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Context: An inverse relationship between brown adipose tissue (BAT) and obesity has previously been reported in older children and adults but is 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 of 198 children aged 4.5 years from a prospective birth cohort study, Growing Up in Singapore Towards Healthy Outcomes (GUSTO) were successfully studied with water-fat magnetic resonance imaging of the supraclavicular and axillary fat depot (FDSA). Regions within FDSA with fat-signal-fraction between 20% and 80% were considered BAT, and percentage BAT (%BAT; 100*BAT volume/ FDSA volume) was calculated., Main Outcome Measures: Abdominal adipose tissue compartment volumes, ectopic fat in the soleus muscle and liver, fatty liver index, metabolic syndrome scores, and markers of insulin sensitivity., Results: A 1% unit increase in %BAT was associated with lower body mass index, difference (95% CI), -0.08 (-0.10, -0.06) kg/m2 and smaller abdominal adipose tissue compartment volumes. Ethnicity and sex modified these associations. In addition, each unit increase in %BAT was associated with lower ectopic fat at 4.5 years in the liver, -0.008% (-0.013%, -0.003%); soleus muscle, -0.003% (-0.006%, -0.001%) of water content and lower fatty liver index at 6 years., Conclusions: Higher %BAT is associated with a more favorable metabolic profile. BAT may thus play a role in the pathophysiology of obesity and related metabolic disorders. The observed ethnic and sex differences imply that the protective effect of BAT may vary among different groups., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

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., Methods: In 6-year-old children (n = 377) from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) prospective birth cohort, whole-body composition was measured by quantitative magnetic resonance, a novel validated technology. Based on fat mass index (FMI) and lean mass index (LMI), 4 body composition phenotypes were derived: low FMI-low LMI (LF-LL), low FMI-high LMI (LF-HL), high FMI-low LMI (HF-LL), high FMI-high LMI (HF-HL)., Main Outcome Measures: Body mass index (BMI) z-score, fasting plasma glucose, insulin resistance, metabolic syndrome risk score, fatty liver index, and blood pressure., Results: Compared with the LF-HL group, children in both high FMI groups had increased BMI z-score (HF-HL: 1.43 units 95% CI [1.11,1.76]; HF-LL: 0.61 units [0.25,0.96]) and metabolic syndrome risk score (HF-HL: 1.64 [0.77,2.50]; HF-LL: 1.28 [0.34,2.21]). The HF-HL group also had increased fatty liver index (1.15 [0.54,1.77]). Girls in HF-HL group had lower fasting plasma glucose (-0.29 mmol/L [-0.55,-0.04]) and diastolic blood pressure (-3.22 mmHg [-6.03,-0.41]) than girls in the HF-LL group. No similar associations were observed in boys., Conclusion: In a multi-ethnic Asian cohort, lean mass seemed to protect against some cardiometabolic risk markers linked with adiposity, but only in girls. The FMI seemed more important than lean mass index in relation to cardiometabolic profiles of young children., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background/objectives: 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 such alterations impact fetal physiology. We aimed to investigate whether the effects of maternal glycaemia on offspring birthweight and adiposity at birth differed across placental inositol levels., Methods: Using longitudinal data from the Growing Up in Singapore Towards healthy Outcomes cohort, maternal fasting glucose (FPG) and 2-hour plasma glucose (2hPG) were obtained in pregnant women by a 75-g oral glucose tolerance test around 26 weeks' gestation. Relative placental inositol was quantified by liquid chromatography-mass spectrometry. Primary outcomes were birthweight (n = 884) and abdominal adipose tissue (AAT) volumes measured by neonatal MRI scanning in a subset (n = 262) of term singleton pregnancies. Multiple linear regression analyses were performed., Results: Placental inositol was lower in those with higher 2hPG, no exposure to tobacco smoke antenatally, with vaginal delivery and shorter gestation. Positive associations of FPG with birthweight (adjusted β [95% CI] 164.8 g [109.1, 220.5]) and AAT (17.3 ml [11.9, 22.6] per mmol glucose) were observed, with significant interactions between inositol tertiles and FPG in relation to these outcomes (p < 0.05). Stratification by inositol tertiles showed that each mmol/L increase in FPG was associated with increased birthweight and AAT volume among cases within the lowest (birthweight = 174.2 g [81.2, 267.2], AAT = 21.0 ml [13.1, 28.8]) and middle inositol tertiles (birthweight = 202.0 g [103.8, 300.1], AAT = 19.7 ml [9.7, 29.7]). However, no significant association was found among cases within the highest tertile (birthweight = 81.0 g [-21.2, 183.2], AAT = 0.8 ml [-8.4, 10.0])., Conclusions: High placental inositol may protect the fetus from the pro-adipogenic effects of maternal glycaemia. Studies are warranted to investigate whether prenatal inositol supplementation can increase placental inositol and reduce fetal adiposity.

