Brain charts for the human lifespan.

Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data ( http://www.brainchart.io/ ). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.

Associations of physical activity levels and screen time with oral glucose tolerance test profiles in Singaporean women of reproductive age actively trying to conceive: the S-PRESTO study.

AIM: To examine the associations of physical activity and screen time, a proxy for sedentary behaviour, with fasting and post-load glucose levels in Singaporean women enrolled in a multi-ethnic Asian preconception study. METHODS: Moderate and vigorous physical activity and screen time (television and other electronic devices) were self-reported by women enrolled in the S-PRESTO cohort. Fasting, 30-min and 120-min glucose levels before and during a 75-g oral glucose tolerance test were measured. Associations of physical activity and screen time with glucose levels were analysed using multivariable linear marginal regression. RESULTS: A total of 946 women aged 31.4±3.7 years were examined, of whom 72% were of Chinese, 15.5% were of Malay, 9.3% were of Indian and 3.2% were of mixed ethnicity. A total of 32% of women reported being active, 36% watched television ≥2 h/day and 26% used electronic devices ≥3 h/day. In adjusted models, vigorous, but not moderate, physical activity was associated with lower overall glucose levels, and was associated more strongly with post-challenge than fasting glucose levels. Compared to women not engaging in vigorous physical activity, those engaging in physical activity ≥75 min/week had lower mean fasting [-0.14 (95% CI -0.28, -0.01) mmol/l], 30-min [0.35 (95% CI -0.68, -0.02) mmol/l] and 120-min [-0.53 (95% CI -0.16, -0.90) mmol/l] glucose levels (overall P value=0.05). We found no associations of screen time with glucose levels. CONCLUSIONS: Independently of the time spent in non-vigorous physical activity and using screens, engaging in vigorous physical activity may be a modifiable factor to improve glucose regulation in women of Asian ethnicity who are attempting to conceive.

Modifiable risk factors in the first 1000 days for subsequent risk of childhood overweight in an Asian cohort: significance of parental overweight status.

BACKGROUND/OBJECTIVE: 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. METHODS: 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 <4 months and early introduction of solid foods (<4 months). Associations between number of risk factors and adiposity measures (BMI, waist-to-height ratio (WHtR), sum of skinfolds (SSFs), fat mass index (FMI) and overweight/obesity) at 48 months were assessed using multivariable regression models. RESULTS: Of 858 children followed up at 48 months, 172 (19%) had none, 274 (32%) had 1, 244 (29%) had 2, 126 (15%) had 3 and 42 (5%) had ⩾4 risk factors. Adjusting for confounders, significant graded positive associations were observed between number of risk factors and adiposity outcomes at 48 months. Compared with children with no risk factors, those with four or more risk factors had s.d. unit increases of 0.78 (95% confidence interval 0.41-1.15) for BMI, 0.79 (0.41-1.16) for WHtR, 0.46 (0.06-0.83) for SSF and 0.67 (0.07-1.27) for FMI. The adjusted relative risk of overweight/obesity in children with four or more risk factors was 11.1(2.5-49.1) compared with children with no risk factors. Children exposed to maternal pre-pregnancy (11.8(9.8-13.8)%) or paternal overweight status (10.6(9.6-11.6)%) had the largest individual predicted probability of child overweight/obesity. CONCLUSIONS: Early-life risk factors added cumulatively to increase childhood adiposity and risk of overweight/obesity. Early-life and preconception intervention programmes may be more effective in preventing overweight/obesity if they concurrently address these multiple modifiable risk factors.

Which anthropometric measures best reflect neonatal adiposity?

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/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 (s.d.) 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<0.01). All anthropometric measures except skinfold thicknesses correlated more strongly with ADP-based fat-free mass than ADPFM, 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 (rp⩾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 ADPFM 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.

Female adiposity and time-to-pregnancy: a multiethnic prospective cohort.

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.

Postnatal height and adiposity gain, childhood blood pressure and prehypertension risk in an Asian birth cohort.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Maternal hyperglycemia in singleton pregnancies conceived by IVF may be modified by first-trimester BMI.

