Early sex-dependent differences in metabolic profiles of overweight and adiposity in young children: a cross-sectional analysis.

BACKGROUND: Childhood obesity is a global health concern and can lead to lifetime cardiometabolic disease. New advances in metabolomics can provide biochemical insights into the early development of obesity, so we aimed to characterize serum metabolites associated with overweight and adiposity in early childhood and to stratify associations by sex. METHODS: Nontargeted metabolite profiling was conducted in the Canadian CHILD birth cohort (discovery cohort) at age 5 years (n = 900) by multisegment injection-capillary electrophoresis-mass spectrometry. Clinical outcome was defined using novel combined measures of overweight (WHO-standardized body mass index ≥ 85th percentile) and/or adiposity (waist circumference ≥ 90th percentile). Associations between circulating metabolites and child overweight/adiposity (binary and continuous outcomes) were determined by multivariable linear and logistic regression, adjusting for covariates and false discovery rate, and by subsequent sex-stratified analysis. Replication was assessed in an independent replication cohort called FAMILY at age 5 years (n = 456). RESULTS: In the discovery cohort, each standard deviation (SD) increment of branched-chain and aromatic amino acids, glutamic acid, threonine, and oxoproline was associated with 20-28% increased odds of overweight/adiposity, whereas each SD increment of the glutamine/glutamic acid ratio was associated with 20% decreased odds. All associations were significant in females but not in males in sex-stratified analyses, except for oxoproline that was not significant in either subgroup. Similar outcomes were confirmed in the replication cohort, where associations of aromatic amino acids, leucine, glutamic acid, and the glutamine/glutamic acid ratio with childhood overweight/adiposity were independently replicated. CONCLUSIONS: Our findings show the utility of combining measures of both overweight and adiposity in young children. Childhood overweight/adiposity at age 5 years has a specific serum metabolic phenotype, with the profile being more prominent in females compared to males.

Prenatal and childhood exposure to per-/polyfluoroalkyl substances (PFASs) and its associations with childhood overweight and/or obesity: a systematic review with meta-analyses.

BACKGROUND: Per-/polyfluoroalkyl substances (PFASs) are persistent organic pollutants and suspected endocrine disruptors. OBJECTIVE: The aim of this work was to conduct a systematic review with meta-analysis to summarise the associations between prenatal or childhood exposure to PFASs and childhood overweight/obesity. METHODS: The search was performed on the bibliographic databases PubMed and Embase with text strings containing terms related to prenatal, breastfeeding, childhood, overweight, obesity, and PFASs. Only papers describing a biomonitoring study in pregnant women or in children up to 18 years that assessed body mass index (BMI), waist circumference (WC), or fat mass in children were included. When the estimates of the association between a PFAS and an outcome were reported from at least 3 studies, a meta-analysis was conducted; moreover, to correctly compare the studies, we developed a method to convert the different effect estimates and made them comparable each other. Meta-analyses were performed also stratifying by sex and age, and sensitivity analyses were also performed. RESULTS: In total, 484 and 779 articles were retrieved from PubMed and Embase, respectively, resulting in a total of 826 articles after merging duplicates. The papers included in this systematic review were 49: 26 evaluating prenatal exposure to PFASs, 17 childhood exposure, and 6 both. Considering a qualitative evaluation, results were conflicting, with positive, negative, and null associations. 30 papers were included in meta-analyses (19 prenatal, 7 children, and 4 both). Positive associations were evidenced between prenatal PFNA and BMI, between PFOA and BMI in children who were more than 3 years, and between prenatal PFNA and WC. Negative associations were found between prenatal PFOS and BMI in children who were 3 or less years, and between PFHxS and risk of overweight. Relatively more consistent negative associations were evidenced between childhood exposure to three PFASs (PFOA, PFOS, and PFNA) and BMI, in particular PFOS in boys. However, heterogeneity among studies was high. CONCLUSION: Even though heterogeneous across studies, the pooled evidence suggests possible associations, mostly positive, between prenatal exposure to some PFASs and childhood BMI/WC; and relatively stronger evidence for negative associations between childhood exposure to PFASs and childhood BMI.

Family socioeconomic status and childhood adiposity in Europe - A scoping review.

