Cannabinoids are compounds found in the cannabis sativa plant. Cannabinoids, such as delta-9tetrahydrocannabinol (THC) and cannabidiol (CBD), have potential therapeutic benefits in various medical conditions. Some can activate the cannabinoid receptors type-1 and -2 (CB1 and CB2), that are part of the endocannabinoid system (ECS), alongside the endocannabinoids and their metabolic enzymes. The ECS regulates physiological and cognitive processes and is a potential therapeutic target for a wide range of health conditions like chronic pain, anxiety, and neurodegenerative diseases. Synthetic cannabinoids, are associated with serious health risks, including addiction, psychosis, and death. Nonetheless, some of these molecules are also being explored for pharmacological applications. Angiogenesis is the process of forming new blood vessels from existing ones, crucial for growth, repair, and tissue maintenance. Dysregulation of this process is associated with several diseases, including cancer, diabetic retinopathy and reproductive pathologies, such as preeclampsia. Recent data suggests that cannabinoids may affect angiogenesis. Here, we reviewed their impact on pro-angiogenic factors, extracellular matrix enzymes and inhibitors, immune-inflammatory responses, angiogenic pathways and functional assays, focusing on the main compounds for each cannabinoid class: THC and CBD for phytocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG) for endocannabinoids and WIN-55, JWH-133, XLR-11, LYR-7 and LYR-8, for the synthetic cannabinoids. Despite conflicting reports about the actions of phytocannabinoids and endocannabinoids on angiogenesis, the ability to modulate the angiogenic process is undoubtedly confirmed. This may open a new therapeutical route for angiogenesis-related pathologies. In addition, synthetic cannabinoids present anti-angiogenic actions in several cell models, hinting their potential as anti-angiogenic drugs.

The interest on the endocannabinoid system (ECS) in human reproduction has grown due to its involvement in placenta development, which led to growing concerns over pregnant cannabis consumer's impact on pregnancy outcome. The endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) modulate placental trophoblast proliferation and apoptosis. However, their role on other placentation events such as angiogenesis and invasion are unknown. Using the human extravillous trophoblast HTR-8/SVneo cells, a well-accepted model of first trimester extravillous trophoblast (EVT), this study aims to investigate whether AEA and 2-AG can modulate the expression of angiogenesis- and invasion-related factors. Transcript analysis of angiogenic factors of the vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP) protein family demonstrated the ability of AEA to increase VEGF-C and VEGFR3 expression via cannabinoid receptors CB1 and CB2 while the placental growth factor (PlGF) was increased through CB1. Moreover, an increase in VEGFR1, sFLT1, VEGFR2, MMP-2 and TIMP-1 independent of cannabinoid receptor activation was verified. However, 2-AG only increased PlGF transcript through CB1/CB2 activation. Both endocannabinoids stimulated HTR8/SVneo endothelial-like tube formation. As for the wound healing assay, only 2-AG was able to increase the percentage of wound closure. Moreover, the data demonstrated that both AEA and 2-AG, via cannabinoid receptors, activated the STAT3 signaling pathway. Distinct effects were observed on transcription factor HIF-1α and AKT phosphorylation that decreased with both endocannabinoids. Although different angiogenic and migration factors are affected the results obtained in this work showcase once more the ability of the endocannabinoids to modulate key processes in placental physiology.

