The effects of acute social ostracism on subsequent snacking behavior and future body mass index in children.

BACKGROUND/OBJECTIVES: Ostracism may lead to increased food intake, yet it is unclear whether greater reactivity to ostracism contributes to higher body mass index (BMI). We investigated whether children who exhibited greater stress to social exclusion subsequently consume more energy and whether this predicts BMI 6- and 18-months later. SUBJECTS/METHODS: Children (8.5 years-old) (N = 262, males = 50.4%; Chinese = 58.4%) completed a laboratory-based manipulation of social exclusion (the Cyberball task) prior to an ad-libitum snack. Heart rate variability (HRV) was measured during the inclusion and exclusion conditions and proportionate changes were calculated as a physiological measure of exclusion-related stress. Social anxiety and social-emotional assets were also measured as moderators. RESULTS: Greater stress (as measured physiologically or by self-report) did not directly, or indirectly via energy intake, predict later BMI (at 9- and 10-years). However, among children reporting higher social anxiety, greater stress as measured by proportionate changes in HRV was associated with increased energy intake (B = 532.88, SE = 226.49, t(255) = 2.35, [CI95 = 86.85,978.92]). A significant moderated mediation was also observed (index: (b = 0.01, bootSE = 0.01, [CI95 = 0.001, 0.036]), such that among children reporting higher social anxiety, greater stress from social exclusion predicted increased energy intake from a subsequent snack, which in turn predicted higher BMI 1.5 years later. CONCLUSION: This prospective study suggests that a pattern of greater snack intake in response to heightened vulnerability to the effects of ostracism may contribute to increases in child BMI scores.

Joint modeling of association networks and longitudinal biomarkers: An application to childhood obesity.

The prevalence of chronic non-communicable diseases such as obesity has noticeably increased in the last decade. The study of these diseases in early life is of paramount importance in determining their course in adult life and in supporting clinical interventions. Recently, attention has been drawn to approaches that study the alteration of metabolic pathways in obese children. In this work, we propose a novel joint modeling approach for the analysis of growth biomarkers and metabolite associations, to unveil metabolic pathways related to childhood obesity. Within a Bayesian framework, we flexibly model the temporal evolution of growth trajectories and metabolic associations through the specification of a joint nonparametric random effect distribution, with the main goal of clustering subjects, thus identifying risk sub-groups. Growth profiles as well as patterns of metabolic associations determine the clustering structure. Inclusion of risk factors is straightforward through the specification of a regression term. We demonstrate the proposed approach on data from the Growing Up in Singapore Towards healthy Outcomes cohort study, based in Singapore. Posterior inference is obtained via a tailored MCMC algorithm, involving a nonparametric prior with mixed support. Our analysis has identified potential key pathways in obese children that allow for the exploration of possible molecular mechanisms associated with childhood obesity.

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

BACKGROUND: Parental 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. METHODS: The 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. RESULTS: Among 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. CONCLUSIONS: Parental 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 REGISTRATION: This study was registered on 4th August 2010 and is available online at ClinicalTrials.gov: NCT01174875.

A machine-learning exploration of the exposome from preconception in early childhood atopic eczema, rhinitis and wheeze development.