Childhood obesity is a considerable public health problem worldwide. In Europe, lower parental socioeconomic status (SES) relates to higher childhood adiposity. This scoping review strives to discover, which SES indicators are the most commonly used and meaningful determinants of childhood adiposity (greater level of continuous adiposity indicator, e.g. body mass index z-score, or overweight or obesity categorized by established definitions). The review focused on studies about European general populations from the 21st century (January 2000-April 2021) considering children and adolescents aged 0-17 years. PubMed and reference lists of articles were searched in February-April 2021. Total of 53 studies with 121 association analyses between different SES indicators and adiposity indicators, were identified and reviewed. Different SES indicators were grouped to 25 indicators and further to six indicator groups. The most used indicator was mother's education (n of association analyses = 24) and the most used indicator group was parental education (n of association analyses = 51). Of all association analyses, 55% were inverse, 36% were non-significant, and 8% were positive. Composite SES (80%), parental education (69%) and parental occupation (64%) indicators showed most frequently inverse associations with obesity measures (i.e. lower parental SES associating with higher adiposity), while parental income (50% inverse; 50% non-significant) and property and affluence (42% inverse; 50% nonsignificant) indicators showed approximately even number of inverse and non-significant associations. Instead, majority of parental employment (60%) indicators, showed non-significant associations and 33% showed positive associations (i.e. higher parental SES associating with higher adiposity). Despite some variation in percentages, majority of the associations were inverse in each age group and with different outcome categorizations. In girls and in boys, non-significant associations predominated. It seems that children with parents of higher SES have lower likelihood of adiposity in Europe. Parents' employment appears to differ from other SES indicators, so that having an employed parent(s) does not associate with lower likelihood of adiposity. Positive associations seem to occur more frequently in poorer countries. Criteria for uniform childhood SES and adiposity measures should be established and used in studies in order to be able to produce comparable results across countries.

Obesity and adiposity of 3- to 6-year-old children born to mothers with hyperglycaemia first detected in pregnancy in an urban South African setting.

BACKGROUND: Understanding the association between maternal metabolic conditions in pregnancy and the risk of childhood overweight, a growing concern in sub-Saharan Africa (SSA), helps to identify opportunities for childhood obesity prevention. AIM: To assess the association between hyperglycaemia first detected in pregnancy (HFDP) (gestational diabetes mellitus [GDM] and diabetes in pregnancy [DIP]) and child obesity and adiposity in pre-school-aged children in South Africa, independently of maternal BMI. SUBJECTS AND METHODS: Measurement of anthropometry and fat mass index (FMI) by the deuterium dilution method was done for 102 3-6-year-old children born to mothers with HFDP and 102 HFDP-unexposed children. Hierarchical regression analysis and generalised structural equation modelling (GSEM) were performed. RESULTS: The prevalence of overweight/obesity was 10.5% and 11.1% in children exposed to GDM and DIP, respectively, and 3.9% in the HFDP-unexposed group. Log-transformed FMI was significantly higher in the DIP-exposed group (ß = 0.166, 95% CI = 0.014-0.217 p= .026), but not when adjusting for maternal pregnancy BMI (ß = 0.226, 95% CI = 0.003-0.015, p = .004). GSEM showed significant total effects of maternal BMI and birth weight on FMI/BMI. CONCLUSIONS: Maternal pregnancy BMI seems to play a greater role in the development of childhood adiposity than maternal hyperglycaemia, requiring further research and identifying maternal BMI as a relevant prevention target in our setting.

Body size from birth through adolescence in relation to risk of benign breast disease in young women.

PURPOSE: Body size, from birth throughout adulthood, is associated with breast cancer risk, but few studies have investigated early-life body size and benign breast disease (BBD), a well-established breast cancer risk factor. We consider whether prenatal factors and size at birth, 10, 18 year, and intervening growth, are related to BBD risk. METHODS: The Growing Up Today Study includes 9032 females who completed questionnaires annually from 1996 to 2001, then 2003, 2005, 2007, 2010, and 2013. In 1996, their mothers provided pregnancy-related data. From 2005 to 2013, participants (18 year+) reported whether they had ever been diagnosed with biopsy-confirmed BBD (N = 142 cases). RESULTS: Girls had greater adiposity (BMI; kg/m2) at 10 year if they were larger at birth, if mother's pre-pregnancy BMI was higher, or if gestational weight gain was greater (all p < .01). Maternal height was (positively) associated (p < .05) with adolescent peak height growth velocity (PHV; in./year). Greater 10 year adiposity was associated with lower PHV and less height growth 10-18 year (both p < .01). Adiposity at 10 year was inversely associated with BBD (OR 0.83/(kg/m2), p < .01) as was increasing adiposity 10-18 year (OR 0.85/(kg/m2), p = .01). In a separate model, 10 year height (OR 1.13/in., p = .02) and height growth 10-18 year (OR 1.19/in.; p < .01) were positively associated. PHV was similarly positively associated (OR 2.58, p = .01, fastest versus slowest growth quartiles). In a multivariable model of BBD risk, gestational weight gain (daughters at highest risk if <20 lb gained), PHV (slowest growing girls at lowest risk), age 10 year height (positive), and BMI (inverse) were the most critical childhood risk factors (each p < .05). CONCLUSIONS: Body size factors from pregnancy through adolescence were independently associated with BBD risk in young women.

