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BACKGROUND: The influence of prenatal exposure to per- and poly- fluoroalkyl substances (PFAS) on birth size and offspring adiposity is unclear, especially for the newer, shorter-chained replacement PFAS. METHODS: In the GUSTO multi-ethnic Singaporean mother-offspring cohort, 12 PFAS were measured in 783 cord plasma samples using ultra-performance-liquid chromatography-tandem-mass-spectrometer (UPLC-MS/MS). Outcomes included offspring anthropometry, other indicators of body composition/metabolic health, and MRI-derived abdominal adiposity (subset) at birth and 6 years of age. PFAS were modeled individually, in categories of long-chain and short-chain PFAS, and as scores of three principal components (PC) derived using PC analysis (PC1, PC2, and PC3 reflect predominant exposure patterns to "very-long-PFAS", "long-PFAS", and "short-PFAS", respectively). Associations with outcomes were assessed using multivariable linear regressions, adjusted for important covariates such as maternal sociodemographic and lifestyle factors. RESULTS: Overall, cord PFAS levels showed either no or positive associations (mostly for long-chain PFAS) with birth weight, length and head circumference. In general, PFAS were associated with higher neonatal abdominal adiposity, driven by shorter-chain PFAS. Perfluoroheptanoic acid (PFHpA) was associated with higher volumes of superficial subcutaneous adipose tissue (sSAT) (3.75 [1.13, 6.37] mL per SD increase in PFAS) and internal adipose tissue (IAT) (1.39 [0.41, 2.38] mL). Higher levels of perfluorobutanesulfonic acid (PFBS), short-chain PFAS, and PC3 were associated with higher IAT volume (ß range 1.22-1.41 mL/SD, all P < 0.02), especially in girls. Higher PC3 score was additionally associated with higher sSAT (3.12 [0.45, 5.80] mL) volume. At age 6 years, most observed associations did not persist. No consistent associations were observed between PFAS and whole-body adiposity measures. CONCLUSIONS: Fetal exposure to emerging short-chain PFAS was associated with higher abdominal adiposity at birth but not at age 6 years. Further research is needed to replicate the findings and to determine if these effects may reappear beyond early childhood. Population exposure to newer PFAS and consequent health impact must be monitored.
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Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorocarbonos , Efeitos Tardios da Exposição Pré-Natal , Recém-Nascido , Gravidez , Criança , Feminino , Humanos , Pré-Escolar , Adiposidade , Cromatografia Líquida , Estudos Prospectivos , Espectrometria de Massas em Tandem , Obesidade , Composição Corporal , Obesidade AbdominalRESUMO
BACKGROUND: Weight loss is the most effective treatment for nonalcoholic fatty liver disease (NAFLD). There is evidence that the Mediterranean diets rich in unsaturated fatty acids and fiber have beneficial effects on weight homeostasis and metabolic risk factors in individuals with NAFLD. Studies have also shown that higher circulating concentrations of pentadecanoic acid (C15:0) are associated with a lower risk for NAFLD. OBJECTIVES: To examine the effects of a Mediterranean-like, culturally contextualized Asian diet rich in fiber and unsaturated fatty acids, with or without C15:0 supplementation, in Chinese females with NAFLD. METHODS: In a double-blinded, parallel-design, randomized controlled trial, 88 Chinese females with NAFLD were randomly assigned to 1 of the 3 groups for 12 wk: diet with C15:0 supplementation (n = 31), diet without C15:0 supplementation (n = 28), or control (habitual diet and no C15:0 supplementation, n = 29). At baseline and after the intervention, body fat percentage, intrahepatic lipid content, muscle and abdominal fat, liver enzymes, cardiometabolic risk factors, and gut microbiome were assessed. RESULTS: In the intention-to-treat analysis, weight reductions of 4.0 ± 0.5 kg (5.3%), 3.4 ± 0.5 kg (4.5%), and 1.5 ± 0.5 kg (2.1%) were achieved in the diet-with-C15:0, diet without-C15:0, and the control groups, respectively. The proton density fat fraction (PDFF) of the liver decreased by 33%, 30%, and 10%, respectively. Both diet groups achieved significantly greater reductions in body weight, liver PDFF, total cholesterol, gamma-glutamyl transferase, and triglyceride concentrations compared with the control group. C15:0 supplementation reduced LDL-cholesterol further, and increased the abundance of Bifidobacterium adolescentis. Fat mass, visceral adipose tissue, subcutaneous abdominal adipose tissue (deep and superficial), insulin, glycated hemoglobin, and blood pressure decreased significantly in all groups, in parallel with weight loss. CONCLUSION: Mild weight loss induced by a Mediterranean-like diet adapted for Asians has multiple beneficial health effects in females with NAFLD. C15:0 supplementation lowers LDL-cholesterol and may cause beneficial shifts in the gut microbiome. TRIAL REGISTRATION NUMBER: This trial was registered at the clinicaltrials.gov as NCT05259475.
