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Introduction: The use of computed tomography (CT) in healthcare institutions has increased rapidly in recent years. The Singapore Health Services (SingHealth) cluster of healthcare institutions has taken the first step in establishing a local cluster-wide CT Diagnostic Reference Levels (DRL) in Singapore. CT dose data from each institution were collected through two primary dosimetry metrics: volume CT dose index (CTDI vol measured in mGy) and dose-length product (DLP measured in mGy.cm)., Methods: Data from 19 CT scanners in seven institutions under one of Singapore healthcare cluster were retrospectively collected and analysed. The five common adult CT examinations analysed were CT Brain (non-contrast enhanced), CT Chest (IV contrast enhanced), CT Kidney-Ureter-Bladder (CT KUB, non-contrast enhanced), CT Pulmonary Angiogram (CT PA, IV contrast enhanced) and CT Abdomen-Pelvis (CT AP, IV contrast enhanced, single phase). Median CTDI vol and DLP values for the five CT examinations from each institution were derived, with the cluster DRLs determined as the 75th percentile of the distribution of the institution median dose values., Results: A total of 2413 dose data points were collected over a six-month period from June to November 2020. The cluster CT DRLs for the five CT examinations were determined to be 47 mGy and 820 mGy.cm for CT Brain, 5.4 mGy and 225 mGy.cm for CT Chest, 6.7 mGy and 248 mGy.cm for CT PA, 4.6 mGy and 190 mGy.cm for CT KUB and 6.9 mGy and 349 mGy.cm for CT AP., Conclusion: The establishment of the cluster CT DRLs provided individual institutions with a better understanding if their CT doses are unusually high or low, while emphasising that these DRLs are not meant as hard dose limits or constraints to follow strictly., Competing Interests: Conflict of interest statement All authors have no conflict of interest to declare., (Copyright © 2022 The College of Radiographers. Published by Elsevier Ltd. All rights reserved.)

Background: Neonatal adiposity is associated with a higher risk of obesity and cardiometabolic risk factors in later life. It is however unknown if central food intake regulating networks in the ventral striatum are altered with in-utero abdominal growth, indexed by neonatal adiposity in our current study. We aim to examine the relationship between striatal microstructure and abdominal adipose tissue compartments (AATCs) in Asian neonates from the Growing Up in Singapore Toward healthy Outcomes mother-offspring cohort., Study Design: About 109 neonates were included in this study. Magnetic resonance imaging (MRI) was performed for the brain and abdominal regions between 5 to 17 days of life. Diffusion-weighted imaging of the brain was performed for the derivation of caudate and putamen fractional anisotropy (FA). Abdominal imaging was performed to quantify AATCs namely superficial subcutaneous adipose tissue (sSAT), deep subcutaneous adipose tissue (dSAT), and internal adipose tissue (IAT). Absolute and percentage adipose tissue of total abdominal volume (TAV) were calculated., Results: We showed that AATCs at birth were significantly associated with increased FA in bilateral ventral caudate heads which are part of the ventral striatum (sSAT: β left  = 0.56, p < 0.001; β right  = 0.65, p < 0.001, dSAT: β left  = 0.43, p < 0.001; β right  = 0.52, p < 0.001, IAT: β left  = 0.30, p = 0.005; β right  = 0.32, p = 0.002) in neonates with low birth weights adjusted for gestational age., Conclusions: Our study provides preliminary evidence of a potential relationship between neonatal adiposity and in-utero programming of the ventral striatum, a brain structure that governs feeding behavior., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

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.)

Introduction: Fibrocartilaginous embolism and spinal cord infarction may resemble transverse myelitis with antecedent minor trauma (sporting activity or minor falls) or with hyperacute (<12-hour) presentation., Methods: Diagnostic criteria for fibrocartilaginous embolism and spinal cord infarction were applied to a 10-year (2007-2016) cohort of children aged 1 month to 16 years with transverse myelitis and clinical, laboratory, neuroimaging, and outcome data compared between those with and without antecedent minor trauma., Results: Thirty-two children of median age 8.9 (range 2.7-15.8) years were included; 19 (59%) were female. Falls at home, school, or play (6 children, 60%), swimming (2, 20%), physical education (1, 10%), and caning (1, 10%) were antecedent events in 10 (31%) children. Six (19%) had hyperacute presentations. One patient met spinal cord infarction criteria; none had fibrocartilaginous embolism. Children with transverse myelitis and antecedent minor trauma had single, short spinal cord lesions (median 3 vertebral bodies) but without a specific neuroimaging lesion pattern. None had intervertebral disc abnormalities or brain involvement and were negative for myelin oligodendrocyte and aquaporin 4 antibodies. Twenty-five (86%) of 29 had cerebrospinal fluid inflammation, and 30 (94%) received immunotherapy. Thirty (97%) were followed for a median of 3.6 (0.1-10.2) years, with good outcome (modified Rankin Scale score 0-1) in the majority (80%). Four (75%) with hyperacute presentation had a good outcome (modified Rankin Scale score 0-1), but the patient with spinal cord infarction was the most disabled (modified Rankin Scale score 4)., Conclusion: Minor trauma or hyperacute presentations does not always indicate fibrocartilaginous embolism or spinal cord infarction. Children with minor trauma preceding transverse myelitis have a distinct clinicoradiologic syndrome, with good outcome following immunotherapy.