Total HDL cholesterol efflux capacity in healthy children - Associations with adiposity and dietary intakes of mother and child.

BACKGROUND AND AIMS: High-density lipoprotein (HDL) cholesterol efflux capacity in adults may be a measure of the atheroprotective property of HDL. Little however, is known about HDL cholesterol efflux capacity in childhood. We aimed to investigate the relationship between HDL cholesterol efflux capacity and childhood anthropometrics in a longitudinal study. METHODS AND RESULTS: Seventy-five children (mean age = 9.4 ± 0.4 years) were followed from birth until the age of 9 years. HDL cholesterol efflux capacity was determined at age 9 by incubating serum-derived HDL-supernatants with 3H-cholesterol labeled J774 macrophages and percentage efflux determined. Mothers provided dietary information by completing food frequency questionnaires in early pregnancy and then 5 years later on behalf of themselves and their children. Pearson's correlations and multiple regression analyses were conducted to confirm independent associations with HDL efflux. There was a negative correlation between HDL cholesterol efflux capacity and waist circumference at age 5 (r = -0.3, p = 0.01) and age 9 (r = -0.24, p = 0.04) and BMI at age 5 (r = -0.45, p = 0.01) and age 9 (r = -0.19, p = 0.1). Multiple regression analysis showed that BMI at age 5 remained significantly associated with reduced HDL cholesterol efflux capacity (r = -0.45, p < 0.001). HDL-C was negatively correlated with energy-adjusted fat intake (r = -0.24, p = 0.04) and positively correlated with energy-adjusted protein (r = 0.24, p = 0.04) and starch (r = 0.29, p = 0.01) intakes during pregnancy. HDL-C was not significantly correlated with children dietary intake at age 5. There were no significant correlations between maternal or children dietary intake and HDL cholesterol efflux capacity. CONCLUSIONS: This novel analysis shows that efflux capacity is negatively associated with adiposity in early childhood independent of HDL-C.

Birth Size, Early Life Weight Gain, and Midchildhood Cardiometabolic Health.

OBJECTIVE: To examine associations of birth size and weight gain during 4 early-life age intervals with midchildhood adiposity and metabolic profile and to evaluate for an interaction between birth size and early-life weight gain. STUDY DESIGN: Using data from 963 participants of Project Viva, a US prebirth cohort, we used multivariable linear regression to examine relations of birth size (tertiles of birthweight-for-gestational-age z-score) and weight gain (body mass index z-score [BMIZ] change) during 4 age intervals (birth-6 months, 6 months-1 year, 1-2 years, 2-3 years) with body composition and metabolic biomarkers during midchildhood (6.6-10.7 years). RESULTS: After accounting for confounders and previous growth, greater BMIZ change during all 4 age intervals corresponded with higher midchildhood adiposity, with larger effect sizes for later (1-2 years and 2-3 years) vs earlier (birth-6 months and 6 months-1 year) time frames. We observed effect modification by birth size for the birth-6 months and 6 months-1 year intervals. Greater birth-6 months BMIZ change was associated with higher overall adiposity (0.40 [95% CI 0.29, 0.51] kg dual x-ray absorptiometry total fat mass per z-score) among children in the highest birth size tertile. Similar associations were observed for central adiposity. Each increment in 6 months-1 year BMIZ change corresponded with 0.55 (0.05, 1.05) units higher homeostatic model assessment of insulin resistance and 2.68 (0.96, 4.40) ng/mL higher leptin among the smallest infants. CONCLUSIONS: BMIZ gain after 1 year is associated with greater midchildhood adiposity regardless of birth size, whereas the long-term influence of weight gain during the first postnatal year may depend on size at birth. Future studies are warranted to validate findings and examine relations with conventional birth size cut-offs.

Childhood adiposity trajectories are associated with late adolescent blood pressure: birth to twenty cohort.

