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AIM The present study aimed to investigate the salivary proteome profiles of pregnant women with gingivitis (PG) or without gingivitis (HP) and non-pregnant healthy controls (HC) by employing iTRAQ-based proteomics. MATERIALS AND METHODS Saliva samples were collected from 30 Chinese women comprising 10 subjects in each of the three groups (PG, HP, and HC). The samples were subjected to iTRAQ-based proteomics analysis, and ELISA was performed to validate the results. The subsequent observations were validated in a cohort of 48 subjects. RESULTS Pathways associated with neutrophil-mediated immune response and antioxidant defence mechanism were significantly higher in PG than HC. The abundance of salivary cystatins (S, SA, and SN) and antimicrobials were significantly decreased in PG and HP, while cystatin C and D were additionally decreased in PG. Cystatin C was mapped to all the major catabolic pathways and was the most re-wired protein in pregnancy gingivitis. Further validation demonstrated cystatin C to be significantly lower in PG than HC. CONCLUSIONS While the decrease in levels of salivary cystatins and antimicrobial proteins may predispose healthy pregnant women to pregnancy gingivitis, it may cause persistence of inflammation in pregnant women with gingivitis.

Lipids play a vital role in human health and development, but changes to their circulatory levels during gestation and in early life are poorly understood. Here we present the first developmental and intergenerational landscape of the human circulatory lipidome, derived by profiling of 480 lipid species representing 25 lipid classes, in mothers and their offspring (n=2491). Levels of 66% of the profiled lipids increased in maternal circulation during gestation, while cord blood had higher concentrations of acylcarnitines and lysophospholipids. The offspring lipidome at age six years revealed striking similarities with postnatal maternal lipidome (adult) in its lipid composition and concentrations. Comparison of lipids associated with child and maternal adiposity identified a 92% overlap, implying intergenerational similarities in the lipid signatures of obesity risk. We also catalogued lipid signatures linked with maternal adiposity during gestation and offspring birthweight, and validated (>70% overlap) the findings in an independent birth-cohort (n=1935).

Background: Infants with atopic dermatitis (AD) are reported to be at higher risk of early childhood caries (ECC) at 3-years, but the clinical validity of the reported link remains unknown. We investigated if clinical severity of AD in young children is associated with increased ECC risk at 3-years. Methods: In Growing Up in Singapore Towards healthy Outcomes (GUSTO) mother-offspring cohort, AD was diagnosed by trained physicians using Hanifin and Rajka criteria at 18-month and 3-year clinic visits (n=837). Of the children diagnosed with AD, disease severity was assessed using SCORAD (SCORing Atopic Dermatitis) index and categorized into moderate-to-severe AD (SCORAD≥25), and mild AD (SCORAD

Contains fulltext : 225413.pdf (Publisher’s version ) (Closed access) Despite development of new technologies for caries control, tooth decay in primary teeth remains a major global health problem. Caries risk assessment (CRA) models for toddlers and preschoolers are rare. Among them, almost all models use dental factors (e.g., past caries experience) to predict future caries risk, with limited clinical/community applicability owing to relatively uncommon dental visits compared to frequent medical visits during the first year of life. The objective of this study was to construct and evaluate risk prediction models using information easily accessible to medical practitioners to forecast caries at 2 and 3 y of age. Data were obtained from the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) mother-offspring cohort. Caries was diagnosed using modified International Caries Detection and Assessment System criteria. Risk prediction models were constructed using multivariable logistic regression coupled with receiver operating characteristic analyses. Imputation was performed using multiple imputation by chained equations to assess effect of missing data. Caries rates at ages 2 y (n = 535) and 3 y (n = 721) were 17.8% and 42.9%, respectively. Risk prediction models predicting overall caries risk at 2 and 3 y demonstrated area under the curve (AUC) (95% confidence interval) of 0.81 (0.75-0.87) and 0.79 (0.74-0.84), respectively, while those predicting moderate to extensive lesions showed 0.91 (0.85-0.97) and 0.79 (0.73-0.85), respectively. Postimputation results showed reduced AUC of 0.75 (0.74-0.81) and 0.71 (0.67-0.75) at years 2 and 3, respectively, for overall caries risk, while AUC was 0.84 (0.76-0.92) and 0.75 (0.70-0.80), respectively, for moderate to extensive caries. Addition of anterior caries significantly increased AUC in all year 3 models with or without imputation (all P < 0.05). Significant predictors/protectors were identified, including ethnicity, prenatal tobacco smoke exposure, history of allergies before 12 mo, history of chronic maternal illness, maternal brushing frequency, childbearing age, and so on. Integrating oral-general health care using medical CRA models may be promising in screening caries-susceptible infants/toddlers, especially when medical professionals are trained to "lift the lip" to identify anterior caries lesions.