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Dieta Mediterrânea , Ácidos Graxos , Hepatopatia Gordurosa não Alcoólica , Feminino , Humanos , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Fígado/metabolismo , Redução de Peso , Ácidos Graxos Insaturados , ColesterolRESUMO
BACKGROUND: Existing literature has highlighted structural, physiological, and pathological disparities among abdominal adipose tissue (AAT) sub-depots. Accurate separation and quantification of these sub-depots are crucial for advancing our understanding of obesity and its comorbidities. However, the absence of clear boundaries between the sub-depots in medical imaging data has challenged their separation, particularly for internal adipose tissue (IAT) sub-depots. To date, the quantification of AAT sub-depots remains challenging, marked by a time-consuming, costly, and complex process. PURPOSE: To implement and evaluate a convolutional neural network to enable granular assessment of AAT by compartmentalization of subcutaneous adipose tissue (SAT) into superficial subcutaneous (SSAT) and deep subcutaneous (DSAT) adipose tissue, and IAT into intraperitoneal (IPAT), retroperitoneal (RPAT), and paraspinal (PSAT) adipose tissue. MATERIAL AND METHODS: MRI datasets were retrospectively collected from Singapore Preconception Study for Long-Term Maternal and Child Outcomes (S-PRESTO: 389 women aged 31.4 ± 3.9 years) and Singapore Adult Metabolism Study (SAMS: 50 men aged 28.7 ± 5.7 years). For all datasets, ground truth segmentation masks were created through manual segmentation. A Res-Net based 3D-UNet was trained and evaluated via 5-fold cross-validation on S-PRESTO data (N = 300). The model's final performance was assessed on a hold-out (N = 89) and an external test set (N = 50, SAMS). RESULTS: The proposed method enabled reliable segmentation of individual AAT sub-depots in 3D MRI volumes with high mean Dice similarity scores of 98.3%, 97.2%, 96.5%, 96.3%, and 95.9% for SSAT, DSAT, IPAT, RPAT, and PSAT respectively. CONCLUSION: Convolutional neural networks can accurately sub-divide abdominal SAT into SSAT and DSAT, and abdominal IAT into IPAT, RPAT, and PSAT with high accuracy. The presented method has the potential to significantly contribute to advancements in the field of obesity imaging and precision medicine.
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Gordura Abdominal , Obesidade , Adulto , Masculino , Criança , Humanos , Feminino , Estudos Retrospectivos , Gordura Abdominal/diagnóstico por imagem , Gordura Subcutânea Abdominal , Redes Neurais de Computação , Tecido Adiposo , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: The timing of introduction of complementary foods and the duration of breastfeeding (BF) have been independently associated with child overweight and obesity; however, their combined influence on body fat partitioning and cardiometabolic risk is unclear. OBJECTIVE: We investigated the associations of the timing of introduction of complementary foods, the duration of BF, and their interaction with child adiposity and cardiometabolic risk markers. METHODS: We analyzed data from 839 children in the prospective Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. Mothers reported the age at which infants were first fed complementary foods and BF duration, classified as early (≤4 mo) versus typical (>4 mo) complementary feeding (CF) and short (≤4 mo) versus long (>4 mo) duration of any BF, respectively. We measured adiposity and cardiometabolic risk markers at the age of 6 y and examined their associations with infant feeding patterns using multiple regression, adjusting for sociodemographics, parents' body mass index (BMI), maternal factors, birth weight for gestational age, and infant weight gain. RESULTS: Of 839 children, 18% experienced early CF, whereas 54% experienced short BF. Short (vs. long) BF and early (vs. typical) CF were independently associated with higher z-scores of BMI [ß (95% confidence interval), short BF, 0.18 standard deviation score (SDS) (-0.01, 0.38); early CF, 0.34 SDS (0.11, 0.57)] and sum of skinfolds [short BF, 1.83 mm (0.05, 3.61); early CF, 2.73 mm (0.55, 4.91)]. Children who experienced both early CF and short BF (vs. typical CF-long BF) had synergistically higher diastolic blood pressure [1.41 mmHg (-0.15, 2.97), P-interaction = 0.023] and metabolic syndrome score [0.81 (0.16, 1.47), P-interaction = 0.081]. Early CF-long BF (vs. early CF-short BF) was associated with a lower systolic blood pressure [-3.74 mmHg (-7.01, -0.48)], diastolic blood pressure [-2.29 mmHg (-4.47, -0.11)], and metabolic syndrome score [-0.90 (-1.80, 0.00)]. CONCLUSIONS: A combination of early CF and short BF was associated with elevated child adiposity and cardiometabolic markers. Longer BF duration may protect against cardiometabolic risk associated with early CF. This trial was registered at clinicaltrials.gov as NCT01174875.