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-measured 2nd-3rd-trimester abdominal circumference decrease by ≥0.67 standard deviation score (SDS) and rapid postnatal weight gain (RPWG) as 0-2-year-old weight increase by ≥0.67 SDS. In the GUSTO mother-offspring cohort, we grouped 797 children into four groups of FGD-only (14.2%), RPWG-only (23.3%), both (mismatch, 10.7%) or neither (reference, 51.8%). Adjusting for confounders and comparing with the reference group, we tested associations of these growth groups with childhood cardiometabolic biomarkers: magnetic resonance imaging (MRI)-measured abdominal fat (n = 262), liver fat (n = 216), intramyocellular lipids (n = 227), quantitative magnetic resonance-measured overall body fat % (BF%) (n = 310), homeostasis model assessment of insulin resistance (HOMA-IR) (n = 323), arterial wall thickness (n = 422) and stiffness (n = 443), and blood pressure trajectories (ages 3-6 years)., Results: Mean±SD birthweights were: FGD-only (3.11 ± 0.38 kg), RPWG-only (3.03 ± 0.37 kg), mismatch (2.87 ± 0.31 kg), reference (3.30 ± 0.36 kg). FGD-only children had elevated blood pressure trajectories without correspondingly increased BF%. RPWG-only children had altered body fat partitioning, higher BF% [BF = 4.26%, 95% confidence interval (CI) (2.34, 6.19)], HOMA-IR 0.28 units (0.11, 0.45)] and elevated blood pressure trajectories. Mismatch children did not have increased adiposity, but had elevated ectopic fat, elevated HOMA-IR [0.29 units (0.04,0.55)] and the highest blood pressure trajectories. Associations remained even after excluding small-for-gestational-age infants from analyses., Conclusions: Fetal growth deceleration coupled with rapid postnatal weight gain was associated with elevated childhood cardiometabolic risk biomarkers without correspondingly increased BF%., (© The Author(s) 2020; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Studying the determinants and the long-term consequences of fetal adipose accretion requires accurate assessment of neonatal body composition. In large epidemiological studies, in-depth body composition measurement methods are usually not feasible for cost and logistical reasons, and there is a need to identify anthropometric measures that adequately reflect neonatal adiposity., Methods: In a multiethnic Asian mother-offspring cohort in Singapore, anthropometric measures (weight, length, abdominal circumference, skinfold thicknesses) were measured using standardized protocols in newborn infants, and anthropometric indices (weight/length, weight/length 2 (body mass index, BMI), weight/length 3 (ponderal index, PI)) derived. Neonatal total adiposity was measured using air displacement plethysmography (ADP) and abdominal adiposity using magnetic resonance imaging (MRI). Correlations of the anthropometric measures with ADP- and MRI-based adiposity were assessed using Pearson's correlation coefficients (r p ), including in subsamples stratified by sex and ethnicity., Results: Study neonates (n=251) had a mean (s.d.) age of 10.2 (2.5) days. Correlations between ADP-based fat mass (ADP FM ) and anthropometric measures were moderate (r p range: 0.44-0.67), with the strongest being with weight/length, weight, BMI and sum of skinfolds (r p =0.67, 0.66, 0.62, 0.62, respectively, all P<0.01). All anthropometric measures except skinfold thicknesses correlated more strongly with ADP-based fat-free mass than ADP FM , indicating that skinfold measures may have more discriminative power in terms of neonatal total body adiposity. For MRI-based measures, weight and weight/length consistently showed strong positive correlations (r p ⩾0.7) with abdominal adipose tissue compartments. These correlations were consistent in boys and girls, across different ethnic groups, and when conventional determinants of neonatal adiposity were adjusted for potential confounding. Abdominal circumference was not strongly associated with ADP FM or abdominal fat mass., Conclusions: Simple anthropometric measures (weight and weight/length) correlated strongly with neonatal adiposity, with some evidence for greater discriminative power for skinfold measures. These simple measures could be of value in large epidemiological studies.