Supplemental material, DS_10.1177_0022034520913476 for Caries Risk Prediction Models in a Medical Health Care Setting by T.A. Kalhan, C. Un Lam, B. Karunakaran, P.L. Chay, C.K. Chng, R. Nair, Y.S. Lee, M.C.F. Fong, Y.S. Chong, K. Kwek, S.M. Saw, L. Shek, F. Yap, K.H. Tan, K.M. Godfrey, J. Huang and C.-Y.S. Hsu in Journal of Dental Research

Supplemental material, DS_10.1177_2380084420948779 for Subgingival Microbiota during Healthy Pregnancy and Pregnancy Gingivitis by P. Balan, B.W. Brandt, Y.S. Chong, W. Crielaard, M.L. Wong, V. Lopez, H.G. He and C.J. Seneviratne in JDR Clinical & Translational Research

The amygdala and hippocampus undergo rapid development in early life. The relative contribution of genetic and environmental factors to the establishment of their developmental trajectories has yet to be examined. We performed imaging on neonates and examined how the observed variation in volume and microstructure of the amygdala and hippocampus varied by genotype, and compared with prenatal maternal mental health and socioeconomic status. Gene × Environment models outcompeted models containing genotype or environment only to best explain the majority of measures but some, especially of the amygdaloid microstructure, were best explained by genotype only. Models including DNA methylation measured in the neonate umbilical cords outcompeted the Gene and Gene × Environment models for the majority of amygdaloid measures and minority of hippocampal measures. This study identified brain region-specific gene networks associated with individual differences in fetal brain development. In particular, genetic and epigenetic variation within CUX1 was highlighted. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) National Medical Research Council (NMRC) National Medical Research Council, Grant/Award Numbers: NMRC/TCR/004-NUS/2008,NMRC/TCR/012-NUHS/2014; NUS Instituteof Data Science, Singapore; Singapore Ministryof Education; Agency for Science Technologyand Research (ASTAR); Singapore Institute forClinical Sciences; Singapore National ResearchFoundation

In Singapore, the obesity prevalence is disproportionately higher in the Asian-Indians and Malays than the Chinese. Lower resting energy expenditure (REE) may be a contributory factor.We explored the association between ethnicity and REE in Chinese, Asian-Indian and Malay men living in Singapore and determined the influence of body composition, mass/volume of high metabolic rate organs, represented by brain volume and trunk fat-free mass (FFM), and physical activity on ethnic differences.Two hundred and forty-four men from Singapore (n=100 Chinese, 70 Asian-Indians and 74 Malays), aged 21-40 years and body mass index of 18.5-30.0 kg m(-2), were recruited in this cross-sectional study. REE was assessed by indirect calorimetry and body composition by dual-energy X-ray absorptiometry. Brain volume was measured by magnetic resonance imaging. Physical activity was assessed by the Singapore Prospective Study Program Physical Activity Questionnaire.REE was significantly lower in Asian-Indians compared with that in Chinese after adjusting for body weight. FFM (total, trunk and limb) and total fat mass were important predictors of REE across all ethnic groups. Brain volume was positively associated with REE only in Malays. Moderate and vigorous physical activity was positively associated with REE only in Asian-Indians and Malays. The difference in REE between Asian-Indians and Chinese was attenuated but remained statistically significant after adjustment for total FFM (59±20 kcal per day), fat mass (67±20 kcal per day) and brain volume (54±22 kcal per day). The association between REE and ethnicity was no longer statistically significant after total FFM was replaced by trunk FFM (which includes heart, liver, kidney and spleen) but not when it was replaced by limb FFM (skeletal muscle).We have demonstrated a lower REE in Asian-Indians compared with Chinese who may contribute to the higher rates of obesity in the former. This difference could be accounted for by differences in metabolically active organs.

