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A balanced excitation-inhibition ratio (E/I ratio) is critical for healthy brain function. Normative development of cortex-wide E/I ratio remains unknown. Here, we noninvasively estimate a putative marker of whole-cortex E/I ratio by fitting a large-scale biophysically plausible circuit model to resting-state functional MRI (fMRI) data. We first confirm that our model generates realistic brain dynamics in the Human Connectome Project. Next, we show that the estimated E/I ratio marker is sensitive to the gamma-aminobutyric acid (GABA) agonist benzodiazepine alprazolam during fMRI. Alprazolam-induced E/I changes are spatially consistent with positron emission tomography measurement of benzodiazepine receptor density. We then investigate the relationship between the E/I ratio marker and neurodevelopment. We find that the E/I ratio marker declines heterogeneously across the cerebral cortex during youth, with the greatest reduction occurring in sensorimotor systems relative to association systems. Importantly, among children with the same chronological age, a lower E/I ratio marker (especially in the association cortex) is linked to better cognitive performance. This result is replicated across North American (8.2 to 23.0 y old) and Asian (7.2 to 7.9 y old) cohorts, suggesting that a more mature E/I ratio indexes improved cognition during normative development. Overall, our findings open the door to studying how disrupted E/I trajectories may lead to cognitive dysfunction in psychopathology that emerges during youth., Competing Interests: Competing interests statement:The authors declare no competing interest.

Early life adversity has been posited to influence the pace of structural neurodevelopment. Most research, however, has relied on cross-sectional data, which do not reveal whether the pace of neurodevelopmental change is accelerated or slowed following early exposures. In a birth cohort study that included neuroimaging data obtained at 4.5, 6, and 7.5 years of age (N = 784), we examined associations among a cumulative measure of perinatal adversity relative to resources, nonlinear trajectories of hippocampal and amygdala volume, and children's subsequent depressive symptoms at 8.5 years of age. Greater adversity was associated with reduced bilateral hippocampal body volume in early childhood, but also to faster growth in the right hippocampal body across childhood. Further, the association between adversity and childhood depressive symptoms was mediated by faster hippocampal body growth. These findings suggest that perinatal adversity is biologically embedded in hippocampal structure development, including an accelerated pace of change in the right hippocampal body that is implicated in children's psychopathology risk. In addition, our findings suggest that reduced hippocampal volume is not inconsistent with accelerated hippocampal change; these aspects of structural development may typically co-occur, as smaller regional volumes in early childhood were associated with faster growth across childhood., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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 (β 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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S.Y.C reports a relationship with Société Des Produits Nestlé S.A. that includes: funding grants, and speaking and lecture fees. K.M.G. reports a relationship with Société Des Produits Nestlé S.A. and BenevolentAI Bio Ltd that includes: funding grants and speaking and lecture fees. Y.S.C. reports a relationship with Société Des Produits Nestlé S.A. that includes: funding grants. K.M.G., Y.S.C. and S.Y.C. are part of an academic consortium that has received research funding from Société Des Produits Nestlé S.A. and BenevolentAI Bio Ltd, and are co-inventors on patents filed on nutritional factors and metabolic risk outside the submitted work. K.M.G. and S.Y.C. have received reimbursement from nutritional companies for speaking at conferences. All other authors declare that they have nothing to disclose., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Advances in four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) have allowed quantification of left ventricular (LV) and right ventricular (RV) blood flow. We aimed to (1) investigate age and sex differences of 4D flow CMR-derived LV and RV relative flow components and kinetic energy (KE) parameters indexed to end-diastolic volume (KEi EDV ) in healthy subjects; and (2) assess the effects of age and sex on these parameters., Methods: We performed 4D flow analysis in 163 healthy participants (42% female; mean age 43 ± 13 years) of a prospective registry study (NCT03217240) who were free of cardiovascular diseases. Relative flow components (direct flow, retained inflow, delayed ejection flow, residual volume) and multiple phasic KEi EDV (global, peak systolic, average systolic, average diastolic, peak E-wave, peak A-wave) for both LV and RV were analysed., Results: Compared with men, women had lower median LV and RV residual volume, and LV peak and average systolic KEi EDV , and higher median values of RV direct flow, RV global KEi EDV , RV average diastolic KEi EDV , and RV peak E-wave KEi EDV . ANOVA analysis found there were no differences in flow components, peak and average systolic, average diastolic and global KEi EDV for both LV and RV across age groups. Peak A-wave KEi EDV increased significantly (r = 0.458 for LV and 0.341 for RV), whereas peak E-wave KEi EDV (r = - 0.355 for LV and - 0.318 for RV), and KEi EDV E/A ratio (r = - 0.475 for LV and - 0.504 for RV) decreased significantly, with age., Conclusion: These data using state-of-the-art 4D flow CMR show that biventricular flow components and kinetic energy parameters vary significantly by age and sex. Age and sex trends should be considered in the interpretation of quantitative measures of biventricular flow. Clinical trial registration  https://www., Clinicaltrials: gov . Unique identifier: NCT03217240., (© 2023. Society for Cardiovascular Magnetic Resonance.)

