Multigenerational adversity impacts on human gut microbiome composition and socioemotional functioning in early childhood.

Adversity exposures in the prenatal and postnatal period are associated with an increased risk for psychopathology, which can be perpetuated across generations. Nonhuman animal research highlights the gut microbiome as a putative biological mechanism underlying such generational risks. In a sample of 450 mother-child dyads living in Singapore, we examined associations between three distinct adversity exposures experienced across two generations-maternal childhood maltreatment, maternal prenatal anxiety, and second-generation children's exposure to stressful life events-and the gut microbiome composition of second-generation children at 2 y of age. We found distinct differences in gut microbiome profiles linked to each adversity exposure, as well as some nonaffected microbiome features (e.g., beta diversity). Remarkably, some of the microbial taxa associated with concurrent and prospective child socioemotional functioning shared overlapping putative functions with those affected by adversity, suggesting that the intergenerational transmission of adversity may have a lasting impact on children's mental health via alterations to gut microbiome functions. Our findings open up a new avenue of research into the underlying mechanisms of intergenerational transmission of mental health risks and the potential of the gut microbiome as a target for intervention.

Maternal and Infant Dietary Patterns Are Not Related to Food Allergy Risk in Singapore Children: GUSTO Cohort Study.

BACKGROUND: We previously reported that delayed allergenic food introduction in infancy did not increase food allergy risk until age 4 y within our prospective cohort. However, it remains unclear whether other aspects of maternal or infant diet play roles in the development of childhood food allergy. OBJECTIVES: We examined the relationship between maternal pregnancy and infant dietary patterns and the development of food allergies until age 8 y. METHODS: Among 1152 Singapore Growing Up in Singapore Towards healthy Outcomes study mother-infant dyads, the infant's diet was ascertained using food frequency questionnaires at 18 mo. Maternal dietary patterns during pregnancy were derived from 24-h diet recalls. Food allergy was determined through interviewer-administered questionnaires at regular time points from infancy to age 8 y and defined as a positive history of allergic reactions, alongside skin prick tests at 18 mo, 3, 5, and 8 y. RESULTS: Food allergy prevalence was 2.5% (22/883) at 12 mo and generally decreased over time by 8 y (1.9%; 14/736). Higher maternal dietary quality was associated with increased risk of food allergy (P ≤ 0.016); however, odds ratios were modest. Offspring food allergy risk ≤8 y showed no associations with measures of infant diet including timing of solids/food introduction (adjusted odds ratio [aOR]: 0.90; 95% confidence interval [CI]: 0.42, 1.92), infant's diet quality (aOR: 0.93; 95% CI: 0.88, 0.99) or diet diversity (aOR: 0.84; 95% CI: 0.6, 1.19). Most infants (89%) were first introduced to cow milk protein within the first month of life, while egg and peanut introduction were delayed (58.3% introduced by mean age 8.8 mo and 59.8% by mean age 18.1 mo, respectively). CONCLUSIONS: Apart from maternal diet quality showing a modest association, infant's allergenic food introduction, diet quality, and dietary diversity were not associated with food allergy development in this Asian pediatric population. Interventional studies are needed to evaluate the efficacy of these approaches to food allergy prevention across different populations.

Development and validation of a lifestyle risk index to screen for metabolic syndrome and its components in two multi-ethnic cohorts.