BACKGROUND: Elevated blood pressure in childhood is a risk factor for adult hypertension which is a global health problem. Excess adiposity in childhood creates a predisposition to develop adult hypertension. Our aim was to explore distinct sex-specific adiposity trajectories from childhood to late adolescence and examined their association with blood pressure. METHODS: Latent Class Growth Mixture Modeling (LCGMM) on longitudinal data was used to derive sex-specific and distinct body mass index (BMI: kg/m(2)) trajectories. We studied 1824 black children (boys = 877, girls = 947) from the Birth to Twenty (Bt20) cohort from Soweto, South Africa, and obtained BMI measures at ages 5 through 18 years. Participants with at least two age-point BMI measures, were included in the analysis. Analysis of variance (ANOVA), chi-square test, multivariate linear and standard logistic regressions were used to test study characteristics and different associations. RESULTS: We identified three (3) and four (4) distinct BMI trajectories in boys and girls, respectively. The overall prevalence of elevated blood pressure (BP) was 34.9 % (39.4 % in boys and 30.38 % in girls). Boys and girls in the early onset obesity or overweight BMI trajectories were more likely to have higher BP values in late adolescence. Compared to those in the normal weight BMI trajectory, girls in early onset obesity trajectories had an increased risk of elevated BP with odds ratio (OR) of 2.18 (95 % confidence interval 1.31 to 4.20) and 1.95 (1.01 to 3.77). We also observed the weak association for boys in early onset overweight trajectory, (p-value = 0.18 and odds ratio of 2.39 (0.67 to 8.57)) CONCLUSIONS: Distinct weight trajectories are observed in black South African children from as early as 5 years. Early onset adiposity trajectories are associated with elevated BP in both boys and girls. It is important to consider individual patterns of early-life BMI development, so that intervention strategies can be targeted to at-risk individuals.

Gestational weight gain and obesity, adiposity and body size in African-American and Dominican children in the Bronx and Northern Manhattan.

Gestational weight gain (GWG) is potentially modifiable and is associated with infant size and body composition; however, long-term effects on childhood obesity have not been reported among multi-ethnic urban populations. We examined the association between GWG and child anthropometric measures and body composition at 7 years [waist circumference (WC), body mass index z-score (BMIZ), obesity (BMIZ ≥95%ile) and bioelectrical impedance analysis estimates of percentage body fat (%fat)] in African-American and Dominican dyads (n = 323) in the Columbia Center for Children's Environmental Health prospective birth cohort study from 1998 to 2013. Linear and logistic regression evaluated associations between excessive GWG [>Institute of Medicine (IOM) 2009 guidelines] and outcomes, adjusting for pre-pregnancy BMI and covariates. Pre-pregnancy BMI (mean ± standard deviation, all such values) and total GWG were 25.8 ± 6.2 kg m(-2) (45% overweight/obese) and 16.4 ± 7.9 kg (64% > IOM guidelines), respectively. Excessive GWG was associated with higher BMIZ {0.44 [95% confidence interval (CI): 0.2, 0.7], P < 0.001}, WC [ß: 2.9 cm (95% CI: 1.1, 4.6), P = 0.002], %fat at 7 years [ß: 2.2% (95% CI: 1.0, 3.5), P = 0.001)] and obesity [odds ratio: 2.93 (95% CI: 1.5, 5.8), P = 0.002]. Pre-pregnancy BMI was positively associated with child size, adiposity and obesity (all P < 0.05). Excessive GWG was highly prevalent and was associated with child obesity, greater percentage body fat and abdominal adiposity. Strategies to support healthy GWG are warranted to promote healthy growth and prevent childhood obesity.

Childhood Adiposity and Risk of Major Clinical Heart Diseases in Adulthood: A Mendelian Randomization Study.

BACKGROUND: The causal relationship between childhood adiposity and adult risk of heart diseases has not been clearly demonstrated. This study aims to ascertain whether genetically predicted childhood body mass index (BMI) and childhood obesity are causally associated with adult coronary heart disease, myocardial infarction, heart failure, atrial fibrillation, hypertrophic cardiomyopathy, and pulmonary heart disease. METHODS AND RESULTS: To investigate the causative relationships and underlying mechanisms between childhood adiposity and adult heart diseases, 3 main methods of Mendelian randomization were used: 2-sample Mendelian randomization, multivariable Mendelian randomization with controlling for several cardiometabolic risk variables, and mediation analysis. Every 1-SD rise in genetically predicted childhood body mass index was associated with 24% (odds ratio [OR], 1.24 [95% CI, 1.12-1.37]), 28% (OR, 1.28 [95% CI, 1.14-1.42]), 28% (OR, 1.28 [95% CI, 1.14-1.42]), and 27% (OR, 1.27 [95% CI, 1.04-1.49]) higher risk of coronary heart disease, myocardial infarction, heart failure, and atrial fibrillation, respectively. Every 1-unit increase in log-odds in childhood obesity was associated with 11% (OR, 1.11 [95% CI, 1.06-1.16]), 14% (OR, 1.14 [95% CI, 1.04-1.23]), 10% (OR, 1.10 [95% CI, 1.03-1.18]), and 20% (OR, 1.20 [95% CI, 1.08-1.32]) higher risk of coronary heart disease, myocardial infarction, heart failure, and atrial fibrillation, respectively. The link between childhood adiposity and adult heart diseases was found to be mediated by high-density lipoprotein cholesterol, triglyceride, hypertension, and type 2 diabetes. CONCLUSIONS: Our findings support the causal relationships between childhood adiposity and risk of adult coronary heart disease, myocardial infarction, heart failure, and atrial fibrillation. Blood lipids, hypertension, and type 2 diabetes are factors that mediate the aforementioned associations.

