Lynette P C Shek

• MBBS, FRCPCH, FAAAAI, FAMS
• National University of Singapore

Observational epidemiological studies have demonstrated that maternal exposure to air pollution increases the risk of adverse pregnancy outcomes. However, interactions among multiple environmental exposures remain underexplored. In this study, we performed an epidemiological analysis of 147,979 pregnant women recruited from nine provinces in southe...

Background In endemic COVID-19, immunocompromised children are vulnerable until vaccinated but the optimal primary vaccination regime and need for booster doses remains uncertain. Methods We recruited 19 immunocompromised children (post-solid organ transplantation, have autoimmune disease or were on current or recent chemotherapy for acute lymphob...

Escalating health risks associated with ambient ozone (O₃) pollution presents a pressing challenge to global population well-being. An ever-increasing body of evidence supports an association between O₃ pollution and cardiorespiratory conditions. However, previous studies only consider exposure-attributable respiratory deaths, completely disregardi...

Background Physical activity (PA), sedentary behavior (SB), and sleep are collectively referred to as 24-h movement behaviors, which may be linked to cognitive development in children. However, most of the evidence was based on cross-sectional studies and/or solely relied on parent-reported information on children’s behaviors, and it remains uncert...

Allergic diseases such as asthma, atopic dermatitis, and food allergies are a burgeoning health challenge in the Asia‐Pacific region. Compounding this, the region has become increasingly susceptible to the impacts of climate change. The region has weathered extreme precipitation, intense heat waves, and dust storms over the recent decades. While th...

China’s “three-child policy”, implemented in response to population aging, has made the protection of maternal and infant health an urgent priority. In this environmental and medical big-data era, the Zhejiang Environmental and Birth Health Research Alliance (ZEBRA) maternity cohort was established with the aim of identifying risk factors for perin...

The paucity of information on longevity of vaccine-induced immune responses and uncertainty of the correlates of protection hinder the development of evidence-based COVID-19 vaccination policies for new birth cohorts. Here, to address these knowledge gaps, we conducted a cohort study of healthy 5–12-year-olds vaccinated with BNT162b2. We serially m...

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–...

While research into gut-microbe interactions is common and advanced, with multiple defined impacts on human health, studies exploring the significance of skin-microbe interactions remain underrepresented. Skin is the largest human organ, has a vast surface area, and is inhabited by a plethora of microorganisms which metabolise sebaceous lipids. Seb...

In response to China’s demographic shift toward an ageing population, introduction of the “three-child policy” has rendered safeguarding perinatal health an urgent priority. However, limited research has focused on pregnancy-related cardiovascular diseases (CVDs). Here we conducted comprehensive epidemiological analyses on 121,893 pregnant women an...

Background Promoting active, balanced lifestyles among children may be an important approach to optimising their health-related quality of life (HRQoL). However, the relationships between children's movement behaviours and HRQoL remain unclear. Methods We examined the associations between movement behaviours (sleep, inactivity, light and moderate-...

The development of evidence-based COVID-19 vaccination policies for new birth cohorts is hindered by the lack of systematic examination of the protective capacity of elements of adaptive immunity besides neutralising antibodies. To address this knowledge gap, we conducted a longitudinal cohort study of healthy 5- to 12-year-olds vaccinated with BNT...

Background: Childhood wheezing is a highly heterogeneous condition with incomplete understanding of the characteristics of wheeze trajectories, particularly for persistent wheeze. Objective: To characterise predictors and allergic comorbidities of distinct wheeze trajectories in a multi-ethnic Asian cohort. Methods: A total of 974 mother-child...

Background and aims: There are significant changes to the maternal inflammatory profile across pregnancy. Recent studies suggest that perturbations in maternal gut microbial and dietary-derived plasma metabolites over the course of pregnancy mediate inflammation through a complex interplay of immunomodulatory effects. Despite this body of evidence...

Study objectives: Spatial working memory (SWM) capacity sub-serves complex cognitive functions, yet it is unclear whether individual diurnal preferences and time-of-day influence SWM in preschool children. The main and interaction effects of chronotype and time-of-day on SWM and SWM differences in preschoolers with different chronotypes within eac...

Objective: Longitudinal changes in physical activity (PA) and sedentary behavior patterns from preconception to postpartum are not fully characterized. We examined changes and baseline sociodemographic/clinical correlates of PA and sedentary behavior in women from preconception to postpartum. Methods: The Singapore Preconception Study of Long-Ter...

