BACKGROUND:Nutrition contributes to bone mineral density (BMD) during infancy and childhood; however, studies focusing on infant nutrition and BMD relationships in childhood are limited. OBJECTIVES:This study aimed to examine relationships of any breastfeeding (BF) duration and timing of complimentary foods and beverages (CFB) introduction with BMD outcomes in young Asian children from the Growing Up in Singapore Toward healthy Outcomes (GUSTO) cohort. METHODS:Healthy term-born children aged 6 y (n = 207) with available BF duration data (months) and dual-energy X-ray (DXA) absorptiometry scans of lumbar spine (LS) and whole body (WB) were included to examine the BF duration and CFB introduction associations with DXA-derived-BMD outcomes; cohort-specific z-scores of areal BMD (aBMD, grams per square centimeter) and bone mineral apparent density (BMAD, grams per cubic centimeter) of WB and LS. Multivariable models utilized regularized regression modeling [least absolute shrinkage and selection operator (LASSO)] to leverage multiple covariates without overfitting the available data. RESULTS:In univariable models, longer BF duration was associated with lower ZWB-BMD [-0.013 ± 0.006 (SE), P = 0.027] and ZLS-aBMD (-0.012 ± 0.006, P = 0.045); in stratified analyses, longer BF duration was associated with lower ZWB-BMD (-0.023 ± 0.008, P = 0.004), ZWB-BMAD (-0.020 ± 0.007, P = 0.006, and ZLS-aBMD (-0.018 ± 0.008, P = 0.037) in females only. Most associations remained significant in adjusted LASSO models. Later CFB introduction was associated with lower ZWB-BMAD (-0.130 ± 0.065, P = 0.045); in stratified analyses, later CFB introduction was associated with lower ZLS-aBMD (-0.166 ± 0.078, P = 0.037) and ZLS-BMAD (-0.205 ± 0.078, P = 0.010) in males only. These associations were no longer apparent in adjusted LASSO models. CONCLUSIONS:A longer BF duration and delayed CFB introduction may reflect reduced bone accrual in early childhood, inferred from bone density at age 6 y, and may vary by child's sex. Recognizing these relationships is crucial for optimizing early nutrition to support strong and healthy bone development. This trial was registered at clinicaltrials.gov as NCT01174875 (https://www. CLINICALTRIALS:gov/study/NCT01174875).

Background Despite Singapore’s top-ranked healthcare system, the country’s low birth weight (LBW) rates exceed the Organisation for Economic Co-operation and Development average. Singapore also has one of the highest proportions of female marriage migrants in Asia, many of whom originate from lower-income neighbouring countries. These marriage migrants often face socioeconomic disadvantages and social integration challenges, and their children tend to exhibit more behavioural problems and lower achievement scores at a young age, raising concerns about potential higher LBW risk in this population. Given the increasing global migration population, this study examines whether foreign-born mothers have higher LBW prevalences than native-born mothers, assesses whether their presence contributes to Singapore’s high LBW rates, and explores the contributing factors underlying any observed differences.Methods Using data from the Singapore Longitudinal Early Development Study, a nationally representative sample of 5005 children born between 2011 and 2019, four family types were identified based on parental nativity: native families; cross-national families with a foreign-born mother; cross-national families with a foreign-born father; and families with both foreign-born parents. Logistic regression was used to measure group differences in LBW prevalence. Fairlie decomposition was applied to quantify the contributions of observed covariates to these differences.Results Cross-national families with a foreign-born mother had a lower LBW prevalence (OR 0.56, 95% CI 0.37 to 0.86) than native families, even after adjusting for risk factors. Fairlie decomposition showed that 75% of the immigrant health advantage in LBW was explained by observed covariates, driven primarily by mismatches in the quality of healthcare systems between the countries of origin and Singapore, followed by group differences in biological and socioeconomic factors.Conclusions The findings reveal an epidemiological paradox in Singapore, echoing immigrant health advantages observed in other developed countries: socioeconomically disadvantaged foreign-born mothers had lower LBW rates than native-born mothers. However, this advantage is not uniform and varies by family type and migration background, highlighting the importance of considering immigrant-family heterogeneity in perinatal health research.

