Early Life Obesity Research Articles

Antibiotic exposure in early life and childhood overweight and obesity: A systematic review and meta-analysis.

We conducted a systematic review and meta-analysis of observational studies investigating the association between antibiotic exposure in infancy and risk of childhood overweight and obesity. Thirteen studies, including a total of 527 504 children, were included in the systematic review and 8 were included in meta-analyses. Exposure to antibiotics in infancy was associated with an increased odds ratio (OR) of childhood overweight and obesity (OR 1.11, 95% confidence interval [CI] 1.02-1.20). Whereas exposure to 1 treatment only and exposure between 6 and 24 months were not associated with increased risk of childhood overweight and obesity, exposure to >1 treatment was associated with an OR of 1.24 (95% CI 1.09-1.43) and exposure within the first 6 months of life was associated with an OR of 1.20 (95% CI 1.04-1.37). In conclusion, antibiotic exposure in infancy was associated with a slightly increased risk of childhood overweight and obesity, mainly if children were exposed to repeated treatments or treatment within the first 6 months of life. It is unclear whether this association is mediated via direct effects of antibiotics on the gut microbiota.

(111) - Investigating the influence of exercise and diet on early life stress-induced pain and obesity in mice

Individuals who experience adverse childhood events show a susceptibility to developing chronic pain disorders. These disorders frequently present co-morbidly and with both mood and obesity-related metabolic disorders. Although the underlying mechanisms of these syndromes are yet to be established, it is recognized that the hypothalamic-pituitary-adrenal (HPA) axis plays a role in the regulation of the stress, nociceptive, and metabolic systems. Therefore, it is hypothesized that HPA axis dysfunction influences their pathogenesis. The present study is investigating the effect of exercise and diet interventions in a mouse model of early life stress that displays molecular evidence of altered HPA axis regulation as well as behavioral evidence of urogenital pain disorders. Neonatal maternal separation (NMS) was performed by separating entire litters from the dam for 3h/day starting on postnatal day 1 (P1) to P21. Naive pups remained undisturbed and all pups were weaned on P22. At 4 weeks of age NMS and naive mice either received free access to a running wheel in their home cage (exercised [-Ex]) or remained in sedentary housing (-Sed). Body composition analysis was assessed in adult mice using EchoMRI. Both male and female NMS-Sed mice weighed significantly more and had greater percent body fat compared to naive or Ex mice. At 16 weeks of age, male mice were placed on a high-fat/sucrose diet for one week. All groups displayed a significant increase in weight and percent body fat. Interestingly, a diet-induced increase in perigenital mechanical sensitivity was observed in all mice except for NMS-Sed, which had an increased withdrawal threshold compared to their baseline measurements. Our findings suggest that exercise can attenuate early life stress-induced development of obesity and potential metabolic syndrome. Future work will investigate the efficacy of an anti-inflammatory diet and long-term consequences of high-fat/sucrose diet consumption. Supported by NIH grants DK099611, DK103872, and HD057850.

Strengthening integration of clinical and public health systems to prevent maternal-child obesity in the First 1,000 Days: A Collective Impact approach

IntroductionObesity interventions may be most effective if they begin in the earliest stages of life, support changes across family, clinical, and public health systems, and address socio-contextual factors. MethodsThe First 1000Days is a systematic program starting in early pregnancy lasting through the first 24months of infancy to prevent obesity among low-income mother-infant pairs in three community health centers in Massachusetts. The program uses a Collective Impact approach to create the infrastructure for sustained, system-wide changes for obesity prevention across early life clinical and public health services, including Obstetrics, Pediatrics, Adult Medicine, Behavioral Health, Nutrition, Community Health, the Women, Infants and Children (WIC) program, and the Maternal, Infant and Childhood Home Visiting program. Program components include 1) staff and provider training; 2) enhanced gestational weight gain and infant overweight tracking; 3) universal screening of adverse health behaviors and socio-contextual factors; 4) universal patient navigation to support individual behavior change and social needs, while strengthening integration of clinical and public health services; 5) individualized health coaching for mother-infant pairs at high risk of obesity; and 6) educational materials to support behavior change. ResultsA quasi-experimental evaluation design will examine changes, between 2015 and 2019, in gestational weight gain and prevalence of infant overweight from 0 to 24months of age. ConclusionsThe First 1000Days program will examine the effectiveness of an early life obesity prevention program for mother-infant pairs. If successful, the program could provide a model for chronic disease prevention and health promotion among vulnerable families starting in early life.

