Association of acylcarnitines with maternal cardiometabolic risk factors is defined by chain length: the S-PRESTO study.

CONTEXT: Due to the essential role of carnitine as an intermediary in amino acid, carbohydrate and lipid metabolism, a detailed characterization of circulating and urinary carnitine concentrations will aid in elucidating the molecular basis of impaired maternal metabolic flexibility and facilitating timely intervention for expectant mothers. OBJECTIVE: To investigate the association of maternal plasma and urinary free carnitine and acylcarnitines with cardiometabolic risk factors. METHODS: LC-MS/MS-based quantification of free carnitine and acylcarnitines (C2-C18) was performed on 765 plasma and 702 urine samples collected at preconception, 26-28 weeks' pregnancy, and three months postpartum in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) cohort study. RESULTS: Plasma concentrations of free carnitine and acylcarnitines decreased coupled with increased renal clearance in pregnancy compared to preconception and postpartum. Renal clearance of carnitine increased with an increase in pre-pregnancy body mass index (ppBMI) and gestational weight gain. Plasma short-chain acylcarnitines were positively associated with ppBMI, irrespective of the physiological state, while medium- and long-chain acylcarnitines were negatively associated with ppBMI at preconception and postpartum but showed a positive association in pregnancy. Similarly, plasma short-chain acylcarnitines were positively associated with HOMA-IR whereas medium- and long-chain acylcarnitines were negatively associated with HOMA-IR at preconception and in pregnancy. Mothers who developed gestational diabetes mellitus during pregnancy had ∼10% higher plasma propionylcarnitine concentration and ∼18% higher urine tiglylcarnitine concentration compared to mothers with normal glucose metabolism at preconception. CONCLUSIONS: This study provides the metabolic and physiological basis of maternal carnitine homeostasis, which can be used in assessment of maternal cardiometabolic health at preconception to improve pregnancy outcomes.

Multidisciplinary Obstetric Simulation Training: Experience at KK Women's and Children's Hospital (KKH), Singapore, a Tertiary Referral Centre.

Background Multidisciplinary simulation training in the management of acute obstetric emergencies has the potential to reduce both maternal and perinatal morbidity. It is a valuable tool that can be adapted for targeted audiences of different specialities at all experience levels from medical students to senior consultants. Methods In this study, pre- and post-course questionnaires of learners with varying levels of clinical experience from Obstetrics and Gynaecology (O&G), Anaesthesia, Neonatology, Emergency Medicine, midwifery, and nursing who undertook two simulation courses (namely the Combined Obstetrics Resuscitation Training course, CORE, and the CORE Lite), which comprised lectures and simulation drills with manikins and standardized patients, between 2015 and 2023 were compared. This also included a period when training was affected by the coronavirus disease 2019 (COVID-19) pandemic.  Results The results showed that both simulation courses increased confidence levels among all learners in the management of obstetric emergencies.  Pre-course, participants were most confident in the management of neonatal resuscitation and severe pre-eclampsia, followed by postpartum haemorrhage. They were least confident in the management of vaginal breech delivery, uterine inversion, and twin delivery. Post-course, participants were most confident in the management of neonatal resuscitation and shoulder dystocia, followed by postpartum haemorrhage. They were least confident in the management of uterine inversion and maternal sepsis, followed by vaginal breech delivery and twin delivery. Whilst we saw a huge improvement in confidence levels for all obstetric emergencies, the greatest improvement in confidence levels was noted in vaginal breech delivery, twin delivery, and uterine inversion. Conclusion The simulation courses were effective in improving the confidence in the management of obstetric emergencies. While it may be difficult to measure the improvement in clinical outcomes as a result of simulation courses alone, the increase in confidence levels of clinicians can be used as a surrogate in measuring their preparedness in facing these emergency scenarios.

Retrospective Study Comparing Treatment Outcomes in Obstetric Patients With Iron Deficiency Anemia Treated With and Without Intravenous Ferric Carboxymaltose.