Background: Metabolic syndrome score in children assesses the risk of developing cardiovascular disease in future. We aim to probe the role of the caudate in relation to the metabolic syndrome score. Furthermore, using both functional and structural neuroimaging, we aim to examine the interplay between functional and structural measures., Methods: A longitudinal birth cohort study with functional and structural neuroimaging data obtained at 4.5, 6.0 and 7.5 years and metabolic syndrome scores at 8.0 years was used. Pearson correlation and linear regression was used to test for correlation fractional anisotropy (FA) and fractional amplitude of low frequency fluctuations (fALFF) of the caudate with metabolic syndrome scores. Mediation analysis was used to test if later brain measures mediated the relation between earlier brain measures and metabolic syndrome scores. Inhibitory control was also tested as a mediator of the relation between caudate brain measures and metabolic syndrome scores., Results: FA at 4.5 years and fALFF at 7.5 years of the left caudate was significantly correlated with metabolic syndrome scores. Post-hoc mediation analysis showed that fALFF at 7.5 years fully mediated the relation between FA at 4.5 years and metabolic syndrome scores. Inhibitory control was significantly correlated with fALFF at 7.5 years, but did not mediate the relation between fALFF at 7.5 years and metabolic syndrome scores., Conclusions: We found that variations in caudate microstructure at 4.5 years predict later variation in functional activity at 7.5 years. This later variation in functional activity fully mediates the relation between microstructural changes in early childhood and metabolic syndrome scores at 8.0 years., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yap-Seng Chong is part of an academic consortium that has received research funding from Abbott Nutrition, Nestec, and Danone. All other authors report no financial relationships with commercial interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Resting-state fMRI is commonly used to derive brain parcellations, which are widely used for dimensionality reduction and interpreting human neuroscience studies. We previously developed a model that integrates local and global approaches for estimating areal-level cortical parcellations. The resulting local-global parcellations are often referred to as the Schaefer parcellations. However, the lack of homotopic correspondence between left and right Schaefer parcels has limited their use for brain lateralization studies. Here, we extend our previous model to derive homotopic areal-level parcellations. Using resting-fMRI and task-fMRI across diverse scanners, acquisition protocols, preprocessing and demographics, we show that the resulting homotopic parcellations are as homogeneous as the Schaefer parcellations, while being more homogeneous than five publicly available parcellations. Furthermore, weaker correlations between homotopic parcels are associated with greater lateralization in resting network organization, as well as lateralization in language and motor task activation. Finally, the homotopic parcellations agree with the boundaries of a number of cortical areas estimated from histology and visuotopic fMRI, while capturing sub-areal (e.g., somatotopic and visuotopic) features. Overall, these results suggest that the homotopic local-global parcellations represent neurobiologically meaningful subdivisions of the human cerebral cortex and will be a useful resource for future studies. Multi-resolution parcellations estimated from 1479 participants are publicly available (https://github.com/ThomasYeoLab/CBIG/tree/master/stable&#95;projects/brain&#95;parcellation/Yan2023&#95;homotopic)., (Copyright © 2023. Published by Elsevier Inc.)

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 [β (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., (Copyright © 2022 American Society for Nutrition. All rights reserved.)

Background: Childhood depression is a highly distinct and prevalent condition with an unknown neurobiological basis. We wish to explore the resting state fMRI data in children for potential associations between neural connectivity and childhood depressive symptoms., Methods: A longitudinal birth cohort study with neuroimaging data obtained at 4.5, 6.0 and 7.5 years of age and the Children Depression Inventory 2 (CDI) administered between 8.5 and 10.5 years was used. The CDI score was used as the dependent variable and tested for correlation, both simple Pearson and network based statistic, with the functional connectivity values obtained from the resting state fMRI. Cross-validated permutation testing with a general linear model was used to validate that the identified functional connections were indeed implicated in childhood depression., Results: Ten functional connections and four brain regions (Somatomotor Area B, Temporoparietal Junction, Orbitofrontal Cortex and Insula) were identified as significantly associated with childhood depressive symptoms for girls at 6.0 and 7.5 years. No significant functional connections were found in girls at 4.5 years or for boys at any timepoint. Network based statistic and permutation testing confirmed these findings., Conclusions: This study revealed significant sex-dependent associations of neural connectivity and childhood depressive symptoms. The regions identified are implicated in speech/language, social cognition and information integration and suggest unique pathways to childhood depressive symptoms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

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, β (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., (© The Author(s) 2022; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Cardiovascular magnetic resonance (CMR) offers comprehensive right ventricular (RV) evaluation in pulmonary arterial hypertension (PAH). Emerging four-dimensional (4D) flow CMR allows visualization and quantification of intracardiac flow components and calculation of phasic blood kinetic energy (KE) parameters but it is unknown whether these parameters are associated with cardiopulmonary exercise test (CPET)-assessed exercise capacity, which is a surrogate measure of survival in PAH. We compared 4D flow CMR parameters in PAH with healthy controls, and investigated the association of these parameters with RV remodelling, RV functional and CPET outcomes., Methods: PAH patients and healthy controls from two centers were prospectively enrolled to undergo on-site cine and 4D flow CMR, and CPET within one week. RV remodelling index was calculated as the ratio of RV to left ventricular (LV) end-diastolic volumes (EDV). Phasic (peak systolic, average systolic, and peak E-wave) LV and RV blood flow KE indexed to EDV (KEI EDV ) and ventricular LV and RV flow components (direct flow, retained inflow, delayed ejection flow, and residual volume) were calculated. Oxygen uptake (VO 2 ), carbon dioxide production (VCO 2 ) and minute ventilation (VE) were measured and recorded., Results: 45 PAH patients (46 ± 11 years; 7 M) and 51 healthy subjects (46 ± 14 years; 17 M) with no significant differences in age and gender were analyzed. Compared with healthy controls, PAH had significantly lower median RV direct flow, RV delayed ejection flow, RV peak E-wave KEI EDV , peak VO 2 , and percentage (%) predicted peak VO 2 , while significantly higher median RV residual volume and VE/VCO 2 slope. RV direct flow and RV residual volume were significantly associated with RV remodelling, function, peak VO 2 , % predicted peak VO 2 and VE/VCO 2 slope (all P < 0.01). Multiple linear regression analyses showed RV direct flow to be an independent marker of RV function, remodelling and exercise capacity., Conclusion: In this 4D flow CMR and CPET study, RV direct flow provided incremental value over RVEF for discriminating adverse RV remodelling, impaired exercise capacity, and PAH with intermediate and high risk based on risk score. These data suggest that CMR with 4D flow CMR can provide comprehensive assessment of PAH severity, and may be used to monitor disease progression and therapeutic response., Trial Registration Number: https://www., Clinicaltrials: gov . Unique identifier: NCT03217240., (© 2022. The Author(s).)

