Growing Up In Singapore Towards Healthy Outcomes Research Articles

The prospective associations of fetal growth-related pregnancy complications with subsequent breastfeeding duration and markers of human milk production.

The development of the breast for lactation occurs throughout pregnancy. It is unknown whether pregnancy complications resulting in poor fetal growth can affect breastfeeding success. We examined whether fetal growth-related pregnancy complications were associated with earlier breastfeeding cessation and changes in the concentrations of human milk biomarkers of low milk production. We used data from the Growing Up in Singapore Toward healthy Outcomes (GUSTO) study (n=954). Human milk concentrations of protein, lactose, citrate, sodium, potassium and zinc at 3 weeks postpartum were available for 180 mother-infant dyads. We examined the associations of fetal growth measures, including term infants born small-for-gestational-age (SGA) (<10th percentile), pregnancies complicated by fetal growth deceleration (FGD) (2nd - 3rd trimester fetal growth dropped between major centiles), elevated umbilical artery resistance (UAR) (> 90th percentile) or hypertensive disorders of pregnancy (HDP) with (i) risk of ceasing breastfeeding (Cox regression) and (ii) concentrations of human milk components (weighted linear regression). Adjusting for maternal education, smoking exposure, breastfeeding intentions and pre-pregnancy BMI, individuals who delivered SGA infants, and those with HDP were more likely to breastfeed for a shorter duration when compared to those with uncomplicated pregnancies (adjusted hazard ratio [95% CI]: 1.45 [1.11, 1.89] and 1.61 [1.14, 2.29], respectively); associations were not significant for FGD and UAR. SGA was not associated with concentrations of human milk biomarkers, but compared to participants with uncomplicated pregnancies, milk produced by those with HDP contained lower zinc concentrations (adjusted beta coefficient [95% CI]: -0.56 mg/L [-1.08, -0.04]). Individuals with HDP and those with SGA infants tend to breastfeed for a shorter duration; however, only HDP appeared to be associated with biomarkers of compromised milk production. Further research and support are needed to help individuals with HDP and SGA achieve their breastfeeding goals. This study was registered as NCT01174875, and can be accessed at https://clinicaltrials.gov/study/NCT01174875.

Harsh parenting, amygdala functional connectivity changes across childhood, and behavioral problems.

Harsh parenting in early childhood is related to offspring's adverse behavioral outcomes. Due to the scarcity of longitudinal neuroimaging data, few studies have explored the neurobiological underpinnings of this association, focusing on within-person variability. This study examined the temporal associations among harsh parenting, later behavioral problems, and the developmental trajectories of amygdala volume and amygdala resting-state functional connectivity (RSFC) profiles, using longitudinal neuroimaging data. The study was embedded in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. T1-weighted (296 children, 642 scans) and resting-state functional scans (256 children, 509 scans) were collected at ages 4.5, 6, 7.5, and 10.5 years. Amygdala volume and RSFC between the amygdala and six brain regions that have leading roles in emotional regulation were extracted. Harsh parenting at 4.5 years and child behavioral problems at 10.5 years were assessed via parent-report questionnaires. Linear regression and linear mixed models were applied. Harsh parenting was associated with more severe externalizing problems in girls (β = 0.24, 95% CI 0.08-0.40) but not boys (pint = 0.07). In the overall sample, harsh parenting was associated with the developmental trajectories of amygdala-ACC, amygdala-OFC, and amygdala-DLPFC RSFC. In addition, the developmental trajectory of amygdala-ACC RSFC mediated the harsh parenting-externalizing problems association in girls (indirect effect = 0.06, 95% CI 0.01-0.14). Harsh parenting in early childhood was associated with amygdala neurocircuitry development and behavioral problems. The developmental trajectory of amygdala-ACC RSFC is a potential neural mechanism linking harsh parenting and externalizing problems in girls.

