The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes

Integrating the genotype with epigenetic marks holds the promise of better understanding the biology that underlies the complex interactions of inherited and environmental components that define the developmental origins of a range of disorders. The quality of the in utero environment significantly influences health over the lifecourse. Epigenetics, and in particular DNA methylation marks, have been postulated as a mechanism for the enduring effects of the prenatal environment. Accordingly, neonate methylomes contain molecular memory of the individual in utero experience. However, interindividual variation in methylation can also be a consequence of DNA sequence polymorphisms that result in methylation quantitative trait loci (methQTLs) and, potentially, the interaction between fixed genetic variation and environmental influences. We surveyed the genotypes and DNA methylomes of 237 neonates and found 1423 punctuate regions of the methylome that were highly variable across individuals, termed variably methylated regions (VMRs), against a backdrop of homogeneity. MethQTLs were readily detected in neonatal methylomes, and genotype alone best explained ?25% of the VMRs. We found that the best explanation for 75% of VMRs was the interaction of genotype with different in utero environments, including maternal smoking, maternal depression, maternal BMI, infant birth weight, gestational age, and birth order. Our study sheds new light on the complex relationship between biological inheritance as represented by genotype and individual prenatal experience and suggests the importance of considering both fixed genetic variation and environmental factors in interpreting epigenetic variation

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 food frequency questionnaire (FFQ) to collect parent-report dietary intakes of 7-year-old children in the GUSTO study. This study aimed to compare intakes estimated from a paper-FFQ and a web-FFQ, and examine the relative validity of both FFQs against 3-day 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 kappa and tertile classification. The paper- and web-FFQ had good correlations (≥0.50) and acceptable-good agreement (Lin's concordance ≥0.30; Cohen's kappa ≥0.41; ≥50% correct and ≤10% mis-classification into same or extreme tertiles). Compared to 3DDR, both FFQs showed poor agreement (&lt;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 (e.g. &gt;89% found it user-friendly), 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 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. </p

Identification of Caries risk determinants in toddlers: results of the GUSTO birth cohort study

The aim of this study was to identify risk determinants leading to early childhood caries (ECC) and visible plaque (VP) in toddlers. Data for mother-child pairs participating in the Growing Up in Singapore towards Healthy Outcomes (GUSTO) birth cohort were collected from pregnancy to toddlerhood. Oral examinations were performed in 543 children during their clinic visit at 24 months to detect ECC and VP. Following logistic regression, ECC and VP were jointly regressed as primary and secondary outcomes, respectively, using the bivariate probit model. The ECC prevalence was 17.8% at 2 years of age, with 7.3% of children having a VP score &gt;1. ECC was associated with nighttime breastfeeding (3 weeks) and biological factors, including Indian ethnicity (lower ECC rate), higher maternal childbearing age and existing health conditions, maternal plasma folate &lt;6 ng/mL, child BMI, and the plaque index, while VP was associated with psychobehavioral factors, including the frequency of dental visits, brushing frequency, lower parental perceived importance of baby teeth, and weaning onto solids. Interestingly, although a higher frequency of dental visits and toothbrushing were associated with lower plaque accumulation, they were associated with increased ECC risk, suggesting that these established caries-risk factors may be a consequence rather than the cause of ECC. In conclusion, Indian toddlers may be less susceptible to ECC, compared to Chinese and Malay toddlers. The study also highlights a problem-driven utilization pattern of dental services (care sought for treatment) in Singapore, in contrast to the prevention-driven approach (care sought to prevent disease) in Western countries

Association of plasma kynurenine pathway metabolite concentrations with metabolic health risk in pre-pubertal Asian children