BACKGROUND: The endocannabinoid system (ECS) consists of the cannabinoid receptors CB1 and CB2, the main endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and their metabolic enzymes N-acylphosphatidylethanolamine-specific phospholipase D, fatty acid amide hydrolase, diacylglycerol lipase and monoacylglycerol lipase. This system is involved in the modulation of essential physiological processes. Its role in the reproductive system has become significantly important in recent years, given its major role in events such as gametogenesis, decidualisation, implantation and placentation. OBJECTIVE AND RATIONALE: In this paper, we review the literature and summarize the role of the ECS elements in reproduction and their potential as early markers for diagnosis of reproductive disorders or as pharmacological targets for treatment. SEARCH METHODS: Original research and review papers published from 1964 to June 2019 were selected in terms of relevance, reliability and quality by searching PubMed, MEDLINE and Web of Science, using the following search terms: endocannabinoid system and endometriosis; endocannabinoid system and ectopic pregnancy; endocannabinoid system and miscarriage; endocannabinoid system and pre-eclampsia; endocannabinoid system and endometrial cancer; endocannabinoid system and reproduction; endocannabinoid, endometrium; placenta; N-acylethanolamines; anandamide; 2-arachidonoylglycerol; and cannabinoids. OUTCOMES: This review demonstrates relevant information concerning ECS alterations in endometriosis, ectopic pregnancy, miscarriage, pre-eclampsia and endometrial cancer. We highlight the importance of the endocannabinoids in endometrial and placental physiology and pathophysiology, from studies in vitro and in vivo and in clinical observations. The most studied of the endogenous cannabinoids is AEA. The levels of AEA were increased in plasma of patients with endometriosis and miscarriage, as well as in the fallopian tube of women with ectopic pregnancy and in endometrial biopsies of endometrial cancer. Changes in the pattern of expression of the cannabinoid receptor CB1 were also observed in endometrial biopsies of endometriosis, fallopian tube and decidua of patients with ectopic pregnancy and pre-eclamptic placenta. Moreover, alterations in CB2 expression have been reported in association with endometrial cancer. In general, studies on the cannabinoid signalling through CB2 and on the biological activities of the other major endocannabinoid, namely 2-AG, as well as its metabolic enzymes are scarce and avidly required. WIDER IMPLICATIONS: The pathophysiological mechanisms involved in the described endometrial and placental pathologies are still unclear and lack the means for an early diagnosis. Based on current evidence, though alterations in ECS are demonstrated at tissue level, it is difficult to associate plasmatic changes in AEA with specific endometrial and placental diseases. Thus, pairing alterations in AEA levels with 2-AG and/or other endocannabinoid-like molecules may provide more accurate and early diagnoses. In addition, patients may benefit from new therapies that target the ECS and endocannabinoid signalling.

Cannabis use has become a hot topic in several countries due to the debate about its legalization for medical purposes. However, data are limited regarding adverse events, safety and potential impact on reproductive health. Cannabis consumption during pregnancy has been associated with gestational disorders such as preterm birth, intrauterine growth restriction, low birth weight and increased risk of miscarriage, though the underlying biochemical mechanisms are still unknown. Given that the endocannabinoid system (ECS) is involved in several reproductive processes, we tested the hypothesis that the negative outcomes may result from the impact on the ECS homeostasis caused by the main psychoactive compound of cannabis, Δ9-tetrahydrocannabinol (THC). We demonstrate that THC (10–40 µM) impairs placental endocannabinoid system by disrupting the endocannabinoid anandamide (AEA) levels and the expression of AEA synthetic and degrading enzymes N-arachidonoylphosphatidylethanolamine-specific phospholipase D (NAPE-PLD) and fatty acid amide hydrolase (FAAH), respectively. Although, no alterations in cannabinoid receptors CB1 and CB2 expression were observed. Thus, long-term local AEA levels are associated with a shift in the enzymatic profile to re-establish ECS homeostasis. In chronic cannabis users, high AEA levels in placenta may disturb the delicate balance of trophoblast cells turnover leading to alterations in normal placental development and foetal growth.