Early differences in reward behavior have been linked to executive functioning development. The nucleus accumbens (NAc) and orbitofrontal cortex (OFC) are activated by reward-related tasks and identified as key nodes of the brain circuit that underlie reward processing. We aimed to investigate the relation between NAc-OFC structural and functional connectivity in preschool children, as well as associations with future reward sensitivity and executive function. We showed that NAc-OFC structural and functional connectivity were not significantly associated in preschool children, but both independently predicted sensitivity to reward in males in a left-lateralized manner. Moreover, significant NAc-OFC structure-function coupling was only found in individuals who performed poorly on executive function tasks in later childhood, but not in the middle- and high-performing groups. As structure-function coupling is proposed to measure functional specialization, this finding suggests premature functional specialization within the reward network, which may impede dynamic communication with other regions, affects executive function development. Our study also highlights the utility of multimodal imaging data integration when studying the effects of reward network functional flexibility in the preschool age, a critical period in brain and executive function development., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) allows quantification of biventricular blood flow by flow components and kinetic energy (KE) analyses. However, it remains unclear whether 4D flow parameters can predict cardiopulmonary exercise testing (CPET) as a clinical outcome in repaired tetralogy of Fallot (rTOF). Current study aimed to (1) compare 4D flow CMR parameters in rTOF with age- and gender-matched healthy controls, (2) investigate associations of 4D flow parameters with functional and volumetric right ventricular (RV) remodelling markers, and CPET outcome., Methods: Sixty-three rTOF patients (14 paediatric, 49 adult; 30 ± 15 years; 29 M) and 63 age- and gender-matched healthy controls (14 paediatric, 49 adult; 31 ± 15 years) were prospectively recruited at four centers. All underwent cine and 4D flow CMR, and all adults performed standardized CPET same day or within one week of CMR. RV remodelling index was calculated as the ratio of RV to left ventricular (LV) end-diastolic volumes. Four flow components were analyzed: direct flow, retained inflow, delayed ejection flow and residual volume. Additionally, three phasic KE parameters normalized to end-diastolic volume (KEi EDV ), were analyzed for both LV and RV: peak systolic, average systolic and peak E-wave., Results: In comparisons of rTOF vs. healthy controls, median LV retained inflow (18% vs. 16%, P = 0.005) and median peak E-wave KEi EDV (34.9 µJ/ml vs. 29.2 µJ/ml, P = 0.006) were higher in rTOF; median RV direct flow was lower in rTOF (25% vs. 35%, P < 0.001); median RV delayed ejection flow (21% vs. 17%, P < 0.001) and residual volume (39% vs. 31%, P < 0.001) were both greater in rTOF. RV KEi EDV parameters were all higher in rTOF than healthy controls (all P < 0.001). On multivariate analysis, RV direct flow was an independent predictor of RV function and CPET outcome. RV direct flow and RV peak E-wave KEi EDV were independent predictors of RV remodelling index., Conclusions: In this multi-scanner multicenter 4D flow CMR study, reduced RV direct flow was independently associated with RV dysfunction, remodelling and, to a lesser extent, exercise intolerance in rTOF patients. This supports its utility as an imaging parameter for monitoring disease progression and therapeutic response in rTOF. Clinical Trial Registration https://www.clinicaltrials.gov . Unique identifier: NCT03217240., (© 2021. The Author(s).)

The developing brain grows exponentially in the first few years of life. There is a need to have age-appropriate brain atlases that coherently characterize the geometry of the cerebral cortex, white matter tracts, and functional organization. This study employed multi-modal brain images of an Asian cohort and constructed brain structural and functional atlases for 6-month-old infants, 4.5-, 6-, and 7.5-year-old children. We exploited large deformation diffeomorphic metric mapping and probabilistic atlas generation approaches to integrate structural MRI and diffusion weighted images (DWIs) and to create the atlas where white matter tracts well fit into the cortical folding pattern. Based on this structural atlas, we then employed spectral clustering to parcellate the brain into functional networks from resting-state fMRI (rs-fMRI). Our results provided the atlas that characterizes the cortical folding geometry, subcortical regions, deep white matter tracts, as well as functional networks in a stereotaxic coordinate space for the four different age groups. The functional networks consisting of the primary cortex were well established in infancy and remained stable to childhood, while specific higher-order functional networks showed specific patterns of hemispherical, subcortical-cerebellar, and cortical-cortical integration and segregation from infancy to childhood. Our multi-modal fusion analysis demonstrated the use of the integrated structural and functional atlas for understanding coherent patterns of brain anatomical and functional development during childhood. Hence, our atlases can be potentially used to study coherent patterns of brain anatomical and functional development., (Copyright © 2021. Published by Elsevier Inc.)

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.)

Maternal childhood maltreatment and depression increase risks for the psychopathology of the offspring. This study employed a longitudinal dataset of mother-child dyads to investigate the developmental trajectories of brain functional networks and behaviors of children in relation with maternal childhood adverse experience and depression. Maternal childhood trauma was retrospectively assessed via childhood trauma questionnaire, whereas maternal depressive symptoms were prospectively evaluated during pregnancy and after delivery (n = 518). Child brain scans were acquired at age of 4.5, 6, and 7.5 years (n = 163) and behavioral problems were measured at 7.5 years using the Child Behavior Checklist. We found the functional connectivity of the language network with the sensorimotor, frontal, and attentional networks as a function of maternal adverse experience that interacted with sex and age. Girls exposed to mothers with depressive symptoms or childhood abuse showed the increased development of the functional connectivity of the language network with the visual networks, which was associated with social problems. Girls exposed to mothers with depressive symptoms showed the slower growth of the functional connectivity of the language network with the sensorimotor networks. Our findings, in a community sample, suggest the language network organization as neuroendophenotypes for maternal childhood trauma and depression., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., Competing Interests: Disclosures of Conflicts of Interest: Y.M.K. disclosed no relevant relationships. K.T. disclosed no relevant relationships. M.T.T. disclosed no relevant relationships. N.M. disclosed no relevant relationships. L.P.C.S. is on the Takeda Pharmaceuticals advisory board for vaccines. F.K.P.Y. disclosed no relevant relationships. K.H.T. receives a consulting fee or honorarium from SingHealth. K.M.G. is part of an academic consortium that has received research funding from Abbott Nutrition, Nestec, BenevolentAI Bio, and Danone; has been reimbursed for speaking at conferences sponsored by companies selling nutritional products. Y.S.C. disclosed no relevant relationships. M.V.F. disclosed no relevant relationships. U.C.M. disclosed no relevant relationships. J.G.E. disclosed no relevant relationships. Y.S.L. disclosed no relevant relationships. S.S.V. received a consulting fee or honorarium from SBIC. M.F. disclosed no relevant relationships. S.A.S. disclosed no relevant relationships., (2021 by the Radiological Society of North America, Inc.)