Dietary pattern trajectories in early childhood and their associations with patterns of maternal feeding practices in a multi-ethnic Asian cohort

BackgroundMaternal feeding practices play a major role in children’s dietary intakes. However, there is limited data on the associations between trajectories of dietary patterns (DPs) and patterns of maternal feeding practices during early childhood.MethodsUsing data from a multi-ethnic Asian cohort study, namely the Growing Up in Singapore Towards healthy Outcomes (GUSTO), dietary intakes were measured using Food Frequency Questionnaires in children at 18 months, 5 and 7 years of age. Maternal feeding practices were assessed using validated questionnaires at 15 months, 3 and 5 years of age. Principal component analysis was used to derive 2 major DPs at all time-points as well as patterns of maternal feeding practices. Group-based trajectory modelling was used to identify trajectory groups for the derived DPs. Multivariable logistic regression examined associations between patterns of maternal feeding practices and DP trajectory groups.ResultsTwo DPs, namely the ‘healthy’ and ‘less healthy’ were consistently derived at 18 months, 5 and 7 years of age. From each DP, 2 stable DP trajectory groups were further identified between 18 months and 7 years of age. For the ‘healthy’ DP trajectory, majority of the children (Group 1) formed a consistent average adherence trajectory group (91.8%) while the remaining children (Group 2) showed a higher but decreasing adherence (8.2%) to this DP. For the ‘less healthy’ DP trajectory, most children (Group 1) formed a consistent average adherence trajectory (95.5%), while the remainder (Group 2) showed consistent higher adherence to this ‘less healthy’ DP (4.5%). Two patterns of maternal feeding practices were derived and labelled as ‘structured with autonomy support’ and ‘coercive control’, respectively, at ages 15 months, 3 and 5 years. Children whose mothers showed high adherence to the structured with autonomy support feeding practices at age 5 years were significantly more likely to be associated with the higher but decreasing ‘healthy’ DP trajectory group [OR = 3.62 (95% CI: 1.64, 7.99)].ConclusionsA small number of children in this multi-ethnic study showed high adherence to the ‘healthy’ or ‘less healthy’ DP trajectory groups, respectively, while the majority showed average adherence to either of these trajectories. The positive association between structured with autonomy support maternal feeding practices and higher z-scores for the healthy DP trajectory highlights the importance of guiding parents on appropriate feeding practices.

Sleep problems in preschool mediate the association between chronotype and socioemotional problems at school-age

ObjectivesEvening-chronotype is associated with increased socioemotional problems among school-aged children. Inadequate sleep and increased sleep problems are also prevalent among evening-chronotype children and may underlie the relationship between chronotype and socioemotional problems. However, it is unclear whether the association between chronotype and socioemotional problems at school-age may be mediated by poorer sleep during late preschool. MethodsOur study utilized cross-sectional data to examine the relations between chronotype, sleep duration, sleep problems and socioemotional problems in preschoolers. We subsequently performed longitudinal mediation analyses to examine how the association between chronotype at preschool-age and later socioemotional problems at school-age may be mediated by sleep problems and sleep duration during late preschool. 399 children from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort study were included for analyses. Children's chronotype were identified with the Children's Chronotype Questionnaire at 4.5 years old. Sleep duration and problems were measured with the Children's Sleep Habits Questionnaire at 4.5 and 6 years old. Socioemotional problems were evaluated using the Child Behavioral Checklist at 4 and 7 years of age. All questionnaires were caregiver-reported. ResultsLinear regressions demonstrated that eveningness was associated with concurrent sleep problems and internalizing, externalizing and total behavioral problems at 4–4.5 years old, but not sleep duration. Mediation analyses supported that sleep problems (and not sleep duration) at 6 years old mediated the relationship between chronotype and socioemotional problems at 7 years old. ConclusionsOur findings suggest addressing sleep problems during early development may reduce socioemotional problems at school-age, especially among evening-chronotype children.

A longitudinal study of breastmilk feeding duration, EEG power and early academic skills