ObjectiveStudies examining associations between movement behaviours (i.e. physical activity, sedentary behaviour and sleep duration) and obesity focus on average values of these movement behaviours, despite important within-country and between-country variability. A better understanding of movement behaviour inequalities is important for developing public health policies and behaviour-change interventions. The objective of this ecologic analysis at the country level was to determine if inequality in movement behaviours is a better correlate of obesity than average movement behaviour volume in children from all inhabited continents of the world. MethodsThis multinational, cross-sectional study included 6,128 children 9-11years of age. Moderate-to-vigorous physical activity (MVPA), total sedentary time (SED) and sleep period time were monitored over 7 consecutive days using waist-worn accelerometry. Screen time was self-reported. Inequality in movement behaviours was determined using Gini coefficients (ranging from 0 [complete equality] to 1 [complete inequality]). ResultsThe largest inequality in movement behaviours was observed for screen time (Gini of 0.32; medium inequality), followed by MVPA (Gini of 0.21; low inequality), SED (Gini of 0.07; low inequality) and sleep period time (Gini of 0.05; low inequality). Average MVPA (hd(-1)) was a better correlate of obesity than MVPA inequality (r=-0.77 vs. r=0.00, p=0.03). Average SED (hd(-1)) was also a better correlate of obesity than SED inequality (r=0.52 vs. r=-0.32, p=0.05). Differences in associations for screen time and sleep period time were not statistically significant. MVPA in girls was found to be disproportionally lower in countries with more MVPA inequality. ConclusionsFindings from this study show that average MVPA and SED should continue to be used in population health studies of children as they are better correlates of obesity than inequality in these behaviours. Moreover, the findings suggest that MVPA inequality could be greatly reduced through increases in girls' MVPA alone.

The association of genetic polymorphisms with low bone mineral density in elite athletes have not been considered previously. The present study found that bone mass phenotypes in elite and pre-elite dancers are related to genetic variants at the Wnt/β-catenin and ER pathways.

SummaryBackgroundThe relationship between children's adiposity and lifestyle behaviour patterns is an area of growing interest.ObjectivesThe objectives of this study are to identify clusters of children based on lifestyle behaviours and compare children's adiposity among clusters.MethodsCross‐sectional data from the International Study of Childhood Obesity, Lifestyle and the Environment were used. Participants: the participants were children (9–11 years) from 12 nations (n = 5710). Measures: 24‐h accelerometry and self‐reported diet and screen time were clustering input variables. Objectively measured adiposity indicators were waist‐to‐height ratio, percent body fat and body mass index z‐scores. Analysis: sex‐stratified analyses were performed on the global sample and repeated on a site‐wise basis. Cluster analysis (using isometric log ratios for compositional data) was used to identify common lifestyle behaviour patterns. Site representation and adiposity were compared across clusters using linear models.ResultsFour clusters emerged: (1) Junk Food Screenies, (2) Actives, (3) Sitters and (4) All‐Rounders. Countries were represented differently among clusters. Chinese children were over‐represented in Sitters and Colombian children in Actives. Adiposity varied across clusters, being highest in Sitters and lowest in Actives.ConclusionsChildren from different sites clustered into groups of similar lifestyle behaviours. Cluster membership was linked with differing adiposity. Findings support the implementation of activity interventions in all countries, targeting both physical activity and sedentary time.

SummaryBackgroundIt is unknown whether moderate‐to‐vigorous physical activity (MVPA) thresholds for obesity should be adapted depending on level of sedentary behaviour in children.ObjectiveThe objective of the study is to determine the MVPA thresholds that best discriminate between obese and non‐obese children, by level of screen time and total sedentary time in 12 countries.MethodsThis multinational, cross‐sectional study included 6522 children 9–11 years of age. MVPA and sedentary time were assessed using waist‐worn accelerometry, while screen time was self‐reported. Obesity was defined according to the World Health Organization reference data.ResultsReceiver operating characteristic curve analyses showed that the best thresholds of MVPA to predict obesity ranged from 53.8 to 73.9 min d−1 in boys and from 41.7 to 58.7 min d−1 in girls, depending on the level of screen time. The MVPA cut‐offs to predict obesity ranged from 37.9 to 75.9 min d−1 in boys and from 32.5 to 62.7 min d−1 in girls, depending on the level of sedentary behaviour. The areas under the curve ranged from 0.57 to 0.73 (‘fail’ to ‘fair’ accuracy), and most sensitivity and specificity values were below 85%, similar to MVPA alone. Country‐specific analyses provided similar findings.ConclusionsThe addition of sedentary behaviour levels to MVPA did not result in a better predictive ability to classify children as obese/non‐obese compared with MVPA alone.