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.)

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., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

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 Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO) is a preconception, longitudinal cohort study that aims to study the effects of nutrition, lifestyle, and maternal mood prior to and during pregnancy on the epigenome of the offspring and clinically important outcomes including duration of gestation, fetal growth, metabolic and neural phenotypes in the offspring. Between February 2015 and October 2017, the S-PRESTO study recruited 1039 Chinese, Malay or Indian (or any combinations thereof) women aged 18-45 years and who intended to get pregnant and deliver in Singapore, resulting in 1032 unique participants and 373 children born in the cohort. The participants were followed up for 3 visits during the preconception phase and censored at 12 months of follow up if pregnancy was not achieved (N = 557 censored). Women who successfully conceived (N = 475) were characterised at gestational weeks 6-8, 11-13, 18-21, 24-26, 27-28 and 34-36. Follow up of their index offspring (N = 373 singletons) is on-going at birth, 1, 3 and 6 weeks, 3, 6, 12, 18, 24 and 36 months and beyond. Women are also being followed up post-delivery. Data is collected via interviewer-administered questionnaires, metabolic imaging (magnetic resonance imaging), standardized anthropometric measurements and collection of diverse specimens, i.e. blood, urine, buccal smear, stool, skin tapes, epithelial swabs at numerous timepoints. S-PRESTO has extensive repeated data collected which include genetic and epigenetic sampling from preconception which is unique in mother-offspring epidemiological cohorts. This enables prospective assessment of a wide array of potential determinants of future health outcomes in women from preconception to post-delivery and in their offspring across the earliest development from embryonic stages into early childhood. In addition, the S-PRESTO study draws from the three major Asian ethnic groups that represent 50% of the global population, increasing the relevance of its findings to global efforts to address non-communicable diseases.

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.)

Background: Prenatal maternal depression may have long-term impacts on amygdala-cortical development. This study explored associations of prenatal maternal depressive symptoms on the amygdala-cortical structural covariance of the offspring from birth to early childhood, derived from a longitudinal birth cohort., Methods: Structural magnetic resonance imaging was performed to obtain the amygdala volume and cortical thickness at each time point. Prenatal maternal depressive symptoms were measured using the Edinburgh Postnatal Depression Scale at 26 weeks of pregnancy. Regression analysis was used to examine the effects of the Edinburgh Postnatal Depression Scale on a structural coupling between the amygdala volume and cortical thickness at birth (n = 167) and 4.5 years of age (n = 199)., Results: Girls whose mothers had high prenatal maternal depressive symptoms showed a positive coupling between the amygdala volume and insula thickness at birth (β = .617, p = .001) but showed a negative coupling between the amygdala volume and inferior frontal thickness at 4.5 years of age (β = -.369, p = .008). No findings were revealed in boys at any time point., Conclusions: The development of the amygdala-prefrontal circuitry is vulnerable to environmental factors related to depression. Such a vulnerability might be sex dependent., (Copyright © 2019. Published by Elsevier Inc.)

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.)

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: Quantitative magnetic resonance (QMR) has been increasingly used to measure human body composition, but its use and validation in children is limited., Objective: We compared body composition measurement by QMR and air displacement plethysmography (ADP) in preschool children from Singapore's multi-ethnic Asian population (n = 152; mean ± SD age: 5.0 ± 0.1 years)., Methods: Agreements between QMR-based and ADP-based fat mass and fat mass index (FMI) were assessed using intraclass correlation coefficient (ICC), reduced major axis regression and Bland-Altman plot analyses. Analyses were stratified for the child's sex., Results: Substantial agreement was observed between QMR-based and ADP-based fat mass (ICC: 0.85) and FMI (ICC: 0.82). Reduced major axis regression analysis suggested that QMR measurements were generally lower than ADP measurements. Bland-Altman analysis similarly revealed that QMR-based fat mass were (mean difference [95% limits of agreement]) -0.5 (-2.1 to +1.1) kg lower than ADP-based fat mass and QMR-based FMI were -0.4 (-1.8 to +0.9) kg/m 2 lower than ADP-based FMI. Stratification by offspring sex revealed better agreement of QMR and ADP measurements in girls than in boys., Conclusions: QMR-based fat mass and FMI showed substantial agreement with, but was generally lower than, ADP-based measures in young Asian children., (© 2017 World Obesity Federation.)