BACKGROUND: Metabolic syndrome (MetS) is a precursor to cardiovascular diseases and type 2 diabetes. Existing MetS prediction models relied heavily on biochemical measures and those based on non-invasive predictors such as lifestyle behaviours were limited. We aim to (1) develop a weighted lifestyle risk index for MetS and (2) externally validate this index using two Asian-based cohorts in Singapore. METHODS: Using data from the Multi-Ethnic Cohort (MEC) 1 (n = 2873, 41% male), multiple logistic regression was used to identify predictors associated with MetS. A weighted lifestyle risk index was generated using coefficients of the selected predictors in the development cohort (MEC1). Subsequently, the performance of the lifestyle risk index in predicting the occurrence of MetS within 10 years was assessed by discrimination and calibration in an external validation cohort (MEC2) (n = 6070, 43% male). RESULTS: A lifestyle risk index for MetS with nine predictors was developed (age, sex, ethnicity, having a family history of diabetes, BMI, diet, physical activity, smoking status, and screen time). This index demonstrated acceptable discrimination in the development cohort [AUC (95% CI) = 0.74 (0.71, 0.76)] and the validation cohort [AUC (95% CI) = 0.79 (0.77, 0.81)]. CONCLUSION: This lifestyle risk index exhibits potential for risk stratification in population-based screening programmes. Future research could apply a similar methodology to develop disease-specific lifestyle risk indices using nationwide registry-based data.

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.

Maternal B-vitamin and vitamin D status before, during, and after pregnancy and the influence of supplementation preconception and during pregnancy: Prespecified secondary analysis of the NiPPeR double-blind randomized controlled trial.

BACKGROUND: Maternal vitamin status preconception and during pregnancy has important consequences for pregnancy outcome and offspring development. Changes in vitamin status from preconception through early and late pregnancy and postpartum have been inferred from cross-sectional data, but longitudinal data on vitamin status from preconception throughout pregnancy and postdelivery are sparse. As such, the influence of vitamin supplementation on vitamin status during pregnancy remains uncertain. This study presents one prespecified outcome from the randomized controlled NiPPeR trial, aiming to identify longitudinal patterns of maternal vitamin status from preconception, through early and late pregnancy, to 6 months postdelivery, and determine the influence of vitamin supplementation. METHODS AND FINDINGS: In the NiPPeR trial, 1,729 women (from the United Kingdom, Singapore, and New Zealand) aged 18 to 38 years and planning conception were randomized to receive a standard vitamin supplement (control; n = 859) or an enhanced vitamin supplement (intervention; n = 870) starting in preconception and continued throughout pregnancy, with blinding of participants and research staff. Supplement components common to both treatment groups included folic acid, ß-carotene, iron, calcium, and iodine; components additionally included in the intervention group were riboflavin, vitamins B6, B12, and D (in amounts available in over-the-counter supplements), myo-inositol, probiotics, and zinc. The primary outcome of the study was glucose tolerance at 28 weeks' gestation, measured by oral glucose tolerance test. The secondary outcome reported in this study was the reduction in maternal micronutrient insufficiency in riboflavin, vitamin B6, vitamin B12, and vitamin D, before and during pregnancy. We measured maternal plasma concentrations of B-vitamins, vitamin D, and markers of insufficiency/deficiency (homocysteine, hydroxykynurenine-ratio, methylmalonic acid) at recruitment, 1 month after commencing intervention preconception, in early pregnancy (7 to 11 weeks' gestation) and late pregnancy (around 28 weeks' gestation), and postdelivery (6 months after supplement discontinuation). We derived standard deviation scores (SDS) to characterize longitudinal changes among participants in the control group and measured differences between the 2 groups. At recruitment, the proportion of patients with marginal or low plasma status was 29.2% for folate (<13.6 nmol/L), 7.5% and 82.0% for riboflavin (<5 nmol/L and ≤26.5 nmol/L, respectively), 9.1% for vitamin B12 (<221 pmol/L), and 48.7% for vitamin D (<50 nmol/L); these proportions were balanced between the groups. Over 90% of all participants had low or marginal status for one or more of these vitamins at recruitment. Among participants in the control group, plasma concentrations of riboflavin declined through early and late pregnancy, whereas concentrations of 25-hydroxyvitamin D were unchanged in early pregnancy, and concentrations of vitamin B6 and B12 declined throughout pregnancy, becoming >1 SDS lower than baseline by 28 weeks gestation. In the control group, 54.2% of participants developed low late-pregnancy vitamin B6 concentrations (pyridoxal 5-phosphate <20 nmol/L). After 1 month of supplementation, plasma concentrations of supplement components were substantially higher among participants in the intervention group than those in the control group: riboflavin by 0.77 SDS (95% CI 0.68 to 0.87, p < 0.0001), vitamin B6 by 1.07 SDS (0.99 to 1.14, p < 0.0001), vitamin B12 by 0.55 SDS (0.46 to 0.64, p < 0.0001), and vitamin D by 0.51 SDS (0.43 to 0.60, p < 0.0001), with higher levels in the intervention group maintained during pregnancy. Markers of vitamin insufficiency/deficiency were reduced in the intervention group, and the proportion of participants with vitamin D insufficiency (<50 nmol/L) during late pregnancy was lower in the intervention group (35.1% versus 8.5%; p < 0.0001). Plasma vitamin B12 remained higher in the intervention group than in the control group 6 months postdelivery (by 0.30 SDS (0.14, 0.46), p = 0.0003). The main limitation is that generalizability to the global population is limited by the high-resource settings and the lack of African and Amerindian women in particular. CONCLUSIONS: Over 90% of the trial participants had marginal or low concentrations of one or more of folate, riboflavin, vitamin B12, or vitamin D during preconception, and many developed markers of vitamin B6 deficiency in late pregnancy. Preconception/pregnancy supplementation in amounts available in over-the-counter supplements substantially reduces the prevalence of vitamin deficiency and depletion markers before and during pregnancy, with higher maternal plasma vitamin B12 maintained during the recommended lactational period. TRIAL REGISTRATION: ClinicalTrials.gov NCT02509988; U1111-1171-8056.