Study question Are higher overall and central adiposity associated with reduced fecundability, measured by time-to-pregnancy (TTP), in Asian women? Summary answer Higher overall adiposity, but not central adiposity, was associated with longer TTP in Asian women. What is known already High body mass index (BMI) has been associated with a longer TTP, although the associations of body composition and distribution with TTP are less clear. There are no previous studies of TTP in Asian women, who have a relatively higher percentage of body fat and abdominal fat at relatively lower BMI. Study design, size, duration Prospective preconception cohort using data from 477 Asian (Chinese, Malay and Indian) women who were planning to conceive and enrolled in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) study, 2015-2017. Participants/materials, setting, methods Women's mean age was 30.7 years. Overall adiposity was assessed by BMI, sum of 4-site skinfold thicknesses (SFT) and total body fat percentage (TBF%, measured using air displacement plethysmography); central adiposity was assessed by waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and A body Shape Index (ABSI). Pregnancy occurring within one year from recruitment was ascertained by ultrasonography. Those who did not conceive within one year of recruitment, were lost to follow-up, or initiated fertility treatment were censored. TTP was measured in cycles. Discrete-time proportional hazards models were used to estimate the fecundability ratio (FR) and 95% confidence interval (CI) for each anthropometric measure in association with fecundability, adjusting for confounders. Main results and the role of chance Compared to women with a normal BMI of 18.5-22.9 kg/m2, women with higher BMI of 23-27.4 and ≥27.5 kg/m2 showed lower FR of 0.66 (95% CI 0.45, 0.97) and 0.53 (0.31, 0.89), respectively. Compared to women in the lowest quartile of SFT (25-52.9 mm), those in the highest quartile of ≥90.1 mm showed lower FR of 0.58 (95% CI 0.36, 0.95). Compared to women in the lowest quartile of TBF% (13.6-27.2%), those in the upper two quartiles of 33.0-39.7% and ≥39.8% showed lower FR of 0.56 (95% CI 0.32, 0.98) and 0.43 (0.24, 0.80), respectively. Association of high BMI with reduced fecundability was particularly evident among nulliparous women. Measures of central adiposity (WC, WHR, WHtR, ABSI) were not associated with fecundability. Limitations reasons for caution Small sample size could restrict power of analysis.The analysis was confined to planned pregnancies, which could limit generalizability of findings to non-planned pregnancies, estimated at around 44% in Singapore. Information on the date of last menstrual period for each month was not available, hence the accuracy of self-reported menstrual cycle length could not be validated, potentially introducing error into TTP estimation. Measures of exposures and covariates such as cycle length were not performed repeatedly over time; cycle length might have changed during the period before getting pregnant. Wider implications of the findings Other than using BMI as the surrogate measure of body fat, we provide additional evidence showing that higher amounts of subcutaneous fat that based on the measure of SFT at the sites of biceps, triceps, suprailiac and subscapular, and TBF% are associated with longer TTP. Achieving optimal weight and reducing total percentage body fat may be a potential intervention target to improve female fertility. The null results observed between central adiposity and TTP requires confirmation in further studies. Study funding/competing interest(s) This research is supported by Singapore National Research Foundation under its Translational and Clinical Research Flagship Programme and administered by the Singapore Ministry of Health's National Medical Research Council, (NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014). Additional funding is provided by the Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore. Y.S.C., K.M.G., F.Y. and Y.S.L. have received reimbursement to speak at conferences sponsored by companies selling nutritional products. Y.S.C., K.M.G. and S.Y.C. are part of an academic consortium that has received research funding from Abbott, Nutrition, Nestle and Danone. Other authors declared no conflicts of interest. Trial registration number N/A.

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/length2 (body mass index, BMI), weight/length3 (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 (rp), including in subsamples stratified by sex and ethnicity. Results Study neonates (n =251) had a mean (SD) age of 10.2 (2.5) days. Correlations between ADP-based fat mass (ADPFM) and anthropometric measures were moderate (rp range: 0.44-0.67), with the strongest being with weight/length, weight, BMI and sum of skinfolds (rp =0.67, 0.66, 0.62, 0.62, respectively, all P

Many studies have identified early-life risk factors for subsequent childhood overweight/obesity, but few have evaluated how they combine to influence risk of childhood overweight/obesity. We examined associations, individually and in combination, of potentially modifiable risk factors in the first 1000 days after conception with childhood adiposity and risk of overweight/obesity in an Asian cohort. Six risk factors were examined: maternal pre-pregnancy overweight/obesity (body mass index (BMI) ⩾25 kg m−2), paternal overweight/obesity at 24 months post delivery, maternal excessive gestational weight gain, raised maternal fasting glucose during pregnancy (⩾5.1 mmol l−1), breastfeeding duration