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Doenças Cardiovasculares , Síndrome Metabólica , Criança , Feminino , Humanos , Lactente , Índice de Massa Corporal , Aleitamento Materno , Doenças Cardiovasculares/prevenção & controle , Estudos de Coortes , Obesidade , Estudos ProspectivosRESUMO
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-offspring cohort (Chinese, Indian and Malay ethnicities) based in Singapore. We evaluated the early-life determinants of the trajectories as well as their associations with cardiometabolic risk markers at age 6 years. RESULTS: Five BMI z-score trajectory patterns were identified, three within the healthy weight range, alongside early-acceleration and late-acceleration obesogenic trajectories. The early-acceleration pattern was characterized by elevated fetal abdominal circumference growth velocity, BMI acceleration immediately after birth and crossing of the obesity threshold by age 2 years. The late-acceleration pattern had normal fetal growth and BMI acceleration after infancy, and approached the obesity threshold by age 6 years. Abdominal fat, liver fat, insulin resistance and odds of pre-hypertension/hypertension were elevated in both groups. Indian ethnicity, high pre-pregnancy BMI, high polygenic risk scores for obesity and shorter breastfeeding duration were common risk factors for both groups. Malay ethnicity and low maternal educational attainment were uniquely associated with early BMI acceleration, whereas nulliparity and obesogenic eating behaviours in early childhood were uniquely associated with late BMI acceleration. CONCLUSION: BMI acceleration starting immediately after birth or after infancy were both linked to early cardiometabolic alterations. The determinants of these trajectories may be useful for developing early risk stratification and intervention approaches to counteract metabolic adversities linked to childhood obesity.
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Doenças Cardiovasculares , Obesidade Infantil , Feminino , Criança , Pré-Escolar , Humanos , Gravidez , Obesidade Infantil/epidemiologia , Estudos Prospectivos , Índice de Massa Corporal , Fatores de RiscoRESUMO
OBJECTIVE: To evaluate whether characterization of maternal and foetoplacental 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 6 years was identified using the simplified paediatric threshold of 110/70âmmHg. We evaluated the associations of pregnancy complications (gestational diabetes, excessive/inadequate gestational weight gain, hypertensive disorders of pregnancy), foetal growth deceleration (decline in foetal abdominal circumference at least 0.67 standard deviations between second and third trimesters), high foetoplacental vascular resistance (third trimester umbilical artery systolic-to-diastolic ratio ≥90th centile), preterm birth, small-for-gestational age and neonatal kidney volumes with risk of prehypertension/hypertension at age 6 years, after adjusting for sex, ethnicity, maternal education and prepregnancy BMI. RESULTS: Pregnancy complications, small-for-gestational age, preterm birth, and low neonatal kidney volume were not associated with an increased risk of prehypertension/hypertension at age 6 years. In contrast, foetal growth deceleration was associated with a 72% higher risk [risk ratio (RR) = 1.72, 95% confidence interval (CI) 1.18-2.52]. High foetoplacental vascular resistance was associated with a 58% higher risk (RR = 1.58, 95% CI 0.96-2.62). Having both these characteristics, relative to having neither, was associated with over two-fold higher risk (RR = 2.55, 95% CI 1.26-5.16). Over 85% of the foetuses with either of these characteristics were born appropriate or large for gestational age. CONCLUSION: Foetal growth deceleration and high foetoplacental vascular resistance may be helpful in prioritizing high-risk children for regular blood pressure monitoring and preventive interventions, across the birthweight spectrum.
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Hipertensão , Complicações na Gravidez , Pré-Hipertensão , Nascimento Prematuro , Peso ao Nascer , Criança , Pré-Escolar , Feminino , Retardo do Crescimento Fetal , Humanos , Hipertensão/epidemiologia , Recém-Nascido , Gravidez , Pré-Hipertensão/epidemiologia , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Estudos Prospectivos , Aumento de PesoRESUMO
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 displacement plethysmography was conducted within 24 h after delivery in 290 naturally conceived singletons. We investigated associations of newborn cohort-specific standardized z-score of fat mass, fat-free mass, body fat percentage and birthweight on child (at 6 years of age) carotid intima-media thickness, pulse wave velocity, blood pressure, prehypertension/hypertension (>110/70 mmHg) and standardized systolic and diastolic blood pressure (SBP and DBP) trajectories (at 3-6 years of age), taking account of maternal education, height, tobacco exposure, parity, ethnicity, child's sex, gestational age, age at follow-up, and other maternal factors. RESULTS: Clear inverse associations were seen for blood pressure with z-score of fat mass [SBP, ß (95% CI): -1.31 mmHg (-2.57, -0.06); DBP: -0.79 mmHg (-1.74, 0.15)] and body fat percentage [SBP: -1.46 mmHg (-2.73, -0.19); DBP: -0.80 mmHg (-1.75, 0.16)], but not with fat-free mass [SBP: 0.27 mmHg (-1.29, 1.83)]; DBP: -0.14 mmHg (-1.30, 1.03)]. Being in the lowest tertile of fat mass or body fat percentage was associated with higher blood pressure trajectories and prehypertension/hypertension risk [OR (95% CI), fat mass: 4.23 (1.41, 12.68); body fat percentage: 3.22 (1.09, 9.53)] without concomitantly higher overweight/obesity risk. CONCLUSIONS: At birth, low adiposity was associated with increased childhood blood pressure. Low newborn adiposity might serve as a marker of poor fetal growth or suboptimal intrauterine conditions associated with hypertension risk later in life.