Background: Evidence linking maternal diet quality during pregnancy with infant birth outcomes is limited in Asia., Objective: We investigated the association of maternal diet quality with the risk of preterm birth, offspring birth size, and adiposity in a multiethnic Asian birth cohort., Design: Dietary intakes of 1051 pregnant women were ascertained at 26-28 wk of gestation with the use of 24-h recalls and 3-d food diaries, from which diet quality (score range: 0-100) was measured by the Healthy Eating Index for pregnant women in Singapore (HEI-SGP). Gestational age was established by first-trimester ultrasound dating scan. Neonatal weight and length were measured at birth. Body composition was assessed by air displacement plethysmography in a subset of infants (n = 313) within 72 h after birth, and abdominal adiposity was assessed by MRI (n = 316) within the first 2 wk of life. Associations were assessed by multivariable linear regression for continuous outcomes and logistic regression for preterm birth., Results: The mean ± SD maternal HEI-SGP score was 52.1 ± 13.6. Maternal diet quality during pregnancy was not associated with preterm birth or birth weight. Greater adherence to the HEI-SGP (per 10-point increment in HEI-SGP score) was associated with longer birth length [β (95% CI): 0.14 (0.03, 0.24 cm)], lower body mass index (in kg/m2) at birth [-0.07 (-0.13, -0.01)], lower sum of triceps and subscapular skinfold thickness [-0.15 (-0.26, -0.05 mm)], lower percentage body fat [-0.52% (-0.84%, -0.20%)], lower fat mass [-17.23 (-29.52, -4.94 g)], lower percentage abdominal superficial subcutaneous adipose tissue [-0.16% (-0.30%, -0.01%)], and lower percentage deep subcutaneous adipose tissue [-0.06% (-0.10%, -0.01%)]., Conclusions: Higher maternal diet quality during pregnancy was associated with longer birth length and lower neonatal adiposity but not with birth weight and preterm birth. These findings warrant further investigation in independent studies. This trial was registered at clinicaltrials.gov as NCT01174875., (© 2018 American Society for Nutrition. All rights reserved.)

