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.

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Integrating the genotype with epigenetic marks holds the promise of better understanding the biology that underlies the complex interactions of inherited and environmental components that define the developmental origins of a range of disorders. The quality of the in utero environment significantly influences health over the lifecourse. Epigenetics, and in particular DNA methylation marks, have been postulated as a mechanism for the enduring effects of the prenatal environment. Accordingly, neonate methylomes contain molecular memory of the individual in utero experience. However, interindividual variation in methylation can also be a consequence of DNA sequence polymorphisms that result in methylation quantitative trait loci (methQTLs) and, potentially, the interaction between fixed genetic variation and environmental influences. We surveyed the genotypes and DNA methylomes of 237 neonates and found 1423 punctuate regions of the methylome that were highly variable across individuals, termed variably methylated regions (VMRs), against a backdrop of homogeneity. MethQTLs were readily detected in neonatal methylomes, and genotype alone best explained~25% of the VMRs. We found that the best explanation for 75% of VMRs was the interaction of genotype with different in utero environments, including maternal smoking, maternal depression, maternal BMI, infant birth weight, gestational age, and birth order. Our study sheds new light on the complex relationship between biological inheritance as represented by genotype and individual prenatal experience and suggests the importance of considering both fixed genetic variation and environmental factors in interpreting epigenetic variation.

Faster eating rates are associated with increased energy intake, but little is known about the relationship between children's eating rate, food intake and adiposity. We examined whether children who eat faster consume more energy and whether this is associated with higher weight status and adiposity. We hypothesised that eating rate mediates the relationship between child weight and ad libitum energy intake. Children (n 386) from the Growing Up in Singapore Towards Healthy Outcomes cohort participated in a video-recorded ad libitum lunch at 4·5 years to measure acute energy intake. Videos were coded for three eating-behaviours (bites, chews and swallows) to derive a measure of eating rate (g/min). BMI and anthropometric indices of adiposity were measured. A subset of children underwent MRI scanning (n 153) to measure abdominal subcutaneous and visceral adiposity. Children above/below the median eating rate were categorised as slower and faster eaters, and compared across body composition measures. There was a strong positive relationship between eating rate and energy intake (r 0·61, P<0·001) and a positive linear relationship between eating rate and children's BMI status. Faster eaters consumed 75 % more energy content than slower eating children (Δ548 kJ (Δ131 kcal); 95 % CI 107·6, 154·4, P<0·001), and had higher whole-body (P<0·05) and subcutaneous abdominal adiposity (Δ118·3 cc; 95 % CI 24·0, 212·7, P=0·014). Mediation analysis showed that eating rate mediates the link between child weight and energy intake during a meal (b 13·59; 95 % CI 7·48, 21·83). Children who ate faster had higher energy intake, and this was associated with increased BMI z-score and adiposity.

For women who undergo caesarean section, carbetocin resulted in a statistically significant reduction in the need for therapeutic uterotonics compared to oxytocin, but there is no difference in the incidence of postpartum haemorrhage. Carbetocin is associated with less blood loss compared to syntometrine in the prevention of PPH for women who have vaginal deliveries and is associated with significantly fewer adverse effects. Further research is needed to analyse the cost-effectiveness of carbetocin as a uterotonic agent.

Background: Infant body mass index (BMI) peak characteristics and early childhood BMI are emerging markers of future obesity and cardiometabolic disease risk, but little is known about their maternal nutritional determinants. Objective: We investigated the associations of maternal macronutrient intake with infant BMI peak characteristics and childhood BMI in the Growing Up in Singapore Towards healthy Outcomes study. Design: With the use of infant BMI data from birth to age 18 mo, infant BMI peak characteristics [age (in months) and magnitude (BMI peak ; in kg/m 2 ) at peak and prepeak velocities] were derived from subjectspecific BMI curves that were fitted with the use of mixed-effects model with a natural cubic spline function. Associations of maternal macronutrient intake (assessed by using a 24-h recall during late gestation) with infant BMI peak characteristics (n = 910) and BMI z scores at ages 2, 3, and 4 y were examined with the use of multivariable linear regression. Results: Mean absolute maternal macronutrient intakes (percentages of energy) were 72 g protein (15.6%), 69 g fat (32.6%), and 238 g carbohydrate (51.8%). A 25-g (w100-kcal) increase in maternal carbohydrate intake was associated with a 0.01/mo (95% CI: 0.0003, 0.01/mo) higher prepeak velocity and a 0.04 (95% CI: 0.01, 0.08) higher BMI peak . These associations were mainly driven by sugar intake, whereby a 25-g increment of maternal sugar intake was associated with a 0.02/mo (95% CI: 0.01, 0.03/mo) higher infant prepeak velocity and a 0.07 (95% CI: 0.01, 0.13) higher BMI peak . Higher maternal carbohydrate and sugar intakes were associated with a higher offspring BMI z score at ages 2-4 y. Maternal protein and fat intakes were not consistently associated with the studied outcomes. Conclusion: Higher maternal carbohydrate and sugar intakes are associated with unfavorable infancy BMI peak characteristics and higher early childhood BMI. This trial was registered at clinicaltrials.gov as NCT01174875.Am J Clin Nutr 2017;105:705-13.