Cardiovascular magnetic resonance (CMR) is the reference standard for non-invasive assessment of right-sided heart function. Recent advances in CMR post-processing facilitate quantification of tricuspid annular (TA) dynamics and longitudinal strains of the right ventricle (RV) and right atrium (RA). We aimed to determine age- and sex-specific changes in CMR-derived TA dynamics, and RV and RA functional parameters in healthy Asian adults. We studied 360 healthy subjects aged 21-79 years, with 30 men and 30 women in each of the six age groups. Functional parameters of RV and RA were measured on standard four-chamber cine CMR using fast feature tracking: (1) TA peak velocities (systolic velocity S', early diastolic velocity E', late diastolic velocity A') and TA plane systolic excursion (TAPSE); (2) RV global longitudinal strain (GLS) and strain rates; and (3) RA phasic longitudinal strains and strain rates. S' and TAPSE exhibited negative correlations with age. RV GLS was significantly higher in females than in males but not associated with age in both sexes. Females had similar E', lower A', and higher E'/A' ratios compared to males. Positive associations of E' and E'/A', and negative association of A' with age were observed in both sexes. Females had higher RA reservoir and conduit strains compared to males. There were significantly negative and positive associations between RA conduit and booster strains, respectively, with age. Age- and sex-specific reference ranges were established, and associations revealed, for fast CMR feature tracking parameters of right heart function in a large normal Asian population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Leng, Guo, Tan, Chai, Teo, Fortier, Gong, Zhao, Ong, Allen, Ruan, Koh, Tan, Yip, Tan, Chen and Zhong.)

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.)

The left atrial appendage (LAA) aneurysm is a rare condition that can produce local compressive effects and complications including supraventricular tachyarrhythmias, thromboembolic events and myocardial ischaemia. We present a rare case of a neonate with a congenital LAA aneurysm which resulted in local compressive effects on the left ventricle, severe mitral regurgitation and malposition of the left anterior descending (LAD) coronary artery. Intraoperatively, the LAD was found to be within the aneurysmal wall exterior to the left ventricular epicardium and was inadvertently injured during LAA aneurysm resection. Retrospective review of the preoperative computed tomography and echocardiography scans demonstrated the LAD lying within the wall of the LAA aneurysm, although this had not been well appreciated at that time. This highlights the importance of thorough multimodal preoperative imaging and intraoperative assessment for recognition of this rare association between the LAA aneurysm and LAD malposition, and prevention of inadvertent LAD injury during aneurysm resection., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Canonical transforming growth factor-beta (TGF-β) signaling exerts neuroprotection and influences memory formation and synaptic plasticity. It has been considered as a new target for the prevention and treatment of depression. This study aimed to examine its modulatory role in linking prenatal maternal depressive symptoms and the amygdala volumes from birth to 6 years of age. We included mother-child dyads (birth: n = 161; 4.5 years: n = 131; 6 years: n = 162) and acquired structural brain images of children at these three time points. Perinatal maternal depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS) questionnaire to mothers at 26 weeks of pregnancy and 3 months postpartum. Our findings showed that the genetic variants of TGF-β type I transmembrane receptor (TGF-βRI) modulated the association between prenatal maternal depressive symptoms and the amygdala volume consistently from birth to 6 years of age despite a trend of significance at 4.5 years of age. Children with a lower gene expression score (GES) of TGF-βRI exhibited larger amygdala volumes in relation to greater prenatal maternal depressive symptoms. Moreover, children with a lower GES of the TGF-β type II transmembrane receptor (TGF-βRII), Smad4, and Smad7 showed larger amygdala volumes at 6 years of age in relation to greater prenatal maternal depressive symptoms. These findings support the involvement of the canonical TGF-β signaling pathway in the brain development of children in the context of in utero maternal environment. Such involvement is age-dependent.

Inflammatory signaling has a role in sensing intrauterine environment, which may be moderators in altering fetal brain development upon maternal environment. This study integrated cytokine transcriptome of post-mortem fetal brains, neonatal brain imaging and genetic variants (n = 161) to examine whether cytokines are candidates for modulating the relationship between prenatal maternal depression and fetal brain development. This study obtained the transcriptome data of 208 cytokine genes in 12 fetal brain regions from the BrainSpan database. We also included 161 mother-child dyads with prenatal maternal depressive symptoms assessed at 26 weeks of gestation, cytokine genotype data extracted from umbilical cord specimens, and neonatal brain images from a longitudinal prospective birth cohort. We revealed that 22 cytokine genes are expressed in specific brain regions in utero, whose variants have roles in modulating the effects of the prenatal environment on the accelerated fetal development of the hippocampus, auditory, parietal, orbitofrontal, and dorsal prefrontal cortex. Neonates high in the genetic expression score (GES) of TNFRSF19 and IL17RB showed a larger right hippocampal volume, high in the GES of BMPR1B showed the thicker thickness of the sensorimotor cortex, and high in the GES of IL1RAP and CXCR4 demonstrated the thicker thickness of the dorsal and orbital prefrontal cortex in relation with greater prenatal maternal depressive symptoms. Our findings suggest that in humans, the cytokine genes are expressed in a brain region-specific manner in utero and may have potential roles in modulating the fetal development of the corresponding brain regions in response to the maternal environment.

Working memory (WM) is defined as the ability to maintain a representation online to guide goal-directed behavior. Its capacity in early childhood predicts academic achievements in late childhood and its deficits are found in various neurodevelopmental disorders. We employed resting-state fMRI (rs-fMRI) of 468 participants aged from 4 to 55 years and connectome-based predictive modeling (CPM) to explore the potential predictive power of intrinsic functional networks to WM in preschoolers, early and late school-age children, adolescents, and adults. We defined intrinsic functional networks among brain regions identified by activation likelihood estimation (ALE) meta-analysis on existing WM functional studies (ALE-based intrinsic functional networks) and intrinsic functional networks generated based on the whole brain (whole-brain intrinsic functional networks). We employed the CPM on these networks to predict WM in each age group. The CPM using the ALE-based and whole-brain intrinsic functional networks predicted WM of individual adults, while the prediction power of the ALE-based intrinsic functional networks was superior to that of the whole-brain intrinsic functional networks. Nevertheless, the CPM using the whole-brain but not the ALE-based intrinsic functional networks predicted WM in adolescents. And, the CPM using neither the ALE-based nor whole-brain networks predicted WM in any of the children groups. Our findings showed the trend of the prediction power of the intrinsic functional networks to cognition in individuals from early childhood to adulthood., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