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Doenças Cardiovasculares , Hipertensão , Pré-Hipertensão , Recém-Nascido , Gravidez , Feminino , Criança , Humanos , Pré-Escolar , Peso ao Nascer , Doenças Cardiovasculares/epidemiologia , Estudos Prospectivos , Espessura Intima-Media Carotídea , Estudos de Coortes , Análise de Onda de Pulso , Fatores de Risco , Pressão Sanguínea , Composição Corporal , Hipertensão/epidemiologia , Obesidade , Fatores de Risco de Doenças Cardíacas , Índice de Massa CorporalRESUMO
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 alcohol consumption in the 12 months prior to pregnancy recognition was categorized as high (≥75th percentile: 1.9âg/day), low (<1.9âg/day), and none, and frequency of alcohol consumption was categorized as high (≥2-3 times/week), low (<2-3 times/week), and none. Offspring MRI-based abdominal fat depot, kidney, and brain volumes, blood pressure, metabolic syndrome score, and cognitive intelligence scores were assessed. Child prehypertension/hypertension at age 6 years was defined using a simplified pediatric threshold of 110/70âmmHg. RESULTS: The average maternal alcohol consumption in the year prior to pregnancy recognition was 2.5âg/day, which is lower than the daily maximal limit of one standard drink (10âg) recommended for women by Singapore's Ministry of Health. After adjusting for participant characteristics, alcohol consumption at least 1.9âg/day was associated with over two-fold higher risk (risk ratioâ=â2.18, Pâ=â0.013) of child prehypertension and 15% greater kidney growth between early infancy and age 6 years (Pâ=â0.040) compared with abstinence. Alcohol consumption was not associated with metabolic and neurocognitive health at age 6-7 years. The associations with high frequency of alcohol consumption were concordant with those obtained for quantity of alcohol consumption. CONCLUSION: Maternal self-reported alcohol consumption at least 1.9âg/day prior to pregnancy recognition was associated with increased risk of child prehypertension and rapid kidney growth. Our findings highlight the potential detrimental effects of low periconceptional alcohol consumption, below national guidelines on offspring cardiorenal health.
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Hipertensão , Pré-Hipertensão , Consumo de Bebidas Alcoólicas/efeitos adversos , Criança , Estudos de Coortes , Feminino , Humanos , Mães , Gravidez , Pré-Hipertensão/epidemiologia , Pré-Hipertensão/etiologia , Estudos Prospectivos , Singapura/epidemiologiaRESUMO
Brown adipose tissue (BAT) is a promising weapon to combat obesity and metabolic disease. BAT is thermogenic and consumes substantial amounts of glucose and fatty acids as fuel for thermogenesis and energy expenditure. To study BAT function in large human longitudinal cohorts, safe and precise detection methodologies are needed. Although regarded a gold standard, the foray of PET-CT into BAT research and clinical applications is limited by its high ionizing radiation doses. Here, we show that brown adipocytes release exosomes in blood plasma that can be utilized to assess BAT activity. In the present study, we investigated circulating protein biomarkers that can accurately and reliably reflect BAT activation triggered by cold exposure, capsinoids ingestion and thyroid hormone excess in humans. We discovered an exosomal protein, methylene tetrahydrofolate dehydrogenase (NADP+ dependent) 1-like (MTHFD1L), to be overexpressed and detectable in plasma for all three modes of BAT activation in human subjects. This mitochondrial protein is packaged as a cargo within multivesicular bodies of the endosomal compartment and secreted as exosomes via exocytosis from activated brown adipocytes into the circulation. To support MTHFD1L as a conserved BAT activation response in other vertebrates, we examined a rodent model and also proved its presence in blood of rats following BAT activation by cold exposure. Plasma concentration of exosomal MTHFD1L correlated with human BAT activity as confirmed by PET-MR in humans and supported by data from rats. Thus, we deduce that MTHFD1L appears to be overexpressed in activated BAT compared to BAT in the basal nonstimulated state.
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Tecido Adiposo Marrom , Exossomos , Adipócitos Marrons/metabolismo , Tecido Adiposo Marrom/metabolismo , Animais , Metabolismo Energético , Exossomos/metabolismo , Humanos , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , Metilenotetra-Hidrofolato Desidrogenase (NADP)/metabolismo , NADP/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Ratos , Tetra-Hidrofolato Desidrogenase/metabolismoRESUMO
Both hyperthyroidism and elevated plasma branched chain amino acids (BCAA) are associated with insulin resistance. BCAA utilization and clearance relative to thyroid status changes remains unclear. We investigate amino acids changes, specifically BCAA, during the transition from hyperthyroidism to euthyroidism, and the impact of active brown adipose tissue (BAT) on the metabolic effects of BCAA. Newly diagnosed Graves' disease participants were recruited. Hyperthyroidism was treated via a titration dosing regimen of thionamide anti-thyroid drug to establish euthyroidism over 12-24 weeks. All underwent energy expenditure (EE) measurement within a chamber calorimeter, 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging and plasma amino acids measurement during hyperthyroidism and euthyroidism. PET BAT maximum standardized uptake value (SUVmax), SUVmean and MR supraclavicular fat fraction (FF) quantified BAT activity. Twenty-two patients completed the study. Plasma BCAA level was significantly reduced in BAT-positive but not in BAT-negative patients during the transition from hyperthyroidism to euthyroidism. Plasma valine but not leucine and isoleucine correlated positively with insulin and HOMA-IR in hyperthyroidism. Plasma valine, leucine and isoleucine correlated with insulin and HOMA-IR in euthyroidism. Plasma valine correlated with insulin and HOMA-IR in BAT-negative but not in BAT-positive participants in both hyperthyroid and euthyroid state. However, the change (i.e. decrease) in plasma valine concentration from hyperthyroid to euthyroid state was affected by BAT-status. BAT utilizes and promotes BCAA plasma clearance from hyperthyroid to euthyroid state. Active BAT can potentially reduce circulating BCAA and may help to ameliorate insulin resistance and improve metabolic health.Clinical trial registration: The trial was registered at clinicaltrials.gov as NCT03064542.