There have been hypotheses that early life adiposity gain may influence blood pressure (BP) later in life. We examined associations between timing of height, body mass index (BMI) and adiposity gains in early life with BP at 48 months in an Asian pregnancy-birth cohort.In 719 children, velocities for height, BMI and abdominal circumference (AC) were calculated at five intervals [0-3, 3-12, 12-24, 24-36 and 36-48 months]. Triceps (TS) and subscapular skinfold (SS) velocities were calculated between 0-18, 18-36 and 36-48 months. Systolic (SBP) and diastolic blood pressure (DBP) was measured at 48 months. Growth velocities at later periods were adjusted for growth velocities in preceding intervals, as well as measurements at birth.After adjusting for confounders and child height at BP measurement, each unit z-score gain in BMI, AC, TS and SS velocities at 36-48 months were associated with 2.3 (95% CI:1.6, 3.1), 2.1 (1.3, 2.8), 1.4 (0.6, 2.2) and 1.8 (1, 2.6) mmHg higher SBP respectively, and 0.9 (0.4, 1.4), 0.9 (0.4, 1.3), 0.6 (0.1, 1.1) and 0.8 (0.3, 1.3) mmHg higher DBP respectively. BMI and adiposity velocities (AC, TS or SS) at various intervals in the first 36 months however, were not associated with BP. Faster BMI, AC, TS and SS velocities, but not height, at 36-48 months were associated with 0.22 (0.15, 0.29), 0.17 (0.10, 0.24), 0.11 (0.04, 0.19) and 0.15 (0.08, 0.23) units higher SBP z-score respectively, and OR=1.46 (95% CI: 1.13-1.90), 1.49 (1.17-1.92), 1.45 (1.09-1.92) and 1.43 (1.09, 1.88) times higher risk of prehypertension/hypertension respectively at 48 months.Our results indicated that faster BMI and adiposity (AC, TS or SS) velocities only at the preceding interval before 48 months (36-48 months), but not at earlier intervals in the first 36 months, are predictive of BP and prehypertension/hypertension at 48 months.

Background There is growing research evidence that subclinical autistic traits are elevated in relatives of individuals with autism spectrum disorder (ASD), continuously distributed in the general population and likely to share common etiology with ASD. A number of measures have been developed to assess autistic traits quantitatively in unselected samples. So far, the Quantitative-Checklist for Autism in Toddlers (Q-CHAT) is one of very few measures developed for use with toddlers as young as 18 months, but little is known about its measurement properties and factor structure. Methods The present study examined internal consistency, factor structure, test-retest stability, and convergent validity of the Q-CHAT in a sample of toddlers in Singapore whose caregivers completed the Q-CHAT at 18 (n = 368) and 24 months (n = 396). Results Three factors were derived accounting for 38.1 % of the variance: social/communication traits, non-social/behavioral traits, and a speech/language factor. Internal consistency was suboptimal for the total and speech/language scores, but acceptable for the social/communication and non-social/behavioral factor scores. Scores were generally stable between 18 and 24 months. Convergent validity was found with the Pervasive Developmental Disorders subscale of the Child Behavior Checklist (CBCL) completed by caregivers when their children were 24 months. Q-CHAT total scores in this sample were higher than those reported in other unselected samples from the UK. Conclusions The Q-CHAT was found to have a three-factor structure, acceptable internal consistency for its two main factor scores (social/communication and non-social/behavioral), normally distributed scores in an unselected sample, and similar structure and measurement properties as those reported in other published studies. Findings are discussed in relation to existing literature and future directions for the validation of the Q-CHAT.

Obesity and osteoporosis are two global health problems with pronounced morbidity and mortality. While body weight appears to mitigate the development of osteoporosis, whether excess body fat promotes or protects against osteoporosis remains a conundrum. The effect of ethnicity on these associations has also been understudied. We hypothesize that (1) fat mass (FM) and lean mass (LM) are independently associated with bone mineral density (BMD) and that (2) ethnic differences exist in the association of FM and LM with BMD among Chinese, Malay and Indian subjects.