Recent findings confirm that faster eating rates support higher energy intakes within a meal and are associated with increased body weight and adiposity in children. The current study sought to identify the eating behaviours that underpin faster eating rates and energy intake in children, and to investigate their variations by weight status and other individual differences. Children (N=386) from the Growing Up in Singapore towards Healthy Outcomes (GUSTO) cohort took part in a video-recorded ad libitum lunch at 4.5years of age to measure acute energy intake. Videos were coded for three eating behaviours (bites, chews and swallows) to derive a measure of eating rate (g/min) and measures of eating microstructure: eating rate (g/min), total oral exposure (min), average bite size (g/bite), chews per gram, oral exposure per bite (s), total bites and proportion of active to total mealtime. Children's BMIs were calculated and a subset of children underwent MRI scanning to establish abdominal adiposity. Children were grouped into faster and slower eaters, and into healthy and overweight groups to compare their eating behaviours. Results demonstrate that faster eating rates were correlated with larger average bite size (r=0.55, p<0.001), fewer chews per gram (r=-0.71, p<0.001) and shorter oral exposure time per bite (r=-0.25, p<0.001), and with higher energy intakes (r=0.61, p<0.001). Children with overweight and higher adiposity had faster eating rates (p<0.01) and higher energy intakes (p<0.01), driven by larger bite sizes (p<0.05). Eating behaviours varied by sex, ethnicity and early feeding regimes, partially attributable to BMI. We propose that these behaviours describe an 'obesogenic eating style' that is characterised by faster eating rates, achieved through larger bites, reduced chewing and shorter oral exposure time. This obesogenic eating style supports acute energy intake within a meal and is more prevalent among, though not exclusive to, children with overweight. Clinical Trial Registry Number: NCT01174875; https://clinicaltrials.gov/., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Polyunsaturated fatty acids (PUFA) are essential for offspring development, but it is less clear whether pregnancy PUFA status affects growth and adiposity., Methods: In 985 mother-offspring pairs from the ongoing Singaporean GUSTO cohort, we analyzed the associations between offspring growth and adiposity outcomes until age 5 years and five PUFAs of interest, measured in maternal plasma at 26-28 weeks' gestation: linoleic acid (LA), arachidonic acid, α-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid (DHA). We measured fetal growth by ultrasound (n=924), neonatal body composition (air displacement plethysmography (n=252 at birth, and n=317 at age 10 days), and abdominal magnetic resonance imaging (n=317)), postnatal growth (n=979) and skinfold thicknesses (n=981). Results were presented as regression coefficients for a 5% increase in PUFA levels., Results: LA levels were positively associated with birthweight (β (95% CI): 0.04 (0.01, 0.08) kg), body mass index (0.13 (0.02, 0.25) kg/m 2 ), head circumference (0.11 (0.03, 0.19) cm), and neonatal abdominal adipose tissue volume (4.6 (1.3, 7.8) mL for superficial subcutanous tissue, and 1.2 (0.1, 2.4) mL for internal tissue), but not with later outcomes. DHA levels, although not associated with birth outcomes, were related to higher postnatal length/height: 0.63 (0.09, 1.16) cm at 12 months and 1.29 (0.34, 2.24) cm at 5 years., Conclusions: LA was positively associated with neonatal body size, and DHA with child height. Maternal PUFA status during pregnancy may influence fetal and child growth and adiposity., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Faster eating rates are associated with increased energy intake, but little is known about the relationship between children's eating rate, food intake and adiposity. We examined whether children who eat faster consume more energy and whether this is associated with higher weight status and adiposity. We hypothesised that eating rate mediates the relationship between child weight and ad libitum energy intake. Children (n 386) from the Growing Up in Singapore Towards Healthy Outcomes cohort participated in a video-recorded ad libitum lunch at 4·5 years to measure acute energy intake. Videos were coded for three eating-behaviours (bites, chews and swallows) to derive a measure of eating rate (g/min). BMI and anthropometric indices of adiposity were measured. A subset of children underwent MRI scanning (n 153) to measure abdominal subcutaneous and visceral adiposity. Children above/below the median eating rate were categorised as slower and faster eaters, and compared across body composition measures. There was a strong positive relationship between eating rate and energy intake (r 0·61, P<0·001) and a positive linear relationship between eating rate and children's BMI status. Faster eaters consumed 75 % more energy content than slower eating children (Δ548 kJ (Δ131 kcal); 95 % CI 107·6, 154·4, P<0·001), and had higher whole-body (P<0·05) and subcutaneous abdominal adiposity (Δ118·3 cc; 95 % CI 24·0, 212·7, P=0·014). Mediation analysis showed that eating rate mediates the link between child weight and energy intake during a meal (b 13·59; 95 % CI 7·48, 21·83). Children who ate faster had higher energy intake, and this was associated with increased BMI z-score and adiposity.