Introduction Iron deficiency anemia is associated with an increased risk of adverse maternal and perinatal outcomes. Intravenous iron preparation containing ferric carboxymaltose has been shown to be a safe and effective way of increasing hemoglobin (Hb) and mean corpuscular volume (MCV) levels and reducing the need for blood transfusion. In our center, it used to be given as an inpatient procedure because of the risks of potential drug reactions. In 2021, we initiated the administration of intravenous ferric carboxymaltose as an outpatient procedure. We compared the outcomes of patients between 2021 and 2023 after the initiation of outpatient administration of intravenous ferric carboxymaltose in 127 obstetric patients with iron deficiency anemia in the second and third trimesters. Methods In this study conducted in a large maternity unit in Singapore between 2021 to 2023, we compared the changes in maternal hematological parameters among obstetric patients with iron deficiency anemia presenting to the day care unit in the second or third trimester with a Hb level of <8 g/dl treated with a single dose of ferric carboxymaltose injection (Ferinject) against a control group who were referred for treatment but defaulted on and declined treatment. Results Ferric carboxymaltose significantly increased the Hb and MCV levels at delivery in obstetric patients with iron deficiency. The mean Hb at delivery was 10.8 g/dL in the case group compared to 8.8 g/dL in the control group. The percentage of patients with Hb ≥10.0 g/dL was 73.4% in the case group compared to 27.8% in the control group. The incidence of adverse side effects was low and mild (2/127; 1.6%). None of the patients received were hospitalized because of ferric carboxymaltose. Conclusion A single injection dose of ferric carboxymaltose as an outpatient antenatal procedure was easily administered and well tolerated. Obstetric patients with iron deficiency anemia who received intravenous ferric carboxymaltose had a significantly higher level of Hb than those who did not.

The cross-sectional and prospective associations of parental practices and environmental factors with 24-hour movement behaviours among school-aged Asian children.

BACKGROUND: Parental practices and neighbourhood environmental factors may influence children's movement behaviours. We aimed to investigate the cross-sectional and prospective associations of parental practices and neighbourhood environmental factors with accelerometer-measured 24-hour movement behaviours (24 h-MBs) among school-aged children in Singapore. METHODS: The Growing Up in Singapore Towards healthy Outcomes (GUSTO) study collected information on dimensions of parental practices and neighbourhood environment at age 5.5 years. Confirmatory factor analyses were performed to generate latent variables and used to compute overall parental practices [involvement in PA + support for PA + control of screen viewing context] and environmental scores [facilities for active play + active mobility facilitators + barriers*-1]. Children wore an accelerometer on their non-dominant wrist for seven consecutive days at ages 5.5 and 8 years. The R-package GGIR 2.6 was used to derive moderate-to-vigorous-intensity physical activity (MVPA), light-intensity physical activity (LPA), inactivity, and total-sleep (napping+night sleep) minutes per day. Associations were determined using compositional data analysis with multivariate linear regression models, taking into account potential confounders. RESULTS: Among 425 children (48% girls, 59% Chinese), higher parental involvement in PA, parental support for PA and overall parental practices were associated with 24 h-MBs at ages 5.5 and 8 years, specifically with greater time spent in MVPA and less time being inactive relative to the remaining movement behaviours. The corresponding mean changes in the overall 24 h-MB for increasing parental practices from lowest to highest scores (- 2 to + 2 z-scores) indicated potential increases of up to 15-minutes in MVPA, 20-minutes in LPA, 5-minutes in sleep duration, and a reduction of 40-minutes in inactivity at age 5.5 years. At age 8 years, this could translate to approximately 15-minutes more of MVPA, 20-minutes more of LPA, a 20-minute reduction in sleep duration, and a 20-minute reduction in inactivity. Parental control of screen viewing contexts and neighbourhood environmental factors were not associated with 24 h-MBs. CONCLUSIONS: Parental practices but not environmental factors were associated with higher MVPA and lower inactivity among Singaporean children, even at a later age. Further research may provide insights that support development of targeted public health strategies to promote healthier movement behaviours among children. STUDY REGISTRATION: This study was registered on 4th August 2010 and is available online at ClinicalTrials.gov: NCT01174875.

Empathy Levels Among Healthcare Professionals: An Asian Multi-professional Cross-Sectional Study.

BACKGROUND: The aim of the study was to measure empathy in healthcare professionals in Singapore and to compare the scores between the different professions: doctors, nurses, and allied health professionals. METHODS: An online survey questionnaire was conducted using the Jefferson Scale of Empathy (JSE) from July 2019 to January 2020. The total JSE score was calculated and compared among the different groups. Multiple linear regression was performed to assess predictors of total empathy scores for groups with statistically lower scores. RESULTS: The survey was completed by 4,188 healthcare professionals (doctors (n=569, 13.6%), nurses (n=3032, 72.4%), and allied health professionals (n=587, 14.0%)) out of the 9,348-strong survey population, with a response rate of 44.8%. The study revealed a mean empathy score (SD) of 103.6 (15.6) for the cohort. The mean empathy score (SD) was 112.3 (14.7), 101.3 (15.2), and 107.0 (15.0), respectively for doctors, nurses, and allied health professionals. These were statistically significantly different among the groups (p< 0.0001), with nurses scoring significantly lower than either doctors (p< 0.0001) or allied health professionals (p< 0.0001). Multiple linear regression showed that age < 30 years old, male gender, Malay ethnicity, and working in a hospital setting were associated with significantly lower empathy scores in the nursing group. CONCLUSION: Nurses in Singapore had significantly lower empathy scores compared to doctors and allied health professionals. Further research on the underlying causes should be undertaken and measures to improve empathy among Singapore nursing staff should be explored and implemented.