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Hipertireoidismo , Resistência à Insulina , Tecido Adiposo Marrom/metabolismo , Aminoácidos de Cadeia Ramificada/metabolismo , Fluordesoxiglucose F18/metabolismo , Humanos , Hipertireoidismo/metabolismo , Insulina/metabolismo , Isoleucina/metabolismo , Leucina/metabolismo , Valina/metabolismoRESUMO
CONTEXT: The kynurenine pathway generates metabolites integral to energy metabolism, neurotransmission, and immune function. Circulating kynurenine metabolites positively correlate with adiposity in children and adults, yet it is not known whether this relationship is present already at birth. OBJECTIVE: In this prospective longitudinal study, we investigate the relationship between cord blood kynurenine metabolites and measures of adiposity from birth to 4.5 years. METHODS: Liquid chromatography-tandem mass spectrometry was used to quantify cord blood kynurenine metabolites in 812 neonates from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study. Fat percentage was measured by air displacement plethysmography and abdominal adipose tissue compartment volumes; superficial (sSAT) and deep subcutaneous (dSAT) and internal adipose tissue were quantified by magnetic resonance imaging at early infancy in a smaller subset of neonates, and again at 4 to 4.5 years of age. RESULTS: Cord blood kynurenine metabolites appeared to be higher in female newborns, higher in Indian newborns compared with Chinese newborns, and higher in infants born by cesarean section compared with vaginal delivery. Kynurenine, xanthurenic acid, and quinolinic acid were positively associated with birthweight, but not with subsequent weight during infancy and childhood. Quinolinic acid was positively associated with sSAT at birth. Kynurenic acid and quinolinic acid were positively associated with fat percentage at 4 years. CONCLUSION: Several cord blood kynurenine metabolite concentrations were positively associated with birthweight, with higher kynurenic acid and quinolinic acid correlating to higher percentage body fat in childhood, suggesting these cord blood metabolites as biomarkers of early childhood adiposity.
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Cinurenina , Obesidade Infantil , Adiposidade , Adulto , Peso ao Nascer , Cesárea , Criança , Pré-Escolar , Feminino , Sangue Fetal/metabolismo , Humanos , Lactente , Recém-Nascido , Ácido Cinurênico/metabolismo , Estudos Longitudinais , Obesidade Infantil/metabolismo , Gravidez , Estudos Prospectivos , Ácido Quinolínico/metabolismoRESUMO
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. METHODS: We included 827 naturally conceived, term singletons from a prospective mother-child cohort. We measured gestational (26-28 weeks) fasting plasma glucose (FPG) and 2-h plasma glucose (2 hPG) after an oral glucose tolerance test as continuous variables. Participants were classified into 2 breastfeeding categories (high/intermediate vs. low) according to their breastfeeding duration and exclusivity. Main outcome measures included magnetic resonance imaging (MRI)-measured abdominal fat, intramyocellular lipids (IMCL), and liver fat, quantitative magnetic resonance (QMR)-measured body fat mass, blood pressure, blood lipids, and insulin resistance at 6 years old (all continuous variables). We evaluated if gestational glycemia (FPG and 2 hPG) modified the association of breastfeeding with offspring outcomes after adjusting for confounders using a multiple linear regression model that included a 'gestational glycemia × breastfeeding' interaction term. RESULTS: With increasing gestational FPG, high/intermediate (vs. low) breastfeeding was associated with lower levels of IMCL (p-interaction = 0.047), liver fat (p-interaction = 0.033), and triglycerides (p-interaction = 0.007), after adjusting for confounders. Specifically, at 2 standard deviations above the mean gestational FPG level, high/intermediate (vs. low) breastfeeding was linked to lower adjusted mean IMCL [0.39% of water signal (0.29, 0.50) vs. 0.54% of water signal (0.46, 0.62)], liver fat [0.39% by weight (0.20, 0.58) vs. 0.72% by weight (0.59, 0.85)], and triglycerides [0.62 mmol/L (0.51, 0.72) vs. 0.86 mmol/L (0.75, 0.97)]. 2 hPG did not significantly modify the association between breastfeeding and childhood cardiometabolic risk. CONCLUSION: Our findings suggest breastfeeding may confer protection against adverse fat partitioning and higher triglyceride concentration among children exposed to increased glycemia in utero.
