Yung Seng Lee

National University of Singapore | NUS · Department of Paediatrics

Background: Obesity and obesity-related morbidities are associated with poor psychosocial adjustment and health-related quality of life (HRQoL). This study aims to examine HRQoL and psychosocial outcomes in children with metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO), and the effects of familial health on these outco...

Objective Health behaviors before, during and after pregnancy can have lasting effects on maternal and infant health outcomes. Although a digital health intervention (DHI) has potential as a pertinent avenue to deliver mechanisms for a healthy behavior change, its success is reliant on addressing the user needs, without creating apprehension that m...

Background: timing of introduction of complementary foods and duration of breastfeeding have been independently associated with child overweight and obesity but their combined influence on body fat partitioning and cardiometabolic risk is unclear. Objective: we investigated associations of timing of introduction of complementary foods, duration o...

The etiology of inflammatory bowel diseases (IBDs) frequently results in the uncontrolled inflammation of intestinal epithelial linings and the local environment. Here, we hypothesized that interferon-driven immunomodulation could promote anti-inflammatory effects. To test this hypothesis, we engineered probiotic Escherichia coli Nissle 1917 (EcN)...

Diet plays a critical role in the development of obesity and obesity-related morbidities. Our study aimed to evaluate the dietary food groups, nutrient intakes and eating behaviors of metabolically healthy and unhealthy obesity phenotypes in an Asian cohort of children and adolescents. Participants (n = 52) were asked to record their diet using a 3...

Asian populations are under-represented in human genomics research. Here, we characterize clinically significant genetic variation in 9051 genomes representing East Asian, South Asian, and severely under-represented Austronesian-speaking Southeast Asian ancestries. We observe disparate genetic risk burden attributable to ancestry-specific recurrent...

The rise in prevalence of childhood obesity is paralleled by an increase in obesity-related metabolic complications, which add significantly to the population burden of cardiovascular morbidity in the long term. Early detection of obesity-related metabolic complications through appropriate screening strategies forms a crucial aspect of obesity mana...

Research on how socioeconomic status interacts with neighbourhood characteristics to influence disparities in obesity outcomes is currently limited by residential segregation-induced structural confounding, a lack of empirical studies outside the U.S. and other ‘Western’ contexts, and an over-reliance on cross-sectional analyses. This study address...

Background Longitudinal assessment of the determinants of obesogenic growth trajectories in childhood can suggest appropriate developmental windows for intervention. Methods Latent class growth mixture modelling was used to identify body mass index (BMI) z-score trajectories from birth to age 6 years in 994 children from a prospective mother–offsp...

Purpose There is altered breastmilk composition among mothers with gestational diabetes and conflicting evidence on whether breastfeeding is beneficial or detrimental to their offspring’s cardiometabolic health. We aimed to investigate associations between breastfeeding and offspring’s cardiometabolic health across the range of gestational glycemia...

Background and Aims Few studies examined influence of carotenoids and vitamin E on blood pressure or hypertension during and after pregnancy. We related perinatal plasma concentrations of individual carotenoids and forms of vitamin E, and their combination, to blood pressure and hypertension at late-pregnancy and 4 years post-pregnancy. Methods an...

Background 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. Methods In the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort, air displace...

Background Lipids play a vital role in health and disease, but changes to their circulating levels and the link with obesity remain poorly characterized in expecting mothers and their offspring in early childhood. Methods LC-MS/MS-based quantitation of 480 lipid species was performed on 2491 plasma samples collected at 4 time points in the mother-...

Clostridioides difficile infection (CDI) results in significant morbidity and mortality in hospitalised patients. The pathogenesis of CDI is intrinsically related to the ability of C. difficile to shuffle between active vegetative cells and dormant endospores through the processes of germination and sporulation. Here, we hypothesise that dysregulat...

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-...

Background The tryptophan-kynurenine (KYN) pathway is linked to obesity-related systemic inflammation and metabolic health. The pathway generates multiple metabolites, with little available data on their relationships to early markers of increased metabolic disease risk in children. The aim of this study was to examine the association of multiple K...

Objective: To evaluate the relationship of the levels of maternal alcohol consumption during the 1 year before pregnancy recognition with childhood cardiorenal, metabolic, and neurocognitive health. Methods: In 1106 women and their children from the Growing Up in Singapore Towards healthy Outcomes mother-offspring cohort, quantity of maternal al...

Background Diet quality indices (DQIs) are useful tools to measure diet quality as they compare dietary intakes against recommendations. A DQI for Asian preschool children is lacking. Objective The aims of this study were to develop and evaluate a DQI for preschool children based on Singapore dietary recommendations and to examine diet quality in...