Restoring Serotonergic Homeostasis in the Lateral Hypothalamus Rescues Sleep Disturbances Induced by Early-Life Obesity.

Early-life obesity predisposes to obesity in adulthood, a condition with broad medical implications including sleep disorders, which can exacerbate metabolic disturbances and disrupt cognitive and affective behaviors. In this study, we examined the long-term impact of transient peripubertal diet-induced obesity (ppDIO, induced between 4 and 10 weeks of age) on sleep-wake behavior in male mice. EEG and EMG recordings revealed that ppDIO increases sleep during the active phase but reduces resting-phase sleep quality. This impaired sleep phenotype persisted for up to 1 year, although animals were returned to a non-obesiogenic diet from postnatal week 11 onwards. To better understand the mechanisms responsible for the ppDIO-induced alterations in sleep, we focused on the lateral hypothalamus (LH). Mice exposed to ppDIO did not show altered mRNA expression levels of orexin and melanin-concentrating hormone, two peptides that are important for sleep-wake behavior and food intake. Conversely, the LH of ppDIO-exposed mice had reduced contents of serotonin (5-hydroxytryptamine, 5-HT), a neurotransmitter involved in both sleep-wake and satiety regulation. Interestingly, an acute peripheral injection of the satiety-signaling peptide YY 3-36 increased 5-HT turnover in the LH and ameliorated the ppDIO-induced sleep disturbances, suggesting the therapeutic potential of this peptide. These findings provide new insights into how sleep-wake behavior is programmed during early life and how peripheral and central signals are integrated to coordinate sleep.SIGNIFICANCE STATEMENT Adult physiology and behavior are strongly influenced by dynamic reorganization of the brain during puberty. The present work shows that obesity during puberty leads to persistently dysregulated patterns of sleep and wakefulness by blunting serotonergic signaling in the lateral hypothalamus. It also shows that pharmacological mimicry of satiety with peptide YY3-36 can reverse this neurochemical imbalance and acutely restore sleep composition. These findings add insight into how innate behaviors such as feeding and sleep are integrated and suggest a novel mechanism through which diet-induced obesity during puberty imposes its long-lasting effects on sleep-wake behavior.

Longitudinal assessment of body composition in healthy Swedish children from 1 week until 4 years of age.

Knowledge of longitudinal body composition development is required to identify the mechanisms behind childhood overweight and obesity and to prevent these conditions. However, accurate data on this development in early childhood are lacking. Our aim was to describe the longitudinal body composition development in healthy young Swedish children. Body size and composition were assessed in 26 children using air-displacement plethysmography (1 and 12 weeks and 4.4 years of age) and isotope dilution (1.5 and 3 years of age) and compared with available reference data. Body fat (%) for boys (n=16) was 12.8±3.9 (1 week), 25.6±4.8 (12 weeks), 28.2±3.8 (1.5 years), 27.3±5.1 (3 years) and 26.1±3.5 (4.4 years). For girls (n=10) these values were 15.3±2.9, 25.7±3.9, 27.9±3.3, 26.3±7.2 and 26.0±5.3, respectively. These values were above the Fomon reference values at 1.5 years of age and later and higher than the Butte reference (P<0.05) for boys at 1.5 years of age. At all ages the coefficients of variation were higher for body fat (%) (12-30%) than for BMI (4-11%). At 4 years of age our children had more body fat than indicated by reference data. This high level may have already been established at 1.5 years of age but our small sample and the lack of appropriate reference data limit the possibility of drawing firm conclusions. Our results demonstrate the limitations of BMI when investigating overweight and obesity in early life and highlight the need for appropriate reference body composition data in infants and young children.European Journal of Clinical Nutrition advance online publication, 23 August 2017; doi:10.1038/ejcn.2017.125.

PTPRS and PER3 methylation levels are associated with childhood obesity: results from a genome-wide methylation analysis.