BackgroundThe 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 KYN pathway metabolites with metabolic risk markers in prepubertal Asian children.MethodsFasting plasma concentrations of KYN pathway metabolites were measured using liquid chromatography-tandem mass spectrometry in 8-year-old children (n = 552) from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) prospective mother-offspring cohort study. The child’s weight and height were used to ascertain overweight and obesity using local body mass index (BMI)-for-age percentile charts. Body fat percentage was measured by quantitative magnetic resonance. Abdominal circumference, systolic and diastolic blood pressure, homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride, and HDL-cholesterol were used for the calculation of Metabolic syndrome scores (MetS). Serum triglyceride, BMI, gamma-glutamyl transferase (GGT), and abdominal circumference were used in the calculation of the Fatty liver index (FLI). Associations were examined using multivariable regression analyses.ResultsIn overweight or obese children (n = 93; 16.9% of the cohort), all KYN pathway metabolites were significantly increased, relative to normal weight children. KYN, kynurenic acid (KA), xanthurenic acid (XA), hydroxyanthranilic acid (HAA) and quinolinic acid (QA) all showed significant positive associations with body fat percentage (B(95% CI) = 0.32 (0.22,0.42) for QA), HOMA-IR (B(95% CI) = 0.25 (0.16,0.34) for QA), and systolic blood pressure (B(95% CI) = 0.14(0.06,0.22) for QA). All KYN metabolites except 3-hydroxykynurenine (HK) significantly correlated with MetS (B (95% CI) = 0.29 (0.21,0.37) for QA), and FLI (B (95% CI) = 0.30 (0.21,0.39) for QA).ConclusionsHigher plasma concentrations of KYN pathway metabolites are associated with obesity and with increased risk for metabolic syndrome and fatty liver in prepubertal Asian children

Perinatal plasma carotenoid and vitamin E concentrations with maternal blood pressure during and after pregnancy.

Background and aims: Few studies examined the influence of carotenoids and vitamin E on blood pressure or hypertension during and after pregnancy. We related perinatal plasma concentrations of carotenoids and vitamin E (in individual forms and in combination) to blood pressure and hypertension at late pregnancy and 4 years post-pregnancy. Methods and results: In 684 women of the Growing Up in Singapore Towards Healthy Outcomes cohort, we quantified plasma carotenoids and vitamin E concentrations at delivery. Systolic blood pressure and diastolic blood pressure (SBP and DBP) around 37–39 weeks’ gestation were extracted from obstetric records and measured at 4 years post-pregnancy. Principal component analysis derived patterns of carotenoids (CP) and vitamin E. Associations were examined using linear or logistic regressions adjusting for confounders. Two carotenoids (CP1: α-carotene, β-carotene, and lutein; CP2: zeaxanthin, lycopene, and β-cryptoxanthin) and one vitamin E (γ-, δ-, and α-tocopherols) patterns were derived. CP1 (1SD score increment) was associated with lower SBP and DBP [β (95% CI): −2.36 (−3.47, −1.26) and −1.37 (−2.21, −0.53) mmHg] at late pregnancy&gt; and 4 years post-pregnancy [-1.45 (−2.72, −0.18) and −0.99 (−1.98, −0.01) mmHg]. Higher β-cryptoxanthin concentrations were associated with lower SBP and DBP [-1.50 (−2.49, −0.51) and −1.20 (−1.95, −0.46) mmHg] at late pregnancy. Individual vitamin E and their pattern were not associated with blood pressure or hypertension. Conclusion: Higher perinatal α-carotene, β-carotene, and lutein concentrations are associated with lower blood pressure in women at late pregnancy and post-pregnancy. Foods rich in these carotenoids, such as red-, orange-, and dark-green-colored vegetables, might be beneficial for blood pressure during and after pregnancy.</p

Relation of preconception eating behaviours to dietary pattern trajectories and gestational weight gain from preconception to late pregnancy

Studies examining preconception eating behaviours with longitudinal dietary patterns from preconception to late pregnancy as well as gestational weight gain (GWG) are limited. We derived dietary pattern trajectories from preconception to late-pregnancy, and related preconception eating behaviours to these trajectories and GWG. Preconception eating behaviours were assessed using the Three-Factor Eating Questionnaire measuring cognitive restraint (CR) - conscious restriction of food intake, emotional eating (EE) - overeating in response to negative emotions, and uncontrolled eating (UE) - overeating with a feeling of lack of control. Dietary intakes were measured at preconception, 20-21 and 34-36 weeks' gestation with food frequency questionnaires. Dietary patterns were determined using factor analysis, and trajectories derived using group-based trajectory modelling. Inadequate and excessive GWG were defined according to Institute of Medicine guidelines based on weights at preconception and the last antenatal visit (median: 38 weeks' gestation). Two dietary patterns were derived: 'Fast Food, Fried Snacks and Desserts (FFD)' and 'Soup, Fish and Vegetables (SFV)'. Adherence trajectories from preconception to late-pregnancy were characterised as consistently high ("stable-high") and low ("stable-low"). Women with higher UE scores had higher odds of being in the "stable-high" trajectory (n = 34) of the FFD pattern [Odds Ratio (OR): 1.25, 95% Confidence Interval (CI): 1.03, 1.51], compared to "stable-low" (n = 260). Percentages of women with inadequate, adequate or excessive GWG were 21.7% (n = 70), 25.8% (n = 83), and 52.5% (n = 169), respectively; women with higher EE scores had a higher likelihood of excessive GWG [Relative Risk Ratio (RRR): 1.35, 95% CI: 1.02, 1.80], but this association was attenuated after adjusting for preconception body mass index. Eating behaviour interventions to improve dietary patterns among pregnant women may need to start as early as preconception, incorporating strategies to manage UE.</p

