Obesity is an escalating health problem worldwide, and hence the causes underlying its development are of primary importance to public health. There is growing evidence that suboptimal intrauterine environment can perturb the metabolic programing of the growing fetus, thereby increasing the risk of developing obesity in later life. However, the link between early exposures in the womb, genetic susceptibility, and perturbed epigenome on metabolic health is not well understood. In this study, we shed more light on this aspect by performing a comprehensive analysis on the effects of variation in prenatal environment, neonatal methylome, and genotype on birth weight and adiposity in early childhood. In a prospective mother-offspring cohort (N = 987), we interrogated the effects of 30 variables that influence the prenatal environment, umbilical cord DNA methylation, and genotype on offspring weight and adiposity, over the period from birth to 48 months. This is an interim analysis on an ongoing cohort study. Eleven of 30 prenatal environments, including maternal adiposity, smoking, blood glucose and plasma unsaturated fatty acid levels, were associated with birth weight. Polygenic risk scores derived from genetic association studies on adult adiposity were also associated with birth weight and child adiposity, indicating an overlap between the genetic pathways influencing metabolic health in early and later life. Neonatal methylation markers from seven gene loci (ANK3, CDKN2B, CACNA1G, IGDCC4, P4HA3, ZNF423 and MIRLET7BHG) were significantly associated with birth weight, with a subset of these in genes previously implicated in metabolic pathways in humans and in animal models. Methylation levels at three of seven birth weight-linked loci showed significant association with prenatal environment, but none were affected by polygenic risk score. Six of these birth weight-linked loci continued to show a longitudinal association with offspring size and/or adiposity in early childhood. This study provides further evidence that developmental pathways to adiposity begin before birth and are influenced by environmental, genetic and epigenetic factors. These pathways can have a lasting effect on offspring size, adiposity and future metabolic outcomes, and offer new opportunities for risk stratification and prevention of obesity. This birth cohort is a prospective observational study, designed to study the developmental origins of health and disease, and was retrospectively registered on 1 July 2010 under the identifier NCT01174875 .

Appetitive traits in childhood such as food responsiveness and enjoyment of food have been associated with body mass index (BMI) in later childhood. However, data on appetitive traits during infancy in relation to BMI in later childhood are sparse. We aimed to relate appetitive traits in infancy to subsequent BMI and weight gain up to 24 months of age. Data of 210 infants from the Singapore GUSTO mother-offspring cohort was obtained. The Baby Eating Behavior Questionnaire (BEBQ) and the Child Eating Behavior Questionnaire (CEBQ) were administered to mothers when their offspring were aged 3 and 12 months respectively. Height and weight of offspring were measured at ages 3, 6, 9,12,15,18 and 24 months. The association of appetitive traits with both BMI z-score and weight gain were evaluated using multivariate linear regression. Food responsiveness at 3 months was associated with higher BMI from 6 months up to 15 months of age (p < 0.01) and with greater weight gain between 3 and 6 months of age (p = 0.012). Slowness in eating and satiety responsiveness at 3 months was significantly associated with lower BMI at 6 months (p < 0.01) and with less weight gain between 3 to 6 months of age (p = 0.034). None of the appetitive traits at 12 months were significantly associated with BMI or weight gain over any time period. Early assessment of appetitive traits at 3 months of age but not at 12 months of age was associated with BMI and weight gain over the first two years of life. Clinical Trials identifier NCT01174875

We investigated body mass index (BMI) trajectories in the first 2 years of life in 1170 children from an Asian mother-offspring cohort in Singapore, and examined their predictors and associations with childhood cardio-metabolic risk measures at 5 years. Latent class growth mixture modelling analyses were performed to identify distinct BMI z-score (BMIz) trajectories. Four trajectories were identified: 73.2%(n = 857) of the children showed a normal BMIz trajectory, 13.2%(n = 155) a stable low-BMIz trajectory, 8.6%(n = 100) a stable high-BMIz trajectory and 5.0%(n = 58) a rapid BMIz gain after 3 months trajectory. Predictors of the stable high-BMIz and rapid BMIz gain trajectories were pre-pregnancy BMI, gestational weight gain, Malay and Indian ethnicity, while predictors of stable low-BMIz trajectory were preterm delivery and Indian ethnicity. At 5 years, children with stable high-BMIz or rapid BMIz gain trajectories had increased waist-to-height ratios [B(95%CI) 0.02(0.01,0.03) and 0.03(0.02,0.04)], sum of skinfolds [0.42(0.19,0.65) and 0.70(0.36,1.03)SD units], fat-mass index [0.97(0.32,1.63)SD units] and risk of obesity [relative risk 3.22(1.73,6.05) and 2.56 (1.19,5.53)], but not higher blood pressure. BMIz trajectories were more predictive of adiposity at 5 years than was BMIz at 2 years. Our findings on BMIz trajectories in the first 2 years suggest important ethnic-specific differences and impacts on later metabolic outcomes.

Most studies linking maternal diet with offspring adiposity have focused on single nutrients or foods, but a dietary pattern approach is more representative of the overall diet. We thus aimed to investigate the relations between maternal dietary patterns and offspring adiposity in a multi-ethnic Asian mother–offspring cohort in Singapore. We derived maternal dietary patterns using maternal dietary intake information at 26–28 weeks of gestation, of which associations with offspring body mass index (BMI), abdominal circumference (AC), subscapular skinfold (SS), and triceps skinfold (TS) were assessed using longitudinal data analysis (linear mixed effects (LME)) and multiple linear regression at ages 0, 3, 6, 9, 12, 15, 18, 24, 36, 48, and 54 months. Three dietary patterns were derived: (1) vegetables-fruit-and-white rice (VFR); (2) seafood-and-noodles (SfN); and (3) pasta-cheese-and-bread (PCB). In the LME model adjusting for potential confounders, each standard deviation (SD) increase in maternal VFR pattern score was associated with 0.09 mm lower offspring TS. Individual time-point analysis additionally revealed that higher VFR score was generally associated with lower postnatal offspring BMI z-score, TS, SS, and sum of skinfolds (SS + TS) at ages 18 months and older. Maternal adherence to a dietary pattern characterized by higher intakes of fruit and vegetables and lower intakes of fast food was associated with lower offspring adiposity.