STUDY QUESTION: Does IVF independently increase the risk of gestational diabetes mellitus (GDM) and is this increase in risk modified by maternal body mass index? SUMMARY ANSWER: IVF appears to be an independent risk factor for GDM and elevated blood glucose levels in overweight women (BMI > 25 kg/m2). WHAT IS KNOWN ALREADY: IVF has been associated with increased risk of GDM, but most previous studies did not adequately assess confounding or effect modification by other risk factors. STUDY DESIGN, SIZE, DURATION: Cross-sectional study using data from 1089 women with singleton pregnancies who participated in a Singaporean birth cohort study (GUSTO) and received a 75 g oral glucose tolerance test (OGTT) at 26-28 weeks gestation. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 1089 women (n = 1013 conceived spontaneously, n = 76 conceived through IVF) with singleton pregnancies received a 75 g OGTT at 26-28 weeks gestation. Fasting and 2 h postprandial blood glucose levels were assayed. World Health Organization criteria (1999) standard criteria were used to classify GDM: ≥7.0 mmol/L for fasting and/or ≥7.8 mmol/L for 2-h postprandial plasma glucose levels, which was the clinical guideline in use during the study. MAIN RESULTS AND THE ROLE OF CHANCE: IVF pregnancies had nearly double the odds of GDM (OR = 1.83, 95% CI: 1.03-3.26) and elevated fasting (mean difference = 0.12 mmol/L, 95% CI: 0.00-0.24) and OGTT 2-h blood glucose levels (mean difference = 0.64 mmol/L, 95% CI: 0.27-1.01), after adjusting for commonly recognized risk factors for GDM. After stratification by first-trimester BMI, these increased risks of GDM (OR = 3.54, 95% CI: 1.44-8.72) and elevated fasting (mean difference = 0.39 mmol/L, 95% CI: 0.13-0.65) and 2-h blood (mean difference = 1.24 mmol/L, 95% CI: 0.56-1.91) glucose levels were significant only in the IVF group who is also overweight or obese (BMI > 25 kg/m2). LIMITATIONS REASONS FOR CAUTION: One limitation of our study is the absence of a 1 h post-OGTT plasma glucose sample, as we were using the 1999 WHO diagnostic criteria (the clinical guideline in Singapore) at the time of our study, instead of the revised 2013 WHO diagnostic criteria. Our cohort may not be representative of the general Singapore obstetric population, although participants were recruited from the two largest maternity hospitals in the country and include both private and subsidized patients. WIDER IMPLICATIONS OF THE FINDINGS: IVF appears to be an independent risk factor for GDM and elevated blood glucose levels in overweight women. Our findings reinforce the need to advise overweight or obese women contemplating IVF to lose weight before the procedure to reduce their risk of GDM and hyperglycemia-related adverse outcomes arising therefrom. In settings where universal GDM screening is not routine, overweight or obese women who conceive by IVF should be screened. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Program and administered by the Singapore Ministry of Health's National Medical Research Council (NMRC), Singapore (NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014). Additional funding was provided by the Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR). K.M.G. and Y.S.C. have received lecture fees from Nestle Nutrition Institute and Danone, respectively. K.M.G., Y.S.C. and S.Y.C. are part of an academic consortium that has received research funding from Abbott Nutrition, Nestec and Danone. The other authors have nothing to disclose. The other authors have nothing to disclose. TRIAL REGISTRATION NUMBER: N/A.

Identification of Caries Risk Determinants in Toddlers: Results of the GUSTO Birth Cohort Study.

The aim of this study was to identify risk determinants leading to early childhood caries (ECC) and visible plaque (VP) in toddlers. Data for mother-child pairs participating in the Growing Up in Singapore towards Healthy Outcomes (GUSTO) birth cohort were collected from pregnancy to toddlerhood. Oral examinations were performed in 543 children during their clinic visit at 24 months to detect ECC and VP. Following logistic regression, ECC and VP were jointly regressed as primary and secondary outcomes, respectively, using the bivariate probit model. The ECC prevalence was 17.8% at 2 years of age, with 7.3% of children having a VP score >1. ECC was associated with nighttime breastfeeding (3 weeks) and biological factors, including Indian ethnicity (lower ECC rate), higher maternal childbearing age and existing health conditions, maternal plasma folate <6 ng/mL, child BMI, and the plaque index, while VP was associated with psychobehavioral factors, including the frequency of dental visits, brushing frequency, lower parental perceived importance of baby teeth, and weaning onto solids. Interestingly, although a higher frequency of dental visits and toothbrushing were associated with lower plaque accumulation, they were associated with increased ECC risk, suggesting that these established caries-risk factors may be a consequence rather than the cause of ECC. In conclusion, Indian toddlers may be less susceptible to ECC, compared to Chinese and Malay toddlers. The study also highlights a problem-driven utilization pattern of dental services (care sought for treatment) in Singapore, in contrast to the prevention-driven approach (care sought to prevent disease) in Western countries.

