Maternal asthma symptoms during pregnancy on child behaviour and executive function: A Bayesian phenomics approach.

OBJECTIVE: Maternal history of inflammatory conditions has been linked to offspring developmental and behavioural outcomes. This phenomenon may be explained by the maternal immune activation (MIA) hypothesis, which posits that dysregulation of the gestational immune environment affects foetal neurodevelopment. The timing of inflammation is critical. We aimed to understand maternal asthma symptoms during pregnancy, in contrast with paternal asthma symptoms during the same period, on child behaviour problems and executive function in a population-based cohort. METHODS: Data were obtained from 844 families from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort. Parent asthma symptoms during the prenatal period were reported. Asthma symptoms in children were reported longitudinally from two to five years old, while behavioural problems and executive functioning were obtained at seven years old. Parent and child measures were compared between mothers with and without prenatal asthma symptoms. Generalized linear and Bayesian phenomics models were used to determine the relation between parent or child asthma symptoms and child outcomes. RESULTS: Children of mothers with prenatal asthma symptoms had greater behavioural and executive problems than controls (Cohen's d: 0.43-0.75; all p < 0.05). This association remained after adjustments for emerging asthma symptoms during the preschool years and fathers' asthma symptoms during the prenatal period. After adjusting for dependence between child outcomes, the Bayesian phenomics model showed that maternal prenatal asthma symptoms were associated with child internalising symptoms and higher-order executive function, while child asthma symptoms were associated with executive function skills. Paternal asthma symptoms during the prenatal period were not associated with child outcomes. CONCLUSIONS: Associations between child outcomes and maternal but not paternal asthma symptoms during the prenatal period suggests a role for MIA. These findings need to be validated in larger samples, and further research may identify behavioural and cognitive profiles of children with exposure to MIA.

Screen time, brain network development and socio-emotional competence in childhood: moderation of associations by parent-child reading.

BACKGROUND: Screen time in infancy is linked to changes in social-emotional development but the pathway underlying this association remains unknown. We aim to provide mechanistic insights into this association using brain network topology and to examine the potential role of parent-child reading in mitigating the effects of screen time. METHODS: We examined the association of screen time on brain network topology using linear regression analysis and tested if the network topology mediated the association between screen time and later socio-emotional competence. Lastly, we tested if parent-child reading time was a moderator of the link between screen time and brain network topology. RESULTS: Infant screen time was significantly associated with the emotion processing-cognitive control network integration (p = 0.005). This network integration also significantly mediated the association between screen time and both measures of socio-emotional competence (BRIEF-2 Emotion Regulation Index, p = 0.04; SEARS total score, p = 0.04). Parent-child reading time significantly moderated the association between screen time and emotion processing-cognitive control network integration (ß = -0.640, p = 0.005). CONCLUSION: Our study identified emotion processing-cognitive control network integration as a plausible biological pathway linking screen time in infancy and later socio-emotional competence. We also provided novel evidence for the role of parent-child reading in moderating the association between screen time and topological brain restructuring in early childhood.

Parental and child genetic burden of glycaemic dysregulation and early-life cognitive development: an Asian and European prospective cohort study.