Objective: to evaluate whether characterization of maternal and fetoplacental factors beyond birthweight can enable early identification of children at risk of developing prehypertension/hypertension. Methods: we recruited 693 mother-offspring dyads from the GUSTO prospective mother-offspring cohort. Prehypertension/hypertension at age 6y was ide...

Background While socioeconomic position (SEP) is consistently related to pregnancy and birth outcome disparities, relevant biological mechanisms are manifold, thus necessitating more comprehensive characterization of SEP-exposome associations during pregnancy. Objectives We implemented an exposomic approach to systematically characterize the socio...

The human body is a natural habitat for a multitude of microorganisms, with bacteria being the major constituent of the microbiota. These bacteria colonize discrete anatomical locations that provide suitable conditions for their survival. Many bacterial species, both symbiotic and pathogenic, interact with the host via biochemical signaling. Based...

Background Cord blood leptin and adiponectin are adipokines known to be associated with birth weight and overall infant adiposity. However, few studies have investigated their associations with abdominal adiposity in neonates. We examined maternal factors associated with cord blood leptin and adiponectin, and the association of these adipokines wit...

Background The kynurenine pathway generates metabolites integral to energy metabolism, neurotransmission, and immune function. Circulating kynurenine metabolites positively correlate with adiposity in children and adults, yet it is not known whether this relationship is present already at birth. In this prospective longitudinal study, we investigat...

Background: Obese individuals who have little or no metabolic syndrome components are proposed to be "metabolically healthy obese (MHO)". This study aim to evaluate the prevalence of MHO and examine the predictors associated with MHO in a multi-ethnic Asian cohort of severely obese children. Methods: This study included a cross-sectional cohort...

Importance: Despite the potential for COVID-19 infection control-related events to have an effect on child well-being, comprehensive assessments of postlockdown changes and persistent outcomes are lacking. Objective: To survey the extent of COVID-19 lockdown-related lifestyle changes, their differences by child age and family socioeconomic statu...

Background: Branched chain amino acids (BCAA) supplementation is reported to aid in lean mass preservation, which may in turn minimize the reduction in resting metabolic rate (RMR) during weight loss. Our study aimed to examine the effect of BCAA supplementation to a hypocaloric diet on RMR and substrate utilization during a weight loss interventi...

Childcare arrangements shape behavioural patterns that influence the risk of childhood obesity. However, little is known of its influence on childhood obesity in Singapore. We aim to examine the associations between childcare arrangements at the age of 5 years and childhood adi-posity at age 6 years. Children from the GUSTO study were grouped into...

Abnormalities of red blood cell (RBC) indices may affect glycated haemoglobin (HbA1c) levels. We assessed the influence of haemoglobin (Hb) and mean corpuscular volume (MCV) on the performance of HbA1c in detecting dysglycaemia among reproductive aged women planning to conceive. Women aged 18–45 years (n = 985) were classified as normal (12 ≤ Hb ≤...

Context: Antenatal hyperglycemia is associated with increased risk of future adverse health outcomes in both mother and child. Variations in offspring's epigenome can reflect the impact and response to in utero glycemic exposure, and may have different consequences for the child. Objective: We examined possible differences in associations of bas...

Background: Modest associations have been reported between specific food groups or nutrients and fecundability [measured by time to pregnancy (TTP)]. Examining overall diets provides a more holistic approach towards understanding the relationships with fecundability. It is not known if plant-based diets indices or exploratory dietary patterns are...

Assisted reproductive technologies (ART) are increasingly used, however little is known about the long-term health of ART-conceived offspring. Weak selection of comparison groups and poorly characterized mechanisms impede current understanding. In a prospective cohort (Growing Up in Singapore Towards healthy Outcomes; GUSTO; Clinical Trials ID: NCT...

Importance: screen-viewing in adults has been associated with greater abdominal adiposity, with the magnitude of associations varying by sex and ethnicity, but the evidence is lacking at younger ages. We aimed to investigate sex- and ethnic-specific associations of screen-viewing time at ages 2 and 3 years with abdominal adiposity measured by magne...

Objective The mainstay management of hyperphagia and obesity in Prader–Willi syndrome (PWS) relies on dietary restrictions, strict supervision and behavioural modifications, which can be stressful for the patient and caregiver. There is no established pharmacological strategy to manage this aspect of PWS. Theoretically, glucagon-like peptide-1 (GLP...

Background: nausea and vomiting of pregnancy (NVP) is common and underlying mechanisms are poorly understood. Longer-term offspring outcomes are also not well documented. This study aimed to determine if NVP, even in milder forms, is associated with adverse pregnancy and childhood growth outcomes. Methods: in the GUSTO prospective mother-offsprin...

Food reward is defined as the momentary value of a food to the individual at the time of ingestion and is characterised by two psychological processes-"liking" and "wanting". We aimed to validate an age-appropriate food reward task to quantify implicit wanting of children from the GUSTO cohort (n = 430). At age 5 years, child appetitive traits and...