Adherence to 24-hour integrated activity guidelines among infants, toddlers and preschool children in Singapore.

This study examined children's adherence to the Singapore Integrated 24-Hour Activity Guidelines for Early Childhood in infants, toddlers and preschoolers aged 0-6 years. A total of 901 caregivers, comprising 219 infants, 379 toddlers, and 303 preschoolers, provided information regarding their children's physical activity (PA), screen viewing time (SVT), and sleep durations on both weekdays and weekends. Meeting the 24-hour integrated activity guidelines was defined as follows: for infants ≥ 30 minutes per day of tummy time or floor-based play; zero SVT; total sleep of 14-17 hours per day for ages 0-3 months, 12-16 hours per day for ages 4-11 months; for toddlers ≥ 180 minutes of total PA per day; zero SVT under 2 years; <1 hour for ages 2 to less than 3 years; and a total sleep of 11-14 hours per day; for preschoolers ≥ 180 minutes of total PA per day; SVT <1 hour per day; total sleep of 10-13 hours per day for those aged 3-5 years, and 10-11 hours per day for 6-year-olds. Chi-squared tests were used to examine the differences in guideline adherence between weekdays and weekends. Compared to weekdays, during weekends there was a higher proportion of toddlers and preschoolers adhering to the PA guidelines (68.9% vs 50.1%; 78.9% vs 55.4%, respectively, p<0.05), and a lower proportion of toddlers adhering to SVT (38.8% vs 21.8%; p = 0.001). There was a declining adherence to all three activity guidelines as age groups progressed from infants (44.7%) to toddlers (15.8%) and then to preschoolers (9.4%). Concurrently, there was a decrease in adherence to SVT recommendations across the age groups, with adherence rates being highest among infants (83.1%), followed by toddlers (15.8%), and preschoolers (9.4%). Decreasing compliance with all three guidelines, coupled with a corresponding decline in adherence to SVT guidelines as children transition from toddlerhood to preschool age, is a cause for concern. This underscores the need for proactive efforts to educate caregivers about reducing or eliminating SVT among infants and young children.

The effects of acute social ostracism on subsequent snacking behavior and future body mass index in children.

BACKGROUND/OBJECTIVES: Ostracism may lead to increased food intake, yet it is unclear whether greater reactivity to ostracism contributes to higher body mass index (BMI). We investigated whether children who exhibited greater stress to social exclusion subsequently consume more energy and whether this predicts BMI 6- and 18-months later. SUBJECTS/METHODS: Children (8.5 years-old) (N = 262, males = 50.4%; Chinese = 58.4%) completed a laboratory-based manipulation of social exclusion (the Cyberball task) prior to an ad-libitum snack. Heart rate variability (HRV) was measured during the inclusion and exclusion conditions and proportionate changes were calculated as a physiological measure of exclusion-related stress. Social anxiety and social-emotional assets were also measured as moderators. RESULTS: Greater stress (as measured physiologically or by self-report) did not directly, or indirectly via energy intake, predict later BMI (at 9- and 10-years). However, among children reporting higher social anxiety, greater stress as measured by proportionate changes in HRV was associated with increased energy intake (B = 532.88, SE = 226.49, t(255) = 2.35, [CI95 = 86.85,978.92]). A significant moderated mediation was also observed (index: (b = 0.01, bootSE = 0.01, [CI95 = 0.001, 0.036]), such that among children reporting higher social anxiety, greater stress from social exclusion predicted increased energy intake from a subsequent snack, which in turn predicted higher BMI 1.5 years later. CONCLUSION: This prospective study suggests that a pattern of greater snack intake in response to heightened vulnerability to the effects of ostracism may contribute to increases in child BMI scores.

A machine-learning exploration of the exposome from preconception in early childhood atopic eczema, rhinitis and wheeze development.