Characterizing the Causal Pathway From Childhood Adiposity to Right Heart Physiology and Pulmonary Circulation Using Lifecourse Mendelian Randomization.

BACKGROUND: Observational epidemiological studies have reported an association between childhood adiposity and altered cardiac morphology and function in later life. However, whether this is due to a direct consequence of being overweight during childhood has been difficult to establish, particularly as accounting for other measures of body composition throughout the lifecourse can be exceptionally challenging. METHODS AND RESULTS: In this study, we used human genetics to investigate this using a causal inference technique known as lifecourse Mendelian randomization. This approach allowed us to evaluate the effect of childhood body size on 11 measures of right heart and pulmonary circulation independent of other anthropometric traits at various stages in the lifecourse. We found strong evidence that childhood body size has a direct effect on an enlarged right heart structure in later life (eg, right ventricular end-diastolic volume: ß=0.24 [95% CI, 0.15-0.33]; P=3×10-7) independent of adulthood body size. In contrast, childhood body size effects on maximum ascending aorta diameter attenuated upon accounting for body size in adulthood, suggesting that this effect is likely attributed to individuals remaining overweight into later life. Effects of childhood body size on pulmonary artery traits and measures of right atrial function became weaker upon accounting for adulthood fat-free mass and childhood height, respectively. CONCLUSIONS: Our findings suggest that, although childhood body size has a long-term influence on an enlarged heart structure in adulthood, associations with the other structural components of the cardiovascular system and their function may be largely attributed to body composition at other stages in the lifecourse.

Reassessing the causal role of obesity in breast cancer susceptibility: a comprehensive multivariable Mendelian randomization investigating the distribution and timing of exposure.

BACKGROUND: Previous Mendelian randomization (MR) studies on obesity and risk of breast cancer adopted a small number of instrumental variables and focused mainly on the crude total effect. We aim to investigate the independent causal effect of obesity on breast cancer susceptibility, considering the distribution of fat, covering both early and late life. METHODS: Using an enlarged set of female-specific genetic variants associated with adult general [body mass index (BMI)] and abdominal obesity [waist-to-hip ratio (WHR) with and without adjustment for BMI, WHR and WHRadjBMI] as well as using sex-combined genetic variants of childhood obesity (childhood BMI), we performed a two-sample univariable MR to re-evaluate the total effect of each obesity-related exposure on overall breast cancer (Ncase = 133 384, Ncontrol = 113 789). We further looked into its oestrogen receptor (ER)-defined subtypes (NER+ = 69 501, NER- = 21 468, Ncontrol = 105 974). Multivariable MR was applied to estimate the independent causal effect of each obesity-related exposure on breast cancer taking into account confounders as well as to investigate the independent effect of adult and childhood obesity considering their inter-correlation. RESULTS: In univariable MR, the protective effects of both adult BMI [odds ratio (OR) = 0.89, 95% CI = 0.83-0.96, P = 2.06 × 10-3] and childhood BMI (OR = 0.78, 95% CI = 0.70-0.87, P = 4.58 × 10-6) were observed for breast cancer overall. Comparable effects were found in ER+ and ER- subtypes. Similarly, genetically predicted adult WHR was also associated with a decreased risk of breast cancer overall (OR = 0.87, 95% CI = 0.80-0.96, P = 3.77 × 10-3), restricting to ER+ subtype (OR = 0.88, 95% CI = 0.80-0.98, P = 1.84 × 10-2). Conditional on childhood BMI, the effect of adult general obesity on breast cancer overall attenuated to null (BMI: OR = 1.00, 95% CI = 0.90-1.10, P = 0.96), whereas the effect of adult abdominal obesity attenuated to some extent (WHR: OR = 0.90, 95% CI = 0.82-0.98, P = 1.49 × 10-2; WHRadjBMI: OR = 0.92, 95% CI = 0.86-0.99, P = 1.98 × 10-2). On the contrary, an independent protective effect of childhood BMI was observed in breast cancer overall, irrespective of adult measures (adjusted for adult BMI: OR = 0.84, 95% CI = 0.77-0.93, P = 3.93 × 10-4; adjusted for adult WHR: OR = 0.84, 95% CI = 0.76-0.91, P = 6.57 × 10-5; adjusted for adult WHRadjBMI: OR = 0.80, 95% CI = 0.74-0.87, P = 1.24 × 10-7). CONCLUSION: Although successfully replicating the inverse causal relationship between adult obesity-related exposures and risk of breast cancer, our study demonstrated such effects to be largely (adult BMI) or partly (adult WHR or WHRadjBMI) attributed to childhood obesity. Our findings highlighted an independent role of childhood obesity in affecting the risk of breast cancer as well as the importance of taking into account the complex interplay underlying correlated exposures.