Background: Poor sleep quality may elevate cortisol levels and affect prenatal mental health through altered HPA axis functioning. This study aims to examine whether subjective sleep quality during preconception moderates the association between preconception hair cortisol levels and mental health from preconception to pregnancy trimesters. Metho...

Purpose To examine the associations between infants’ dietary nutrient trajectories and subsequent neurodevelopment during childhood in the Growing Up in Singapore Towards healthy Outcomes study. Methods One-day food records were collected at ages 6, 9 and 12 months, whilst Bayley Scales of Infant and Toddler Development-III and Kaufman Brief Intel...

Purpose This study explores the association between the duration and variation of infant sleep trajectories and subsequent cognitive school readiness at 48–50 months. Methods Participants were 288 multi-ethnic children, within the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. Caregiver-reported total, night and day sleep duratio...

Background Adaptations in lipid metabolism are essential to meet the physiological demands of pregnancy and any aberration may result in adverse outcomes for both mother and offspring. However, there is a lack of population-level studies to define the longitudinal changes of maternal circulating lipids from preconception to postpartum in relation t...

Importance: Although multiple modifiable risk factors have been identified for reduced fecundability (defined as lower probability of conception within a menstrual cycle), no scoring system has been established to systematically evaluate fecundability among females who are attempting to conceive. Objective: To examine the association of a risk s...

For improved safety, children are vaccinated with a lower dose and extended interval for mRNA COVID-19 vaccines; however, whether there is protection before dose 2 is unknown. We recruited 113 children receiving BNT162b2 primary vaccination during an Omicron wave. After dose 1, 96% had detectable anti-Spike(S) IgG and 100% had S-reactive T cells; t...

Subfertility is a global problem affecting millions worldwide, with declining total fertility rates. Preconception dietary supplementation may improve fecundability, but the magnitude of impact remains unclear. This prospective cohort study aimed to examine the association of preconception micronutrient supplements with fecundability, measured by t...

Perinatal depression and anxiety are common and associated with sleep problems in the offspring. Depression and anxiety are commonly comorbid, yet often studied independently. Our study used an integrative measure of anxiety and depressive symptoms to examine the associations of maternal mental health (mid‐pregnancy and postnatal) with infant sleep...

Study Objectives Examine how different trajectories of reported sleep duration associate with early childhood cognition. Methods Caregiver-reported sleep duration data (n=330) were collected using the Brief Infant Sleep Questionnaire at 3, 6, 9, 12, 18 and 24 months and Children’s Sleep Habits Questionnaire at 54 months. Multiple group-based day-,...

Human cells homozygous for rare loss-of-expression (LOE) TYK2 alleles have impaired, but not abolished, cellular responses to IFN-α/β (underlying viral diseases in the patients) and to IL-12 and IL-23 (underlying mycobacterial diseases). Cells homozygous for the common P1104A TYK2 allele have selectively impaired responses to IL-23 (underlying isol...

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...

COVID-19 can be severe in pregnant women, and have adverse consequences for the subsequent infant. We profiled the post-infectious immune responses in maternal and child blood as well as breast milk in terms of antibody and cytokine expression and performed histopathological studies on placentae obtained from mothers convalescent from antenatal COV...

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 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: The rising prevalence of food allergy reported in the United States, UK, and Australia may be attributable to the rise in peanut allergy prevalence. The food allergy prevalence in other parts of the world such as Asia is, however, less well documented. Objective: This study aimed to evaluate the prevalence of cow's milk, egg, and pea...

To address inborn errors of immunity (IEI) which were underdiagnosed in resource-limited regions, our centre developed and offered free genetic testing for the most common IEI by Sanger sequencing (SS) since 2001. With the establishment of The Asian Primary Immunodeficiency (APID) Network in 2009, the awareness and definitive diagnosis of IEI were...

Background Allergic sensitization is linked to allergy development, with early sensitization often associated with worse outcomes. We aimed to identify if distinct allergic sensitization trajectories existed within a diverse and multi-ethnic Asian cohort. Methods We administered modified ISAAC questionnaires in the first 8 years and conducted skin...

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-...

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...

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...