The global prevalence of childhood overweight and obesity has increased in the last years. Epigenetic dysregulation affecting gene expression could be a determinant in early-life obesity onset and accompanying complications. The aim of the present investigation was to analyse the putative association between DNA methylation and childhood obesity. DNA was isolated from white blood cells of 24 children obtained from the GENOI study and was hybridized in a 450K methylation array. Two CpG sites associated with obesity were validated in 91 children by MassArray® EpiTyper™ technology. Genome-wide analysis identified 734 CpGs (783 genes) differentially methylated between cases (n=12) and controls (n=12). Ingenuity Pathway Analysis showed that these genes were involved in oxidative stress and circadian rhythm signalling pathways. Moreover, the DNA methylation levels of VIPR2, GRIN2D, ADCYAP1R1, PER3 and PTPRS regions correlated with the obesity trait. EpiTyper™ validation also identified significant correlations between methylation levels of CpG sites on PTPRS and PER3 with BMI z-score. This study identified several CpG sites and specifically several CpGs in the PTPRS and PER3 genes differentially methylated between obese and non-obese children, suggesting a role for DNA methylation concerning development of childhood obesity.

Overweight or obesity in children aged 0 to 6 and the risk of adult metabolic syndrome: A systematic review and meta-analysis.

To identify an association between overweight or obesity in early childhood and metabolic syndrome in adults. Early childhood overweight or obesity is important because it can predict metabolic syndrome in adulthood. A longer period of overweight or obesity leads to the accumulation of more risk factors. However, there are insufficient and inconsistent studies on this issue. A systematic review and meta-analysis. We followed the Meta-Analysis of Observational Studies in Epidemiology guideline, MEDLINE, EMBASE, Cochrane library and CINAHL electronic databases as well as reference lists of included studies were searched, without published date restriction. We used the Newcastle-Ottawa Scale to assess the quality of the observational studies in the systematic review, and the meta-analysis was performed using random-effects models. All of the included studies were published from 2008-2014, and the participants of this study were only Asians or Europeans. A total of 12 results from five studies were included in the meta-analysis. Overweight or obesity in early childhood was associated with a higher risk of adult metabolic syndrome compared with the controls. When confirmed in each age group (at birth, 0-2 and 2-6years), there was a statistically significant difference before and after the age of 2years. As a result of the meta-regression, when the age of the children increased, the effect size of adult metabolic syndrome for overweight or obesity also increased. The results confirm that the aetiology of metabolic syndrome includes long-term impacts from the early stage of life and indicate that early intervention for overweight or obesity is needed. these findings could help community and clinical health nurses recognize the risk of overweight or obesity in early life, and provide evidence to develop and implement the preventive intervention for early childhood.

Targeting Sleep, Food, and Activity in Infants for Obesity Prevention: An RCT.

The few existing early-life obesity prevention initiatives have concentrated on nutrition and physical activity, with little examination of sleep. This community-based, randomized controlled trial allocated 802 pregnant women (≥16 years, <34 weeks' gestation) to: control, FAB (food, activity, and breastfeeding), sleep, or combination (both interventions) groups. All groups received standard well-child care. FAB participants received additional support (8 contacts) promoting breastfeeding, healthy eating, and physical activity (antenatal-18 months). Sleep participants received 2 sessions (antenatal, 3 weeks) targeting prevention of sleep problems, as well as a sleep treatment program if requested (6-24 months). Combination participants received both interventions (9 contacts). BMI was measured at 24 months by researchers blinded to group allocation, and secondary outcomes (diet, physical activity, sleep) were assessed by using a questionnaire or accelerometry at multiple time points. At 2 years, 686 women remained in the study (86%). No significant intervention effect was observed for BMI at 24 months (P = .086), but there was an overall group effect for the prevalence of obesity (P = .027). Exploratory analyses found a protective effect for obesity among those receiving the "sleep intervention" (sleep and combination compared with FAB and control: odds ratio, 0.54 [95% confidence interval, 0.35-0.82]). No effect was observed for the "FAB intervention" (FAB and combination compared with sleep and control: odds ratio, 1.20 [95% confidence interval, 0.80-1.81]). A well-developed food and activity intervention did not seem to affect children's weight status. However, further research on more intensive or longer running sleep interventions is warranted.