BACKGROUND: Most previous research on the environmental epidemiology of childhood atopic eczema, rhinitis and wheeze is limited in the scope of risk factors studied. Our study adopted a machine learning approach to explore the role of the exposome starting already in the preconception phase. METHODS: We performed a combined analysis of two multi-ethnic Asian birth cohorts, the Growing Up in Singapore Towards healthy Outcomes (GUSTO) and the Singapore PREconception Study of long Term maternal and child Outcomes (S-PRESTO) cohorts. Interviewer-administered questionnaires were used to collect information on demography, lifestyle and childhood atopic eczema, rhinitis and wheeze development. Data training was performed using XGBoost, genetic algorithm and logistic regression models, and the top variables with the highest importance were identified. Additive explanation values were identified and inputted into a final multiple logistic regression model. Generalised structural equation modelling with maternal and child blood micronutrients, metabolites and cytokines was performed to explain possible mechanisms. RESULTS: The final study population included 1151 mother-child pairs. Our findings suggest that these childhood diseases are likely programmed in utero by the preconception and pregnancy exposomes through inflammatory pathways. We identified preconception alcohol consumption and maternal depressive symptoms during pregnancy as key modifiable maternal environmental exposures that increased eczema and rhinitis risk. Our mechanistic model suggested that higher maternal blood neopterin and child blood dimethylglycine protected against early childhood wheeze. After birth, early infection was a key driver of atopic eczema and rhinitis development. CONCLUSION: Preconception and antenatal exposomes can programme atopic eczema, rhinitis and wheeze development in utero. Reducing maternal alcohol consumption during preconception and supporting maternal mental health during pregnancy may prevent atopic eczema and rhinitis by promoting an optimal antenatal environment. Our findings suggest a need to include preconception environmental exposures in future research to counter the earliest precursors of disease development in children.

Correlates of lifestyle patterns among children in Singapore aged 10 years: the growing up in Singapore towards healthy outcomes (GUSTO) study.

OBJECTIVE: To characterise lifestyle patterns (comprising dietary and movement behaviour aspects) of children in Singapore and examine the correlates of these patterns. DESIGN: An 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. SETTING: Children of the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. PARTICIPANTS: Ten-year-old children (n = 397). RESULTS: Three 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. CONCLUSIONS: These findings provide direction for future interventions by identifying vulnerable groups and contexts that should be prioritised.

Relation of preconception eating behaviours to dietary pattern trajectories and gestational weight gain from preconception to late pregnancy.

Studies examining preconception eating behaviours with longitudinal dietary patterns from preconception to late pregnancy as well as gestational weight gain (GWG) are limited. We derived dietary pattern trajectories from preconception to late-pregnancy, and related preconception eating behaviours to these trajectories and GWG. Preconception eating behaviours were assessed using the Three-Factor Eating Questionnaire measuring cognitive restraint (CR) - conscious restriction of food intake, emotional eating (EE) - overeating in response to negative emotions, and uncontrolled eating (UE) - overeating with a feeling of lack of control. Dietary intakes were measured at preconception, 20-21 and 34-36 weeks' gestation with food frequency questionnaires. Dietary patterns were determined using factor analysis, and trajectories derived using group-based trajectory modelling. Inadequate and excessive GWG were defined according to Institute of Medicine guidelines based on weights at preconception and the last antenatal visit (median: 38 weeks' gestation). Two dietary patterns were derived: 'Fast Food, Fried Snacks and Desserts (FFD)' and 'Soup, Fish and Vegetables (SFV)'. Adherence trajectories from preconception to late-pregnancy were characterised as consistently high ("stable-high") and low ("stable-low"). Women with higher UE scores had higher odds of being in the "stable-high" trajectory (n = 34) of the FFD pattern [Odds Ratio (OR): 1.25, 95% Confidence Interval (CI): 1.03, 1.51], compared to "stable-low" (n = 260). Percentages of women with inadequate, adequate or excessive GWG were 21.7% (n = 70), 25.8% (n = 83), and 52.5% (n = 169), respectively; women with higher EE scores had a higher likelihood of excessive GWG [Relative Risk Ratio (RRR): 1.35, 95% CI: 1.02, 1.80], but this association was attenuated after adjusting for preconception body mass index. Eating behaviour interventions to improve dietary patterns among pregnant women may need to start as early as preconception, incorporating strategies to manage UE.

Preliminary assessment of the Healthy Early Life Moments (HELMS) webinars in empowering Developmental Origins of Health and Disease (DOHaD) concept among healthcare professionals - a pragmatic serial cross-sectional study.