Introduction Studies have shown that mental health problems during pregnancy have adverse effects on fetal growth. The impact of depressive and anxiety symptoms during pregnancy on the fetus have not yet been examined in Singapore. Objectives To examine the association between mental health problems during the second trimester of pregnancy on the quality of the pregnancy, reflected by birth weight and birth length of the newborn. Aims This study aims to understand the importance of mental health during pregnancy on the development of the child in an Asian population. Methods Preliminary data of a prospective cohort study of pregnant women (GUSTO), were followed from pregnancy onwards. At 26 weeks of the pregnancy, the Edinburgh Postnatal Depression Scale (EPDS), the Beck Depression Inventory (BDI) and the State Trait Anxiety Inventory (STAI) were administered. Data on birth parameters were collected from medical records. Results Linear regression analyses of preliminary data show negative correlations between depressive symptoms measured with EPDS (n = 1025, P = 0.54), BDI (n = 1012, P = 0.001), and anxiety symptoms measured with STAI (n = 1023, P = 0.002) and birth length (corrected for gestational age and gender). No associations were found for birth weight. Conclusions There is an association between depressive and anxiety symptoms reported at the end of the second trimester of the pregnancy and birth length, but not birth weight, of the newborn. As it is known that fetal length increases mainly in the second trimester, it suggests that stress of the mother influences the development of the fetus during this trimester.

Rationale Data on symptom prevalence of common childhood allergies in early life is scant although their onset can occur in early childhood. Data for Singapore's pediatric population is obtained for the first time. Methods 1026 children took part in this cross-sectional allergy survey. Median age is 21 months (range:18.5 to 23 months old). Eczema was described as an ‘itchy rash that persisted or recurred' with an optional flexural distribution. ‘Current' symptoms imply occurrence in past 12 months. Results Cumulative prevalence of eczema (i.e. a persistent/recurrent rash) and wheeze in the second year of life are 22.7% (227/1000) and 23.2% (235/1014) respectively, this is in contrast to the low 8.4% (86/1005) reported for current rhinoconjunctivitis. The majority of subjects (86.4%, n=192/222) who reported eczema also reported current flexural distribution characteristic of atopic dermatitis; yet only 35.6% (78/219) reported doctor-diagnosed eczema. Neither sex is at higher risk of reporting eczema (p>0.05). Factors which increase the risk of eczema include ethnic Chinese (OR1.4, 95% CI:1.0-2.0); tertiary-educated mothers (OR1.7, 95%CL:1.3-2.3); dog-keeping during mother's pregnancy with child (OR2.0, 95% CI:1.2-3.4), family history of allergy (OR1.9, 95%CI:1.4-2.5); and comorbid allergy symptoms such as wheeze (OR1.5, 95% CI:1.1-2.1) and rhinoconjunctivitis (OR2.1, 95% CI:1.3-3.4). Conclusions More than one in five children develop eczema (i.e. persistent/recurrent rash) by the second year of life. While the majority exhibited the classic flexural pattern seen in atopic dermatitis, nearly two-thirds were undiagnosed. Chronic rash in early life also shows association with comorbid allergy symptoms and with dog-keeping during pregnancy.

Solid particles of uniform size and shape were used to study the effect of particle shape on hindered settling in creeping flow ( Re o s 0.2), where fluid flow patterns are independent of Reynolds number and the effect of shape is most prominent. The particles of different shape studied were spherical glass beads, cubical sodium chloride crystals and ABS plastic pellets, brick-like sugar crystals, and angular (imperfect octahedral) mineral silicate crystals. The liquids used were aqueous polyethylene glycol solutions and various blends of hydrocarbon oils. Two particle sizes on the average were investigated for each particle shape, and five settling column diameters were employed, so that the overall range of column-to-particle diameter ratio covered was 22 – 226. A Richardson—Zaki type equation of the form u = u i ϵ n was found to correlate the constant settling rate data for each particle size and shape over the voidage range ϵ = 0.65 – 0.9. However, the wall effect on hindered settling rate was found in most cases to be considerably smaller than that predicted by Richardson and Zaki. The term u i , obtained by linearly extrapolating the settling velocity u (below ϵ = 0.9) to ϵ = 1 on a log—log plot of u versus ϵ, was found to be measurably lower than the corresponding free settling velocity. The index n varied from an average value of 4.8 for the smooth spheres to 5.4 for the cubes to 5.8 for both the brick-like and the angular particles. These values graphically display a definite trend with settled bed voidage, ϵ b , which is shape-dependent and easily measured, and may therefore be a convenient parameter for taking account of shape variation generally. The method proposed by Beranek and Klumpar for correlating fluidization data on different shaped particles, which depends on ϵ b , was found to be moderately successful in correlating the present settling data for different shapes.