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Aleitamento Materno , Doenças Cardiovasculares , Diabetes Gestacional , Glicemia , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Criança , Diabetes Gestacional/patologia , Feminino , Humanos , Lipídeos , Gravidez , Estudos Prospectivos , Triglicerídeos , ÁguaRESUMO
BACKGROUND: Cord blood leptin and adiponectin are adipokines known to be associated with birth weight and overall infant adiposity. However, few studies have investigated their associations with abdominal adiposity in neonates. We examined maternal factors associated with cord blood leptin and adiponectin, and the association of these adipokines with neonatal adiposity and abdominal fat distribution measured by magnetic resonance imaging (MRI) in an Asian mother-offspring cohort. METHODS: Growing Up in Singapore Towards healthy Outcomes (GUSTO), is a prospective mother-offspring birth cohort study in Singapore. Cord blood plasma leptin and adiponectin concentrations were measured using Luminex and Enzyme-Linked Immunosorbent Assay respectively in 816 infants. A total of 271 neonates underwent MRI within the first 2-weeks after delivery. Abdominal superficial (sSAT), deep subcutaneous (dSAT), and intra-abdominal (IAT) adipose tissue compartment volumes were quantified from MRI images. Multivariable regression analyses were performed. RESULTS: Indian or Malay ethnicity, female sex, and gestational age were positively associated with cord blood leptin and adiponectin concentrations. Maternal gestational diabetes (GDM) positively associated with cord blood leptin concentrations but inversely associated with cord blood adiponectin concentrations. Maternal pre-pregnancy body mass index (BMI) showed a positive relationship with cord blood leptin but not with adiponectin concentrations. Each SD increase in cord blood leptin was associated with higher neonatal sSAT, dSAT and IAT; differences in SD (95% CI): 0.258 (0.142, 0.374), 0.386 (0.254, 0.517) and 0.250 (0.118, 0.383), respectively. Similarly, each SD increase in cord blood adiponectin was associated with higher neonatal sSAT and dSAT; differences in SD (95% CI): 0.185 (0.096, 0.274) and 0.173 (0.067, 0.278), respectively. The association between cord blood adiponectin and neonatal adiposity was observed in neonates of obese mothers only. CONCLUSIONS: Cord blood leptin and adiponectin concentrations were associated with ethnicity, maternal BMI and GDM, sex and gestational age. Both adipokines showed positive association with neonatal abdominal adiposity.
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Diabetes Gestacional , Leptina , Gordura Abdominal , Adipocinas , Adiponectina , Estudos de Coortes , Feminino , Sangue Fetal , Humanos , Lactente , Recém-Nascido , Obesidade , Obesidade Abdominal , Gravidez , Estudos ProspectivosRESUMO
PURPOSE: To develop and evaluate an automated segmentation method for accurate quantification of abdominal adipose tissue (AAT) depots (superficial subcutaneous adipose tissue [SSAT], deep subcutaneous adipose tissue [DSAT], and visceral adipose tissue [VAT]) in neonates and young children. MATERIALS AND METHODS: This was a secondary analysis of prospectively collected data, which used abdominal MRI data from Growing Up in Singapore Towards healthy Outcomes, or GUSTO, a longitudinal mother-offspring cohort, to train and evaluate a convolutional neural network for volumetric AAT segmentation. The data comprised imaging volumes of 333 neonates obtained at early infancy (age ≤2 weeks, 180 male neonates) and 755 children aged either 4.5 years (n = 316, 150 male children) or 6 years (n = 439, 219 male children). The network was trained on images of 761 randomly selected volumes (neonates and children combined) and evaluated on 100 neonatal volumes and 227 child volumes by using 10-fold validation. Automated segmentations were compared with expert-generated manual segmentation. Segmentation performance was assessed using Dice scores. RESULTS: When the model was tested on the test datasets across the 10 folds, the model had strong agreement with the ground truth for all testing sets, with mean Dice similarity scores for SSAT, DSAT, and VAT, respectively, of 0.960, 0.909, and 0.872 in neonates and 0.944, 0.851, and 0.960 in children. The model generalized well to different body sizes and ages and to all abdominal levels. CONCLUSION: The proposed segmentation approach provided accurate automated volumetric assessment of AAT compartments on MR images of neonates and children.Keywords Pediatrics, Deep Learning, Convolutional Neural Networks, Water-Fat MRI, Image Segmentation, Deep and Superficial Subcutaneous Adipose Tissue, Visceral Adipose TissueClinical trial registration no. NCT01174875 Supplemental material is available for this article. © RSNA, 2021.