OBJECTIVES: The Developmental Origins of Health and Disease (DOHaD) concept has gained prominence in maternal and child health (MCH), emphasizing how early-life factors impact later-life non-communicable diseases. However, a knowledge-practice gap exists in applying DOHaD principles among healthcare professionals. Healthy Early Life Moments in Singapore (HELMS) introduced webinars to bridge this gap and empower healthcare professionals. We aimed to conduct a preliminary assessment to gain early insights into the outreach and effectiveness of the educational initiative offered with the HELMS webinars. METHODS: We employed a pragmatic serial cross-sectional study approach and targeted healthcare professionals involved in MCH care. We also collected and analyzed data on webinar registration and attendance, participants' profession and organizational affiliations, and post-webinar survey responses. RESULTS: The median webinar attendance rate was 59.6 % (25th-75th percentile: 58.4-60.8 %). Nurses represented 68.6 % of attendees (n=2,589 out of 3,774). Post-webinar surveys revealed over 75 % of the participants providing positive responses to 14 out of 15 survey questions concerning content, delivery, applicability to work, and organization. CONCLUSIONS: Assessment of the HELMS webinars provided insight into the outreach and early effectiveness in enhancing healthcare professionals' knowledge and confidence in delivering DOHaD education. Bridging the knowledge-practice gap remains a crucial goal.

Holistic preconception care: Providing real-time guidance via a mobile app to optimise maternal and child health.

Introduction: Preconception is a critical period to optimise gamete function and early placental development, essential for successful conception and long-term maternal-child health. However, there is a lack of preconception services and consequently, global fertility rates continue to fall and mothers embark on their pregnancy journey in poor health. There is an urgent need to implement a holistic community-level preconception care programme to optimise risk factors for poor fecundability and improve long-term maternal-child health. Method: We reviewed current evidence on fecundability lifestyle risk factors, the efficacy of existing preconception interventions and the use of digital platforms for health optimisation, to create a new digital-based preconception intervention model that will be implemented via an app. We present the theory, content and mode of delivery of this holistic model targeting couples planning for pregnancy. Results: We propose a new model featuring a user-friendly mobile app, which enables couples to self-assess fecundability risks through a personalised risk score that drives a tailored management plan. This tiered management provides anticipatory guidance supported by evidence-based recommen-dations, and promotes ongoing engagement for behavioural optimisation and specialist referrals as required. Based on the health belief model, this new model delivered with a mobile app seeks to shift couples' perceptions about their susceptibility and severity of subfertility, benefits of making a change and barriers to change. Conclusion: Our proposed digital-based intervention model via a mobile app stands to enhance preconcep-tion care by providing personalised risk assessments, real-time feedback and tiered management to optimise preconception reproductive health of couples. This model forms a reference content framework for future preconception care intervention delivery.

Umbilical Cord Plasma Lysophospholipids and Triacylglycerols Associated with Birthweight Percentiles.

Dysregulated transplacental lipid transfer and fetal-placental lipid metabolism affect birthweight, as does maternal hyperglycemia. As the mechanisms are unclear, we aimed to identify the lipids in umbilical cord plasma that were most associated with birthweight. Seventy-five Chinese women with singleton pregnancies recruited into the GUSTO mother-offspring cohort were selected from across the glycemic range based on a mid-gestation 75 g oral glucose tolerance test, excluding pre-existing diabetes. Cord plasma samples collected at term delivery were analyzed using targeted liquid-chromatography tandem mass-spectrometry to determine the concentrations of 404 lipid species across 17 lipid classes. The birthweights were standardized for sex and gestational age by local references, and regression analyses were adjusted for the maternal age, BMI, parity, mode of delivery, insulin treatment, and fasting/2 h glucose, with a false discovery-corrected p < 0.05 considered significant. Ten lysophosphatidylcholines (LPCs) and two lysophosphatidylethanolamines were positively associated with the birthweight percentiles, while twenty-four triacylglycerols were negatively associated with the birthweight percentiles. The topmost associated lipid was LPC 20:2 [21.28 (95%CI 12.70, 29.87) percentile increase in the standardized birthweight with each SD-unit increase in log10-transformed concentration]. Within these same regression models, maternal glycemia did not significantly associate with the birthweight percentiles. Specific fetal circulating lysophospholipids and triacylglycerols associate with birthweight independently of maternal glycemia, but a causal relationship remains to be established.