BACKGROUND: Most previous research on the environmental epidemiology of childhood atopic eczema, rhinitis and wheeze is limited in the scope of risk factors studied. Our study adopted a machine learning approach to explore the role of the exposome starting already in the preconception phase. METHODS: We performed a combined analysis of two multi-ethnic Asian birth cohorts, the Growing Up in Singapore Towards healthy Outcomes (GUSTO) and the Singapore PREconception Study of long Term maternal and child Outcomes (S-PRESTO) cohorts. Interviewer-administered questionnaires were used to collect information on demography, lifestyle and childhood atopic eczema, rhinitis and wheeze development. Data training was performed using XGBoost, genetic algorithm and logistic regression models, and the top variables with the highest importance were identified. Additive explanation values were identified and inputted into a final multiple logistic regression model. Generalised structural equation modelling with maternal and child blood micronutrients, metabolites and cytokines was performed to explain possible mechanisms. RESULTS: The final study population included 1151 mother-child pairs. Our findings suggest that these childhood diseases are likely programmed in utero by the preconception and pregnancy exposomes through inflammatory pathways. We identified preconception alcohol consumption and maternal depressive symptoms during pregnancy as key modifiable maternal environmental exposures that increased eczema and rhinitis risk. Our mechanistic model suggested that higher maternal blood neopterin and child blood dimethylglycine protected against early childhood wheeze. After birth, early infection was a key driver of atopic eczema and rhinitis development. CONCLUSION: Preconception and antenatal exposomes can programme atopic eczema, rhinitis and wheeze development in utero. Reducing maternal alcohol consumption during preconception and supporting maternal mental health during pregnancy may prevent atopic eczema and rhinitis by promoting an optimal antenatal environment. Our findings suggest a need to include preconception environmental exposures in future research to counter the earliest precursors of disease development in children.

Neonatal Nucleus Accumbens Microstructure Modulates Individual Susceptibility to Preconception Maternal Stress in Relation to Externalizing Behaviors.

OBJECTIVE: Maternal stress influences in utero brain development and is a modifiable risk factor for offspring psychopathologies. Reward circuitry dysfunction underlies various internalizing and externalizing psychopathologies. This study examined (1) the association between maternal stress and microstructural characteristics of the neonatal nucleus accumbens (NAcc), a major node of the reward circuitry, and (2) whether neonatal NAcc microstructure modulates individual susceptibility to maternal stress in relation to childhood behavioral problems. METHOD: K-means longitudinal cluster analysis was performed to determine trajectories of maternal stress measures (Perceived Stress Scale [PSS], hair cortisol) from preconception to the third trimester. Neonatal NAcc microstructural measures (orientation density index [ODI] and intracellular volume fraction [ICVF]) were compared across trajectories. We then examined the interaction between maternal stress and neonatal NAcc microstructure on child internalizing and externalizing behaviors, assessed between ages 3 and 4 years. RESULTS: Two trajectories of maternal stress magnitude ("low"/"high") were identified for both PSS (n = 287) and hair cortisol (n = 336). Right neonatal NAcc ODI (rNAcc-ODI) was significantly lower in "low" relative to "high" PSS trajectories (n = 77, p = .04). PSS at preconception had the strongest association with rNAcc-ODI (r = 0.293, p = .029). No differences in NAcc microstructure were found between hair cortisol trajectories. A significant interaction between preconception PSS and rNAcc-ODI on externalizing behavior was observed (n = 47, p = .047). CONCLUSION: Our study showed that the preconception period contributes to in utero NAcc development, and that NAcc microstructure modulates individual susceptibility to preconception maternal stress in relation to externalizing problems.

Parental and child genetic burden of glycaemic dysregulation and early-life cognitive development: an Asian and European prospective cohort study.

Insulin resistance and glucose metabolism have been associated with neurodevelopmental disorders. However, in the metabolically more susceptible Asian populations, it is not clear whether the genetic burden of glycaemic dysregulation influences early-life neurodevelopment. In a multi-ethnic Asian prospective cohort study in Singapore (Growing Up in Singapore Towards healthy Outcomes (GUSTO)), we constructed child and parental polygenic risk scores (PRS) for glycaemic dysregulation based on the largest genome-wide association studies of type 2 diabetes and fasting glucose among Asians. We found that child PRS for HOMA-IR was associated with a lower perceptual reasoning score at ~7 years (ß = -0. 141, p-value = 0.024, 95% CI -0. 264 to -0. 018) and a lower WIAT-III mean score at ~9 years (ß = -0.222, p-value = 0.001, 95% CI -0.357 to -0.087). This association were consistent in direction among boys and girls. These inverse associations were not influenced by parental PRS and were likely mediated via insulin resistance rather than mediators such as birth weight and childhood body mass index. Higher paternal PRS for HOMA-IR was suggestively associated with lower child perceptual reasoning at ~7 years (ß = -0.172, p-value = 0.002, 95% CI -0.280 to -0.064). Replication analysis in a European cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort, showed that higher child PRS for fasting glucose was associated with lower verbal IQ score while higher maternal PRS for insulin resistance was associated with lower performance IQ score in their children at ~8.5 years. In summary, our findings suggest that higher child PRS for HOMA-IR was associated with lower cognitive scores in both Asian and European replication cohorts. Differential findings between cohorts may be attributed to genetic and environmental factors. Further investigation of the functions of the genetic structure and ancestry-specific PRS and a more comprehensive investigation of behavioural mediators may help to understand these findings better.

Continuous Glucose Monitoring Feedback in the Subsequent Development of Gestational Diabetes: A Pilot, Randomized, Controlled Trial in Pregnant Women.