BackgroundThe cognitive benefits of breastfeeding are widely recognized; however, its effects on brain development and later academic skills require further examination. This study aimed to examine the longitudinal relations between breastmilk feeding, neurophysiological changes, and early academic skills. MethodsIn the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort, breastmilk feeding practices were collected every 3 months from 3 weeks to 18 months postpartum. Resting electroencephalography (EEG) was recorded at 18 months and power spectral density was derived. The outcomes were a set of early academic assessments administered at age 4 (n = 810). Structural equation modelling was used to investigate EEG power as a mediator between breastmilk duration and early academic skills. ResultsBreastmilk feeding for ≥12 months was associated with better general knowledge, numeracy, and language at age 4 compared to shorter durations of breastmilk feeding (Cohen's d: 1.53–17.44). Linear regression showed that breastmilk duration was negatively and positively associated with low- (i.e., delta, theta) and high-frequency power (i.e., gamma), respectively (Cohen's f2: 0.03–0.09). After adjusting for demographic and child baseline covariates, a decrease in absolute and relative delta, as well as relative theta was associated with better general knowledge and numeracy (Cohen's f2: 0.16–0.25). Relative delta power provided an indirect path between breastmilk duration and early academic skills (x2: 18.390, p = 0.010; CFI: 0.978; TLI: 0.954; RMSEA: 0.040). ConclusionsExtended breastmilk feeding is associated with reduced low-frequency power and better early academic skills, suggesting benefits to brain development. Additional research to confirm this finding is warranted.

Correlates of lifestyle patterns among children in Singapore aged 10 years: the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study

ObjectiveTo characterise lifestyle patterns (comprising dietary and movement behaviour aspects) of children in Singapore and examine the correlates of these patterns.DesignAn observational study approach was used. Children recorded their diet and activities over two weekdays and two weekend days on a validated web-based assessment, My E-Diary for Activities and Lifestyle (MEDAL). Lifestyle patterns were derived using principal component analysis, and the correlations of these with multiple known determinants organised by distal, intermediate, and proximal levels of influence were studied.SettingChildren of the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort.ParticipantsTen-year-old children (n = 397).ResultsThree lifestyle patterns, “high snacks and processed food”, “balanced” and “mixed”, were identified. We focused on the more health-promoting “balanced” pattern, characterised by lower screen-viewing and higher consumption of fruits, vegetables, wholegrains, and dairy. Among the distal factors, girls were more adherent to the “balanced” pattern compared to boys, and children of parents with lower education levels were less adherent to this pattern. Among intermediate factors, children of mothers with higher diet quality were more adherent to the “balanced” pattern. Among the proximal factors, engagement in active transport, leisure sports, and educational activities outside of school were positively associated with the “balanced” pattern, whereas screen-viewing while travelling was negatively associated with this pattern. Having siblings, pet ownership, mother’s physical activity, parenting style, parental bonding, child’s outdoor time, and breakfast consumption were not associated with children’s lifestyle patterns.ConclusionsThese findings provide direction for future interventions by identifying vulnerable groups and contexts that should be prioritised.

Examining the interaction between prenatal stress and polygenic risk for attention-deficit/hyperactivity disorder on brain growth in childhood: Findings from the DREAM BIG consortium.

This study explored the interactions among prenatal stress, child sex, and polygenic risk scores (PGS) for attention-deficit/hyperactivity disorder (ADHD) on structural developmental changes of brain regions implicated in ADHD. We used data from two population-based birth cohorts: Growing Up in Singapore Towards healthy Outcomes (GUSTO) from Singapore (n=113) and Generation R from Rotterdam, the Netherlands (n=433). Prenatal stress was assessed using questionnaires. We obtained latent constructs of prenatal adversity and prenatal mood problems using confirmatory factor analyses. The participants were genotyped using genome-wide single nucleotide polymorphism arrays, and ADHD PGSs were computed. Magnetic resonance imaging scans were acquired at 4.5 and 6 years (GUSTO), and at 10 and 14 years (Generation R). We estimated the age-related rate of change for brain outcomes related to ADHD and performed (1) prenatal stress by sex interaction models, (2) prenatal stress by ADHD PGS interaction models, and (3) 3-way interaction models, including prenatal stress, sex, and ADHD PGS. We observed an interaction between prenatal stress and ADHD PGS on mean cortical thickness annual rate of change in Generation R (i.e., in individuals with higher ADHD PGS, higher prenatal stress was associated with a lower rate of cortical thinning, whereas in individuals with lower ADHD PGS, higher prenatal stress was associated with a higher rate of cortical thinning). None of the other tested interactions were statistically significant. Higher prenatal stress may promote a slower brain developmental rate during adolescence in individuals with higher ADHD genetic vulnerability, whereas it may promote a faster brain developmental rate in individuals with lower ADHD genetic vulnerability.