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: Gestational diabetes is associated with unfavorable body fat distribution in offspring. However, less is known about the effects across the range of maternal gestational glycemia on offspring abdominal adiposity (AA) in infancy and early childhood., Objectives: This study determined the association between gestational glycemia and offspring AA measured by MRI in the neonatal period and during the preschool years., Methods: Participants were mother-offspring pairs from the GUSTO (Growing Up in Singapore Towards healthy Outcomes) prospective cohort study. Children who underwent MRI within 2 wk postdelivery (n = 305) and/or at preschool age, 4.5 y (n = 273), and whose mothers had a 2-h 75-g oral-glucose-tolerance test (OGTT) at 26-28 weeks of gestation were included. AA measured by adipose tissue compartment volumes-abdominal superficial (sSAT), deep subcutaneous (dSAT), and internal (IAT) adipose tissue-was quantified from MRI images., Results: Adjusting for potential confounders including maternal prepregnancy BMI, each 1-mmol/L increase in maternal fasting glucose was associated with higher SD scores for sSAT (0.66; 95% CI: 0.45, 0.86), dSAT (0.65; 95% CI: 0.44, 0.87), and IAT (0.64; 95% CI: 0.42, 0.86) in neonates. Similarly, each 1-mmol/L increase in 2-h OGTT glucose was associated with higher neonatal sSAT (0.11; 95% CI: 0.03, 0.19) and dSAT (0.09; 95% CI: 0.00, 0.17). These associations were stronger in female neonates but only persisted in girls between fasting glucose, and sSAT and dSAT at 4.5 y., Conclusions: A positive association between maternal glycemia and neonatal AA was observed across the whole range of maternal mid-gestation glucose concentrations. These findings may lend further support to efforts toward optimizing maternal hyperglycemia during pregnancy. The study also provides suggestive evidence on sex differences in the impact of maternal glycemia, which merits further confirmation in other studies.This trial was registered at clinicaltrials.gov as NCT01174875., (Copyright © The Author(s) 2020.)

During development, cellular events such as cell proliferation, migration, and synaptogenesis determine the structural organization of the brain. These processes are driven in part by spatiotemporally regulated gene expression. We investigated how the genetic signatures of specific neural cell types shape cortical organization of the human brain throughout infancy and childhood. Using a transcriptional atlas and in vivo magnetic resonance imaging (MRI) data, we demonstrated time-dependent associations between the expression levels of neuronal and glial genes and cortical macro- and microstructure. Neonatal cortical phenotypes were associated with prenatal glial but not neuronal gene expression. These associations reflect cell migration and proliferation during fetal development. Childhood cortical phenotypes were associated with neuronal and astrocyte gene expression related to synaptic signaling processes, reflecting the refinement of cortical connections. These findings indicate that sequential developmental stages contribute to distinct MRI measures at different time points. This helps to bridge the gap between the genetic mechanisms driving cellular changes and widely used neuroimaging techniques., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Maternal depression is associated with disrupted neurodevelopment in offspring. This study examined relationships among postnatal maternal depressive symptoms, the functional reward network and behavioral problems in 4.5-year-old boys (57) and girls (65). We employed canonical correlation analysis to evaluate whether the resting-state functional connectivity within a reward network, identified through an activation likelihood estimation (ALE) meta-analysis of fMRI studies, was associated with postnatal maternal depressive symptoms and child behaviors. The functional reward network consisted of three subnetworks, that is, the mesolimbic, mesocortical, and amygdala-hippocampus reward subnetworks. Postnatal maternal depressive symptoms were associated with the functional connectivity of the mesocortical subnetwork with the mesolimbic and amygdala-hippocampus complex subnetworks in girls and with the functional connectivity within the mesocortical subnetwork in boys. The functional connectivity of the amygdala-hippocampus subnetwork with the mesocortical and mesolimbic subnetworks was associated with both internalizing and externalizing problems in girls, while in boys, the functional connectivity of the mesocortical subnetwork with the amygdala-hippocampus complex and the mesolimbic subnetworks was associated with the internalizing and externalizing problems, respectively. Our findings suggest that the functional reward network might be a promising neural phenotype for effects of maternal depression and potential intervention to nurture child behavioral development., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Maternal care may predict limbic development, though relations may vary by age and type of assessment. Here, we examined maternal behavior during early infancy (i.e., six months postpartum) in relation to offspring hippocampal and amygdala volume and microstructure development between 4.5 (n = 99) and 6 (n = 111) years. In interaction with offspring sex, maternal sensitivity predicted left amygdala volume at 6.0 years (β=-0.214, p = 0.032, df = 89) and independently predicted predominately left lateralized aspects of amygdala and hippocampal microstructure at both time points (hippocampus: left FA at 4.5 years [β=-0.241, p = 0.043, df = 68], and, in interaction with sex, left [(β = 0.349, p = 0.022, df = 86) and right FA at 6 years (β = 0.357, p = 0.016, df = 86] and left MD growth [β = -0.517, p = 0.021, df = 37]; amygdala: left MD at 4.5 years [β = -0.319, p = 0.007, df = 69] and, in interaction with offspring sex, left MD growth [β = -0.546, p = 0.019, df = 37]). Results suggest exposure to non-extreme, early insensitive care impacts neuroanatomy important to learning and stress regulation, perhaps by accelerating development. This underscores the need to promote sensitive caregiving during early infancy within community samples., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The amygdala and hippocampus undergo rapid development in early life. The relative contribution of genetic and environmental factors to the establishment of their developmental trajectories has yet to be examined. We performed imaging on neonates and examined how the observed variation in volume and microstructure of the amygdala and hippocampus varied by genotype, and compared with prenatal maternal mental health and socioeconomic status. Gene × Environment models outcompeted models containing genotype or environment only to best explain the majority of measures but some, especially of the amygdaloid microstructure, were best explained by genotype only. Models including DNA methylation measured in the neonate umbilical cords outcompeted the Gene and Gene × Environment models for the majority of amygdaloid measures and minority of hippocampal measures. This study identified brain region-specific gene networks associated with individual differences in fetal brain development. In particular, genetic and epigenetic variation within CUX1 was highlighted., (© 2019 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.)