Insulin resistance and glucose metabolism have been associated with neurodevelopmental disorders. However, in the metabolically more susceptible Asian populations, it is not clear whether the genetic burden of glycaemic dysregulation influences early-life neurodevelopment. In a multi-ethnic Asian prospective cohort study in Singapore (Growing Up in Singapore Towards healthy Outcomes (GUSTO)), we constructed child and parental polygenic risk scores (PRS) for glycaemic dysregulation based on the largest genome-wide association studies of type 2 diabetes and fasting glucose among Asians. We found that child PRS for HOMA-IR was associated with a lower perceptual reasoning score at ~7 years (ß = -0. 141, p-value = 0.024, 95% CI -0. 264 to -0. 018) and a lower WIAT-III mean score at ~9 years (ß = -0.222, p-value = 0.001, 95% CI -0.357 to -0.087). This association were consistent in direction among boys and girls. These inverse associations were not influenced by parental PRS and were likely mediated via insulin resistance rather than mediators such as birth weight and childhood body mass index. Higher paternal PRS for HOMA-IR was suggestively associated with lower child perceptual reasoning at ~7 years (ß = -0.172, p-value = 0.002, 95% CI -0.280 to -0.064). Replication analysis in a European cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort, showed that higher child PRS for fasting glucose was associated with lower verbal IQ score while higher maternal PRS for insulin resistance was associated with lower performance IQ score in their children at ~8.5 years. In summary, our findings suggest that higher child PRS for HOMA-IR was associated with lower cognitive scores in both Asian and European replication cohorts. Differential findings between cohorts may be attributed to genetic and environmental factors. Further investigation of the functions of the genetic structure and ancestry-specific PRS and a more comprehensive investigation of behavioural mediators may help to understand these findings better.

Variations in Cortical Functional Gradients Relate to Dimensions of Psychopathology in Preschool Children.

OBJECTIVE: It is unclear how the functional brain hierarchy is organized in preschool-aged children, and whether alterations in the brain organization are linked to mental health in this age group. Here, we assessed whether preschool-aged children exhibit a brain organizational structure similar to that of older children, how this structure might change over time, and whether it might reflect mental health. METHOD: This study derived functional gradients using diffusion embedding from resting state functional magnetic resonance imaging data of 4.5-year-old children (N = 100, 42 male participants) and 6.0-year-old children (N = 133, 62 male participants) from the longitudinal Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. We then conducted partial least-squares correlation analyses to identify the association between the impairment ratings of different mental disorders and network gradient values. RESULTS: The main organizing axis of functional connectivity (ie, principal gradient) separated the visual and somatomotor regions (ie, unimodal) in preschool-aged children, whereas the second axis delineated the unimodal-transmodal gradient. This pattern of organization was stable from 4.5 to 6 years of age. The second gradient separating the high- and low-order networks exhibited a diverging pattern across mental health severity, differentiating dimensions related to attention-deficit/hyperactivity disorder and phobic disorders. CONCLUSION: This study characterized, for the first time, the functional brain hierarchy in preschool-aged children. A divergence in functional gradient pattern across different disease dimensions was found, highlighting how perturbations in functional brain organization can relate to the severity of different mental health disorders.

Associations of screen use with cognitive development in early childhood: the ELFE birth cohort.

BACKGROUND: The associations of screen use with children's cognition are not well evidenced and recent, large, longitudinal studies are needed. We aimed to assess the associations between screen use and cognitive development in the French nationwide birth cohort. METHODS: Time and context of screen use were reported by parents at ages 2, 3.5 and 5.5. Vocabulary, non-verbal reasoning and general cognitive development were assessed with the MacArthur-Bates Communicative Development Inventory (MB) at age 2, the Picture Similarities subtest from the British Ability Scales (PS) at age 3.5 and the Child Development Inventory (CDI) at ages 3.5 and 5.5. Outcome variables were age-adjusted and standardized (mean = 100, SD = 15). Multiple imputations were performed among children (N = 13,763) with ≥1 screen use information and ≥1 cognitive measures. Cross-sectional and longitudinal associations between screen use and cognitive development were assessed by linear regression models adjusted for sociodemographic and birth factors related to the family and children, and children's lifestyle factors competing with screen use. Baseline cognitive scores were further considered in longitudinal analysis. RESULTS: TV-on during family meals at age 2, not screen time, was associated with lower MB scores at age 2 (ß [95% CI] = -1.67 [-2.21, -1.13]) and CDI scores at age 3.5 (-0.82 [-1.31, -0.33]). In cross-sectional analysis, screen time was negatively associated with CDI scores at ages 3.5 (-0.67 [-0.94, -0.40]) and 5.5 (-0.47 [-0.77, -0.16]), and, in contrast, was positively associated with PS scores (0.39 [0.07, 0.71]) at age 3.5. Screen time at age 3.5 years was not associated with CDI scores at age 5.5 years. CONCLUSIONS: Our study found weak associations of screen use with cognition after controlling for sociodemographic and children's birth factors and lifestyle confounders, and suggests that the context of screen use matters, not solely screen time, in children's cognitive development.