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

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

Understanding knowledge, attitudes and behaviours related to dietary sodium intake in a multi-ethnic population in Singapore.

OBJECTIVE: This study aimed to fill the current gap in the understanding of the knowledge, attitudes and behaviours (KAB) related to dietary Na among adult residents in Singapore. DESIGN: A cross-sectional online survey was conducted between October and December 2020 on 955 participants selected through random sampling. SETTING: The survey was conducted in Singapore. PARTICIPANTS: Participants were recruited from the Singapore Population Health Study Online Panel. RESULTS: Participants' mean age was 46·6 ± 14·1 years old and 58 % of them were females. Most of the participants were Chinese (82·1 %), 10·5 % were Indian and 4·5 % were Malay. Findings from the weighted data showed that most participants were aware of the health impact of high Na consumption. However, many participants were unaware of the recommended intake for salt (68%) and Na (83%), had misconceptions, and were unable to correctly use food labels to assess NA content (69%). Findings also alluded to the presence of knowledge gaps in the sources of Na in their diet. While 59 % of the participants reported to be limiting their consumption of Na, many reported facing barriers such as not knowing how to limit their Na intake. Participants also felt that there were limited options for low-Na foods when eating out and were lacking awareness of low-Na products. CONCLUSIONS: Findings highlighted substantial gaps in participants' knowledge and skills in managing their Na consumption. This suggests the need for more public education and improvements in the food environment.

Results from the Singapore 2022 report card on physical activity for children and adolescents.