Smaller size of high metabolic rate organs explains lower resting energy expenditure in Asian-Indian Than Chinese men.

BACKGROUND: 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. OBJECTIVE: 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. DESIGN: 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. RESULTS: 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). CONCLUSIONS: 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.

Tobacco smoke exposure and respiratory morbidity in young children.

OBJECTIVE: Secondhand smoke exposure is a potentially preventable cause of significant respiratory morbidity in young children. Our study aimed to quantify respiratory morbidity in young children exposed to secondhand smoke to identify potentially modifiable factors. MATERIALS AND METHODS: This study was embedded in a prospective birth cohort study of pregnant women and their children from fetal life onwards in Singapore (Growing Up in Singapore Towards healthy Outcomes, or GUSTO). Data on prenatal, antenatal and postnatal active and secondhand tobacco smoke exposure were obtained by an investigator-administered questionnaire for the periods before pregnancy, at 26-28 weeks' gestation and 24 months after delivery. Data on respiratory morbidity (wheezing episodes, croupy cough, nebuliser use, snoring) and other morbidity (fever, hospitalisation, ear infection) of the child was collected at week 3 and at months 3, 6, 9, 12, 15, 18 and 24 after delivery. Information on parental atopy and potential confounders such as socioeconomic status and maternal educational level were also obtained. Statistical analysis of the data was performed to quantify any significant differences in incidence of respiratory morbidity in children exposed to tobacco smoke in utero and postdelivery, compared with those in smoke-free environments. RESULTS: Women who smoked regularly prior to pregnancy comprised 12.5% (n=155) of the study population; this number fell to 2.3% (n=29) during pregnancy. Mothers exposed to secondhand smoke in the household before pregnancy comprised 35.7% of the study population (n=441) and 31.5% (n=389) were exposed during pregnancy. Postnatally, the prevalence of secondhand tobacco smoke exposure from birth to 2 years of age was 29% (n=359). Participants of Malay ethnicity (p<0.001), mothers with no or primary level education (p<0.001) and mothers with low socioeconomic status (p<0.001) had the highest exposure to tobacco smoke. Offspring secondhand smoke exposure at home by 12 months and by 24 months of age was associated with an increase in hospital admissions due to respiratory disease (RR 1.89, 95% CI 1.02 to 3.50, p=0.04 by 12 months and RR 1.64, 95% CI 1.05 to 2.55, p=0.03 by 24 months) as well as all-cause hospitalisation (RR 1.57, 95% CI 1.14 to 2.17, p=0.01 by 12 months and RR 1.49, 95% CI 1.17 to 1.90, p=0.001 by 24 months), adjusting for parental atopy and child atopic dermatitis. Participants exposed to secondhand smoke by 12 months postdelivery had a significantly increased risk of having at least one wheezing episode (RR 1.71, 95% CI 1.38 to 2.11, p<0.001). CONCLUSIONS: Secondhand smoke exposure during the prenatal and postnatal periods is associated with increased respiratory morbidity in children. Opportunistic screening and targeted smoking cessation counselling for parents at child hospital admissions and well-child outpatient visits, as well as preconception smoking cessation counselling for future pregnancies, may be beneficial to protect the child from negative health impacts.

Differentiating mass-forming intrahepatic cholangiocarcinoma from atypical hepatocellular carcinoma using gadoxetic acid-enhanced MRI.