Validity and feasibility of using the Modified Checklist for Autism in Toddlers, Revised with Follow-Up (M-CHAT-R/F) in primary care clinics in Singapore.

LAY ABSTRACT: Systematic screening for autism in early childhood has been suggested to improve eventual outcomes by facilitating earlier diagnosis and access to intervention. However, clinical implementation of screening has to take into account effectiveness and feasibility of use within a healthcare setting for accurate diagnosis of autism. In Singapore, autism screening using a structured screening tool is not currently employed as a part of routine well-child visits for children in primary care clinics. In this study, 5336 children (aged 17-20 months) were screened for autism using the Modified Checklist for Autism in Toddlers, Revised with Follow-Up (M-CHAT-R/F) during their 18-month well-child visit in seven primary care clinics. Screening and follow-up interviews were administered by nursing staff at each clinic. Children screened positive and a portion of those screened negative then underwent diagnostic assessments to determine whether they met the diagnostic criteria for autism. In total, 113 (2.1%) were screened positive, of which 54 (1.0%) met the criteria for autism. Children who screened positive and received a diagnosis accessed autism-specific intervention at an average age of 22 months. Nurses and physicians rated the acceptability and practicality of the M-CHAT-R/F highly. Therefore, the M-CHAT-R/F questionnaire was an effective and feasible tool for autism screening among 18-month-old children in this study. Future studies will be designed to determine the optimal age of screening and role of repeated screening in Singapore, as well as to better understand any potential improved outcomes nationwide compared with pre-implementation of autism screening.

Associations Between Infant Screen Use, Electroencephalography Markers, and Cognitive Outcomes.

Importance: Research evidence is mounting for the association between infant screen use and negative cognitive outcomes related to attention and executive functions. The nature, timing, and persistence of screen time exposure on neural functions are currently unknown. Electroencephalography (EEG) permits elucidation of the neural correlates associated with cognitive impairments. Objective: To examine the associations between infant screen time, EEG markers, and school-age cognitive outcomes using mediation analysis with structural equation modeling. Design, Setting, and Participants: This prospective maternal-child dyad cohort study included participants from the population-based study Growing Up in Singapore Toward Healthy Outcomes (GUSTO). Pregnant mothers were enrolled in their first trimester from June 2009 through December 2010. A subset of children who completed neurodevelopmental visits at ages 12 months and 9 years had EEG performed at age 18 months. Data were reported from 3 time points at ages 12 months, 18 months, and 9 years. Mediation analyses were used to investigate how neural correlates were involved in the paths from infant screen time to the latent construct of attention and executive functioning. Data for this study were collected from November 2010 to March 2020 and were analyzed between October 2021 and May 2022. Exposures: Parent-reported screen time at age 12 months. Main Outcomes and Measures: Power spectral density from EEG was collected at age 18 months. Child attention and executive functions were measured with teacher-reported questionnaires and objective laboratory-based tasks at age 9 years. Results: In this sample of 437 children, the mean (SD) age at follow-up was 8.84 (0.07) years, and 227 children (51.9%) were male. The mean (SD) amount of daily screen time at age 12 months was 2.01 (1.86) hours. Screen time at age 12 months contributed to multiple 9-year attention and executive functioning measures (η2, 0.03-0.16; Cohen d, 0.35-0.87). A subset of 157 children had EEG performed at age 18 months; EEG relative theta power and theta/beta ratio at the frontocentral and parietal regions showed a graded correlation with 12-month screen use (r = 0.35-0.37). In the structural equation model accounting for household income, frontocentral and parietal theta/beta ratios partially mediated the association between infant screen time and executive functioning at school age (exposure-mediator ß, 0.41; 95% CI, 0.22 to 0.59; mediator-outcome ß, -0.38; 95% CI, -0.64 to -0.11), forming an indirect path that accounted for 39.4% of the association. Conclusions and Relevance: In this study, infant screen use was associated with altered cortical EEG activity before age 2 years; the identified EEG markers mediated the association between infant screen time and executive functions. Further efforts are urgently needed to distinguish the direct association of infant screen use compared with family factors that predispose early screen use on executive function impairments.