‘Mixed Milk Feeding’ (MMF), whereby infants are fed with both breastmilk and infant formula during the same period, is a common feeding practice. Despite its high prevalence, knowledge regarding MMF practices and their association with (health) outcomes is limited, potentially because MMF behaviours are highly variable and difficult to standardise...

Objective: Screen time in early childhood has been associated with children's prosocial and behavioral skills; however, the directionality of this relationship is unclear. We aimed to determine the direction of the relationship between screen time, social skills, and nonsocial behavioral traits in young children. Methods: This was a population-b...

Background COVID-19 has been a major public health threat for the past two years, with disproportionate effects on the elderly, immunocompromised, and pregnant women. While much has been done in delineating immune dysfunctions and pathogenesis in the former two groups, less is known about the disease’s progression in expectant women and children bo...

Introduction Short chain fatty acids (SCFAs) are the main intestinal intermediate and end products of metabolism of dietary fibers/polyphenols by the gut microbiota. The aim of this study was to evaluate the biological implication of stool SCFA profiles determined in the first year of life on the clinical presentation of allergic outcomes in childh...

Background Epidemiological studies suggest a link between eczema and attention deficit hyperactivity disorder (ADHD), but underlying mechanisms have not been examined. Objective We aim to investigate the association between eczema and subsequent ADHD symptoms in the Growing Up in Singapore Towards healthy Outcomes cohort and explore the role of pr...

Background: increasing evidence suggests that maternal distress is a risk factor for development of respiratory infections and allergic diseases in the offspring. We aim to evaluate the link between maternal distress during critical periods in early life, namely the preconception, pregnancy and postnatal periods, and development of respiratory infe...

Background Integrated patterns of energy balance-related behaviours of preschool children in Asia are sparse, with few comparative analyses. Purpose Using cohorts in Singapore (GUSTO) and France (EDEN), we characterized lifestyle patterns of children and investigated their associations with family-focused contextual factors. Methods Ten behaviour...

Purpose Few studies have described adherence to dietary patterns over time in women of childbearing age. This study aims to describe, examine the stability and changes in dietary patterns between pregnancy and 6 years post-pregnancy and the sociodemographic and lifestyle factors influencing the adherence over time. Methods During pregnancy and at...

Introduction: Infant gastroesophageal reflux disease (GERD) is a significant cause of concern to parents. This study seeks to describe GERD prevalence in infants, evaluate possible risk factors and assess common beliefs influencing management of GERD among Asian parents. Methods: Mother-infant dyads in the Singapore PREconception Study of long-T...

Lipids are essential for healthy infant growth and development. The structural complexity of lipids in human milk is not present in infant milk formula (IF). A concept IF was developed mimicking more closely the structure and composition of human milk fat globules. The current study evaluates whether a concept IF with large, milk phospholipid-coate...

The prevalence of food allergy (FA) is increasing in some areas of the globe, highlighting the need for better strategies for prevention, diagnosis, and therapy. In the last few decades, we have made great strides in understanding the causes and mechanisms underlying FAs, prompting guideline updates. Earlier guidelines recommended avoidance of comm...

Background Obesity compromises metabolic health and female fertility, yet not all obese women are similar in metabolic status. The extent to which fecundability is influenced by the metabolic health status of women who are overweight or obese before conception is unknown. Objective This study aimed to (1) determine the metabolic health status and...

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...

Background Time spent in movement behaviours, including physical activity (PA), sedentary behaviour (SB) and sleep, across the 24-h day may have distinct health consequences. We aimed to describe 24-h movement behaviour (24 h-MB) profiles in children and how profile membership changed from age 5.5 to 8 years. Methods Children in the Growing Up in...

The developing brain grows exponentially in the first few years of life. There is a need to have age-appropriate brain atlases that coherently characterize the geometry of the cerebral cortex, white matter tracts, and functional organization. This study employed multi-modal brain images of an Asian cohort and constructed brain structural and functi...

My E-Diary for Activities and Lifestyle (MEDAL), a web-based application, was developed to assess the diets of children. This study examined the validity of school recess meals reported by children on MEDAL, using meal photography as the reference. Recess meals were photographed by trained researchers, and food items and portion sizes of recess mea...

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 ≤...

Eczema or atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease with a peak incidence in the first 2 years of life1. Physician diagnosis of AD is still problematic as there is variability in diagnosing AD, especially in young children, and validation studies on diagnostic accuracy and criteria of physician diagnosis of AD are lack...