IntroductionEarly-life health behaviors are shaped within the family environment, influencing long-term metabolic and developmental outcomes. Mobile health (mHealth) applications are widely available but most lack clinical integration, behavioral theory grounding, and personalized interactivity. This study describes the development and feasibility testing of the FamNucleus minimum viable product (MVP) and evaluates its usability and perceived quality among parents and healthcare professionals (HCPs) in supporting infant and parental health from a life-course behavioral perspective.MethodsFamNucleus was co-developed by a multidisciplinary clinical team, guided by the UK Medical Research Council framework for complex interventions, informed by the Capability, Opportunity, Motivation-Behavior model and Behavior Change Wheel. In this mixed-methods study, 25 parents and 6 HCPs used the MVP for one month (December 2024-January 2025). User experience was assessed using the User Experience Questionnaire-Key Performance Indicator (UEQ-KPI), UEQ, and user version of the Mobile App Rating Scale (uMARS). HCPs additionally completed the mHealth App Usability Questionnaire (MAUQ). Content validity was evaluated using the Content Validity Index (I-CVI). Focus group discussions were thematically analyzed using NVivo to explore user perceptions and conditions for adoption.ResultsUEQ-KPI perspicuity decreased significantly among parents and HCPs from prototype to MVP. On UEQ, parents rated attractiveness, perspicuity, and stimulation above average, while efficiency, dependability, and novelty were lower. HCPs reported higher UEQ scores overall, with excellent ratings for attractiveness, perspicuity, and novelty. On uMARS, overall app quality was rated positive by both groups. Clinical usability was rated positively by HCPs on MAUQ. Content validity was acceptable (parents: ≥0.92 across domains except ambiguity at 0.80; HCPs: ≥0.83). Qualitative findings indicated that FamNucleus was perceived as a family-oriented caregiving platform, with generally positive initial experiences, intuitive onboarding, and appealing app interface. Participants engaged with key features, including artificial intelligence-driven Chatbot, Diary, Trackers/Survey, Enrich modules, and Nudges. Mixed usability findings and challenges related to app clarity, navigation, and sustained engagement were reported.ConclusionFamNucleus demonstrated preliminary feasibility and acceptable usability as a family-centered mHealth app with perceived value in supporting early caregiving and complementing routine clinical care. Nevertheless, mixed usability findings indicate the need for further refinement prior to broader implementation.

The rising prevalence of metabolic syndrome (MetS) and gestational diabetes mellitus (GDM) in women of reproductive age highlights their growing susceptibility to future cardiometabolic diseases. Both conditions signal early metabolic dysfunction tied to abdominal adiposity. We investigated whether relative abdominal adipose tissue (AAT) distribution characterises metabolic risk beyond general adiposity. Using magnetic resonance imaging, we quantified superficial (SSAT) and deep (DSAT) subcutaneous, intraperitoneal (IPAT), and retroperitoneal (RPAT) adipose tissue compartments to derive AAT distribution phenotypes from their relative contributions. These phenotypes were characterized with respect to MetS, GDM risk, ectopic fat accumulation, and metabolic profiles. The relative AAT distribution of higher %IPAT and lower %DSAT was a significant determinant for MetS. Women with both lower %IPAT and higher %DSAT exhibited the most favourable metabolic profiles, whereas women with higher %IPAT and lower %DSAT showed increased prevalence of MetS, hepatic steatosis, elevated high-sensitivity C-reactive protein, and 5.36-fold higher odds of developing GDM (95% CI 1.12-27.85). Notably, metabolic differences were observed despite similar overall adiposity including total AAT, body fat percentage, body mass index, and waist circumference. This suggests that AAT accumulation, particularly preferential DSAT over IPAT, captures metabolic heterogeneity and may support precision risk stratification of cardiometabolic disease in women.