AIM: To examine the differential features of mass-forming intrahepatic cholangiocarcinoma (ICC) from atypical hypovascular hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced magnetic resonance imaging (MRI). MATERIALS AND METHODS: The institutional review board approved this retrospective study and waived informed patient consent. Seventy patients with pathologically proven ICCs (35) and hypovascular atypical HCCs (35) who had undergone preoperative gadoxetic acid-enhanced MRI were enrolled in this study. Images were analysed for the shape of the lesions and presence of hyperintensity on the T1-weighted image (T1WI) and hypo- or hyperintense areas on the T2-weighted image (T2WI). In addition, images were analysed for the presence of linear hyperintensity or multifocal, tiny, hyperintense foci on T2WI and the presence of rim enhancement during early dynamic phases and a central enhancement with a hypointense rim (target appearance) on the 10 and 20 min hepatobiliary phase images. The significance of these findings was determined by the X(2) test. RESULTS: Univariate analysis revealed that the following significant parameters favour ICC or hypovascular HCC; the presence of T2 hypo- and hyperintense areas and target appearance on the 10 min hepatobiliary phase images favour ICC, and the presence of T2 linear hyperintensity and T2 multifocal hyperintense foci favour hypovascular HCC (p < 0.05). Multivariate analysis revealed that only target appearance on the 10 min hepatobiliary phase was predictive of ICC (p = 0.002) as 30 ICCs (85.7%) showed this feature. However, the target appearance was also observed in all six scirrhous HCCs. CONCLUSION: A target appearance on the 10 min hepatobiliary phase images is the best predictor for identifying mass-forming ICC at gadoxetic acid-enhanced MRI.

Subgingival Microbiota during Healthy Pregnancy and Pregnancy Gingivitis.

INTRODUCTION: Previous studies have largely explored the microbial composition and pathogenesis of pregnancy gingivitis. However, the patterns of microbial colonization during pregnancy in the absence of pregnancy gingivitis have rarely been studied. Characterization of the oral microbiome in pregnant women with healthy gingiva is an important initial step in understanding the role of the microbiome in progression to pregnancy gingivitis. OBJECTIVES: In this study, we compared the oral microbiome of pregnant women without gingivitis (healthy pregnancy) with pregnant women having gingivitis and nonpregnant healthy women to understand how pregnancy modifies the oral microbiome and induces progression to pregnancy gingivitis. METHODS: Subgingival plaque samples were collected from Chinese pregnant women with gingivitis (n = 10), healthy pregnant women (n = 10), and nonpregnant healthy women (n = 10). The Illumina MiSeq platform was used to perform 16S rRNA gene sequencing targeting the V4 region. RESULTS: The alpha and beta diversity was significantly different between pregnant and nonpregnant women, but minimal differences were observed between pregnant women with and without gingivitis. Interestingly, the oral bacterial community showed higher abundance of pathogenic taxa during healthy pregnancy as compared with nonpregnant women despite similar gingival and plaque index scores. However, when compared with overt pregnancy gingivitis, pathogenic taxa were less abundant during healthy pregnancy. PICRUSt analysis (phylogenetic investigation of communities by reconstruction of unobserved states) also suggested no difference in the functional capabilities of the microbiome during pregnancy, irrespective of gingival disease status. However, metabolic pathways related to amino acid metabolism were significantly increased in healthy pregnant women as compared with nonpregnant women. CONCLUSION: The presence of pathogenic taxa in healthy pregnancy and pregnancy gingivitis suggests that bacteria may be necessary for initiating disease development but progression to gingivitis may be influenced by the host environmental factors. More efforts are required to plan interventions aimed at sustaining health before the appearance of overt gingivitis. KNOWLEDGE TRANSFER STATEMENT: The results of this study draw attention to the importance of oral health maintenance during pregnancy, as women without any prenatal oral conditions are predisposed to the risk of developing pregnancy gingivitis. Hence, it is important to incorporate comprehensive assessment of oral health in the prenatal health care schedules. Pregnant woman should be screened for oral risks, counseled on proper oral hygiene and expected oral changes, and referred for dental treatment, when necessary.

Income disparity in school readiness and the mediating role of perinatal maternal mental health: a longitudinal birth cohort study.

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.

A randomised controlled trial of low-dose misoprostol and dinoprostone vaginal pessaries for cervical priming.

OBJECTIVE: We studied the efficacy of 25-microg misoprostol pessaries as either single or double dose compared with a 3-mg dinoprostone pessary for cervical priming. DESIGN AND SETTING: A randomised controlled trial in Singapore. POPULATION: One hundred and seventy-one women with term pregnancies and modified Bishop scores (mBS) < or =6 from 2003 to 2004. METHOD: Patients were randomised to single misoprostol dose, double misoprostol dose or the current dinoprostone regimen. MAIN OUTCOME MEASURES: Primary outcome was number of women who achieved favourable mBS >6 or active labour by day 2. Secondary outcomes were time interval from insertion to delivery, cardiotocographic abnormalities, delivery and neonatal outcome. RESULTS: More women in the misoprostol double-dose group (96.6%) and dinoprostone group (93%) achieved the primary outcome compared with the single-dose group (77.8%) (P = 0.003 and P = 0.03, respectively). There was no difference in secondary outcomes. More multiparous women achieve primary outcome compared with nulliparous women (odds ratio 0.21, 95% confidence interval 0.06-0.77). CONCLUSION: Double-dose misoprostol 25 microg is as effective as dinoprostone 3 mg inserts for cervical priming; both are more efficacious than a single-dose misoprostol pessary. Parity prognosticates the success of induction.