Background: While it has been established that physical activity (PA) is key to promote overall health and well-being, insufficient physical activity among children and adolescents is a global problem, including Singapore. It is important to understand the local PA landscape among children and adolescents to decrease surveillance gaps and identify areas for improvement in promoting PA. The present article provides an overview of the development of the 2022 Active Healthy Kids Singapore Report Card and the results, as well as underscore limitations and gaps in the available evidence related to PA among children and adolescents in Singapore. Methods: Following the Global Matrix 4.0, the available data between July 2010 to July 2020 was synthesized for all 10 indicators by the work group and reviewed by a panel of experts. Data sources included published scientific articles, government and non-government reports, national surveys, and unpublished data from on-going research studies. Where possible, grades were informed by nationally representative surveys or large-scale longitudinal studies. Results: The grades assigned were: Overall Physical Activity (C-), Organized Sport and Physical Activity (B-), Active Play (C-), Active Transportation (C), Sedentary Behaviours (C-), Physical Fitness (Incomplete), Family and Peers (C-), School (Incomplete), Community and Environment (A+), Government (B). Conclusion: This is the first comprehensive evaluation of PA among children and adolescents in Singapore. It provides baseline grades valuable for future comparison. It also illustrates gaps in the existing evidence which can inform future surveillance, facilitate international comparisons and enable global efforts in promoting physical activity.

Dietary trajectories through the life course: opportunities and challenges.

Studying the dynamic patterns of dietary changes or stability (otherwise known as dietary trajectories) across the life course can provide important information about when and in whom to intervene with nutritional interventions. This article reviews evidence from longitudinal studies that describe dietary trajectories through the different life stages, covering early life, adolescence to young adulthood and from mid to late adulthood. Current findings suggest that the establishment of diet patterns likely occurs before 3 years of age and allude to other potential 'windows of change' in the life course such as the period of 7­9 years of age and during the period of adolescence and early adulthood. Examining diets using various diet parameters appears to be valuable in elucidating different aspects of the diet that can be changed to potentially alter trajectories. In adults, examining long-term diet trends at a population level can reveal shifts in eating patterns as countries undergo epidemiological and nutrition transitions and elucidate the longer-term impact of adherence to particular diets on the development of chronic diseases. While challenges such as the availability of adequate diet data points, consistency in the dietary assessment tools used and the limitations of statistical methods for trajectory modelling remain, integrating diet data with other lifestyle behaviours, high-dimensional biomarkers and genetics data into pattern analyses and examining them from a longitudinal approach, open up potential opportunities to gain deeper insights into diet­disease relationships and support the development of more holistic lifestyle disease prevention recommendations stratified for population groups.

Evaluation of paper-based and web-based food frequency questionnaires for 7-year-old children in Singapore.

Advances in technology enabled the development of a web-based, pictorial FFQ to collect parent-report dietary intakes of 7-year-old children in the Growing Up in Singapore Towards healthy Outcomes study. This study aimed to compare intakes estimated from a paper-FFQ and a web-FFQ and examine the relative validity of both FFQ against 3-d diet records (3DDR). Ninety-two mothers reported food intakes of their 7-year-old child on a paper-FFQ, a web-FFQ and a 3DDR. A usability questionnaire collected participants' feedback on the web-FFQ. Correlations and agreement in energy, nutrients and food groups intakes between the dietary assessments were evaluated using Pearson's correlation, Lin's concordance, Bland-Altman plots, Cohen's κ and tertile classification. The paper- and web-FFQ had good correlations (≥ 0·50) and acceptable-good agreement (Lin's concordance ≥ 0·30; Cohen's κ ≥ 0·41; ≥ 50 % correct and ≤ 10 % misclassification into same or extreme tertiles). Compared with 3DDR, both FFQ showed poor agreement (< 0·30) in assessing absolute intakes except micronutrients (web-FFQ had acceptable-good agreement), but showed acceptable-good ability to classify children into tertiles (κ ≥ 0·21; ≥ 40 % and ≤ 15 % correct or misclassification). Bland-Altman plots suggest good agreement between web-FFQ and 3DDR in assessing micronutrients and several food groups. The web-FFQ was well-received, and majority (81 %) preferred the web-FFQ over the paper-FFQ. The newly developed web-FFQ produced intake estimates comparable to the paper-FFQ, has acceptable-good agreement with 3DDR in assessing absolute micronutrients intakes and has acceptable-good ability to classify children according to categories of intakes. The positive acceptance of the web-FFQ makes it a feasible tool for future dietary data collection.