BACKGROUND:Folic acid (FA), an essential nutrient for one-carbon metabolism, has been implicated in metabolic disease development. Although FA supplementation during pregnancy prevents neural tube defects, its broader metabolic effects remain unclear. METHODS:Eight-week-old C57BL/6 female mice were mated and fed an FA-deficient or control diet during gestation. Male offspring were weaned onto either a normal or Western-type diet, and monitored until 3 months of age. In the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort, associations between maternal plasma FA levels during pregnancy and ectopic fat accumulation in offspring at age 6 years were examined. RESULTS:Maternal FA deficiency promoted ectopic fat accumulation in the liver and skeletal muscle of male offspring and increased obesity susceptibility. These effects were associated with disrupted one-carbon metabolism and impaired fatty acid β-oxidation, potentially due to reduced expression of Adenosylmethionine Decarboxylase 1 (Amd1) in male offspring. Consistently, in the GUSTO cohort, maternal plasma FA concentrations were inversely associated with hepatic and muscular fat accumulation in children. CONCLUSION:Maternal FA status plays a critical role in regulating male offspring metabolic health. Maintaining adequate maternal plasma FA levels, rather than focusing solely on dietary intake, may be essential for preventing ectopic fat accumulation in the next generation.

Early eating behaviours have been associated with later weight outcomes, yet their longitudinal development and relationship with growth trajectories remain insufficiently understood. This study aims to investigate how appetite-related behaviours in early childhood co-evolve with growth patterns and contribute to obesity risk. We develop a Bayesian semi-parametric joint modelling framework to analyse repeated measures of growth indicators, such as body mass index, alongside questionnaire-based eating behaviour scores collected at multiple time points in children from the Singaporean GUSTO cohort (“Growing Up in Singapore Towards Healthy Outcomes”). The approach extends established models for ordinal questionnaire data to accommodate longitudinal observations and covariate effects, while growth trajectories are flexibly represented using spline-based regressions. Subject-specific demographic and clinical covariates are incorporated into both components of the model, allowing their effects on growth and eating behaviour to be assessed simultaneously. The two components are linked through a Bayesian nonparametric prior, specifically a Normalised Generalised Gamma Process, that enables data-driven identification of subgroups of children with similar developmental profiles. The proposed framework captures the dynamic interplay between appetite phenotypes and growth trajectories over time, allowing the identification of clinically meaningful clusters characterised by distinct behavioural and growth patterns. The proposed integrated modelling strategy provides a nuanced understanding of how eating behaviours and growth co-develop in early life, offering new insights into mechanisms underlying childhood obesity risk and supporting the design of targeted early interventions.

Movement behaviours, including moderate-to-vigorous-intensity physical activity (MVPA), light-intensity physical activity (LPA), sedentary behaviour (SB), and sleep, influence childhood adiposity. However, their collective impact on adiposity from a sex-specific perspective remains underexplored. Our research examined the sex-specific longitudinal associations of 24-h movement behaviours with body mass index (BMI) and abdominal adiposity among children. In the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort study, we repeatedly measured 24-h movement behaviours using wrist-worn accelerometers (ActiGraph GT3x) and assessed adiposity (BMI, abdominal circumference, and MRI-based abdominal fat volumes) at three time points (ages 5.5–6, 7.5–8, and 10–10.5 years) within the same children in a longitudinal design. Compositional multivariable linear mixed-effect modelling and isotemporal substitution were used to estimate the associations. 531 children (49.5

This study develops a Bayesian semi-parametric model to examine the longitudinal growth and appetite phenotypes in children from the GUSTO cohort, with a focus on understanding the relationship between eating behaviours and growth outcomes over time. While eating behaviours, such as picky eating, have been shown to influence future weight and obesity risk, their developmental patterns and associations with growth trajectories remain under-explored. This work addresses these gaps by modelling longitudinal data, including both growth metrics (e.g., BMI) and eating behaviours (e.g., Child Eating Behaviour Questionnaire, CEBQ), across multiple time points. We extend the Partial Credit Model, commonly used for questionnaire data analysis, to accommodate repeated measurements and incorporate covariates. The growth outcomes are modelled using flexible splines regression. The two components of the model are linked through a shared Bayesian nonparametric prior distribution, specifically a Normalized Generalized Gamma process, allowing to identify clinically relevant subgroups. This joint modelling approach offers a more nuanced understanding of how early eating behaviours relate to growth patterns and developmental outcomes, providing insights into childhood obesity risk.

