1.35%, 4.73%]) and suicide plan (ABPC = 4.03% [95% CI: 2.47%, 5.62%]) among female adolescents with insufficient sleep increased, but nonsignificant among male adolescents with insufficient sleep. Suicidal ideation (ABPC = 1.73% [95% CI: 0.51%, 2.97%]) and suicide plan (ABPC = 2.31% [95% CI: 0.70%, 3.95%]) increased among younger adolescents only with insufficient sleep, whereas suicide trends by sleep duration were similar among older adolescents. Suicide plan among insufficient sleep group increased across the four racial groups, with BPC highest for the White (BPC = 3.48% [95% CI: 1.31%, 5.69%]), and lowest for the Hispanic/Latino (BPC = 1.18% [95% CI: 0.15%, 2.23%]), but were nonsignificant among sufficient sleep group except for the White (BPC = 2.83% [95% CI: 0.62%, 5.09%]). DISCUSSION: Insufficient sleep was disproportionately associated with increasing trends in suicidal behaviors among female, younger, and non-White adolescent students. Ensuring sufficient sleep can potentially reduce suicide among school adolescents.

In-Depth Structure and Function Characterization of Heterogeneous Interchain Cysteine-Conjugated Antibody-Drug Conjugates.

Antibody-drug conjugates (ADCs), integrating high specificity of antigen-targeting antibodies and high potency of cell-killing chemical drugs, have become one of the most rapidly expanding therapeutic biologics in oncology. Although ADCs were widely studied from multiple aspects, overall structural elucidation with comprehensive understanding of variants is scarcely reported. Here, for the first time, we present a holistic and in-depth characterization of an interchain cysteine-conjugated ADC, focusing on conjugation and charge heterogeneity, and in vitro biological activities. Conjugation mapping utilized a bottom-up approach, unraveled positional isomer composition, provided insights into the conjugation process, and elucidated how conjugation affects the physicochemical and biological properties of an ADC. Charge profiling combined bottom-up and top-down approaches to interrogate the origin of charge heterogeneity, its impact on function, and best practice for characterization. Specifically, we pioneered the utilization of capillary isoelectric focusing-mass spectrometry to decode not only critical post-translational modifications but also drug load and positional isomer distribution. The study design provides general guidance for in-depth characterization of ADCs, and the analytical findings in turn benefit the discovery and development of future ADCs.

Analysis of neural stem cell self-renewal and differentiation by transgenic RNAi in Drosophila.

The fruit fly, Drosophila melanogaster, has proved to be a useful model organism for studying the biology of neural stem cells. Notably, significant progress has been made in identifying the molecular mechanisms that regulate the asymmetric cell divisions of the neural stem cell-like neuroblasts during brain development. Recently, the emerging technology of genome-wide transgenic RNA interference (RNAi), which makes it possible to analyze complicated developmental processes in a targeted, tissue-specific way, has been used for the analysis of gene function in Drosophila neuroblasts. Here, we review the key molecular mechanisms that regulate the asymmetric cell divisions of neuroblasts during brain development in Drosophila. We then summarize recent genome-wide transgenic RNAi screens in Drosophila and report on the identification of new regulators and gene networks that are required in balancing neuroblast self-renewal and differentiation.

The association between sleep and early pubertal development in Chinese children: a school population-based cross-sectional study.

Background: There is an increasing tendency toward early pubertal development, and sleep might be related to pubertal onset. We aimed to investigate the association of sleep duration and bedtime with early pubertal development. Methods: This was a cross-sectional study of 8,007 children (53.6% boys) from Qufu city, Shandong province and Zhongshan city, Guangdong province, China. Data on sleep duration and bedtime were obtained by questionnaire. Early pubertal development was the primary outcome and it was evaluated by the pediatrician according to Tanner staging. Logistic regression models were used to separately examine the association between sleep duration or bedtime and early pubertal development, controlling body mass index (BMI), dietary pattern, soft drink, feeding pattern and mother's BMI. Results: In boys, short sleep duration was strongly related to early pubertal development [OR (95%CI): 4.26 (1.30, 13.94)], and this association was intensified after adjusted BMI, dietary pattern, soft drink, feeding pattern and mother's BMI. In girls, OR (95%CI) was 1.62 (1.04, 2.51), and increased after controlling BMI. Bedtime was associated with early pubertal development on weekdays [OR (95%CI): 6.39 (1.54, 26.45) in boys and 1.93 (1.23, 3.05) in girls], but not on weekends [OR (95%CI): 2.49 (0.61, 10.21) in boys; 1.31 (0.76, 2.25) in girls]. Conclusion: This study underscores the positive association between the risk of early pubertal development and insufficient sleep duration and late bedtime.