Maternal and Cord Blood Serum Metabolite Associations with Childhood Adiposity and Body Composition Outcomes.

Maternal metabolites influence the size of newborns independently of maternal body mass index (BMI) and glycemia, highlighting the importance of maternal metabolism on offspring outcomes. This study examined associations of maternal metabolites during pregnancy with childhood adiposity, and cord blood metabolites with childhood adiposity using phenotype and metabolomic data from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and the HAPO Follow-Up Study. The maternal metabolites analyses included 2324 mother-offspring pairs, while the cord blood metabolites analyses included 937 offspring. Multiple logistic and linear regression were used to examine associations between primary predictors, maternal or cord blood metabolites, and childhood adiposity outcomes. Multiple maternal fasting and 1 hr metabolites were significantly associated with childhood adiposity outcomes in Model 1 but were no longer significant after adjusting for maternal BMI and/or maternal glycemia. In the fully adjusted model, fasting lactose levels were negatively associated with child BMI z-scores and waist circumference, while fasting urea levels were positively associated with waist circumference. One-hour methionine was positively associated with fat-free mass. There were no significant associations between cord blood metabolites and childhood adiposity outcomes. Few metabolites were associated with childhood adiposity outcomes after adjusting for maternal BMI and glucose, suggesting that maternal BMI accounts for the association between maternal metabolites and childhood adiposity.

Associations of Cord Blood Lipids with Childhood Adiposity at the Age of Three Years: A Prospective Birth Cohort Study.

We aimed to examine the associations between cord blood lipids and childhood adiposity and to investigate whether these associations vary across birth weight categories (small for gestational age (SGA), appropriate for gestational age (AGA) and large for gestational age (LGA)) in 1306 infants in the Born in Guangzhou Cohort Study, China. Adiposity outcomes at the age of three years included z-scores of weight-for-length/height (WFLZ), body mass index (BMIZ), subscapular (SSTZ) and triceps skinfold thickness (TSTZ), and the sum of skinfold thicknesses (SSFTZ). Cord blood triglycerides (TG) levels were negatively associated with WFLZ and BMIZ, whereas high density lipoprotein (HDL) levels were positively associated with WFLZ, BMIZ, TSTZ and SSFTZ. These associations were attenuated after adjustment for birth weight. Stratified analyses revealed that total cholesterol (TC) and low-density lipoprotein (LDL) levels were positively associated with childhood adiposity indicators among AGA infants but tended to be negatively associated with the adiposity indicators among LGA infants (p values for interaction <0.05). Furthermore, TG levels appeared to be positively associated with adiposity indicators among SGA infants but negatively associated with the outcomes among LGA infants (p values for interaction <0.05). Cord blood lipids levels might be associated with childhood adiposity, and these associations appear to differ across different birth weight categories. If confirmed in future studies, our findings suggest that individualized management plans might be warranted in preventing obesity.

The mediating effect of DNA methylation in the association between maternal sleep during pregnancy and offspring adiposity status: a prospective cohort study.