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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-offspring cohort, women with singleton pregnancies (n = 1172) recruited in first trimester responded to interviewer-administered questions at 26-28 weeks' gestation about earlier episodes of NVP since becoming pregnant. Pregnancy outcomes were obtained from medical records. Offspring height and weight measured at 15 time-points between birth to 72 months (m) were standardised for age and sex. RESULTS: 58.5% (n = 686) reported mild-moderate vomiting (mNVP), 10.5% (n = 123) severe vomiting (sNVP) and 5.7% (n = 67) severe vomiting with hospitalisation (shNVP). There was no difference in odds of gestational diabetes, hypertensive disorders of pregnancy, labour induction or caesarean section after adjustment for covariates. sNVP was associated with late preterm delivery [34+ 0-36+ 6 weeks', adjusted OR = 3.04 (95% CI 1.39,6.68)], without increased odds of neonatal unit admission. Compared with no NVP, boys born to mothers with sNVP were longer at birth [adjusted ß = 0.38 standard deviations (SDs) (95% CI 0.02,0.73)], remained taller [0.64 SDs (0.23,1.04) at 72 m] and heavier [0.57 SDs (0.05,1.08) at 60 m] without differences in BMI. Conversely, girls born to mothers with shNVP were lighter from 48 m [- 0.52 SDs (- 1.00, - 0.03)] onwards with lower BMI [- 0.61 SDs (- 1.12,-0.09)]. Conditional growth modelling revealed significant sex-divergence in weight-gain at birth-3 m, 6-9 m and 4-5 years. CONCLUSIONS: Severe NVP was associated with late preterm delivery, and both mild-moderate and severe NVP associated with sex-dependent differences in early childhood growth. Boys whose mothers had NVP were taller and heavier from birth with faster growth in the first year, whereas, girls had poorer weight gain and were lighter by 48 m. As even milder severities of NVP could have long-term impact on offspring growth, further research is needed to determine mechanisms involved and implications on future health. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01174875 .
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Náusea/complicações , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Vômito/complicações , Adulto , Antropometria , Peso ao Nascer , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Náusea/epidemiologia , Gravidez , Estudos Prospectivos , Distribuição por Sexo , Singapura , Vômito/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: Brown adipose tissue (BAT) controls metabolic rate through thermogenesis. As its regulatory factors during the transition from hyperthyroidism to euthyroidism are not well established, our study investigated the relationships between supraclavicular brown adipose tissue (sBAT) activity and physiological/metabolic changes with changes in thyroid status. DESIGN: Participants with newly diagnosed Graves' disease were recruited. A thionamide antithyroid drug (ATD) such as carbimazole (CMZ) or thiamazole (TMZ) was prescribed in every case. All underwent energy expenditure (EE) measurement and supraclavicular infrared thermography (IRT) within a chamber calorimeter, as well as 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging scanning, with clinical and biochemical parameters measured during hyperthyroidism and repeated in early euthyroidism. PET sBAT mean/maximum standardized uptake value (SUV mean/max), MR supraclavicular fat fraction (sFF) and mean temperature (Tscv) quantified sBAT activity. RESULTS: Twenty-one (16 female/5 male) participants aged 39.5 ± 2.5 years completed the study. The average duration to attain euthyroidism was 28.6 ± 2.3 weeks. Eight participants were BAT-positive while 13 were BAT-negative. sFF increased with euthyroidism (72.3 ± 1.4% to 76.8 ± 1.4%; P < 0.01), but no changes were observed in PET SUV mean and Tscv. Significant changes in serum-free triiodothyronine (FT3) levels were related to BAT status (interaction P value = 0.04). FT3 concentration at hyperthyroid state was positively associated with sBAT PET SUV mean (r = 0.58, P = 0.01) and resting metabolic rate (RMR) (P < 0.01). CONCLUSION: Hyperthyroidism does not consistently lead to a detectable increase in BAT activity. FT3 reduction during the transition to euthyroidism correlated with BAT activity.
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Tecido Adiposo Marrom/metabolismo , Hipertireoidismo/metabolismo , Hipertireoidismo/reabilitação , Tecido Adiposo Marrom/diagnóstico por imagem , Tecido Adiposo Marrom/efeitos dos fármacos , Adulto , Idoso , Antitireóideos/farmacologia , Antitireóideos/uso terapêutico , Composição Corporal/efeitos dos fármacos , Composição Corporal/fisiologia , Carbimazol/uso terapêutico , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/fisiologia , Feminino , Fluordesoxiglucose F18 , Doença de Graves/tratamento farmacológico , Doença de Graves/metabolismo , Doença de Graves/reabilitação , Humanos , Hipertireoidismo/diagnóstico , Hipertireoidismo/tratamento farmacológico , Imageamento por Ressonância Magnética , Masculino , Metimazol/uso terapêutico , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Indução de Remissão , Singapura , Termogênese/efeitos dos fármacos , Termogênese/fisiologia , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Glândula Tireoide/fisiologia , Adulto JovemRESUMO
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.