The cross-sectional and prospective associations of parental practices and environmental factors with 24-hour movement behaviours among school-aged Asian children

BackgroundParental practices and neighbourhood environmental factors may influence children’s movement behaviours. We aimed to investigate the cross-sectional and prospective associations of parental practices and neighbourhood environmental factors with accelerometer-measured 24-hour movement behaviours (24 h-MBs) among school-aged children in Singapore.MethodsThe Growing Up in Singapore Towards healthy Outcomes (GUSTO) study collected information on dimensions of parental practices and neighbourhood environment at age 5.5 years. Confirmatory factor analyses were performed to generate latent variables and used to compute overall parental practices [involvement in PA + support for PA + control of screen viewing context] and environmental scores [facilities for active play + active mobility facilitators + barriers*-1]. Children wore an accelerometer on their non-dominant wrist for seven consecutive days at ages 5.5 and 8 years. The R-package GGIR 2.6 was used to derive moderate-to-vigorous-intensity physical activity (MVPA), light-intensity physical activity (LPA), inactivity, and total-sleep (napping+night sleep) minutes per day. Associations were determined using compositional data analysis with multivariate linear regression models, taking into account potential confounders.ResultsAmong 425 children (48% girls, 59% Chinese), higher parental involvement in PA, parental support for PA and overall parental practices were associated with 24 h-MBs at ages 5.5 and 8 years, specifically with greater time spent in MVPA and less time being inactive relative to the remaining movement behaviours. The corresponding mean changes in the overall 24 h-MB for increasing parental practices from lowest to highest scores (− 2 to + 2 z-scores) indicated potential increases of up to 15-minutes in MVPA, 20-minutes in LPA, 5-minutes in sleep duration, and a reduction of 40-minutes in inactivity at age 5.5 years. At age 8 years, this could translate to approximately 15-minutes more of MVPA, 20-minutes more of LPA, a 20-minute reduction in sleep duration, and a 20-minute reduction in inactivity. Parental control of screen viewing contexts and neighbourhood environmental factors were not associated with 24 h-MBs.ConclusionsParental practices but not environmental factors were associated with higher MVPA and lower inactivity among Singaporean children, even at a later age. Further research may provide insights that support development of targeted public health strategies to promote healthier movement behaviours among children.Study registrationThis study was registered on 4th August 2010 and is available online at ClinicalTrials.gov: NCT01174875.

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

ObjectiveMaternal 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. MethodsData 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. ResultsChildren 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. ConclusionsAssociations 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.

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 (β = −0. 141, p-value = 0.024, 95% CI −0. 264 to −0. 018) and a lower WIAT-III mean score at ~9 years (β = −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 (β = −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.

Maternal glycemic status during pregnancy and mid-childhood plasma amino acid profiles: findings from a multi-ethnic Asian birth cohort

BackgroundIncreasing maternal glycaemia across the continuum during pregnancy may predispose offspring to subsequent cardiometabolic risk later in life. However, evidence of long-term impacts of maternal glycemic status on offspring amino acid (AA) profiles is scarce. We aimed to investigate the association between maternal antenatal glycaemia and offspring mid-childhood amino acid (AA) profiles, which are emerging cardiometabolic biomarkers.MethodsData were drawn from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study, a multi-ethnic Asian birth cohort. A subset of 422 mother–child dyads from the GUSTO study, who was followed from early pregnancy to mid-childhood, was included. Mothers underwent an oral glucose tolerance test (OGTT) at 26–28 weeks gestation, with fasting and 2-h plasma glucose concentrations measured and gestational diabetes mellitus (GDM) diagnosed per WHO 1999 guidelines. Offspring fasting plasma samples were collected at mean age 6.1 years, from which AA profiles of nine AAs, alanine, glutamine, glycine, histidine, isoleucine, leucine, valine, phenylalanine, and tyrosine were measured. Total branched-chain amino acids (BCAAs) were calculated as the sum of isoleucine, leucine, and valine concentrations. Multi-variable linear regression was used to estimate the association of maternal glycemic status and offspring mid-childhood AA profiles adjusting for maternal age, ethnicity, maternal education, parity, family history of diabetes, ppBMI, child sex, age and BMI z-scores.ResultsApproximately 20% of mothers were diagnosed with GDM. Increasing maternal fasting glucose was significantly associated with higher offspring plasma valine and total BCAAs, whereas higher 2-h glucose was significantly associated with higher histidine, isoleucine, valine, and total BCAAs. Offspring born to mothers with GDM had higher valine (standardized mean difference 0.27 SD; 95% CI: 0.01, 0.52), leucine (0.28 SD; 0.02, 0.53), and total BCAAs (0.26 SD; 0.01, 0.52) than their counterparts. Inconsistent associations were found between maternal GDM and other amino acids among offspring during mid-childhood.ConclusionsIncreasing maternal fasting and post-OGTT glucose concentrations at 26–28 weeks gestation were significantly associated with mid-childhood individual and total BCAAs concentrations. The findings suggest that elevated maternal glycaemia throughout pregnancy, especially GDM, may have persistent programming effects on offspring AA metabolism which were strongly associated with adverse cardiometabolic profiles at mid-childhood.