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

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

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.)

Mechanisms underlying the profound parental effects on cognitive, emotional and social development in humans remain poorly understood. Studies with nonhuman models suggest variations in parental care affect the limbic system, influential to learning, autobiography and emotional regulation. In some research, nonoptimal care relates to decreases in neurogenesis, although other work suggests early-postnatal social adversity accelerates the maturation of limbic structures associated with emotional learning. We explored whether maternal sensitivity predicts human limbic system development and functional connectivity patterns in a small sample of human infants. When infants were 6 months of age, 20 mother-infant dyads attended a laboratory-based observational session and the infants underwent neuroimaging at the same age. After considering age at imaging, household income and postnatal maternal anxiety, regression analyses demonstrated significant indirect associations between maternal sensitivity and bilateral hippocampal volume at six months, with the majority of associations between sensitivity and the amygdala demonstrating similar indirect, but not significant results. Moreover, functional analyses revealed direct associations between maternal sensitivity and connectivity between the hippocampus and areas important for emotional regulation and socio-emotional functioning. Sensitivity additionally predicted indirect associations between limbic structures and regions related to autobiographical memory. Our volumetric results are consistent with research indicating accelerated limbic development in response to early social adversity, and in combination with our functional results, if replicated in a larger sample, may suggest that subtle, but important, variations in maternal care influence neuroanatomical trajectories important to future cognitive and emotional functioning.

Objective: Exposure to antenatal maternal anxiety and complex genetic variations may shape fetal brain development. In particular, the catechol-O-methyltransferase (COMT) gene, located on chromosome 22q11.2, regulates catecholamine signaling in the prefrontal cortex and is implicated in anxiety, pain, and stress responsivity. This study examined whether individual single-nucleotide polymorphisms (SNPs) of the COMT gene and their haplotypes moderate the association between antenatal maternal anxiety and in utero cortical development., Method: A total of 146 neonates were genotyped and underwent MRI shortly after birth. Neonatal cortical morphology was characterized using cortical thickness. Antenatal maternal anxiety was assessed using the State-Trait Anxiety Inventory at week 26 of pregnancy., Results: Individual COMT SNPs (val158met, rs737865, and rs165599) modulated the association between antenatal maternal anxiety and the prefrontal and parietal cortical thickness in neonates. Based on haplotype trend regression analysis, findings also showed that among rs737865-val158met-rs165599 haplotypes, the A-val-G (AGG) haplotype probabilities modulated positive associations of antenatal maternal anxiety with cortical thickness in the right ventrolateral prefrontal cortex and the right superior parietal cortex and precuneus. In contrast, the G-met-A (GAA) haplotype probabilities modulated negative associations of antenatal maternal anxiety with cortical thickness in bilateral precentral gyrus and the dorsolateral prefrontal cortex., Conclusions: These results suggest that the association between maternal anxiety and in utero neurodevelopment is modified through complex genetic variation in COMT. Such genetic moderation may explain, in part, the variation in phenotypic outcomes in offspring associated with maternal emotional well-being.

Background: Antenatal maternal cortisol levels associate with alterations in the amygdala, a structure associated with emotion regulation, in the offspring. However, because offspring brain and behavior are commonly assessed years after birth, the timing of such maternal influences is unclear. This study aimed to examine the association between antenatal maternal depressive symptomatology and neonatal amygdala volume and microstructure and thus establish evidence for the transgenerational transmission of vulnerability for affective disorders during prenatal development., Methods: Our study recruited Asian mothers at 10 to 13 weeks pregnancy and assessed maternal depression at 26 weeks gestation using the Edinburgh Postnatal Depression Scale. Structural magnetic resonance imaging and diffusion tensor imaging were performed with 157 nonsedated, 6- to 14-day-old newborns and then analyzed to extract the volume, fractional anisotropy, and axial diffusivity values of the amygdala., Results: Adjusting for household income, maternal age, and smoking exposure, postconceptual age at magnetic resonance imaging, and birth weight, we found significantly lower fractional anisotropy (p = .009) and axial diffusivity (p = .028), but not volume (p = .993), in the right amygdala in the infants of mothers with high compared with those with low-normal Edinburgh Postnatal Depression Scale scores., Conclusions: The results reveal a significant relation between antenatal maternal depression and the neonatal microstructure of the right amygdala, a brain region closely associated with stress reactivity and vulnerability for mood anxiety disorders. These findings suggest the prenatal transmission of vulnerability for depression from mother to child and that interventions targeting maternal depression should begin early in pregnancy., (© 2013 Society of Biological Psychiatry.)