Objectives: To examine whether meeting vs not meeting movement/non-movement guidelines (moderate-to-vigorous physical activity [MVPA], screen time, sleep duration), and combinations of these recommendations, are associated with health-related quality of life (HRQoL) in children from 12 countries in five major geographic regions of the world and explore whether the associations vary by study site. Study design: Observational, multinational cross-sectional study. Methods: This study included 6106 children aged 9-11 years from sites in Australia, Brazil, Canada, China, Colombia, Finland, India, Kenya, Portugal, South Africa, the United Kingdom, and the United States. Participants completed the KIDSCREEN-10 to provide a global measure of their HRQoL. Sleep duration and MVPA were assessed using 24-h accelerometry. Screen time was assessed through self-report. Meeting the recommendations was defined as >= 60 min/day for MVPA, <= 2 h/day for screen time, and between 9 and 11 h/night for sleep duration. Age, sex, highest parental education, unhealthy diet pattern score, and body mass index z-score were included as covariates in statistical models. Results: In the full sample, children meeting the screen time recommendation, the screen time + sleep recommendation, and all three recommendations had significantly better HRQoL than children not meeting any of these guidelines. Differences in HRQoL scores between sites were also found within combinations of movement/non-movement behaviors. For example, while children in Australia, Canada, and USA self-reported better HRQoL when meeting all three recommendations, children in Kenya and Portugal reported significantly lower HRQoL when meeting all three recommendations (relative to not meeting any). Conclusions: Self-reported HRQoL is generally higher when children meet established movement/non-movement recommendations. However, differences between study sites also suggest that interventions aimed at improving lifestyle behaviors and HRQoL should be locally and culturally adapted. (C) 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

According to existing literature, bone health in ballet dancers is controversial. We have verified that, compared to controls, young female and male vocational ballet dancers have lower bone mineral density (BMD) at both impact and non-impact sites, whereas female professional ballet dancers have lower BMD only at non-impact sites.

Aim: To describe the reactivity of the rat distal colon to AT1R-Abs and to compare it to that of Ang II.Introduction: Agonistic IgG (IgG1 and IgG3 subclasses) autoantibodies against the angiotensin II type 1 receptor (AT1R-Abs) have been associated with hypertension, preeclampsia, placental ischemia, renal-allograft rejection and systemic sclerosis.It is though that AT1R-Abs mimic the action of angiotensin II (Ang II) and contribute to the physiopathology of several diseases and the associated complications.Methods: Male Wistar rats (9-12 weeks of age) were killed by decapitation and strips of the distal colon were mounted in organ baths along their longitudinal axis.Tissues were stretch to 1 g of resting force and isometric responses to AT1R-Abs (25, 50 and 100 mg/dl) obtained from sera of systemic sclerosis and renal-allograft rejection patients and to Ang II (10pM-1 M) were recorded on a polygraph.The response of Ang II were expressed as % of the response to 125 mM potassium chloride (KCl).Results: AT1R-Abs caused a long-lasting response.Very often, AT1R-Abs induced an increase in the frequency and amplitude of distal colon spontaneous contractions.Occasionally, AT1R-Abs caused a slight decrease in the resting tone and, more rarely, they caused colonic contraction.The effects of the AT1R-Abs seem to be attenuated by candesartan.The pattern of the response to Ang II was different; Ang II caused a fast developing contraction of the colon with an Emax of 64.37 ± 12.68 (%KCl) and EC50 of 1.22 ± 0.20 nM.Conclusion: AT1R-Abs change the normal rhythm of spontaneous contractions of the rat distal colon but more studies are necessary to evaluate whether this reactivity is mediated by AT1 receptors.Moreover, Ang II cause a marked AT1 receptor-mediated contraction of the rat distal colon.