Physical Activity and Nutrition Interventions for Type 1 Diabetes: A Meta-analysis.

BACKGROUND AND OBJECTIVES: Current evidence is lacking on physical activity and nutrition-based interventions focusing on the management of type 1 diabetes mellitus (T1DM) and health-related quality of life among children. To assess the effects of physical activity interventions and nutrition-based interventions for children with T1DM. METHODS: Data sources include the Cochrane Central Register of Controlled Trials, Medline, clinicaltrials.gov, the World Health Organization International Clinical Trials Registry Platform, CINAHL through January 2022. Study selection includes randomized controlled trials of children aged 18 years and below with T1DM comparing either a physical activity intervention, a nutrition-based intervention, or hybrid physical activity and nutrition-based intervention with placebo or no-treatment control. Data were pooled using a random-effects model. Primary outcomes were hemoglobin A1c (HbA1c), and health-related quality of life. RESULTS: Eighteen trials were included. Physical activity compared with the no-treatment group showed a lack of effect on HbA1c (mean difference = -0.58, 95% confidence interval -1.20 to 0.05; P value = .07). Nutrition-based intervention compared with no-treatment control for HbA1c level revealed a lack of effect (mean difference = -0.61, 95% confidence interval -1.48 to 0.26; P value = .17). Limitations include paucity of studies and low quality of evidence caused by the risk of bias. CONCLUSIONS: Despite the lack of significant evidence, the generally favorable results highlight the potential of such interventions in enhancing glycemic control and health-related quality of life. Additionally, promising results from a single physical activity-nutrition-based hybrid intervention in terms of glycemic control indicate the plausible effectiveness of a mixed intervention.

Are There Bidirectional Influences Between Screen Time Exposure and Social Behavioral Traits in Young Children?

OBJECTIVE: Screen time in early childhood has been associated with children's prosocial and behavioral skills; however, the directionality of this relationship is unclear. We aimed to determine the direction of the relationship between screen time, social skills, and nonsocial behavioral traits in young children. METHODS: This was a population-based, prospective cohort study with data across 5 time points. We examined the reciprocal relationships between caregiver-reported children's screen time at 12, 18, 24, 36, and 54 months and social behaviors collected using the Infant-Toddler Social-Emotional Assessment at 12 months; the Quantitative Checklist for Autism at 18, 24, and 36 months; and the Social Responsiveness Scale at 54 months. Cross-lagged path models were used for analysis. RESULTS: A multiple imputation data set and complete data from 229 participants were included in the analyses. Screen time at 12, 18, and 36 months predicted nonsocial behavioral traits at 54 months. Cross-lagged path models showed a clear direction from increased screen time at earlier time points to both poorer social skills and atypical behaviors at later time points (Akaike information criterion 18936.55, Bayesian information criterion 19210.73, root mean square error of approximation 0.037, and comparative fit index 0.943). Social skills or behavioral traits at a younger age did not predict later screen time at any of the time points. CONCLUSION: Screen time in early childhood has lagged influences on social skills and nonsocial behaviors; the reverse relationship is not found. Close monitoring of social behaviors may be warranted in the setting of excessive screen time during early childhood.

The socioeconomic landscape of the exposome during pregnancy.