Exposure to maternal anxiety predicts offspring brain development. However, because children's brains are commonly assessed years after birth, the timing of such maternal influences in humans is unclear. This study aimed to examine the consequences of antenatal and postnatal exposure to maternal anxiety upon early infant development of the hippocampus, a key structure for stress regulation. A total of 175 neonates underwent magnetic resonance imaging (MRI) at birth and among them 35 had repeated scans at 6 months of age. Maternal anxiety was assessed using the State-Trait Anxiety Inventory (STAI) at week 26 of pregnancy and 3 months after delivery. Regression analyses showed that antenatal maternal anxiety did not influence bilateral hippocampal volume at birth. However, children of mothers reporting increased anxiety during pregnancy showed slower growth of both the left and right hippocampus over the first 6 months of life. This effect of antenatal maternal anxiety upon right hippocampal growth became statistically stronger when controlling for postnatal maternal anxiety. Furthermore, a strong positive association between postnatal maternal anxiety and right hippocampal growth was detected, whereas a strong negative association between postnatal maternal anxiety and the left hippocampal volume at 6 months of life was found. Hence, the postnatal growth of bilateral hippocampi shows distinct responses to postnatal maternal anxiety. The size of the left hippocampus during early development is likely to reflect the influence of the exposure to perinatal maternal anxiety, whereas right hippocampal growth is constrained by antenatal maternal anxiety, but enhanced in response to increased postnatal maternal anxiety.

Purpose: To determine the eye size and shape obtained by magnetic resonance imaging (MRI), and to determine associations with antenatal factors in newborn children., Methods: A subset of 173 full-term newborn children from the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) birth cohort underwent MRI. Eye volume and surface area were measured. Eye shape was assessed qualitatively from three-dimensional models, and quantitatively by measurement of longitudinal axial length (AL, the length from the posterior corneal surface to the retinal surface), and horizontal width and vertical height of the internal eye along the cardinal axes. Oblateness was calculated as 1-(AL/width) or 1-(AL/height). Oblate eyes had oblateness>+0.01, spherical eyes had oblateness between +0.01 and -0.01, and prolate eyes had oblateness<-0.01., Results: A total of 346 eyes of 173 children were included. Mean oblateness using width was -0.06±0.05 (range, -0.23 to +0.08), and mean oblateness using height was -0.01±0.04 (range, -0.19 to +0.13). Using width, most eyes were prolate (294 eyes, 85%); and using height, the largest proportion of eyes was prolate (163 eyes, 47%). Eyes with longer ALs had greater widths, heights, volumes, and surface areas than eyes with shorter ALs (P<0.001 for all). With increasing AL, eyes became increasingly prolate. Children of less educated mothers had longer ALs (P=0.02). Malay children had larger eye volumes and surface areas than Chinese or Indian children., Conclusions: Most newborn Singaporean Asian children are born with prolate eyes. A longitudinal study is required to determine if globe shape at birth influences subsequent refractive changes.

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. [ABSTRACT FROM AUTHOR]

Purpose: Few studies have described adherence to dietary patterns over time in women of childbearing age. This study aims to describe, examine the stability and changes in dietary patterns between pregnancy and 6 years post-pregnancy and the sociodemographic and lifestyle factors influencing the adherence over time. Methods: During pregnancy and at 6 years post-pregnancy, 24-h recalls and food frequency questionnaires were collected, respectively, from 709 women. Data on sociodemographic and lifestyle factors were collected via questionnaires. Dietary patterns were identified using principal component analysis and stability assessed using Pearson's correlation coefficients (r) and Cohen's weighted kappa (κ). Associations with sociodemographic characteristics were assessed by multiple logistic regression. Results: The 'Fruits, Vegetables and Legumes' (FVL) and 'Seafood, Noodle, Soup' (SNS) patterns were identified at both time points, with low correlation for the dietary pattern z scores (r 0.2 and 0.3, respectively) and modest agreement in tertile assignment, suggesting poor stability. An 'unhealthy' pattern was only observed at 6 years post-pregnancy. Women who showed increased adherence to FVL pattern had higher educational attainment and exhibited healthy lifestyle behaviours. Women who had gestational diabetes during pregnancy were less likely to decrease adherence to FVL pattern over time. Women who adhered more closely to the 'unhealthy' pattern at 6 years post-pregnancy tended to be younger, of Malay ethnicity, had lower socioeconomic status, were less physically active and had additional pregnancies. Conclusions: Dietary habits of women became less healthy during the transition from pregnancy to 6 years post-pregnancy. However, results should be interpreted with caution due to the different dietary assessment tools used at the two time points. [ABSTRACT FROM AUTHOR]