The endocannabinoid system (ECS) is involved in several physiological events that resulted in a growing interest in its modulation. Moreover, the uterine levels of anandamide (AEA), the major endocannabinoid, must be tightly regulated to create proper embryo implantation conditions. However, there are no evidences about the regulation of AEA in uterus by estrogen. Thus, the aim of this study is to elucidate whether estradiol benzoate (EB) and tamoxifen (TAM) administration to ovariectomized (OVX) rats can induce changes in the expression of cannabinoid receptors and AEA-metabolic enzymes in uterus by evaluating gene transcription and protein levels by qPCR, Western blot and immunohistochemistry. Moreover, the plasmatic and uterine levels of AEA and of prostaglandin E-2 (PGE(2)) and prostaglandin F-2 alpha (PGF(2 alpha)), the major cyclooxygenase-2 (COX-2) products, were determined by UPLC MS/MS. The immunohistochemistry showed that cannabinoid receptors, as well as AEA metabolic enzymes are mainly located in the epithelial cells of both lumen and glands and, to a lesser extent, in the muscle cells. Moreover, EB administration to OVX rats significantly increased CB1, CB2, NAPE-PLD, FAAH and COX-2 expression and transcription. These effects were absent in TAM and TAM + EB treatments showing that this response is estrogen receptor dependent. Additionally, although uterine levels of AEA remained unchanged in EB or TAM treated animals, they showed a rise with EB treatment in plasma. The latter also produced a decrease in uterine PGE(2) levels. In summary, these data collectively indicate that the expression of ECS components, as well as, the AEA and PGE(2) levels in rat uterus is modulated by EB. Thus, estradiol may have a direct regulatory role in the modulation of ECS in female reproductive tissues.

The purpose of this study was to describe sources of variability in obesity-related variables in 6022 children aged 9–11 years from 12 countries. The study design involved recruitment of students, nested within schools, which were nested within study sites. Height, weight and waist circumference (WC) were measured and body mass index (BMI) was calculated; sleep duration and total and in-school moderate-to-vigorous physical activity (MVPA) and sedentary time were measured by accelerometry; and diet scores were obtained by questionnaire. Variance in most variables was largely explained at the student level: BMI (91.9%), WC (93.5%), sleep (75.3%), MVPA (72.5%), sedentary time (76.9%), healthy diet score (88.3%), unhealthy diet score (66.2%), with the exception of in-school MVPA (53.8%) and in-school sedentary time (25.1%). Variance explained at the school level ranged from 3.3% for BMI to 29.8% for in-school MVPA, and variance explained at the site level ranged from 3.2% for WC to 54.2% for in-school sedentary time. In general, more variance was explained at the school and site levels for behaviors than for anthropometric traits. Given the variance in obesity-related behaviors in primary school children explained at school and site levels, interventions that target policy and environmental changes may enhance obesity intervention efforts.