Background: Infant body composition has been associated with later metabolic disease risk, but few studies have examined the association between maternal macronutrient intake and neonatal body composition. Furthermore, most of those studies have used proxy measures of body composition that may not reflect body fat distribution, particularly abdominal internal adiposity., Objective: We investigated the relation between maternal macronutrient intake and neonatal abdominal adiposity measured by using MRI in a multiethnic Asian mother-offspring cohort., Methods: The macronutrient intake of mothers was ascertained by using a 24-h dietary recall at 26-28 wk gestation. Neonatal abdominal adiposity was assessed by using MRI in week 2 of life. Mother-offspring dyads with complete macronutrient intake and adiposity information (n = 320) were included in the analysis. Associations were assessed by both substitution and addition models with the use of multivariable linear regressions., Results: Mothers (mean age: 30 y) consumed (mean ± SD) 15.5% ± 4.3% of their energy from protein, 32.4% ± 7.7% from fat, and 52.1% ± 9.0% from carbohydrate. A higher-protein, lower-carbohydrate or -fat diet during pregnancy was associated with lower abdominal internal adipose tissue (IAT) in the neonates [β (95% CI): -0.18 mL (-0.35, -0.001 mL) per 1% protein-to-carbohydrate substitution and -0.25 mL (-0.46, -0.04 mL) per 1% protein-to-fat substitution]. These associations were stronger in boys than in girls (P-interaction < 0.05). Higher maternal intake of animal protein, but not plant protein, was associated with lower offspring IAT. In contrast, maternal macronutrient intake was not associated consistently with infant anthropometric measurements, including abdominal circumference and subscapular skinfold thickness., Conclusions: Higher maternal protein intake at the expense of carbohydrate or fat intake at 26-28 wk gestation was associated with lower abdominal internal adiposity in neonates. Optimizing maternal dietary balance might be a new approach to improve offspring body composition. This trial was registered at clinicaltrials.gov as NCT01174875., (© 2016 American Society for Nutrition.)

Background: A susceptibility to metabolic diseases is associated with abdominal adipose tissue distribution and varies between ethnic groups. The distribution of abdominal adipose tissue at birth may give insights into whether ethnicity-associated variations in metabolic risk originate partly in utero., Objective: We assessed the influence of ethnicity on abdominal adipose tissue compartments in Asian neonates in the Growing Up in Singapore Toward Healthy Outcomes mother-offspring cohort., Design: MRI was performed at ≤2 wk after birth in 333 neonates born at ≥34 wk of gestation and with birth weights ≥2000 g. Abdominal superficial subcutaneous tissue (sSAT), deep subcutaneous tissue (dSAT), and internal adipose tissue (IAT) compartment volumes (absolute and as a percentage of the total abdominal volume) were quantified., Results: In multivariate analyses that were controlled for sex, age, and parity, the absolute and percentage of dSAT and the percentage of sSAT (but not absolute sSAT) were greater, whereas absolute IAT (but not the percentage of IAT) was lower, in Indian neonates than in Chinese neonates. Compared with Chinese neonates, Malay neonates had greater percentages of sSAT and dSAT but similar percentages of IAT. Marginal structural model analyses largely confirmed the results on the basis of volume percentages with controlled direct effects of ethnicity on abdominal adipose tissue; dSAT was significantly greater (1.45 mL; 95% CI: 0.49, 2.41 mL, P = 0.003) in non-Chinese (Indian or Malay) neonates than in Chinese neonates. However, ethnic differences in sSAT and IAT were NS [3.06 mL (95% CI:-0.27, 6.39 mL; P = 0.0712) for sSAT and -1.30 mL (95% CI: -2.64, 0.04 mL; P = 0.057) for IAT in non-Chinese compared with Chinese neonates, respectively]., Conclusions: Indian and Malay neonates have a greater dSAT volume than do Chinese neonates. This finding supports the notion that in utero influences may contribute to higher cardiometabolic risk observed in Indian and Malay persons in our population. If such differences persist in the longitudinal tracking of adipose tissue growth, these differences may contribute to the ethnic disparities in risks of cardiometabolic diseases. This trial was registered at clinicaltrials.gov as NCT01174875., (© 2016 American Society for Nutrition.)