Although the associations between cord blood lipidome and neonatal birth weight are established, it remains uncertain whether sexual dimorphism in fetal fat accumulation extends to the relationship between cord blood lipid profiles and neonatal abdominal fat compartments. Understanding these relationships could provide insights into early sex-specific differences in lipid metabolism. We conducted lipidomics of umbilical cord blood plasma samples (350 (46.6

OBJECTIVE:This study aimed to examine sex-stratified associations between meeting recommended sleep duration and adiposity in 10-year-old children. METHODS:Using the GUSTO cohort (51% boys, 10.2 ± 0.2 years), we evaluated the associations of meeting sleep duration recommendations (total daily sleep duration of ≥ 9 h, caregiver-reported and actigraphy) throughout the week with obesity and BMI z-scores (N = 638), glycoprotein acetyls (n = 436), fat mass measured by quantitative magnetic resonance (n = 528), and abdominal adipose tissue volumes measured by magnetic resonance imaging (N = 377). Multivariable linear and logistic regressions were used, adjusted for ethnicity and maternal education. RESULTS:Boys, but not girls, whose caregiver-reported sleep duration met recommendations throughout the entire week had a lower risk of obesity (BMIz > 2.0) (OR = 0.49, 95% CI 0.27-0.87), BMIz (0.34 ± 0.16 vs. 0.98 ± 0.12) (p = 0.001), glycoprotein acetyls levels (0.65 ± 0.01 mmol/L vs. 0.70 ± 0.01 mmol/L) (p < 0.001), total fat mass (8.77 ± 0.69 kg vs. 11.31 ± 0.51 kg) (p = 0.002), and deep subcutaneous (492 ± 86 mL vs. 729 ± 56 mL) (p = 0.014), superficial subcutaneous (651 ± 85 mL vs. 888 ± 55 mL) (p = 0.013), and visceral (415 ± 51 mL vs. 557 ± 33 mL) (p = 0.013) adipose tissue volumes. CONCLUSIONS:Interventions to help children attain recommended sleep duration for weekdays and weekends may reduce abdominal and total adiposity, especially in boys.

Background Using longitudinal ultrasounds as an improved fetal growth marker, we aimed to investigate if increased postnatal growth following fetal abdominal circumference (AC) growth deceleration is associated with improved child cognition.Methods Among 797 term-born singletons in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort, we derived 2nd-3rd trimester fetal AC growth z-score, fetal AC growth deceleration, standardized height, weight, and body mass index (BMI) growth at early infancy (0-4 months), late infancy (4-15 months), toddlerhood (15-37 months), and early childhood (3-7 years), and investigated their associations with intelligence quotient (IQ) at ages 4.5 years (verbal, non-verbal) and 7 years (non-verbal-block design, matrix reasoning), adjusting for socio-demographic and biological confounders.Results Among term-born newborns, 23.3% experienced fetal AC growth deceleration, which was associated with lower non-verbal IQ (4.5 years) [beta (95% CI), -4.00 (-7.49, -0.51)]. Higher 0-7 years z-BMI gain was associated with lower non-verbal IQ (block design) (7 years) [-1.33 (-2.51, -0.14)]. Higher late infancy z-BMI gain was associated with higher verbal IQ (4.5 years) [3.36 (0.82,5.90)] but lower non-verbal IQ (matrix reasoning) (7 years) [-2.32 (-4.48, -0.17)]. Among those with fetal AC growth deceleration, higher 0-7 years z-weight gain was associated with lower non-verbal IQ (block design) (7 years) (P-interaction = .049); at z-weight gain of +2 standard deviation score (SDS), those with fetal AC growth deceleration had lower IQ [margins (95% CI), -2.6 (-7.1,1.9)]. On average, children with fetal AC growth deceleration caught up in z-height, z-weight, and z-BMI by 7 years.Conclusion Fetal AC growth deceleration was associated with lower cognition scores at preschool age. Increased weight or BMI growth from 0-7 years following fetal AC growth deceleration might not be favorable to cognition among generally well-nourished term-born children.