BACKGROUND: While socioeconomic position (SEP) is consistently related to pregnancy and birth outcome disparities, relevant biological mechanisms are manifold, thus necessitating more comprehensive characterization of SEP-exposome associations during pregnancy. OBJECTIVES: We implemented an exposomic approach to systematically characterize the socioeconomic landscape of prenatal exposures in a setting where social segregation was less distinct in a hypotheses-generating manner. METHODS: We described the correlation structure of 134 prenatal exogenous and endogenous sources (e.g., micronutrients, hormones, immunomodulatory metabolites, environmental pollutants) collected in a diverse, population-representative, urban, high-income longitudinal mother-offspring cohort (N = 1341; 2009-2011). We examined the associations between maternal, paternal, household, and areal level SEP indicators and 134 exposures using multiple regressions adjusted for precision variables, as well as potential effect measure modification by ethnicity and nativity. Finally, we generated summary SEP indices using Multiple Correspondence Analysis to further explore possible curved relationships. RESULTS: Individual and household SEP were associated with anthropometric/adiposity measures, folate, omega-3 fatty acids, insulin-like growth factor-II, fasting glucose, and neopterin, an inflammatory marker. We observed paternal education was more strongly and consistently related to maternal exposures than maternal education. This was most apparent amongst couples discordant on education. Analyses revealed additional non-linear associations between areal composite SEP and particulate matter. Environmental contaminants (e.g., per- and polyfluoroalkyl substances) and micronutrients (e.g., folate and copper) showed opposing associations by ethnicity and nativity, respectively. DISCUSSION: SEP-exposome relationships are complex, non-linear, and context specific. Our findings reinforce the potential role of paternal contributions and context-specific modifiers of associations, such as between ethnicity and maternal diet-related exposures. Despite weak presumed areal clustering of individual exposures in our context, our approach reinforces subtle non-linearities in areal-level exposures.

Severity of nausea and vomiting in pregnancy and early childhood neurobehavioural outcomes: The Growing Up in Singapore Towards Healthy Outcomes study.

BACKGROUND: Nausea and vomiting of pregnancy (NVP) affects 50 to 80 per cent of women. The existing literature has examined NVP from the perspective of the mother, and relatively less is known about offspring outcomes. OBJECTIVES: To study the relationships of NVP with social-emotional, behavioural, and cognitive outcomes of the offspring in a multi-ethnic Asian cohort. METHODS: In the Growing Up in Singapore Towards Healthy Outcomes prospective mother-offspring cohort study, mothers responded to a structured NVP questionnaire at 26-28 weeks' gestation (n = 1172) and participants with severe NVP were confirmed using medical records. Children underwent multiple neurodevelopmental assessments throughout childhood. We conducted multivariable regressions with post-estimation predictive margins to understand the associations of NVP with offspring neurobehavioural outcomes, which included 1-year Infant-Toddler Social and Emotional Assessment, 1.5-year Quantitative Checklist for Autism in Toddlers, 2-year Bayley Scales of Infant and Toddler Development, 2- and 4-year Child Behavior Checklist, and 4.5-year Kaufman Brief Intelligence Test. Analyses were adjusted for household income, birth variables, maternal mental health, and other relevant medical variables. Cohen's d effect sizes were calculated using standardised mean differences (µd ). RESULTS: Mothers were categorised into no (n = 296, 25.3%), mild-moderate (n = 686, 58.5%), and severe NVP (n = 190, 16.2%), of whom 67 (5.7%) required admission. Compared to children of mothers who had no or mild-moderate NVP, children with exposure to severe NVP exhibited more externalising behaviours (µd 2.0, 95% CI 0.3, 3.6; Cohen's d = 0.33) and social communication difficulties before 2 years (µd 4.1, 95% Cl 0.1, 8.0; Cohen's d = 0.38), both externalising (µd 1.5, 95% CI 0.4, 2.6; Cohen's d = 0.43) and internalising behaviours at 2 years (µd 1.2, 95% CI 0.1, 2.2; Cohen's d = 0.35), and only internalising behaviours after 2 years (µd 1.1, 95% CI 0.4, 2.0; Cohen's d = 0.37). CONCLUSIONS: Severe NVP is highly prevalent in this Asian cohort and may be adversely associated with multiple offspring neurobehavioural outcomes.