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Tecido Adiposo Marrom/metabolismo , Adiposidade/fisiologia , Doenças Metabólicas/metabolismo , Metaboloma/fisiologia , Obesidade Infantil/metabolismo , Gordura Abdominal/metabolismo , Povo Asiático/estatística & dados numéricos , Índice de Massa Corporal , Criança , Pré-Escolar , Feminino , Humanos , Resistência à Insulina , Fígado/metabolismo , Imageamento por Ressonância Magnética , Masculino , Músculo Esquelético/metabolismo , Estudos Prospectivos , SingapuraRESUMO
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 magnetic resonance imaging at age 4.5 years. METHODS: The Growing Up in Singapore Towards healthy Outcomes is an ongoing prospective mother-offspring cohort study. Parents/caregivers reported the time their child spent viewing television, handheld devices, and computer screens at ages 2 and 3 years. Superficial and deep subcutaneous and visceral abdominal adipose tissue volumes were quantified from magnetic resonance images acquired at age 4.5 years. Associations between screen-viewing time and abdominal adipose tissue volumes were examined by multivariable linear regression adjusting for confounding factors. RESULTS: In the overall sample (n = 307), greater total screen-viewing time and handheld device times were associated with higher superficial and deep subcutaneous adipose tissue volumes, but not with visceral adipose tissue volumes. Interactions with child sex were found, with significant associations with superficial and deep subcutaneous and visceral adipose tissue volumes in boys, but not in girls. Among boys, the increases in mean (95% CI) superficial and deep subcutaneous and visceral adipose tissue volumes were 24.3 (9.9, 38.7), 17.6 (7.4, 27.8), and 7.8 (2.1, 13.6) mL per hour increase in daily total screen-viewing time, respectively. Ethnicity-specific analyses showed associations of total screen-viewing time with abdominal adiposity only in Malay children. Television viewing time was not associated with abdominal adiposity. CONCLUSION: Greater total screen-viewing time (and in particular, handheld device viewing time) was associated with higher abdominal adiposity in boys and Malay children. Additional studies are necessary to confirm these associations and to examine screen-viewing interventions for preventing excessive abdominal adiposity and its adverse cardiometabolic consequences.
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Gordura Abdominal/fisiopatologia , Tempo de Tela , Experiências Adversas da Infância/psicologia , Pré-Escolar , Estudos de Coortes , Correlação de Dados , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Obesidade Infantil/epidemiologia , Fatores de Risco , Singapura/epidemiologiaRESUMO
Fetal growth restriction arising from placental insufficiency is a leading cause of stillbirth. We recently identified low maternal circulating SPINT1 concentrations as a novel biomarker of poor fetal growth. Here we measured SPINT1 in a prospective cohort in Singapore. Circulating SPINT1 concentrations were significantly lower among 141 pregnant women destined to deliver small-for-gestational age infants (birthweight <10th centile), compared to 772 controls (p < 0.01) at as early as 26 weeks' gestation. There were no correlations between infant body composition and circulating SPINT1 concentrations at 26 weeks. This provides validation that low maternal SPINT1 concentration is associated with poor fetal growth.
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Retardo do Crescimento Fetal/sangue , Insuficiência Placentária/sangue , Proteínas Secretadas Inibidoras de Proteinases/sangue , Adulto , Peso ao Nascer/fisiologia , Estudos de Casos e Controles , Estudos de Coortes , Regulação para Baixo , Feminino , Retardo do Crescimento Fetal/epidemiologia , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Avaliação de Resultados em Cuidados de Saúde , Insuficiência Placentária/epidemiologia , Gravidez , Resultado da Gravidez/epidemiologia , Segundo Trimestre da Gravidez/sangue , Proteínas Secretadas Inibidoras de Proteinases/análise , Singapura/epidemiologia , Natimorto/epidemiologiaRESUMO
OBJECTIVE: To identify systolic blood pressure (SBP) percentile trajectories in children and to describe the early-life risk factors and cardiometabolic correlates of those trajectories. STUDY DESIGN: Using age-, sex-, and height-specific SBP percentiles based on the American Academy of Pediatrics reference, we examined SBP trajectories using latent class mixed models from ages 3 to 8 years (n = 844) from the Growing Up in Singapore Towards healthy Outcomes-study, a Singaporean mother-offspring cohort study. We analyzed associations between SBP trajectories and early-life risk factors using multinomial logistic regression and differences across trajectories in cardiometabolic outcomes using multiple linear regression. RESULTS: Children were classified into 1 of 4 SBP percentile trajectories: "low increasing" (15%), "high stable" (47%), "high decreasing" (20%), and "low stable" (18%). Maternal hypertension during early pregnancy was a predictor of the "high stable" and "low increasing" SBP trajectories. Rapid child weight gain in the first 2 years of life was only associated with the "high stable" trajectory. Compared with children in the "low stable" trajectory, children in the "high stable" SBP trajectory had greater body mass index z scores, sum of skinfold thicknesses, waist circumference from ages 3 to 8 years, and abdominal adipose tissue (milliliters) at 4.5 years (adjusted mean difference [95% CI]: superficial and deep subcutaneous abdominal adipose tissue: 115.2 [48.1-182.3] and 85.5 [35.2-135.8]). Their fat mass (kilograms) (1.3 [0.6-2.0]), triglyceride levels (mmol/L) (0.10 [0.02-0.18]), and homeostasis model assessment of insulin resistance (0.28 [0.11 0.46]) at age 6 years were also greater but not their arterial thickness and stiffness. CONCLUSIONS: Reducing maternal blood pressure during pregnancy and infant weight gain in the first 2 years of life might help to prevent the development of high SBP.