Perinatal maternal symptoms of depression and anxiety compromise psychosocial function and influence developmental outcomes in the offspring. The onset of symptoms remains unclear with findings that suggest a preconceptual origin. We addressed this issue with a prospective analysis of anxiety and depressive symptom profiles from preconception through to parturition. Women were recruited into a preconception study to assess (a) variation in symptom levels of depression and anxiety from pre- to post-conception and (b) if the symptom network profiles of depression and anxiety change from pre-conception to post-conception. A within-subject intraclass correlation analyses revealed that symptoms of depression or anxiety in the preconception phase strongly predicted those across pregnancy and into the early postnatal period. The symptom network analysis revealed that the symptom profiles remained largely unchanged from preconception into the second trimester. Our findings suggest that for a significant portion of women, maternal mental health remains stable from preconception into pregnancy. This finding highlights the need for early intervention studies on women's mental health to be targeted during the preconception period and to be extended across the population. [ABSTRACT FROM AUTHOR]

Aims: There is compelling evidence for gradient effects of household income on school readiness. Potential mechanisms are described, yet the growth curve trajectory of maternal mental health in a child's early life has not been thoroughly investigated. We aimed to examine the relationships between household incomes, maternal mental health trajectories from antenatal to the postnatal period, and school readiness. Methods: Prospective data from 505 mother–child dyads in a birth cohort in Singapore were used, including household income, repeated measures of maternal mental health from pregnancy to 2-years postpartum, and a range of child behavioural, socio-emotional and cognitive outcomes from 2 to 6 years of age. Antenatal mental health and its trajectory were tested as mediators in the latent growth curve models. Results: Household income was a robust predictor of antenatal maternal mental health and all child outcomes. Between children from the bottom and top household income quartiles, four dimensions of school readiness skills differed by a range of 0.52 (95% Cl: 0.23, 0.67) to 1.21 s.d. (95% CI: 1.02, 1.40). Thirty-eight percent of pregnant mothers in this cohort were found to have perinatal depressive and anxiety symptoms in the subclinical and clinical ranges. Poorer school readiness skills were found in children of these mothers when compared to those of mothers with little or no symptoms. After adjustment of unmeasured confounding on the indirect effect, antenatal maternal mental health provided a robust mediating path between household income and multiple school readiness outcomes (χ2 126.05, df 63, p < 0.001; RMSEA = 0.031, CFI = 0.980, SRMR = 0.034). Conclusions: Pregnant mothers with mental health symptoms, particularly those from economically-challenged households, are potential targets for intervention to level the playing field of their children. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The dramatic emergence of noncommunicable diseases (NCD) in Asia, albeit with ethnic variation, has coincided with the rapid socioeconomic and nutritional transition taking place in the region, with the prevalence of diabetes rising 5-fold in Singapore in less than 4 decades. The Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort study recruited 1,247 expectant mothers of Chinese, Malay, or Indian ethnicity in their first trimester, with detailed longitudinal tracking - through the antenatal period, birth, and the child's first 4 years of life - to examine the potential roles of fetal, developmental, and epigenetic factors in early pathways to metabolic and neurodevelopmental outcomes. Key Messages: A number of findings with a translational and clinical focus have already emerged. In the mothers, we found that changes and differences in food consumption varied across ethnic groups, with persistence of traditional beliefs, during pregnancy and the postpartum period. During pregnancy, higher maternal glucose levels, even in the absence of gestational diabetes mellitus, had graded relations with infant adiposity. Relations between maternal emotional health and birth outcomes and neurodevelopment have been identified. Genotype (25%) and in particular gene × environment interactions (75%) shape interindividual variations in the DNA methylome at birth. The complex effects of fixed genetic variations and different in utero environments can influence the epigenetic status at birth and the later-life phenotype. Conclusions: The richness of the clinical data in 3 ethnicities, the extent of the biospecimen collection, and the extensive infancy and preschool follow-up have allowed us to study the biological pathways that link fetal development to health outcomes. In the coming years, more sophisticated analyses of epigenotype-phenotype relationships will become possible as the children grow and develop. Our studies will lead to the development of clinical and population-based interventions to reduce the burden of NCD. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]