Television viewing and child cognition in a longitudinal birth cohort in Singapore: the role of maternal factors.

BACKGROUND: Although infant media exposure has received attention for its implications on child development, upstream risk factors contributing to media exposure have rarely been explored. The study aim was to examine the relationship between maternal risk factors, infant television (TV) viewing, and later child cognition. METHODS: We used a prospective population-based birth cohort study, Growing Up in Singapore Towards healthy Outcomes (GUSTO), with 1247 pregnant mothers recruited in their first trimester. We first explored the relationship of infant TV exposure at 12 months and the composite IQ score at 4.5 years, as measured by the Kaufman Brief Intelligence Test, Second Edition (KBIT-2). Multivariable linear regressions were adjusted for maternal education, maternal mental health, child variables, birth parameters, and other relevant confounders. We then examined the associations of maternal risk factors with the amount of daily TV viewing of 12-month-old infants. Path analysis followed, to test a conceptual model designed a priori to test our hypotheses. RESULTS: The average amount of TV viewing at 12 months was 2.0 h/day (SD 1.9). TV viewing in hours per day was a significant exposure variable for composite IQ (ß = - 1.55; 95% CI: - 2.81 to - 0.28) and verbal IQ (ß = - 1.77; 95% CI: - 3.22 to - 0.32) at 4.5 years. Our path analysis demonstrated that lower maternal education and worse maternal mood (standardized ß = - 0.27 and 0.14, respectively, p < 0.01 for both variables) were both risk factors for more media exposure. This path analysis also showed that maternal mood and infant TV strongly mediated the relationship between maternal education and child cognition, with an exceptional model fit (CFI > 0.99, AIC 15249.82, RMSEA < 0.001). CONCLUSION: Infant TV exposure has a negative association with later cognition. Lower maternal education and suboptimal maternal mental health are risk factors for greater television viewing. Paediatricians have a role in considering and addressing early risks that may encourage television viewing.

Attention-deficit/hyperactivity disorder in young children: predictors of diagnostic stability.

OBJECTIVES: The goals of this study were (1) to provide estimates of diagnostic stability for a sample of young children diagnosed with attention-deficit/hyperactivity disorder (ADHD) after undergoing comprehensive multidisciplinary assessments and (2) to identify baseline child and family characteristics that predict diagnostic stability over time. METHODS: Children aged 3 to 6 years, 11 months consecutively diagnosed with ADHD after multidisciplinary consultations at a tertiary care clinic between 2003 and 2008 were recontacted in 2012 and 2013 (N = 120). At follow-up, the primary outcome was the proportion of children who continued to meet diagnostic criteria for ADHD. To identify predictors of diagnostic stability, logistic regression models were used. In addition, a latent class model was used to independently classify subjects into distinct clusters. RESULTS: In this cohort, 70.4% of the children contacted at follow-up continued to meet diagnostic criteria for ADHD. Predictors of diagnostic stability included externalizing and internalizing symptoms at baseline, parental history of psychopathology, and family socioeconomic status. The latent class model independently identified 3 distinct profiles: (1) children who no longer met ADHD criteria; (2) children with persistent ADHD and high parental psychopathology; and (3) children with persistent ADHD and low family socioeconomic status. CONCLUSIONS: Young children who underwent comprehensive developmental and psychological assessments before receiving an ADHD diagnosis, had higher rates of diagnostic stability than in previous studies of community samples. Child and family factors that predict diagnostic stability have the potential to guide treatment planning for children diagnosed with ADHD before 7 years of age.