OBJECTIVE: This study evaluated the effects of receiving glucose feedback from continuous glucose monitoring (CGM) by intermittent scanning (unblinded group), and CGM with masked feedback (blinded group) in the subsequent development of gestational diabetes mellitus (GDM). STUDY DESIGN: This was a prospective, single-center, pilot, randomized controlled trial including n = 206 pregnant women in the first trimester of pregnancy with no prior diagnosis of type 1 or type 2 diabetes. The participants were randomized into the unblinded group or blinded group and wore the CGM in the first trimester of pregnancy (9-13 weeks), the second trimester of pregnancy (18-23 weeks), and late-second to early-third trimester (24-31 weeks). The primary outcome was GDM rate as diagnosed by the 75-g oral glucose tolerance test (OGTT) at 24 to 28 weeks. RESULTS: Over 47 months, 206 pregnant women were enrolled at 9 to 13 weeks. The unblinded group had a higher prevalence of women who developed GDM (21.5 vs. 14.9%; p > 0.05), compared to the blinded group. In the unblinded group compared to the blinded group, plasma glucose values were higher at 1 hour (median 7.7 [interquartile range {IQR}: 6.3-9.2] vs. 7.5 [6.3-8.7]) and 2 hours (6.3 [5.8-7.7] vs. 6.2 [5.3-7.2]), but lower at 0 hour (4.2 [4.0-4.5] vs. 4.3 [4.1-4.6]; p > 0.05). All these differences were not statistically significant. CONCLUSION: Glucose feedback from CGM wear in the first to the third trimester of pregnancy without personalized patient education failed to alter GDM rate. KEY POINTS: · Continuous glucose monitoring (CGM) is feasible for use in pregnant women.. · No significant difference in gestational diabetes rates with or without CGM feedback.. · Future clinical trials should incorporate CGM education and personalized guidance to enhance study outcomes..

Umbilical Cord Plasma Lysophospholipids and Triacylglycerols Associated with Birthweight Percentiles.

Dysregulated transplacental lipid transfer and fetal-placental lipid metabolism affect birthweight, as does maternal hyperglycemia. As the mechanisms are unclear, we aimed to identify the lipids in umbilical cord plasma that were most associated with birthweight. Seventy-five Chinese women with singleton pregnancies recruited into the GUSTO mother-offspring cohort were selected from across the glycemic range based on a mid-gestation 75 g oral glucose tolerance test, excluding pre-existing diabetes. Cord plasma samples collected at term delivery were analyzed using targeted liquid-chromatography tandem mass-spectrometry to determine the concentrations of 404 lipid species across 17 lipid classes. The birthweights were standardized for sex and gestational age by local references, and regression analyses were adjusted for the maternal age, BMI, parity, mode of delivery, insulin treatment, and fasting/2 h glucose, with a false discovery-corrected p < 0.05 considered significant. Ten lysophosphatidylcholines (LPCs) and two lysophosphatidylethanolamines were positively associated with the birthweight percentiles, while twenty-four triacylglycerols were negatively associated with the birthweight percentiles. The topmost associated lipid was LPC 20:2 [21.28 (95%CI 12.70, 29.87) percentile increase in the standardized birthweight with each SD-unit increase in log10-transformed concentration]. Within these same regression models, maternal glycemia did not significantly associate with the birthweight percentiles. Specific fetal circulating lysophospholipids and triacylglycerols associate with birthweight independently of maternal glycemia, but a causal relationship remains to be established.

Joint modelling of mental health markers through pregnancy: a Bayesian semi-parametric approach.

Maternal depression and anxiety through pregnancy have lasting societal impacts. It is thus crucial to understand the trajectories of its progression from preconception to postnatal period, and the risk factors associated with it. Within the Bayesian framework, we propose to jointly model seven outcomes, of which two are physiological and five non-physiological indicators of maternal depression and anxiety over time. We model the former two by a Gaussian process and the latter by an autoregressive model, while imposing a multidimensional Dirichlet process prior on the subject-specific random effects to account for subject heterogeneity and induce clustering. The model allows for the inclusion of covariates through a regression term. Our findings reveal four distinct clusters of trajectories of the seven health outcomes, characterising women's mental health progression from before to after pregnancy. Importantly, our results caution against the loose use of hair corticosteroids as a biomarker, or even a causal factor, for pregnancy mental health progression. Additionally, the regression analysis reveals a range of preconception determinants and risk factors for depressive and anxiety symptoms during pregnancy.

Trajectories of lifestyle patterns from 2 to 8 years of age and cardiometabolic risk in children: the GUSTO study.