Purpose: to develop and evaluate an automated segmentation method for accurate quantification of abdominal adipose tissue (AAT) depots (superficial subcutaneous [SSAT], deep subcutaneous [DSAT], and visceral adipose tissue [VAT]) in neonates and young children. Methods: this was a secondary analysis of prospectively collected data, which used abdo...

Aims To explore the glucose-overload hypothesis of artefactual gestational diabetes (GDM) diagnosis in shorter women during oral glucose tolerance testing (OGTT), by investigating associations between height and maternal glycemia; and GDM and pregnancy complications in height-groups. Methods Women from GUSTO (n=1100, 2009-2010) and NUH (n=4068, 20...

Context An inverse relationship between brown adipose tissue (BAT) and obesity has previously been reported in older children and adults, but unknown in young children. Objective We investigated the influence of BAT in thermoneutral condition on adiposity and metabolic profile in Asian preschool children. Design, Setting and Participants A total...

Fetal growth restriction arising from placental insufficiency is a leading cause of stillbirth. We recently identified low maternal circulating SPINT1 concentrations as a novel biomarker of poor fetal growth. Here we measured SPINT1 in a prospective cohort in Singapore. Circulating SPINT1 concentrations were significantly lower among 141 pregnant w...

Objective To identify systolic blood pressure (SBP) percentile trajectories in children and to describe the early-life risk factors and cardiometabolic correlates of those trajectories. Study design Using age-, sex-, and height-specific SBP percentiles based on the American Academy of Pediatrics reference, we examined SBP trajectories using latent...

There is limited data on the dietary patterns of 5-year-old children in Asia. The study examined childhood dietary patterns and their maternal and child correlates in a multi-ethnic Asian cohort. Based on caregiver-reported one-month quantitative food frequency questionnaires of 777 children from the Growing Up in Singapore Towards healthy Outcomes...

Lipids play a vital role in human health and development, but changes to their circulatory levels during gestation and in early life are poorly understood. Here we present the first developmental and intergenerational landscape of the human circulatory lipidome, derived by profiling of 480 lipid species representing 25 lipid classes, in mothers and...

Introduction: To determine if variations in the neonatal amygdala mediate the association between maternal antenatal glycemia and offspring adiposity in early childhood. Research design and methods: 123 non-obese pregnant women with no pregnancy complications aside from gestational diabetes underwent a 75 g 2-hour oral glucose tolerance test at...

Objective To identify a posteriori dietary patterns among women planning pregnancy and assess the reproducibility of these patterns in a subsample using two dietary assessment methods. Design A semi-quantitative Food Frequency Questionnaire (FFQ) was administered to women enrolled in the S-PRESTO study. Dietary patterns from the FFQ were identifie...

We examined the associations of gestational diabetes mellitus (GDM) and women’s weight status from pre-pregnancy through post-delivery with the risk of developing dysglycaemia [impaired fasting glucose, impaired glucose tolerance, and type 2 diabetes (T2D)] 4–6 years post-delivery. Using Poisson regression with confounder adjustments, we assessed a...

Background: Branched-chain amino acid (BCAA) supplementation has been shown to increase muscle mass or prevent muscle loss during weight loss. Objective: We aimed to investigate the effects of a BCAA-supplemented hypocaloric diet on lean mass preservation and insulin sensitivity. Methods: A total of 132 Chinese adults (63 men and 69 women aged...

Context: Cardiometabolic profiles of different body composition phenotypes are poorly characterized in young children, where it is well-established that high adiposity is unfavorable, but the role of lean mass is unclear. Objective: We hypothesized that higher lean mass attenuates cardiometabolic risk in children with high fat mass. Design, set...

Background Leukocyte telomere length (LTL) is associated with obesity and obesity‐related traits, and there are ethnic‐specific determinants of LTL. Objective To evaluate LTL associations with obesity and metabolic parameters in Asian children with early‐onset obesity. Methods Genomic DNA was extracted from peripheral blood leukocytes of a cohort...

Maternal glycaemia promotes fetal adiposity. Inositol, an insulin sensitizer, has been trialled for gestational diabetes prevention. The placenta has been implicated in how maternal hyperglycaemia generates fetal pathophysiology, but no studies have examined whether placental inositol biology is altered with maternal hyperglycaemia, nor whether suc...

The Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO) is a preconception, longitudinal cohort study that aims to study the effects of nutrition, lifestyle, and maternal mood prior to and during pregnancy on the epigenome of the offspring and clinically important outcomes including duration of gestation, fetal growth,...

Introduction: This study examined maternal, delivery and infant factors associated with cord thyroid-stimulating hormone (TSH) concentrations in an Asian population. Methods: The Growing Up in Singapore Towards healthy Outcomes (GUSTO) study is a mother-offspring birth cohort from 2 major hospitals in Singapore. Cord serum TSH was measured using...

The Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO) is a preconception, longitudinal cohort study that aims to study the effects of nutrition, lifestyle, and maternal mood prior to and during pregnancy on the epigenome of the offspring and clinically important outcomes including duration of gestation, fetal growth,...

The cover image depicts the consumption of prebiotics, probiotics and engineered microbes (use of microbiome‐base therapies) by an obese individual (left side of image) and these microbes caused a shift in the gut microbiota composition which resulted in the treatment of obesity/weight loss (as observed on right side of image). This is reported by...

Background: using longitudinal ultrasounds as an improved fetal growth marker, we aimed to investigate if fetal growth deceleration followed by rapid postnatal weight gain is associated with childhood cardiometabolic risk biomarkers in a contemporary well-nourished population. Methods: we defined fetal growth deceleration (FGD) as ultrasound-meas...

Androgen dependent tissue factor pathway inhibitor regulating protein (ADTRP) is a novel protein associated with coronary artery disease (CAD) susceptibility, and reduced mRNA expression of ADTRP was shown to be associated with increased CAD risk. This study aimed to determine and compare circulating ADTRP levels between CAD patients and controls,...

Purpose: Consideration of health-related quality of life (HRQoL) and wellbeing outcomes is important to guide healthcare services for youth with obesity, yet youth perspectives may differ from their parents. This study compared youth and parental HRQoL reports and evaluated levels of concordance across HRQoL domains and as a function of youth age,...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background Obesity is a complex, multifactorial disease that is increasing in prevalence despite extensive research and efforts to curb it. Over the last decade, gut microbiome has emerged as an important contributor to the pathogenesis of obesity. Microbiome profile is altered in obese phenotype and the causative role of microbiome in obesity is d...

In animal studies early life antibiotic exposure causes metabolic abnormalities including obesity through microbiota disruption, but evidence from human studies is scarce. We examined involvement of gut microbiota in the associations between infant antibiotic exposure and childhood adiposity. Infant antibiotic exposure in the first year of life was...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Infant adiposity may be related to later metabolic health. Maternal metabolite profiling reflects both genetic and environmental influences and allows elucidation of metabolic pathways associated with infant adiposity. In this multi-ethnic Asian cohort, we aimed to (i) identify maternal plasma metabolites associated with infant adiposity and other...

We investigated whether adding anthropometric measures to HbA1c would have stronger discriminative ability over HbA1c alone in detecting dysglycemia (diabetes and prediabetes) among Asian women trying to conceive. Among 971 Singaporean women, multiple regression models and area under receiver-operating characteristic (AUROC) curves were used to ana...

The human gut microbiota develops soon after birth and can acquire inter-individual variation upon exposure to intrinsic and environmental cues. However, inter-individual variation has not been comprehensively assessed in a multi-ethnic study. We studied a longitudinal birth cohort of 106 infants of three Asian ethnicities (Chinese, Malay, and Indi...

Background/objectives: Accumulation of lipid droplets inside skeletal muscle fibers (intramyocellular lipids or IMCL) with increasing obesity has been linked to skeletal muscle insulin resistance and risk of type 2 diabetes in both adults and prepubertal children. We aimed to evaluate the associations of race, genotype, prenatal factors, and postn...

Background in women without diabetes, little is known about the consequences of hyperglycaemia during pregnancy for the offspring cardiovascular structure and function. Objective To investigate the association of maternal glycaemia during pregnancy with cardiovascular risk markers in their children in GUSTO, a Singaporean birth cohort study. Meth...

Background: Several risk factors in the first 1000 d are linked with increased obesity risk in later childhood. The role of potentially modifiable eating behaviors in this association is unclear. Objectives: This study examined whether the association between cumulated risk factors in the first 1000 d and adiposity at 6 y is moderated by eating...

INTRODUCTION: Despite development of new technologies for caries control, tooth decay in primary teeth remains a major global health problem. Caries risk assessment models for toddlers and preschoolers are rare. Among them, almost all models use dental factors (e.g. past caries experience) to predict future caries risk, with limited clinical/commun...

Maternal and child health are intrinsically linked. With accumulating evidence over the past two decades supporting the developmental origins of health and diseases hypothesis, it is now widely recognised that nutrition in the first 1000 d sets the foundation for long-term health. Maternal diet before, during and after pregnancy can influence the d...

Consumption of sugar sweetened beverages (SSBs) in infants and young children are less explored in Asian populations. The Growing in Singapore Towards healthy Outcomes (GUSTO) cohort study examined associations between SSB intakes at ages 18 months and 5 years with adiposity measures at age 6 years. We studied Singaporean infants/children with SSB...