Caries Risk Prediction Models in a Medical Health Care Setting.

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.

Probiotic supplementation in the first 6 months of life in at risk Asian infants--effects on eczema and atopic sensitization at the age of 1 year.

BACKGROUND: The role of probiotics in allergy prevention remains uncertain but has been shown in some studies to have a possible protective effect on eczema. OBJECTIVE: We aimed to assess the effect of probiotic supplementation in the first 6 months of life on eczema and allergic sensitization at 1 year of age in Asian infants at risk of allergic disease. METHODS: A double-blind, placebo-controlled randomized clinical trial involving 253 infants with a family history of allergic disease was carried out. Infants received at least 60 mL of commercially available cow's milk formula with or without probiotic supplementation [Bifidobacterium longum (BL999) 1 x 10(7) colony forming unit (CFU)/g and Lactobacillus rhamnosus (LPR) 2 x 10(7) CFU/g] daily for the first 6 months. Clinical evaluation was performed at 1, 3, 6 and 12 months of age, with serum total IgE measurement and skin prick tests conducted at the 12-month visit. The primary and secondary end-points were eczema and allergen sensitization, respectively. RESULTS: The incidence of eczema in the probiotic (22%) group was similar to that in the placebo group (25%) (P=0.53). The median Scoring Atopic Dermatitis score at 12 months was 17.10 (9.74) in the probiotic group and 11.60 (8.40) in the placebo group (P=0.17). The prevalence of allergen sensitization showed no difference (probiotic=24% vs. placebo=19%, P=0.26). The total IgE geometric mean (95% confidence interval) was 18.76 (12.54-24.98) kU/L in the probiotic group and 23.13 (16.01-30.24) kU/L in the placebo group (P=0.15). Atopic eczema (with sensitization) in the probiotic (7.3%) group was comparable to the placebo group (5.8%) (P=0.86). CONCLUSION: Early life administration of a cow's milk formula supplemented with probiotics showed no effect on prevention of eczema or allergen sensitization in the first year of life in Asian infants at risk of allergic disease. Further work is needed to determine whether timing of supplementation, dose and probiotic strain are important considerations.

Carbetocin versus syntometrine for the third stage of labour following vaginal delivery--a double-blind randomised controlled trial.

OBJECTIVE: Prevention of postpartum haemorrhage is essential in the pursuit of improved health care for women. However, limited literature is available for comparing the use of oxytocin agonist carbetocin with syntometrine in women undergoing vaginal deliveries. We aimed to compare intramuscular carbetocin with intramuscular syntometrine for the routine prevention of postpartum haemorrhage in women who deliver vaginally. DESIGN: Prospective double-blind randomised controlled trial. SETTING: Tertiary referral centre. POPULATION: Pregnant women with no contraindication for vaginal delivery recruited from January 2005 to April 2008. METHODS: Participants were randomised to receive either syntometrine or carbetocin during the third stage of labour. MAIN OUTCOME MEASURES: Primary outcome measure was postpartum haemorrhage requiring additional uterotonics. Secondary outcome measures were the incidence of postpartum haemorrhage (> or =500 ml), severe postpartum haemorrhage (> or =1000 ml) and adverse effects profile. RESULTS: Women in the carbetocin group (13.5%) and in the syntometrine group (16.8%) had postpartum haemorrhage requiring additional uterotonics (P = 0.384). 1.6% of women in each group had postpartum haemorrhage (P = 1.0) and the estimated blood loss during the third stage of labour was similar between the two groups (P = 0.294). Women who had syntometrine were four times more likely to experience nausea (RR = 4.2; 95% CI 2.2-7.8) and vomiting (RR = 4.3; 95% CI 1.9-9.5) compared with women who had carbetocin. Tremor, sweating, retching and uterine pain were also more likely in the syntometrine group compared with the carbetocin group (P < 0.05). CONCLUSIONS: Carbetocin has an efficacy similar to syntometrine for prevention of postpartum haemorrhage, but is associated with less adverse effects.