BackgroundGreater adherence to the Mediterranean Diet (MedDiet) has been associated with improved inflammatory biomarkers in Western populations, suggesting that the anti-inflammatory effect is crucial for improvements in body weight, body composition, and cardiometabolic risk factors observed with the MedDiet. We previously reported that a calorie-restricted MedDiet adapted to the Asian food culture has beneficial effects on body composition, liver fat, and cardiometabolic risk markers in Chinese women with fatty liver disease.ObjectiveTo evaluate the effects of MedDiet on inflammation and examine the relationship between dietary adherence and changes in health outcomes.Methods88 non-diabetic Chinese women with fatty liver who participated in a 3-arm, 12-week dietary randomized controlled trial were included in this secondary analysis. Adherence to the MedDiet was assessed using a validated questionnaire. Correlation analysis was performed to identify the relationships between changes in total and food group-specific MedDiet scores and changes in anthropometric measures, body fat percentage, liver fat, muscle and abdominal fat, as well as cardiometabolic and inflammation markers from baseline to post-intervention. Analyses were conducted both without adjustments and after adjusting for weight change.ResultsBody weight, total body fat, visceral and subcutaneous adipose tissues, and liver fat decreased significantly after the intervention, in tandem with improvements in markers of glucose and lipid metabolism and inflammation. The change in MedDiet scores (total and individual food groups) correlated with changes in liver fat and improvements in lipid profile, but not with changes in measures of glucose regulation and inflammation after adjusting for changes in body weight. Increased intake of vegetables, nuts, fish, legumes and olive oil appears to be the main driver of these associations.ConclusionGreater adherence to the MedDiet among nondiabetic Asian women with fatty liver is associated with greater improvements in hepatic fat and lipid profile, but the association with glucose regulation and inflammation is less pronounced. It thus remains unclear whether resolution of inflammation is the key mechanism for the health benefits of MedDiet.Clinical trial registrationclinicaltrials.gov, identifier [NCT05259475].

It is not clear if conventional liver fat cutoff of 5.56

Background: Weight loss is the most effective treatment for nonalcoholic fatty liver disease (NAFLD). There is evidence that the Mediterranean diets rich in unsaturated fatty acids and fiber have beneficial effects on weight homeostasis and metabolic risk factors in individuals with NAFLD. Studies have also shown that higher circulating concentrations of pentadecanoic acid (C15:0) are associated with a lower risk for NAFLD. Objectives: To examine the effects of a Mediterranean-like, culturally contextualized Asian diet rich in fiber and unsaturated fatty acids, with or without C15:0 supplementation, in Chinese females with NAFLD. Methods: In a double-blinded, parallel-design, randomized controlled trial, 88 Chinese females with NAFLD were randomly assigned to 1 of the 3 groups for 12 wk: diet with C15:0 supplementation (n = 31), diet without C15:0 supplementation (n = 28), or control (habitual diet and no C15:0 supplementation, n = 29). At baseline and after the intervention, body fat percentage, intrahepatic lipid content, muscle and abdominal fat, liver enzymes, cardiometabolic risk factors, and gut microbiome were assessed. Results: In the intention-to-treat analysis, weight reductions of 4.0 +/- 0.5 kg (5.3%), 3.4 +/- 0.5 kg (4.5%), and 1.5 +/- 0.5 kg (2.1%) were achieved in the diet-with-C15:0, diet without-C15:0, and the control groups, respectively. The proton density fat fraction (PDFF) of the liver decreased by 33%, 30%, and 10%, respectively. Both diet groups achieved significantly greater reductions in body weight, liver PDFF, total cholesterol, gamma-glutamyl transferase, and triglyceride concentrations compared with the control group. C15:0 supplementation reduced LDL-cholesterol further, and increased the abundance of Bifidobacterium adolescentis. Fat mass, visceral adipose tissue, subcutaneous abdominal adipose tissue (deep and superficial), insulin, glycated hemoglobin, and blood pressure decreased significantly in all groups, in parallel with weight loss. Conclusion: Mild weight loss induced by a Mediterranean-like diet adapted for Asians has multiple beneficial health effects in females with NAFLD. C15:0 supplementation lowers LDL-cholesterol and may cause beneficial shifts in the gut microbiome. Trial registration number: This trial was registered at the clinicaltrials.gov as NCT05259475.