Clinical predictors of wheeze trajectories and associations with allergy in Asian children

BackgroundChildhood wheezing is a highly heterogeneous condition with an incomplete understanding of the characteristics of wheeze trajectories, particularly for persistent wheeze. ObjectiveTo characterize predictors and allergic comorbidities of distinct wheeze trajectories in a multiethnic Asian cohort. MethodsA total of 974 mother-child pairs from the prospective Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort were included in this study. Wheeze and allergic comorbidities in the first 8 years of life were assessed using the modified International Study of Asthma and Allergies in Childhood questionnaires and skin prick tests. Group-based trajectory modeling was used to derive wheeze trajectories and regression was used to assess associations with predictive risk factors and allergic comorbidities. ResultsThere were 4 wheeze trajectories derived, including the following: (1) early-onset with rapid remission from age 3 years (4.5%); (2) late-onset peaking at age 3 years and rapidly remitting from 4 years (8.1%); (3) persistent with a steady increase to age 5 years and high wheeze occurrence until 8 years (4.0%); and (4) no or low wheeze (83.4%). Early-onset wheezing was associated with respiratory infections during infancy and linked to subsequent nonallergic rhinitis throughout childhood. Late-onset and persistent wheeze shared similar origins characterized by parent-reported viral infections in later childhood. However, persistent wheezing was generally more strongly associated with a family history of allergy, parent-reported viral infections in later childhood, and allergic comorbidities as compared with late-onset wheezing. ConclusionThe timing of viral infection occurrence may determine the type of wheeze trajectory development in children. Children with a family history of allergy and viral infections in early life may be predisposed to persistent wheeze development and the associated comorbidities of early allergic sensitization and eczema.

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

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. 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. 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. 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.

208-LB: Plasma Lipidomics Reveals Sex-Specific Associations with? Brown Adipose Tissue in Asian Children

Brown adipose tissue (BAT) plays a crucial role in lipid metabolism. Activated BAT oxidizes fatty acids from triglycerides in lipid droplets during thermogenesis, increasing energy expenditure. The lipidomic profile of BAT has been primarily studied in animals but little in humans. We sought to identify the plasma lipidomic profile associated with BAT in a thermoneutral condition in 6-year-old children (n=134) in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. LC-MS/MS-based quantification of 480 lipids was performed on plasma samples; %BAT was quantified based on fat-signal-fractions of water-fat-MRI. Associations between plasma lipids and the child's %BAT were investigated using multivariate regression analysis adjusting for sex, ethnicity, and BMI. Sex stratification was applied to investigate the sex-specific lipid signatures of %BAT among the 68 boys and 66 girls. The inverse association between %BAT and BMI was stronger in boys (R2 =0.28) than in girls (R2 =0.07). More lipid signatures of %BAT were observed in boys compared to girls; of 63 unique lipid species significantly associated with %BAT, 12 were associated in both genders, 50 in boys and 11 in girls. In boys, lipid species representing triacylglycerol, cholesteryl ester, acylcarnitine, sphingomyelin, ceramide, hexosylceramides and lysophosphatidylcholine classes showed negative associations with %BAT, whereas several phosphatidylethanolamine lipids displayed positive association with %BAT. In girls, opposite trends in effect sizes (R=-0.44) were, however, observed; several lipids in acylcarnitine, diacylglycerol and sphingolipid classes presented positive association with %BAT, while phosphatidylethanolamine lipids showed negative associations with %BAT. These unique associations between plasma lipid species and BAT in a sex-specific manner provide insights into the different potential lipidomic pathways involved in BAT energy metabolism. Disclosure M. Tint: None. M. Fortier: None. K. Godfrey: Other Relationship; See box. M. Wenk: None. J. Eriksson: None. L. Chen: None. N. Kothandaraman: None. M. K. Leow: None. B. Kn: None. F. Yap: None. Y. Lee: None. E. H. Tham: None. Y. Chong: None. Funding Open Fund Large-Collaborative Grant (000504)