The Infinium Human Methylation450 BeadChip ArrayTM (Infinium 450K) is an important tool for studying epigenetic patterns associated with disease. This array offers a high-throughput, low cost alternative to more comprehensive sequencing-based methodologies. Here we compare data generated by interrogation of the same seven clinical samples by Infinium 450K and reduced representation bisulfite sequencing (RRBS). This is the largest data set comparing Infinium 450K array to the comprehensive RRBS methodology reported so far. We show good agreement between the two methodologies. A read depth of four or more reads in the RRBS data was sufficient to achieve good agreement with Infinium 450K. However, we observe that intermediate methylation values (20–80%) are more variable between technologies than values at the extremes of the bimodal methylation distribution. We describe careful processing of Infinium 450K data to correct for known limitations and batch effects. Using methodologies proposed by others and newly implemented and combined in this report, agreement of Infinium 450K data with independent techniques can be vastly improved.

Recent findings confirm that faster eating rates support higher energy intakes within a meal and are associated with increased body weight and adiposity in children. The current study sought to * Author to whom correspondence should be addressed: Ciaran Gerard Forde; Centre for Translational Medicine, 14 Medical Drive #07-02, MD 6 Building, Yong Loo Lin School of Medicine, Singapore 117599; Tel: +65 64070104; ciaran_forde@sics.astar.edu.sg. Clinical Trial Registry Number: NCT01174875; https://clinicaltrials.gov/ Authors' Contributions: This study was conceived and designed by CGF, AF, MFFC and LRF. Clinical analyses were performed by SS, SV, AF, ATG, and CGF and data analysis and interpretation were carried out by AF and CGF. AF and CGF prepared the draft manuscript and all authors reviewed and approved the final draft. This study was given ethical approval by ethical review boards of the KK Women's and Children's Hospital and National University Hospital in Singapore.Author disclosures: Keith Godfrey, Lee Yung-Seng and Yap Seng Chong have received reimbursement for speaking at conferences sponsored by companies selling nutritional products. They are part of an academic consortium that has received research funding from Abbott Nutrition, Nestec and Danone. Lisa Fries is an employee of Nestec SA, working at the Nestlé Research Center. The other authors have no financial or personal conflict of interests. Europe PMC Funders GroupAuthor Manuscript Physiol Behav. Author manuscript; available in PMC 2018 January 01. Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts identify the eating behaviours that underpin faster eating rates and energy intake in children, and to investigate their variations by weight status and other individual differences. Children (N=386) from the Growing Up in Singapore towards Healthy Outcomes (GUSTO) cohort took part in a video-recorded ad libitum lunch at 4.5 years of age to measure acute energy intake. Videos were coded for three eating behaviours (bites, chews and swallows) to derive a measure of eating rate (g/min) and measures of eating microstructure: eating rate (g/min), total oral exposure (minutes), average bite size (g/bite), chews per gram, oral exposure per bite (seconds), total bites and proportion of active to total mealtime. Children's BMIs were calculated and a subset of children underwent MRI scanning to establish abdominal adiposity. Children were grouped into faster and slower eaters, and into healthy and overweight groups to compare their eating behaviours. Results demonstrate that faster eating rates were correlated with larger average bite size (r=0.55, p<0.001), fewer chews per gram (r=-0.71, p<0.001) and shorter oral exposure time per bite (r=-0.25, p<0.001), and with higher energy intakes (r=0.61, p<0.001). Children with overweight and higher adiposity had faster eating rates (p<0.01) and higher energy intakes (p<0.01), driven by larger bite sizes (p<0.05). Eating behaviours varied by sex, ethnicity and early feeding regimes, partial...