BACKGROUND: Tracking combinations of lifestyle behaviours during childhood ("lifestyle pattern trajectories") can identify subgroups of children that might benefit from lifestyle interventions aiming to improve health outcomes later in life. However, studies on the critical transition period from early to middle childhood are limited. We aimed to describe lifestyle patterns trajectories in children from 2 to 8 years of age and evaluated their associations with cardiometabolic risk markers at age 8 years in a multi-ethnic Asian cohort. METHODS: Twelve lifestyle behaviours related to child's diet, physical activity, screen use, and sleep were ascertained using questionnaires at ages 2, 5, and 8 years. Age-specific lifestyle patterns were derived using principal component analysis and trajectories were determined using group-based multi-trajectory modelling. Child cardiometabolic risk markers were assessed at age 8 years, and associations with trajectories examined using multiple regression, adjusted for confounders. RESULTS: Among 546 children, two lifestyle patterns "healthy" and "unhealthy" were observed at ages 2, 5, and 8 years separately. Three trajectory groups from 2 to 8 years were identified: consistently healthy (11%), consistently unhealthy (18%), and mixed pattern (71%). Children in the consistently unhealthy group (vs. mixed pattern) had increased odds of pre-hypertension (OR = 2.96 [95% CI 1.18-7.41]) and higher levels of diastolic blood pressure (ß = 1.91 [0.27-3.55] mmHg), homeostasis model assessment of insulin resistance (ß = 0.43 [0.13-0.74]), triglycerides (ß = 0.11 [0.00-0.22] mmol/L), and metabolic syndrome score (ß = 0.85 [0.20-1.49]), but not with BMI z-score or any anthropometric measurements. The consistently healthy group showed no differences in cardiometabolic outcomes compared to the mixed pattern group. CONCLUSION: Three distinct lifestyle pattern trajectories were identified from early to middle childhood. Children in the consistently unhealthy lifestyle group did not have a raised BMI but was associated with several elevated cardiometabolic risk markers. These findings suggest the potential benefits of initiating holistic lifestyle interventions to improve children's health and well-being from an early age. TRIAL REGISTRATION: Trial registration number: NCT01174875. Name of registry: ClinicalTrials.gov. URL of registry: https://classic. CLINICALTRIALS: gov/ct2/show/NCT01174875 . Date of registration: August 4, 2010. Date of enrolment of the first participant to the trial: June 2009.

Associations of cord plasma per- and polyfluoroakyl substances (PFAS) with neonatal and child body composition and adiposity: The GUSTO study.

BACKGROUND: The influence of prenatal exposure to per- and poly- fluoroalkyl substances (PFAS) on birth size and offspring adiposity is unclear, especially for the newer, shorter-chained replacement PFAS. METHODS: In the GUSTO multi-ethnic Singaporean mother-offspring cohort, 12 PFAS were measured in 783 cord plasma samples using ultra-performance-liquid chromatography-tandem-mass-spectrometer (UPLC-MS/MS). Outcomes included offspring anthropometry, other indicators of body composition/metabolic health, and MRI-derived abdominal adiposity (subset) at birth and 6 years of age. PFAS were modeled individually, in categories of long-chain and short-chain PFAS, and as scores of three principal components (PC) derived using PC analysis (PC1, PC2, and PC3 reflect predominant exposure patterns to "very-long-PFAS", "long-PFAS", and "short-PFAS", respectively). Associations with outcomes were assessed using multivariable linear regressions, adjusted for important covariates such as maternal sociodemographic and lifestyle factors. RESULTS: Overall, cord PFAS levels showed either no or positive associations (mostly for long-chain PFAS) with birth weight, length and head circumference. In general, PFAS were associated with higher neonatal abdominal adiposity, driven by shorter-chain PFAS. Perfluoroheptanoic acid (PFHpA) was associated with higher volumes of superficial subcutaneous adipose tissue (sSAT) (3.75 [1.13, 6.37] mL per SD increase in PFAS) and internal adipose tissue (IAT) (1.39 [0.41, 2.38] mL). Higher levels of perfluorobutanesulfonic acid (PFBS), short-chain PFAS, and PC3 were associated with higher IAT volume (ß range 1.22-1.41 mL/SD, all P < 0.02), especially in girls. Higher PC3 score was additionally associated with higher sSAT (3.12 [0.45, 5.80] mL) volume. At age 6 years, most observed associations did not persist. No consistent associations were observed between PFAS and whole-body adiposity measures. CONCLUSIONS: Fetal exposure to emerging short-chain PFAS was associated with higher abdominal adiposity at birth but not at age 6 years. Further research is needed to replicate the findings and to determine if these effects may reappear beyond early childhood. Population exposure to newer PFAS and consequent health impact must be monitored.

Preconception maternal retinal arteriolar narrowing and fetal growth throughout pregnancy: A prospective cohort study.