Validating the Children's Depression Inventory-2: Results from the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) study.

Childhood-onset depression has adverse consequences that are sustained into adulthood, which increases the significance of detection in early childhood. The Children's Depression Inventory (CDI) is used globally in evaluating depressive symptom severity in adolescents, and its second version, the CDI-2, was developed by taking into account advances in childhood depression research. Prior research has reported inconsistencies in its factor structure across populations. In addition, the CDI-2 has not yet been empirically validated with Southeast Asian populations. This study sought to empirically validate the CDI-2's psychometric properties and evaluate its factorial structure with a Singaporean community sample of non-clinical respondents. A total sample of 730 Singaporean children aged between 8.5 and 10.5 years was used. Psychometric properties of the CDI-2, including internal consistency as well as convergent and discriminant validity, were assessed. Factor analyses were conducted to assess the developers' original two-factor structure for a Southeast Asian population. This two-factor structure was not supported in our sample. Instead, the data provided the best fit for a hierarchical two-factor structure with factors namely, socio-emotional problems and cognitive-behavioural problems. This finding suggests that socio-cultural and demographic elements influence interpretation of depressive symptoms and therefore the emerging factor structure of the construct under scrutiny. This study highlights the need to further examine the CDI-2 and ensure that its interpretation is culture-specific. More qualitative work could also bring to light the idiosyncratic understanding of depressive symptomatology, which would then guide culture-specific validation of the CDI-2.

Associations between sleep trajectories up to 54 months and cognitive school readiness in 4 year old preschool children.

This study explores the association between the duration and variation of infant sleep trajectories and subsequent cognitive school readiness at 48-50 months. Participants were 288 multi-ethnic children, within the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. Caregiver-reported total, night and day sleep durations were obtained at 3, 6, 9, 12, 18, 24 using the Brief Infant Sleep Questionnaire and 54 months using the Child Sleep Habits Questionnaire. Total, night and day sleep trajectories with varying durations (short, moderate, or long) and variability (consistent or variable; defined by standard errors) were identified. The cognitive school readiness test battery was administered when the children were between 48 and 50 months old. Both unadjusted adjusted analysis of variance models and adjusted analysis of covariance models (for confounders) were performed to assess associations between sleep trajectories and individual school readiness tests in the domains of language, numeracy, general cognition and memory. In the unadjusted models, children with short variable total sleep trajectories had poorer performance on language tests compared to those with longer and more consistent trajectories. In both unadjusted and adjusted models, children with short variable night sleep trajectories had poorer numeracy knowledge compared to their counterparts with long consistent night sleep trajectories. There were no equivalent associations between sleep trajectories and school readiness performance for tests in the general cognition or memory domains. There were no significant findings for day sleep trajectories. Findings suggest that individual differences in longitudinal sleep duration patterns from as early as 3 months of age may be associated with language and numeracy aspects of school readiness at 48-50 months of age. This is important, as early school readiness, particularly the domains of language and mathematics, is a key predictor of subsequent academic achievement.

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

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. To examine the associations between infant screen time, EEG markers, and school-age cognitive outcomes using mediation analysis with structural equation modeling. 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. Parent-reported screen time at age 12 months. 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. 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 β, 0.41; 95% CI, 0.22 to 0.59; mediator-outcome β, -0.38; 95% CI, -0.64 to -0.11), forming an indirect path that accounted for 39.4% of the association. 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.

The global agenda on obesity: what does this mean for Singapore?

The global agenda on obesity: what does this mean for Singapore?