Background: Choline status has been positively associated with weight and fat mass in animal and human studies. As evidence examining maternal circulating choline concentrations and offspring body composition in human infants/children is lacking, we investigated this in two cohorts., Methods: Maternal choline concentrations were measured in the UK Southampton Women's Survey (SWS; serum, n = 985, 11 weeks' gestation) and Singapore Growing Up Towards healthy Outcomes (GUSTO); n = 955, 26-28 weeks' gestation) mother-offspring cohorts. Offspring anthropometry was measured at birth and up to age 5 years. Body fat mass was determined using dual-energy x-ray absorptiometry at birth and age 4 years for SWS; and using air-displacement plethysmography at birth and age 5 years for GUSTO. Linear-regression analyses were performed, adjusting for confounders., Results: In SWS, higher maternal choline concentrations were associated with higher neonatal total body fat mass {β = 0.60 standard deviation [SD]/5 µmol/L maternal choline [95% confidence interval (CI) 0.04-1.16]} and higher subscapular skinfold thickness [β = 0.55 mm/5 µmol/L (95% CI, 0.12-1.00)] at birth. In GUSTO, higher maternal choline concentrations were associated with higher neonatal body mass index-for-age z-score [β = 0.31 SD/5 µmol/L (0.10-0.51)] and higher triceps [β = 0.38 mm/5 µmol/L (95% CI, 0.11-0.65)] and subscapular skinfold thicknesses [β = 0.26 mm/5 µmol/L (95% CI, 0.01-0.50)] at birth. No consistent trends were observed between maternal choline and offspring gain in body mass index, skinfold thicknesses, abdominal circumference, weight, length/height and adiposity measures in later infancy and early childhood., Conclusion: Our study provides evidence that maternal circulating choline concentrations during pregnancy are positively associated with offspring BMI, skinfold thicknesses and adiposity at birth, but not with growth and adiposity through infancy and early childhood to the age of 5 years., (© The Author(s) 2019; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Objective: The aim of this study was to investigate the independent associations between age-specific annual weight gain from birth to age 4 years and fat deposition in metabolically distinct compartments at age 4.5 years in a South Asian longitudinal birth cohort., Methods: Volumetric abdominal magnetic resonance imaging with comprehensive segmentation of deep and superficial subcutaneous adipose tissue (SAT) and visceral adipose tissues (VAT) was performed in 316 children (150 boys and 166 girls in three ethnic groups; 158 Chinese, 94 Malay, and 64 Indian) aged 4.5 years. Associations between fat volumes and annual relative weight gain conditional on past growth were assessed overall and stratified by sex and ethnicity., Results: Conditional relative weight gain had stronger associations with greater SAT and VAT at age 4.5 years in girls than boys and in Indians compared with Malay and Chinese. Overall, the magnitude of association was the largest during 2 to 3 years for SAT and 1 to 2 years for VAT. Despite similar body weight, Indian children and girls had the highest deep and superficial SAT volumes at age 4.5 years (all interactions P < 0.05). No significant sex or ethnic differences were observed in VAT. With increasing BMI, Indian children had the highest tendency to accumulate VAT, and girls accumulated more fat than boys in all depots (all interactions P < 0.001)., Conclusions: Indian ethnicity and female sex predisposed children to accumulate more fat in the VAT depot with increasing conditional relative weight gain in the second year of life. Thus, 1 to 2 years of age may be a critical window for interventions to reduce visceral fat accumulation., (© 2019 The Obesity Society.)

This study aimed to identify distinct behavioral profiles in a population-based sample of 654 4-year-old children and characterize their relationships with brain functional networks using resting-state functional magnetic resonance imaging data. Young children showed 7 behavioral profiles, including a super healthy behavioral profile with the lowest scores across all Child Behavior CheckList (CBCL) subscales (G1) and other 6 behavioral profiles, respectively with pronounced withdrawal (G2), somatic complaints (G3), anxiety and withdrawal (G4), somatic complaints and withdrawal (G5), the mixture of emotion, withdrawal, and aggression (G6), and attention (G7) problems. Compared with children in G1, children with withdrawal shared abnormal functional connectivities among the sensorimotor networks. Children in emotionally relevant problems shared the common pattern among the attentional and frontal networks. Nevertheless, children in sole withdrawal problems showed a unique pattern of connectivity alterations among the sensorimotor, cerebellar, and salience networks. Children with somatic complaints showed abnormal functional connectivities between the attentional and subcortical networks, and between the language and posterior default mode networks. This study provides novel evidence on the existence of behavioral heterogeneity in early childhood and its associations with specific functional networks that are clinically relevant phenotypes for mental illness and are apparent from early childhood.

Objectives: Lower vitamin D status has been associated with adiposity in children through adults. However, the evidence of the impact of maternal vitamin-D status during pregnancy on offspring's adiposity is mixed. The objective of this study was to examine the associations between maternal vitamin-D [25(OH)D] status at mid-gestation and neonatal abdominal adipose tissue (AAT) compartments, particularly the deep subcutaneous adipose tissue linked with metabolic risk., Methods: Participants (N = 292) were Asian mother-neonate pairs from the mother-offspring cohort, Growing Up in Singapore Towards healthy Outcomes. Neonates born at ≥34 weeks gestation with birth weight ≥2000 g had magnetic resonance imaging (MRI) within 2-weeks post-delivery. Maternal plasma glucose using an oral glucose tolerance test and 25(OH)D concentrations were measured. 25(OH)D status was categorized into inadequate (≤75.0 nmol/L) and sufficient (>75.0 nmol/L) groups. Neonatal AAT was classified into superficial (sSAT), deep subcutaneous (dSAT), and internal (IAT) adipose tissue compartments., Results: Inverse linear correlations were observed between maternal 25(OH)D and both sSAT (r = -0.190, P = 0.001) and dSAT (r = -0.206, P < 0.001). Each 1 nmol/L increase in 25(OH)D was significantly associated with reductions in sSAT (β = -0.14 (95% CI: -0.24, -0.04) ml, P = 0.006) and dSAT (β = -0.04 (-0.06, -0.01) ml, P = 0.006). Compared to neonates of mothers with 25(OH)D sufficiency, neonates with maternal 25(OH)D inadequacy had higher sSAT (7.3 (2.1, 12.4) ml, P = 0.006), and dSAT (2.0 (0.6, 3.4) ml, P = 0.005) volumes, despite similar birth weight. In the subset of mothers without gestational diabetes, neonatal dSAT was also greater (1.7 (0.3, 3.1) ml, P = 0.019) in neonates with maternal 25(OH)-inadequacy. The associations with sSAT and dSAT persisted even after accounting for maternal glycemia (fasting and 2-h plasma glucose)., Conclusions: Neonates of Asian mothers with mid-gestation 25(OH)D inadequacy have a higher abdominal subcutaneous adipose tissue volume, especially dSAT (which is metabolically similar to visceral adipose tissue in adults), even after accounting for maternal glucose levels in pregnancy.