Clinicians often investigate the body mass index (BMI) trajectories of children to assess their growth with respect to their peers, as well as to anticipate future growth and disease risk. While retrospective modelling of BMI trajectories has been an active area of research, prospective prediction of continuous BMI trajectories from historical growth data has not been well investigated. Using weight and height measurements from birth to age 10 years from a longitudinal mother-offspring cohort, we leveraged a multi-task Gaussian processes model, called MagmaClust, to derive probabilistic predictions for BMI trajectories over various forecasting periods. Experiments were conducted to evaluate the accuracy, sensitivity to missing values, and number of clusters. The results were compared with cubic B-spline regression and a parametric Jenss-Bayley mixed effects model. A downstream tool computing individual overweight probabilities was also proposed and evaluated. In all experiments, MagmaClust outperformed conventional models in prediction accuracy while correctly calibrating uncertainty regardless of the missing data amount (up to 90\% missing) or the forecasting period (from 2 to 8 years in the future). Moreover, the overweight probabilities computed from MagmaClust's uncertainty quantification exhibited high specificity ($0.94$ to $0.96$) and accuracy ($0.86$ to $0.94$) in predicting the 10-year overweight status even from age 2 years. MagmaClust provides a probabilistic non-parametric framework to prospectively predict BMI trajectories, which is robust to missing values and outperforms conventional BMI trajectory modelling approaches. It also clusters individuals to identify typical BMI patterns (early peak, adiposity rebounds) during childhood. Overall, we demonstrated its potential to anticipate BMI evolution throughout childhood, allowing clinicians to implement prevention strategies.

BACKGROUND:The development of the breast for lactation occurs throughout pregnancy. It is unknown whether pregnancy complications resulting in poor fetal growth can affect breastfeeding (BF) success. OBJECTIVES:We examined whether fetal growth-related pregnancy complications were associated with earlier BF cessation and changes in the concentrations of human milk biomarkers of low milk production. METHODS:We used data from the Growing Up in Singapore Toward healthy Outcomes study (n = 954). Human milk concentrations of protein, lactose, citrate, sodium, potassium, and zinc at 3 wk 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 (second to third trimester fetal growth dropped between major centiles), elevated umbilical artery resistance (>90th percentile) or hypertensive disorders of pregnancy (HDP) with 1) risk of ceasing BF (Cox regression) and 2) concentrations of human milk components (weighted linear regression). RESULTS:Adjusting for maternal education, smoking exposure, BF intentions, and prepregnancy BMI (in kg/m2), 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% confidence interval (CI)]: 1.45 (1.11, 1.89) and 1.61 (1.14, 2.29), respectively}; associations were nonsignificant for fetal growth deceleration and umbilical artery resistance. 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 β coefficient (95% CI): -0.56 mg/L (-1.08, -0.04) mg/L]. CONCLUSIONS:Individuals with HDP and those with SGA infants tend to breastfeed for a shorter duration; however, only HDP appear to be associated with biomarkers of compromised milk production. Further research and support are needed to help individuals with HDP and SGA achieve their BF goals. This trial was registered at clinicaltrials.gov as NCT01174875.