Aim: We aim to investigate in cytotrophoblasts whether these effects on cell viability loss are due to endoplasmic reticulum (ER) stress mediated apoptosis. Introduction: Placental development relies on a balance between proliferation, differentiation and apoptosis of trophoblasts, a process tightly regulated by growth factors, cytokines and hormones. Endocannabinoids (eCB), such as 2-arachidonoylglycerol (2-AG) and anandamide (AEA) may play a role in these processes. We previously demonstrated that both eCB induced trophoblast cell death.1,2 Here we investigated in cytotrophoblasts whether these effects on cell viability loss are due to endoplasmic reticulum (ER) stress mediated apoptosis. ER stress is caused by the accumulation of unfolded proteins leading to an unfold protein response (UPR) triggered by transmembrane ER signaling proteins including: pancreatic ER kinase (PKR)-like ER kinase (PERK), inositol-requiring enzyme 1 (Ire1) and Activating transcription factor 6 (ATF6). The dissociation of Grp78 (BiP) from these sensors triggers a series of mechanisms that can restore homeostasis or lead to apoptosis. Placental stress has been implicated in the pathophysiology of pregnancy complications, including growth restriction and pre-eclampsia. Methods: BeWo cells (ATCC, USA), an accepted model of cytotrophoblast stem cells were treated with AEA or 2-AG (10 micromolar) for 24h. Through quantitative real time polymerase chain reaction (qPCR), we evaluated mRNA levels of ER stress markers: CHOP, Grp78, ATF4 and spliced mXBP1. Protein expression of CHOP was evaluated by western-blot. Results: After 24h of treatment with both eCB, we found an increase in mRNA levels of ER stress markers: CHOP, Grp78, ATF4 and spliced mXBP1. Protein expression of CHOP also increased in both cases. Conclusion: These results suggest that cell viability loss promoted by 2-AG and AEA was associated with ER-stress since both PERK and IRE1 arms of UPR are activated. Prolonged ER-stress, contributes to the expression of pro-apoptotic proteins, such as CHOP. These findings shed light to the impact of endocannabinoids induced-ER stress which may negatively affect trophoblast cell turnover and pregnancy outcomes. Acknowledgements: This work received support from European Union (FEDER funds through COMPETE) and FCT through project PTDC/DTP-FTO/5651/2014-POCI-01-0145-FEDER-016562; FCT/MEC through national funds and co-financed by FEDER, under PT2020 (UID/01/0145/FERDER/007728) and CCDR-N/NORTE2020/Portugal 2020 (norte-01-0145-FEDER-000024).

SummaryBackgroundNo studies have examined if mid‐upper arm circumference (MUAC) can be an alternative screening tool for obesity in an international sample of children differing widely in levels of human development.ObjectiveOur aim is to determine whether MUAC could be used to identify obesity in children from 12 countries in five major geographic regions of the world.MethodsThis observational, multinational cross‐sectional study included 7337 children aged 9–11 years. Anthropometric measurements were objectively assessed, and obesity was defined according to the World Health Organization reference data.ResultsIn the total sample, MUAC was strongly correlated with adiposity indicators in both boys and girls (r > 0.86, p < 0.001). The accuracy level of MUAC for identifying obesity was high in both sexes and across study sites (overall area under the curve of 0.97, sensitivity of 95% and specificity of 90%). The MUAC cut‐off value to identify obesity was ~25 cm for both boys and girls. In country‐specific analyses, the cut‐off value to identify obesity ranged from 23.2 cm (boys in South Africa) to 26.2 cm (girls in the UK).ConclusionsResults from this 12‐country study suggest that MUAC is a simple and accurate measurement that may be used to identify obesity in children aged 9–11 years. MUAC may be a promising screening tool for obesity in resource‐limited settings.

We investigated the roles of home and school environments on dietary patterns among children from 12 countries differing widely in geographic region and levels of human and economic development. The sample included a total of 6685 (54% girls) 9–11-year-old children. Parents/guardians reported the availability of certain foods in the home, and trained researchers performed school audits recording the availability of foods for sale at schools. Foods were then divided into wholesome (nutrient-dense) and empty-calorie (nutrient-poor) foods and scored according to their availability. Children reported if their school provided school lunch and how many times during the last week they had eaten meals prepared away from home and school. Via principal components analysis, data-driven dietary pattern scores were calculated from food frequency questionnaires. Multilevel models were used to study the associations between home and school food environments (wholesome and empty-calorie foods) and dietary patterns (healthy and unhealthy diet pattern scores). For low unhealthy diet pattern scores, low availability of empty-calorie foods at home was found to be more important than high availability of wholesome foods. More meals eaten outside home and school were associated with the higher unhealthy diet pattern scores. The availability of wholesome foods at home was positively associated with the healthy diet pattern scores. Food availability at school was not associated with the dietary patterns. In this sample, the home food environment was more significant than the school food environment in predicting the dietary patterns. The availability of empty-calorie foods was associated with the unhealthy dietary pattern even when the availability of wholesome foods at home was high. Meals prepared away from home contributed to the unhealthy dietary pattern. Therefore, parents should be encouraged to limit the availability of empty-calorie foods and eating outside the home.