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.

Perinatal maternal depressive symptoms influence brain development of offspring. Such effects are particularly notable in the amygdala, a key structure involved in emotional processes. This study investigated whether the functional organization of the amygdala varies as a function of pre- and postnatal maternal depressive symptoms. The amygdala functional network was assessed using resting-state functional magnetic resonance imaging (rs-fMRI) in 128 children at age of 4.4 to 4.8 years. Maternal depressive symptoms were obtained at 26 weeks of gestation, 3 months, 1, 2, 3, and 4.5 years after delivery. Linear regression was used to examine associations between maternal depressive symptoms and the amygdala functional network. Prenatal maternal depressive symptoms were significantly associated with the functional connectivity between the amygdala and the cortico-striatal circuitry, especially the orbitofrontal cortex (OFC), insula, subgenual anterior cingulate (ACC), temporal pole, and striatum. Interestingly, greater pre- than post-natal depressive symptoms were associated with lower functional connectivity of the left amygdala with the bilateral subgenual ACC and left caudate and with lower functional connectivity of the right amygdala with the left OFC, insula, and temporal pole. These findings were only observed in girls but not in boys. Early exposure to maternal depressive symptoms influenced the functional organization of the cortico-striato-amygdala circuitry, which is intrinsic to emotional perception and regulation in girls. This suggests its roles in the transgenerational transmission of vulnerability for socio-emotional problems and depression. Moreover, this study underscored the importance of gender-dependent developmental pathways in defining the neural circuitry that underlies the risk for depression., (© 2017 Wiley Periodicals, Inc.)

Antenatal maternal depressive symptoms influence fetal brain development and increase the risk for depression in offspring. Such vulnerability is often moderated by the offspring's genetic variants. This study aimed to examine whether FKBP5, a key regulator of the hypothalamic-pituitary-adrenal (HPA) axis, moderates the association between antenatal maternal depressive symptoms and in utero brain development, using an Asian cohort with 161 mother-offspring dyads. Antenatal maternal depressive symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS) during the second trimester of pregnancy. Neonatal structural brain images were acquired using magnetic resonance imaging (MRI) shortly after birth. Maternal and neonatal FKBP5 gene was genotyped using Illumina OmniExpress arrays. A gene set-based mixed effect model for gene-environment interaction (MixGE) was used to examine interactive effects between neonatal genetic variants of FKBP5 and antenatal maternal depressive symptoms on neonatal amygdala and hippocampal volumes, and cortical thickness. Our study revealed that genetic variants in neonatal FKBP5 moderate the association between antenatal maternal depressive symptoms and right hippocampal volume but only show a trend for such moderation on amygdala volumes and cortical thickness. Our findings are the first to reveal that the association between maternal depressive symptoms and in utero neurodevelopment of specific brain regions is modified through complex genetic variation in neonatal FKBP5. Our results suggest that an increased risk for depression may be transmitted from mother to child during fetal life and that the effect is dependent upon neonatal FKBP5 genotype.

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.)

Background: Antral follicle count (AFC) and anti-Mullerian hormone (AMH) are known as the most reliable markers of a woman's ovarian reserve and are related to age. There is currently no specific local age-related centile charts for AFC and AMH. Therefore, we aim to examine the relationship between AFC and AMH with age and construct age-related nomograms among a subfertile Asian population., Methods: This is a study involving Chinese women who had their AFC and AMH measured as part of their subfertility screening from December 2010 until November 2014 in KK Women's and Children's Hospital, Singapore. Ordinary least squares regression analysis was used to estimate the relationship of AFC and AMH with age, while age-related AFC and AMH nomograms for the 3rd, 10th, 25th, 50th, 75th, 90th and 97th percentiles were produced using the lambda-mu-sigma method., Results: A total of 1,009 women, aged 26 to 44 year-old, were included. On average, the AFC and AMH decreased respectively by 0.79 follicle (95% confidence interval -0.93, -0.64) and 0.38 ng/mL (95% confidence interval -0.43, -0.32) per year of age. The age-related nomograms of AFC showed an approximately linear pattern, inversely correlated with age, regardless of the percentile. For AMH, the pattern is linear for the 75th percentile and below but shows a slightly accelerating decline for the 90th and 97th percentile. Overall, there were large inter-individual variations in AFC and AMH up to about 40 year-old., Conclusion: The declines of AFC and AMH over age are mostly linear among subfertile Chinese women in Singapore. The age-related AFC and AMH nomograms could be used as a reference chart by fertility practitioners. However, future validation with longitudinal data is required.