OBJECTIVE: To investigate the association between preconception maternal retinal arteriolar calibre and fetal growth. DESIGN, SETTING AND POPULATION: A hospital-based, prospective preconception cohort including 369 women with a singleton live birth. METHODS: We collected detailed information on sociodemographic status, pregnancy history and lifestyle, and performed retinal imaging at the preconception visit. MAIN OUTCOME MEASURES: We retrieved medical records documenting fetal growth biometrics (e.g., abdominal circumference [AC], head circumference [HC], femur length [FL]) at 11-13, 18-21, 24-28, and 32-34 weeks throughout pregnancy. We then computed the z scores for all fetal growth biometrics from 14 weeks of gestation where data were available, referencing the INTERGROWTH-21st fetal growth chart. We used a linear mixed model to estimate the association between maternal preconception retinal arteriolar calibre and fetal growth biometrics z scores throughout pregnancy, with random intercept accounting for repeated measures within individuals. We then performed a multivariable linear regression of maternal preconception retinal arteriolar calibre and z score changes for all fetal growth biometrics between 24-28 weeks and 32-34 weeks of gestation, after full adjustment. RESULTS: Maternal preconception generalised retinal arteriolar narrowing was consistently associated with a reduction in fetal AC z scores (-0.34; 95% CI -0.66 to -0.03) throughout pregnancy. In addition, women with preconception generalised retinal arteriolar narrowing tended to have significantly reduced z score changes in AC (-0.41; 95% CI -0.90 to -0.001) and fetal FL (-0.55; 95% CI -1.00 to -0.10) between 24-28 weeks and 32-34 weeks of gestation, respectively. CONCLUSIONS: Our findings suggest that women with narrower preconception retinal arterioles had smaller fetuses, evidenced by reductions in AC and FL z score throughout pregnancy.

Clinical practice of vitamin D screening and supplementation in pregnancy in Asia-pacific countries: A cross-sectional study.

Background: Vitamin D deficiency is common in pregnant women. There is scarce information in the Asia-Pacific region on the understanding of vitamin D screening and supplementation in pregnancy among health care professionals. Methods: We performed a cross-sectional study among health care professionals who are part of the Integrated Platform for Research in Advancing Metabolic Health outcomes of Women and Children (IPRMAHO) international study group on their understanding and perception of Vitamin D screening and supplementation in pregnancy. The cross-sectional survey comprised 4 main sections: demographics, existing policies, nutrient supplementation in pregnancy and various practices on screening, treatment and perceptions, with a total of 22 questions. A total of 15 responses were obtained from attendees from distinct health facilities across eleven participating Asia-Pacific countries. Results: Majority of the surveyed hospitals (11/15, 78.6 %) did not have a national policy or regional guideline regarding Vitamin D screening and supplementation in pregnancy. More than half of respondents were (9/14, 64.3 %) were unsure of the percentage of women seen with Vitamin D deficiencies each year and were unsure of Vitamin D dosage prescribed to pregnant women with (8/15, 53.3 %) or without (6/14, 42.9 %) Vitamin D deficiency. Vitamin D was rarely prescribed in pregnancy when compared to other nutrient supplements such as folic acid and iron. Majority of respondents (9/11, 72.7 %) indicated that their hospital did not screen for Vitamin D deficiencies in pregnancy, even amongst high risk pregnant women. Nevertheless, majority of respondents indicated a need (12/15, 80.0 %) for a guideline or consensus regarding Vitamin D screening and supplementation in pregnancy. Conclusion: While majority of the surveyed hospitals did not have a national policy or regional guideline regarding Vitamin D screening and supplementation in pregnancy, majority of respondents indicated a need for the policy or guideline. There were varying clinical knowledge gaps and different perceptions on Vitamin D screening and supplementation in pregnancy among healthcare professionals.

Perinatal Plasma Carotenoids and Vitamin E Concentrations with Glycemia and Insulin Resistance in Women during and after Pregnancy.

We examined the associations of perinatal plasma carotenoids and E vitamers concentrations with glycemia, insulin resistance, and gestational and type 2 diabetes mellitus during pregnancy and post-pregnancy in GUSTO women. Plasma carotenoid and E vitamer concentrations were measured at delivery, and principal component analysis was used to derive the patterns of their concentrations. Fasting and 2 h glucose levels and fasting insulin were measured at 26-28 weeks gestation and 4-6 years post-pregnancy, with the derivation of homeostatic model assessment for insulin resistance (HOMA-IR). In 678 women, two carotenoid patterns (CP1: α- and ß-carotene and lutein; CP2: zeaxanthin, lycopene, and ß-cryptoxanthin) and one E vitamer pattern (VE: γ-, δ-, and α-tocopherols) were derived. A higher CP1 score (1-SD) was associated with lower gestational fasting glucose (ß (95%CI): -0.06 (-0.10, -0.02) mmol/L) and lower gestational (-0.17 (-0.82, 0.01) mmol/L, p = 0.06) and post-pregnancy HOMA-IR (-0.11 (-0.15, -0.08) mmol/L). A higher VE score (1 SD) was associated with higher gestational and post-pregnancy fasting and 2 h glucose (gestational: 0.05 (0.01, 0.08) and 0.08 (0.01, 0.16); post-pregnancy: 0.19 (0.07, 0.31) and 0.24 (0.06, 0.42) mmol/L). Higher α- and ß-carotene and lutein may be beneficial for gestational fasting glycemia, but higher vitamin E may increase gestational and post-pregnancy glycemia, although these findings require confirmation in cohorts with prospective longitudinal measurements of these vitamins.