Ethnic diversity in infant gut microbiota is apparent before the introduction of complementary diets

10.1080/19490976.2020.1756150Gut Microbes11051362-137

Macronutrient composition and food groups associated with gestational weight gain: the GUSTO study

Purpose:To examine the associations of energy, macronutrient and food intakes with GWG on 960 pregnant women from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) mother-offspring cohort.Methods:Dietary intake was assessed at 26–28 weeks’ gestation with a 24-hour recall and 3-day food diary. GWG z-scores were calculated from first (4–13 weeks’ gestation) and last (30–40 weeks gestation) measured weights; inadequate and excessive GWG were defined using the Institute of Medicine recommendations based on weights between 15 and 35 weeks’ gestation. Associations were examined using substitution models for macronutrient composition, with linear or multinomial logistic regressions.Results:Mean ± SD daily energy intake was 1868 ± 598 kcal, and percentage energy intakes were 51.8 ± 8.9% from carbohydrate, 15.7 ± 3.9% from protein and 32.6 ± 7.7% from fat. Higher energy intake (per 500 kcal increment) was associated with 0.18 SD higher GWG. In isocaloric diets, higher-carbohydrate and lower-fat intakes (at 5% energy substitution) were associated with 0.07 SD higher GWG, and 14% higher likelihood of excessive GWG. Concordantly, the highest tertile of carbohydrate-rich foods intake was associated with 0.20 SD higher GWG, but the highest tertile of fruit and vegetable intake was independently associated with 60% lower likelihood of inadequate GWG. Additionally, the highest tertile of dairy intake was associated with 0.18 SD lower GWG; and the highest tertile of plant-based protein foods intake was associated with 60% and 34% lower likelihood of inadequate and excessive GWG.Conclusions:Balancing the proportions of carbohydrates and fat, and a higher intake of plant-based protein foods may be beneficial for achieving optimal GWG

Children’s perceptions of factors influencing their physical activity: a focus group study on primary school children

10.1080/17482631.2021.1980279International Journal of Qualitative Studies on Health and Well-being1611-1

Sleep and dietary patterns in pregnancy: Findings from the gusto cohort

Evidence on the association between sleep, diet, and eating behaviors in pregnant women is lacking. We examine this in a cohort of apparently healthy pregnant women. At 26–28 weeks gestation, 497 participants completed the Pittsburgh Sleep Quality Index to assess sleep and a 24-h recall to assess dietary intake. Diet quality was assessed by the Healthy Eating Index for pregnant women in Singapore (HEI-SGP) score and previously derived dietary patterns (vegetables-fruit-rice, seafood-noodles, and pasta-cheese-meat pattern). Eating behaviors studied included the longest night-time fasting interval, frequency of consumption occasions, energy from discretionary foods, and night-time eating. Adjusted means were estimated between poor/good quality and short/normal sleepers using linear regressions, including covariates. Good sleep quality versus poor sleep quality, was associated with better diet quality (mean HEI‐SGP 54.6 vs. 52.0; p = 0.032), greater adherence to the vegetables-fruit-rice pattern (mean 0.03 vs. −0.15; p = 0.039), lesser adherence to the seafood-noodle pattern (mean −0.14 vs. 0.03; p = 0.024), and a trending lower calories from discretionary foods (mean 330.5 vs. 382.6 kcal; p = 0.073), after adjusting for covariates. After additional adjustment for anxiety, only sleep quality and the seafood‐noodle pattern remained significantly associated (p = 0.018). Short sleep was not associated with any diet or eating behavior. In conclusion, good sleep quality is associated with a better diet quality and a greater adherence to the vegetable-fruit-rice pattern, but with lesser adherence to the seafood-noodle diets in pregnant women