BACKGROUND: Childhood overweight/obesity is a global public health concern. It is important to identify its early-life risk factors. Maternal poor sleep is common in late pregnancy, and previous studies indicated that poor sleep may influence the offspring's adiposity status. However, very few studies in humans investigated the effect of the different sleep parameters (sleep quantity, quality, and timing) on the offspring's adiposity indicators, and long-term studies are even more scarce. In addition, the underlying mechanism remains unclear. The present study therefore aimed to examine the association between the three maternal sleep dimensions in the late pregnancy and the offspring adiposity indicators and to explore the potential mediating effect of the cord blood DNA methylation in the above association. METHODS: Included participants in the current study were 2211 healthy pregnant women with singleton gestation from the Shanghai Birth Cohort (SBC) and Shanghai Sleep Birth Cohort (SSBC). Maternal nighttime sleep duration, quality, and midpoint (an indicator of circadian rhythm) were assessed by the same instrument in both cohorts during late pregnancy, and the offspring's body mass index (BMI) and subcutaneous fat (SF) were measured at 2 years old. Additionally, in 231 SSBC samples, the genome-wide DNA methylation levels were measured using the Illumina Infinium Methylation EPIC BeadChip. The multivariate linear regression was used to determine the associations between the maternal sleep parameters and the offspring adiposity indicators. The epigenome-wide association study was conducted to identify the maternal sleep-related CpG sites. The mediation analysis was performed to evaluate the potential intermediate role of DNA methylation in the association between maternal sleep and offspring adiposity indicators. RESULTS: The mean maternal nighttime sleep duration and the sleep midpoint for combined cohorts were 9.24 ± 1.13 h and 3.02 ± 0.82, respectively, and 24.5% of pregnant women experienced poor sleep quality in late pregnancy. After adjusting for the covariates, the maternal later sleep midpoint was associated with the increased SF in offspring (Coef. = 0.62, 95% CI 0.37-0.87, p < 0.001) at 2 years old. However, no significant associations of the nighttime sleep duration or sleep quality with the offspring adiposity indicators were found. In the SSBC sample, 45 differential methylated probes (DMPs) were associated with the maternal sleep midpoint, and then, we observed 10 and 3 DMPs that were also associated with the offspring's SF and BMI at 2 years, of which cg04351668 (MARCH9) and cg12232388 significantly mediated the relationship of sleep midpoint and SF and cg12232388 and cg12225226 mediated the sleep midpoint-BMI association, respectively. CONCLUSIONS: Maternal later sleep timing in late pregnancy was associated with higher childhood adiposity in the offspring. Cord blood DNA methylation may play a mediation role in that relationship.

Organic UV filters mixture exposure and childhood adiposity: A prospective follow-up study in China.

BACKGROUND: UV filters are emerging contaminants with endocrine disrupting effects, but little is known about their health effects, especially for children. OBJECTIVE: To assess the association between multiple organic UV filters exposure and adiposity measures and by gender in peripubertal children. METHODS: This prospective follow-up study included 327 children aged 7-15 years old. Urinary organic UV filters including benzophenone derivatives (BP-2, BP-3), octyl dimethyl para-aminobenzoic acid (OD-PABA), ethylhexyl methoxycinnamate (EHMC) and its metabolite (4-MCA and 4'-MAP) were quantified. Six adiposity biometrics including height, weight, waist and hip circumferences, and triceps and subscapular skinfold thickness were measured with 1.5-year duration. The Bayesian kernel machine regression method was used to estimate the associations of UV filters mixture with adiposity measurements, and longitudinal analyses were then considered to further evaluate the associations between individual UV filters and trajectories of growth development using linear mixed models or generalized linear mixed models. RESULTS: Exposure to mixture of UV filters was negatively associated with most adiposity measurements, with a reduction of 1.399 kg/m2 (95% CI: -2.246 to -0.551 kg/m2) in BMI, 0.674 (95% CI: -1.045 to -0.304) in BMI z-score, 0.033 BF% (95% CI: -0.053 to -0.013), and 2.301 mm (95% CI: -3.823 to -0.78) in subscapular skinfold thickness at baseline, comparing the 75th percentile to the 25th level of UV filters mixture exposure. Consistent associations were found at follow-up. Both baseline and follow-up results suggested that EHMC was identified as the most important contributor to lower adiposity measurements, which was also confirmed by linear mixed models in longitudinal analyses. No significant effects were found in girls. CONCLUSION: This study found that childhood organic UV filters exposure was negatively associated with adiposity measures in peripubertal boys, but not girls.

Adiposity may confound the association between vitamin D and disease risk - a lifecourse Mendelian randomization study.

Background: Vitamin D supplements are widely prescribed to help reduce disease risk. However, this strategy is based on findings using conventional epidemiological methods which are prone to confounding and reverse causation. Methods: In this short report, we leveraged genetic variants which differentially influence body size during childhood and adulthood within a multivariable Mendelian randomization (MR) framework, allowing us to separate the genetically predicted effects of adiposity at these two timepoints in the lifecourse. Results: Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), there was strong evidence that higher childhood body size has a direct effect on lower vitamin D levels in early life (mean age: 9.9 years, range = 8.9-11.5 years) after accounting for the effect of the adult body size genetic score (beta = -0.32, 95% CI = -0.54 to -0.10, p=0.004). Conversely, we found evidence that the effect of childhood body size on vitamin D levels in midlife (mean age: 56.5 years, range = 40-69 years) is putatively mediated along the causal pathway involving adulthood adiposity (beta = -0.17, 95% CI = -0.21 to -0.13, p=4.6 × 10-17). Conclusions: Our findings have important implications in terms of the causal influence of vitamin D deficiency on disease risk. Furthermore, they serve as a compelling proof of concept that the timepoints across the lifecourse at which exposures and outcomes are measured can meaningfully impact overall conclusions drawn by MR studies. Funding: This work was supported by the Integrative Epidemiology Unit which receives funding from the UK Medical Research Council and the University of Bristol (MC_UU_00011/1).