A fully convolutional neural network for comprehensive compartmentalization of abdominal adipose tissue compartments in MRI.

BACKGROUND: Existing literature has highlighted structural, physiological, and pathological disparities among abdominal adipose tissue (AAT) sub-depots. Accurate separation and quantification of these sub-depots are crucial for advancing our understanding of obesity and its comorbidities. However, the absence of clear boundaries between the sub-depots in medical imaging data has challenged their separation, particularly for internal adipose tissue (IAT) sub-depots. To date, the quantification of AAT sub-depots remains challenging, marked by a time-consuming, costly, and complex process. PURPOSE: To implement and evaluate a convolutional neural network to enable granular assessment of AAT by compartmentalization of subcutaneous adipose tissue (SAT) into superficial subcutaneous (SSAT) and deep subcutaneous (DSAT) adipose tissue, and IAT into intraperitoneal (IPAT), retroperitoneal (RPAT), and paraspinal (PSAT) adipose tissue. MATERIAL AND METHODS: MRI datasets were retrospectively collected from Singapore Preconception Study for Long-Term Maternal and Child Outcomes (S-PRESTO: 389 women aged 31.4 ± 3.9 years) and Singapore Adult Metabolism Study (SAMS: 50 men aged 28.7 ± 5.7 years). For all datasets, ground truth segmentation masks were created through manual segmentation. A Res-Net based 3D-UNet was trained and evaluated via 5-fold cross-validation on S-PRESTO data (N = 300). The model's final performance was assessed on a hold-out (N = 89) and an external test set (N = 50, SAMS). RESULTS: The proposed method enabled reliable segmentation of individual AAT sub-depots in 3D MRI volumes with high mean Dice similarity scores of 98.3%, 97.2%, 96.5%, 96.3%, and 95.9% for SSAT, DSAT, IPAT, RPAT, and PSAT respectively. CONCLUSION: Convolutional neural networks can accurately sub-divide abdominal SAT into SSAT and DSAT, and abdominal IAT into IPAT, RPAT, and PSAT with high accuracy. The presented method has the potential to significantly contribute to advancements in the field of obesity imaging and precision medicine.

Associations of predominant night-eating with plasma glycemic status and continuous glucose monitoring measures among pregnant women.

BACKGROUND & AIMS: To examine whether predominant night-eating, defined as more than 50% of total daily energy intake consumed between 1900 and 0659 h, is associated with glycemic outcomes in pregnancy. METHODS: This was a prospective cohort study of 277 healthy pregnant women with complete 4-day dietary intake records at 18-24 weeks gestation, recruited from KK Women's and Children's Hospital, Singapore. Primary outcomes were fasting, 1-h, and 2-h plasma glucose after a 75-g oral glucose tolerance test at 24-28 weeks gestation. Secondary outcomes were gestational diabetes mellitus (GDM), fasting insulin, homeostasis model assessment of insulin resistance (HOMA2-IR), ß-cell function (HOMA2-%B), and continuous glucose monitoring (CGM) measures. Glucose variables in continuous form were loge-transformed before analyses. RESULTS: Predominant night-eating (11.6%) was associated with higher fasting glucose (geometric mean ratio (95% confidence interval) 1.05 (1.01, 1.08)) and 1-h glucose (1.11 (1.01, 1.21)), but not with 2-h glucose or GDM risk. Predominant night-eating women had lower fasting insulin (0.77 (0.63, 0.95)), lower HOMA2-IR (0.78 (0.64, 0.97)), and lower HOMA2-%B (0.77 (0.67, 0.89)) than their predominant day-eating counterparts. For CGM measures, predominant night-eating was associated with higher mean glucose (1.07 (1.00, 1.15)), higher glucose management indicator (1.05 (1.00, 1.10)), and higher overall glucose levels throughout 24 h (1.10 (1.02, 1.19)). All these associations were adjusted for socio-demographic, lifestyle factors, and diet composition. CONCLUSION: Predominant night-eating was mainly associated with less desirable glycemic outcomes during pregnancy. Future studies should explore dietary interventions aimed at reducing consumption of relatively more calories at night than day during pregnancy.