Timing of introduction of complementary foods, breastfeeding, and child cardiometabolic risk: a prospective multiethnic Asian cohort study

BackgroundThe timing of introduction of complementary foods and the duration of breastfeeding (BF) have been independently associated with child overweight and obesity; however, their combined influence on body fat partitioning and cardiometabolic risk is unclear. ObjectiveWe investigated the associations of the timing of introduction of complementary foods, the duration of BF, and their interaction with child adiposity and cardiometabolic risk markers. MethodsWe analyzed data from 839 children in the prospective Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. Mothers reported the age at which infants were first fed complementary foods and BF duration, classified as early (≤4 mo) versus typical (>4 mo) complementary feeding (CF) and short (≤4 mo) versus long (>4 mo) duration of any BF, respectively. We measured adiposity and cardiometabolic risk markers at the age of 6 y and examined their associations with infant feeding patterns using multiple regression, adjusting for sociodemographics, parents’ body mass index (BMI), maternal factors, birth weight for gestational age, and infant weight gain. ResultsOf 839 children, 18% experienced early CF, whereas 54% experienced short BF. Short (vs. long) BF and early (vs. typical) CF were independently associated with higher z-scores of BMI [β (95% confidence interval), short BF, 0.18 standard deviation score (SDS) (−0.01, 0.38); early CF, 0.34 SDS (0.11, 0.57)] and sum of skinfolds [short BF, 1.83 mm (0.05, 3.61); early CF, 2.73 mm (0.55, 4.91)]. Children who experienced both early CF and short BF (vs. typical CF–long BF) had synergistically higher diastolic blood pressure [1.41 mmHg (−0.15, 2.97), P-interaction = 0.023] and metabolic syndrome score [0.81 (0.16, 1.47), P-interaction = 0.081]. Early CF–long BF (vs. early CF–short BF) was associated with a lower systolic blood pressure [−3.74 mmHg (−7.01, −0.48)], diastolic blood pressure [−2.29 mmHg (−4.47, −0.11)], and metabolic syndrome score [−0.90 (−1.80, 0.00)]. ConclusionsA combination of early CF and short BF was associated with elevated child adiposity and cardiometabolic markers. Longer BF duration may protect against cardiometabolic risk associated with early CF.This trial was registered at clinicaltrials.gov as NCT01174875.

Newborn body composition and child cardiovascular risk markers: a prospective multi-ethnic Asian cohort study.

Early epidemiological studies have associated low birthweight with increased cardiovascular risk. We aimed to examine whether the fat and fat-free components of birthweight have differing relationships with childhood cardiovascular risk markers. In the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort, air displacement plethysmography was conducted within 24 h after delivery in 290 naturally conceived singletons. We investigated associations of newborn cohort-specific standardized z-score of fat mass, fat-free mass, body fat percentage and birthweight on child (at 6 years of age) carotid intima-media thickness, pulse wave velocity, blood pressure, prehypertension/hypertension (>110/70 mmHg) and standardized systolic and diastolic blood pressure (SBP and DBP) trajectories (at 3-6 years of age), taking account of maternal education, height, tobacco exposure, parity, ethnicity, child's sex, gestational age, age at follow-up, and other maternal factors. Clear inverse associations were seen for blood pressure with z-score of fat mass [SBP, β (95% CI): -1.31 mmHg (-2.57, -0.06); DBP: -0.79 mmHg (-1.74, 0.15)] and body fat percentage [SBP: -1.46 mmHg (-2.73, -0.19); DBP: -0.80 mmHg (-1.75, 0.16)], but not with fat-free mass [SBP: 0.27 mmHg (-1.29, 1.83)]; DBP: -0.14 mmHg (-1.30, 1.03)]. Being in the lowest tertile of fat mass or body fat percentage was associated with higher blood pressure trajectories and prehypertension/hypertension risk [OR (95% CI), fat mass: 4.23 (1.41, 12.68); body fat percentage: 3.22 (1.09, 9.53)] without concomitantly higher overweight/obesity risk. At birth, low adiposity was associated with increased childhood blood pressure. Low newborn adiposity might serve as a marker of poor fetal growth or suboptimal intrauterine conditions associated with hypertension risk later in life.