The Effect of Vitamin D Supplementation in Pregnant Women with Overweight and Obesity: A Randomised Controlled Trial.

The impact of vitamin D supplementation on 25-hydroxyvitamin D (25OHD) levels, metabolic status, and pregnancy outcomes in pregnant women with overweight and obesity (OW/OB) is uncertain. This study aimed to examine whether administrating 800 IU of vitamin D3 orally would improve maternal serum 25OHD levels, lipid profile, and pregnancy outcomes compared to 400 IU. This was a two-arm, parallel, non-blinded randomised controlled trial involving 274 pregnant women recruited from KK Women's and Children's Hospital, with a body mass index of ≥25 kg/m2 within 16 weeks gestation. The participants were randomly assigned to receive 800 IU/day (intervention group) or 400 IU/day (control group) of oral vitamin D3 supplements. The primary outcomes were maternal serum 25OHD and lipid levels at 24-28 weeks gestation. The secondary outcomes included maternal and birth outcomes. Compared with controls (n = 119), the intervention group (n = 112) exhibited higher 25OHD levels at 24-28 weeks gestation (adjusted mean difference 6.52 nmol/L; 95% confidence interval 2.74, 10.31). More women in the intervention group achieved sufficient 25OHD levels (77.7% vs. 55.5%; p < 0.001). No differences were observed in lipid profiles or maternal or birth outcomes between the groups. An additional 400 IU of oral vitamin D3 supplementation increased serum 25OHD levels but did not impact lipid profiles or pregnancy outcomes.

Comparing feature selection and machine learning approaches for predicting CYP2D6 methylation from genetic variation.

Introduction: Pharmacogenetics currently supports clinical decision-making on the basis of a limited number of variants in a few genes and may benefit paediatric prescribing where there is a need for more precise dosing. Integrating genomic information such as methylation into pharmacogenetic models holds the potential to improve their accuracy and consequently prescribing decisions. Cytochrome P450 2D6 (CYP2D6) is a highly polymorphic gene conventionally associated with the metabolism of commonly used drugs and endogenous substrates. We thus sought to predict epigenetic loci from single nucleotide polymorphisms (SNPs) related to CYP2D6 in children from the GUSTO cohort. Methods: Buffy coat DNA methylation was quantified using the Illumina Infinium Methylation EPIC beadchip. CpG sites associated with CYP2D6 were used as outcome variables in Linear Regression, Elastic Net and XGBoost models. We compared feature selection of SNPs from GWAS mQTLs, GTEx eQTLs and SNPs within 2 MB of the CYP2D6 gene and the impact of adding demographic data. The samples were split into training (75%) sets and test (25%) sets for validation. In Elastic Net model and XGBoost models, optimal hyperparameter search was done using 10-fold cross validation. Root Mean Square Error and R-squared values were obtained to investigate each models' performance. When GWAS was performed to determine SNPs associated with CpG sites, a total of 15 SNPs were identified where several SNPs appeared to influence multiple CpG sites. Results: Overall, Elastic Net models of genetic features appeared to perform marginally better than heritability estimates and substantially better than Linear Regression and XGBoost models. The addition of nongenetic features appeared to improve performance for some but not all feature sets and probes. The best feature set and Machine Learning (ML) approach differed substantially between CpG sites and a number of top variables were identified for each model. Discussion: The development of SNP-based prediction models for CYP2D6 CpG methylation in Singaporean children of varying ethnicities in this study has clinical application. With further validation, they may add to the set of tools available to improve precision medicine and pharmacogenetics-based dosing.