This study sought to examine the effects of a recreational physical activity summer camp on body composition, metabolic syndrome, and physical fitness in obese children. Forty-eight children (8-10 years; Body Mass Index ≥85th percentile) completed 4-weeks of a structured recreational physical activity program summer camp (5 hours/day, 5 days/week). Over the 4-weeks, significant reductions (P<0.05) in weight, waist circumference, Body Mass Index, percentage of body fat, and systolic and diastolic blood pressure were observed. Additionally, a significant increase was observed in HDL-cholesterol, handgrip, trunk lift, and shuttle run (P<0.05). These findings suggest that a 4-week recreational physical activity summer camp yields several body-composition, metabolic-syndrome, and physical fitness benefits in obese children and should represent an effective support for their health development.

Although evidence is accumulating on the importance of a good night’s sleep for healthy eating and activity behaviors, existing research has mainly been conducted in high-income, developed countries with limited sociocultural variability. This study is the first to examine the associations between sleep patterns and lifestyle behaviors in children from 12 countries in five major geographic regions of the world. This observational, multinational cross-sectional study included 5777 children aged 9–11 years from sites in Australia, Brazil, Canada, China, Colombia, Finland, India, Kenya, Portugal, South Africa, the United Kingdom and the United States. Nocturnal sleep duration (hours per night), sleep efficiency (%) and bedtime (h:min) were monitored over 7 consecutive days using an accelerometer. Lifestyle behaviors included moderate-to-vigorous physical activity (MVPA), total sedentary time (SED), self-reported screen time (ST) and healthy/unhealthy diet patterns (HDP/UDP). Multilevel modeling analyses were used to account for the hierarchical nature of the data. Overall, participants averaged 8.8 (s.d. 0.9) hours of sleep with 96.2% (s.d. 1.4) sleep efficiency and a mean bedtime of 2218 hours. After adjustment for age, sex, highest parental education and BMI z-score, results showed that (i) sleep duration was negatively associated with MVPA, SED and UDP score; (ii) sleep efficiency was negatively associated with MVPA and UDP score, and positively associated with SED; and (iii) later bedtime was positively associated with SED, ST and UDP score, and negatively associated with MVPA and HDP score. Results using categories of sleep patterns were consistent with the linear associations. Results also revealed that associations between sleep patterns and MVPA, SED and ST were significantly different between study sites, with stronger associations in high-income countries compared with low/middle-income countries. Sleep characteristics are important correlates of lifestyle behaviors in children. Differences between countries suggest that interventions aimed at improving sleep and lifestyle behaviors should be culturally adapted.

Childhood obesity is now recognized as a global public health issue. Social patterning of obesity, consistent with the theory of epidemiologic transition, has not been well described in children, and the limited research has focused on developed settings. The aim of this study was to describe the relationship between childhood obesity and household income using objective measures of adiposity and to explore how this relationship differs across levels of country human development. The International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE) was a multi-national cross-sectional study conducted in 12 urban/suburban study sites that represented all inhabited continents and wide ranges of development. ISCOLE collected objectively measured height, body mass and percentage body fat in 7341 10-year-old children. Multi-level random-effects models were used to examine income gradients in several obesity measures. The mean age of the children was 10.4 years, and 12.6% were obese, ranging from 5.4% (Finland) to 23.8% (China). For both boys and girls, obesity prevalence, body fat percentage and body mass index (BMI) z-score increased linearly with higher income at lower levels of development (all P for trend ⩽0.0012), but decreased linearly with higher income at higher levels of development (all P for trend ⩽0.0003). Country human development explained 75% of the variation in the country-specific income–obesity relationships (r=−0.87, P=0.0003). Results are consistent with the theory of epidemiologic transition. Global efforts to control obesity must account for socioeconomic factors within a country’s context. Future research should seek to understand global socioeconomic patterns in obesity-related lifestyle behaviors.