The effects of maternal prenatal depression on child mental health: The moderating role of maternal childhood trauma.

BACKGROUND: There is a large body of evidence suggesting that maternal prenatal depression significantly predicts mental health problems in children. However, little is known about the role of maternal childhood trauma within this effect. METHODS: The current study utilized a sample of 187 mother-child dyads (51.3 % boys) from the Shanghai Sleep Birth Cohort (SSBC), a six-year prospective longitudinal study. The effects of maternal depression at late pregnancy (Center for Epidemiological Survey-Depression Scale) on the child mental health at six years old (Strengths and Difficulties Questionnaire) were analyzed, with different types of maternal childhood trauma (Childhood Trauma Questionnaire) being examined as moderators. RESULTS: The results showed that maternal prenatal depression positively predicted child mental health problems (ß = 0.13, p < .05) and there was a significant moderating effect of maternal childhood emotional abuse (ß = -0.05, p < .05); that is, in mothers with high childhood emotional abuse, child mental health problems remained high regardless of maternal prenatal depression (ß = -0.02, p = .78), while in mothers with low childhood emotional abuse, maternal prenatal depression significantly predicted child behavioral and emotional problems (ß = 0.20, p < .05). LIMITATIONS: Relatively high socio-economic status samples, retrospective reports of maternal childhood trauma and the single reporter were the limitations of this study. CONCLUSIONS: The findings provided new insights into the impact of maternal prenatal depression on child mental health, highlighting the importance of intervention efforts targeting mothers with prenatal depression and childhood trauma history.

Sleep Disturbances and Emotional and Behavioral Difficulties Among Preschool-Aged Children.

Importance: Sleep disturbances and mental health problems are highly comorbid and bidirectionally correlated across childhood. The association between the natural history of sleep disturbances and the transition of mental health problems has not been quantified. Objective: To examine the association between the natural history of sleep disturbances and resolved and incident emotional and behavioral difficulties (EBDs). Design, Setting, and Participants: This cohort study used data from the Shanghai Children's Health, Education and Lifestyle Evaluation-Preschool (SCHEDULE-P), a prospective and population-based longitudinal cohort study of children enrolled in preschools in Shanghai, China, from November 10 to 24, 2016. A total of 20 324 children aged 3 to 4 years were recruited from the junior class of 191 kindergartens, of whom 17 233 (84.8%) participated in the 2-year follow-up. A multilevel regression model was used to evaluate the association between the development of sleep disturbances and the occurrence of resolved and incident EBDs. The data analysis spanned from August 4, 2021, to October 31, 2023. Exposures: Sleep disturbances were assessed using the Children's Sleep Habit Questionnaire; EBDs were assessed using the Strengths and Difficulties Questionnaire. Main Outcomes and Measures: Occurrence of incident and resolved EBDs at the 2-year follow-up. Results: The cohort included 17 182 participants, with a mean (SD) age of 3.73 (0.29) years at enrollment; 52.0% were boys. The prevalence of EBDs at school entry and graduation years was 27.8% and 18.7%, respectively, while the prevalence of sleep disturbances was 41.3% and 31.5%, respectively. Among those with EBDs at the entry year, 35.0% maintained stability in the graduation year, while sleep disturbances were stable in 50.0% of those with sleep disturbances. After controlling for confounding factors, the odds ratio (OR) for resolved EBDs was lower in the incident sleep disturbance (ISD) group (OR, 0.50 [95% CI, 0.41-0.62]; P < .001) and stable sleep disturbance (SSD) group (OR, 0.47 [95% CI, 0.40-0.56]; P < .001) compared with the group with no sleep disturbances. The ORs for incident EBDs among the ISD group (OR, 2.58 [95% CI, 2.22-3.01]; P < .001) and SSD group (OR, 2.29, [95% CI, 1.98-2.64]; P < .001) were higher than among the group with no sleep disturbances. Conclusions and Relevance: In this prospective cohort study, the natural history of sleep disturbances among preschool-aged children was associated with both resolved and incident EBDs. Routine screening and precise intervention for sleep disturbances may benefit the psychosocial well-being of this population.