Prenatal exposure to per- and polyfluoroalkyl substances and childhood adiposity at 7 years of age.

BACKGROUND: An increasing number of studies have reported that prenatal per- and polyfluoroalkyl substances (PFAS) exposure may increase childhood adiposity. However, limited data is available in China, and the overall effects of PFAS mixture remain unclear. OBJECTIVE: To examine the association of prenatal exposure to individual PFAS and their mixture with childhood adiposity at 7 years of age. METHODS: A total of 206 mother-infant pairs were recruited from the Laizhou Wan (Bay) Birth Cohort in China between 2010 and 2013. Ten PFAS were measured in maternal serum. The measurements of fat mass, body fat percentage, body mass index, waist circumference, waist-to-height ratio and overweight/obesity were used to assess adiposity in children aged 7. We fitted logistic regression, linear regression and weighted quantile sum (WQS) regression models to estimate the association of prenatal exposure to individual PFAS and their mixture with childhood adiposity. RESULTS: We found negative associations of perfluoroheptanoic acid (PFHpA) and perfluorooctane sulfonamide (PFOSA) exposure with adiposity measurements in all children. The result from the WQS model consistently revealed that the PFAS mixture was inversely related to adiposity measurements. Each quartile increase of the PFAS mixture was associated with a 1.14 kg decrease (95% CI: -2.27, -0.02) in fat mass and a 2.32% decrease (95% CI: -4.51, -0.14) in body fat. Moreover, significant sex differences were found. PFAS mixture was negatively associated with five adiposity measurements in boys, but positively associated with all adiposity measurements except body fat percentage in girls. PFOSA, PFHpA and perfluorobutanesulfonate (PFBS) with weights >0.300 were the main contributors to the overall effects observed among all children, boys and girls, respectively. CONCLUSION: This study suggests potential sex-specific associations of prenatal exposure to individual PFAS and their mixture with childhood adiposity, with the observed relationship being negative for boys but positive for girls.

Associations between Cord Blood Leptin Levels and Childhood Adiposity Differ by Sex and Age at Adiposity Assessment.

Lower cord blood leptin levels have been associated with lower and higher adiposity in childhood and associations seem to differ according to the child's age, methods of adiposity assessment and sex. Our aim was to investigate sex-specific associations of cord blood leptinemia with childhood adiposity at birth, 3 and 5 years of age. We measured cord blood leptin using Luminex immunoassays in 520 offspring from the Gen3G cohort. We tested associations between cord blood leptin and body mass index (BMI) z-score, skinfolds thicknesses (SFT), and body composition using dual-energy X-ray absorptiometry, adjusted for confounders. At birth, girls had almost twice as much leptin in cord blood as boys (15.5 [8.9; 25.6] vs. 8.6 [4.9; 15.0] ng/mL; p < 0.0001) as well as significantly greater adiposity. Lower levels of cord blood leptin were associated with higher sum of SFT (ß = −0.05 ± 0.02; p = 0.03) and higher BMI z-score (ß= −0.22 ± 0.08; p = 0.01) in 3-year-old boys only. We did not observe these associations at age 5, or in girls. Our results suggest a sexual dimorphism in the programming of leptin sensitivity and childhood adiposity, but further observational and functional studies are needed to better understand the role of leptin in early life.

ADHD and Risk of Childhood Adiposity: a Review of Recent Research.

PURPOSE OF REVIEW: Attention deficit/hyperactivity disorder (ADHD) is considered as a risk factor for childhood adiposity and obesity. Studies on ADHD have provided limited data concerning the connections between eating habits, body mass index, and obesity. The purpose of this review was to examine the current literature regarding recent cohort and cross-sectional studies to determine the links between ADHD and childhood adiposity. RECENT FINDINGS: Studies in this review were classified into dietary features, nutritional status, neuroimaging findings, genetic overlapping, behavioral, cognitive, and neurocognitive aspects that play a role in mediating and moderating the relationship between ADHD and obesity. While ADHD, childhood adiposity, and overweight/obesity co-occur in children and adolescents, this relationship is largely explained by a variety of multidirectional factors.