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...

Background: Although most studies have reported unfavorable short-term effects of breastfeeding on early-childhood sleep-wake behaviors that potentially attenuate over time, findings have remained inconsistent. Objectives: We assessed associations of breastfeeding with longitudinal day-, night-, and total-sleep trajectories and with sleep-wake b...

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...

BACKGROUND Existing modes of collecting self-reported 24-hour movement information from children, including digital assessments, have not been demonstrated to be of acceptable validity when compared to objective measurements. My E-Diary for Activities and Lifestyle (MEDAL) is an interactive web-based diary developed to collect time-use information...

Background: Existing modes of collecting self-reported 24-hour movement information from children, including digital assessments, have not been demonstrated to be of acceptable validity when compared to objective measurements. My E-Diary for Activities and Lifestyle (MEDAL) is an interactive web-based diary developed to collect time-use informatio...

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...

A concept infant formula (IF) was developed with physical properties of lipid droplets mimicking more closely those in human milk. This paper describes the unique design of a randomised controlled trial evaluating the impact of the concept IF on infant growth and body composition development whilst applying a cohort-like recruitment approach that f...

Background Gestational diabetes mellitus (GDM) has been associated with adverse health outcomes for mothers and offspring. Prevalence of GDM differs by country/region due to ethnicity, lifestyle and diagnostic criteria. We compared GDM rates and risk factors in two Asian cohorts using the 1999 WHO and the International Association of Diabetes and P...

Oral health status ideally warrants for a holistic biopsychosocial approach to health and wellness. Little is known about the impact of behavioral problems on oral health-related quality of life (OHRQoL) in children due to the paucity of studies in early childhood, particularly in Asian multi-ethnic populations. This study evaluated the relationshi...

Exposure to a diverse microbial environment during pregnancy and early postnatal period is important in determining predisposition towards allergy. However, the effect of environmental microbiota exposure on allergy during preconception, pregnancy and postnatal life on development of allergy in the child has not been investigated so far. In the S‐P...

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...

In recent years, there appears to be a rise in the diagnosis and treatment of child mental health disorders in many countries, including Singapore. While this increase may be alarming, it could possibly be attributed to factors such as changes in diagnostic criteria, improved screening in schools and primary health settings, changes in clinical pra...

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...

Introduction Egg allergy is the most common food allergy in children but recent studies have shown persistence or delayed resolution into adolescence. As there is currently no effective long-term treatment, definitive treatments that improve quality of life and prevent fatalities for food allergies are required. We have previously shown that a nove...

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...

Background: The heterogeneity of childhood atopic dermatitis (AD) underscores the need to understand latent phenotypes that may inform risk stratification and disease prognostication. Objective: To identify AD trajectories across the first 8 years of life, investigate risk factors associated with each trajectory and their relationships with othe...

Background Female sexual dysfunction (FSD) is a prevalent problem, affecting up to 41% of reproductive aged women worldwide. However, the association between female sexual function (FSF) and fecundability in women attempting to conceive remains unclear. We aimed 1) to examine the association between FSF in reproductive-aged preconception Asian wome...

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...

Background Web-based time-use diaries for schoolchildren are limited, and existing studies focus mostly on capturing physical activities and sedentary behaviors but less comprehensively on dietary behaviors. Objective This study aims to describe the development of My E-Diary for Activities and Lifestyle (MEDAL)—a self-administered, web-based time-u...

Spontaneous miscarriage is one of the most common complications of pregnancy. Even though some risk factors are well documented, there is a paucity of risk scoring tools during preconception. In the S-PRESTO cohort study, Asian women attempting to conceive, aged 18-45 years, were recruited. Multivariable logistic regression model coefficients were...

Objectives We assessed the stability of maternal dietary patterns from pregnancy to 6 years post-pregnancy and their associated-sociodemographic and lifestyle factors. Methods At 26–28 weeks’ gestation and 6 years post-pregnancy, 24-hour recalls and food frequency questionnaires were collected, respectively, from women in the GUSTO mother-offsprin...

Objective Maternal depression during pregnancy has long-term impacts on offspring. This study employed neuroimaging and behavioral data from children aged 4 to 6 years and investigated whether prenatal maternal depressive symptoms (pre-MDS) associate with child cortical morphological development and subsequent reward-related behaviors in preschoole...