Evidence from clinical studies shows that early cerebellar injury can cause abnormal development of the cerebral cortex in children. Characterization of normative development of the cerebellar and cerebello-cortical organization in early life is of great clinical importance. Here, we analyzed cerebellar, cerebello-cortical, and cortico-cortical functional networks using resting-state functional magnetic resonance imaging data of healthy infants (6 months, n = 21), children (4-10 years, n = 68), and adults (23-38 years, n = 25). We employed independent component analysis and identified 7 cerebellar functional networks in infants and 12 in children and adults. We revealed that the cerebellum was functionally connected with the sensorimotor cortex in infants but with the sensorimotor, executive control, and default mode systems of the cortex in children and adults. The functional connectivity strength in the cerebello-cortical functional networks of sensorimotor, executive control, and default mode systems was the strongest in middle childhood, but was weaker in adulthood. In contrast, the functional coherence of the cortico-cortical networks was stronger in adulthood. These findings suggest early synchronization of the cerebello-cortical networks in infancy, particularly in the early developing primary sensorimotor system. Conversely, age-related differences of cerebellar, cerebello-cortical, and cortico-cortical functional networks in childhood and adulthood suggest potential asynchrony of the cerebellar and cortical functional maturation., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

This study included 168 and 85 mother-infant dyads from Asian and United States of America cohorts to examine whether a genomic profile risk score for major depressive disorder (GPRSMDD) moderates the association between antenatal maternal depressive symptoms (or socio-economic status, SES) and fetal neurodevelopment, and to identify candidate biological processes underlying such association. Both cohorts showed a significant interaction between antenatal maternal depressive symptoms and infant GPRSMDD on the right amygdala volume. The Asian cohort also showed such interaction on the right hippocampal volume and shape, thickness of the orbitofrontal and ventromedial prefrontal cortex. Likewise, a significant interaction between SES and infant GPRSMDD was on the right amygdala and hippocampal volumes and shapes. After controlling for each other, the interaction effect of antenatal maternal depressive symptoms and GPRSMDD was mainly shown on the right amygdala, while the interaction effect of SES and GPRSMDD was mainly shown on the right hippocampus. Bioinformatic analyses suggested neurotransmitter/neurotrophic signaling, SNAp REceptor complex, and glutamate receptor activity as common biological processes underlying the influence of antenatal maternal depressive symptoms on fetal cortico-limbic development. These findings suggest gene-environment interdependence in the fetal development of brain regions implicated in cognitive-emotional function. Candidate biological mechanisms involve a range of brain region-specific signaling pathways that converge on common processes of synaptic development., (© The Author 2017. Published by Oxford University Press.)

Maternal depressive symptoms influence neurodevelopment in the offspring. Such effects may appear to be gender-dependent. The present study examined contributions of prenatal and postnatal maternal depressive symptoms to the volume and microstructure of the amygdala in 4.5-year-old boys and girls. Prenatal maternal depressive symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS) at 26 weeks of gestation. Postnatal maternal depression was assessed at 3 months using the EPDS and at 1, 2, 3 and 4.5 years using the Beck's Depression Inventory-II. Structural magnetic resonance imaging and diffusion tensor imaging were performed with 4.5-year-old children to extract the volume and fractional anisotropy (FA) values of the amygdala. Our results showed that greater prenatal maternal depressive symptoms were associated with larger right amygdala volume in girls, but not in boys. Increased postnatal maternal depressive symptoms were associated with higher right amygdala FA in the overall sample and girls, but not in boys. These results support the role of variation in right amygdala structure in transmission of maternal depression to the offspring, particularly to girls. The differential effects of prenatal and postnatal maternal depressive symptoms on the volume and FA of the right amygdala suggest the importance of the timing of exposure to maternal depressive symptoms in brain development of girls. This further underscores the need for intervention targeting both prenatal and postnatal maternal depression to girls in preventing adverse child outcomes.

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.

This study aimed to examine heterogeneity of neonatal brain network and its prediction to child behaviors at 24 and 48 months of age. Diffusion tensor imaging (DTI) tractography was employed to construct brain anatomical network for 120 neonates. Clustering coefficients of individual structures were computed and used to classify neonates with similar brain anatomical networks into one group. Internalizing and externalizing behavioral problems were assessed using maternal reports of the Child Behavior Checklist (CBCL) at 24 and 48 months of age. The profile of CBCL externalizing and internalizing behaviors was then examined in the groups identified based on the neonatal brain network. Finally, support vector machine and canonical correlation analysis were used to identify brain structures whose clustering coefficients together significantly contribute the variation of the behaviors at 24 and 48 months of age. Four meaningful groups were revealed based on the brain anatomical networks at birth. Moreover, the clustering coefficients of the brain regions that most contributed to this grouping of neonates were significantly associated with childhood internalizing and externalizing behaviors assessed at 24 and 48 months of age. Specially, the clustering coefficient of the right amygdala was associated with both internalizing and externalizing behaviors at 24 months of age, while the clustering coefficients of the right inferior frontal cortex and insula were associated with externalizing behaviors at 48 months of age. Our findings suggested that neural organization established during fetal development could to some extent predict individual differences in behavioral-emotional problems in early childhood. Hum Brain Mapp 38:1362-1373, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: Betaine supplementation results in lower body weight and fat mass and higher lean mass in animals and adult humans. However, the relation between maternal betaine status and offspring birth weight and body composition is less known., Objective: The aim was to examine the association between maternal betaine status and neonatal birth size and adiposity in an Asian mother-offspring cohort., Design: We included 955 pregnant women whose plasma betaine concentrations were measured at 26-28 wk of gestation. Neonatal anthropometric values were measured at birth, and abdominal adipose tissue compartments were assessed by MRI in a subset of infants (n = 307) in the first 14 d after birth. Multivariate general linear models were used to adjust for gestational age; fetal sex; and maternal age, height, education, ethnicity, prepregnancy body mass index, and plasma folate, vitamin B-12, and choline concentrations., Results: The mean ± SD plasma concentration of betaine was 13.2 ± 2.7 μmol/L (range: 5.3-25.0 μmol/L). After adjustment for covariates, higher maternal plasma betaine was associated with lower birth weight (β: -57.6 g; 95% CI: -109.9, -5.3 g), shorter birth length (β: -0.29 cm per 5-μmol/L increment; 95% CI: -0.55, -0.03 cm), smaller head circumference (-0.20 cm; 95% CI: -0.38, -0.02 cm), smaller midupper arm circumference (-0.16 cm; 95% CI: -0.30, -0.03 cm), lower volumes of abdominal superficial subcutaneous adipose tissue (-4.53 mL; 95% CI: -8.70, -0.36 mL), and a higher risk of small-for-gestational-age birth (OR: 1.57; 95% CI: 1.05, 2.35)., Conclusions: Higher maternal betaine status was generally associated with smaller infant birth size and less abdominal fat mass. Further studies are needed to replicate these findings and to understand their biological mechanisms. This study was registered at clinicaltrials.gov as NCT01174875., (© 2016 American Society for Nutrition.)

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.)