Timing of an accelerated body mass increase in children exposed to lead in early life: A longitudinal study.

In utero exposure to lead is known to cause various adverse health outcomes and early life obesity can affect permanent metabolic alterations leading to adverse health outcomes. To examine the relation between perinatal lead exposure and childhood obesity, lead level in cord bloods and growth- and obesity-related markers at birth were measured from 280 mother-child pairs. The weight, height, and body mass index (BMI) of children were measured at birth and followed up several times up to 27months of age. The relations between lead level and growth- and obesity-related markers were evaluated using a generalized linear model after adjustment for maternal age, maternal BMI, gestational period, cesarean section, and smoking status. The changes of child weight, height, and BMI z-scores at followed-up months of age after birth by lead exposure were evaluated using a generalized linear model after adjustment for covariates used in the analyses for growth- and obesity-related markers and child's gender. The lead level was positively associated with an increase of birth height (p=0.019) and a decrease of ponderal index at birth (p=0.027) in boys, but not in girls. Moreover, the lead level was positively associated with increases of BMI z-score after 18months of age (p=0.070 at 18months of age; p=0.003 at 24months of age; and p=0.002 at 27months of age). Perinatal lead exposure affected accelerated body mass increases at specific times of the children' development.

Early-Life Obesity May Be Associated With Later Knee Osteoarthritis and Pain

Lippincott's Bone and Joint Newsletter 23(2):p 20, February 2017. | DOI: 10.1097/01.BONEJ.0000512325.61524.ba

Characterizing a "Big Data" Cohort of Over 200,000 Low-Income U.S. Infants and Children for Obesity Research: The ADVANCE Early Life Cohort.

Introduction Low-income populations have elevated exposure to early life risk factors for obesity, but are understudied in longitudinal research. Our objective was to assess the utility of a cohort derived from electronic health record data from safety net clinics for investigation of obesity emerging in early life. Methods We examined data from the PCORNet ADVANCE Clinical Data Research Network, a national network of Federally-Qualified Health Centers serving >1.7million safety net patients across the US. This cohort includes patients who, in 2012-2014, had ≥1 valid body mass index measure when they were 0-5 years of age. We characterized the cohort with respect to factors required for early life obesity research in vulnerable subgroups: sociodemographic diversity, weight status based on World Health Organization (<2 years) or Centers for Disease Control (≥2 years) growth curves, and data longitudinality. Results The cohort includes 216,473 children and is racially/ethnically diverse (e.g., 17.9% Black, 45.4% Hispanic). A majority (56.9%) had family incomes below the Federal Poverty Level (FPL); 32% were <50% of FPL. Among children <2 years, 7.6 and 5.3% had high and low weight-for-length, respectively. Among children 2-5 years, 15.0, 12.7 and 2.4% were overweight, obese, and severely obese, respectively; 5.3% were underweight. In the study period, 79.2% of children had ≥2 BMI measures. Among 4-5year olds, 21.9% had >1 BMI measure when they were <2 years. Discussion The ADVANCE Early Life cohort offers unique opportunities to investigate early life determinants of obesity in the understudied population of low income and minority children.

Multiple Sclerosis: Implications of Obesity in Neuroinflammation.

Since the discovery of the remarkable properties of adipose tissue as a metabolically active organ, several evidences on the possible link between obesity and the pathogenesis of multiple sclerosis (MS) have been gathered. Obesity in early life, mainly during adolescence, has been proposed as a relevant risk factor for late MS development. Moreover, once MS is initiated, obesity can contribute to increase disease severity by negatively influencing disease progress. Despite the fact that clinical data are not yet conclusive, many biochemical links have been recently disclosed. The "low-grade inflammation" that characterizes obesity can lead to neuroinflammation through different mechanisms, including choroid plexus and blood-brain barrier disruption. Furthermore, it is well known that resident immune cells of central nervous system and peripheral immune cells are involved in the pathogenesis of MS, and adipokines and neuropeptides such as neuropeptide Y may mediate the cross talk between them.

Early Life Exposures and Adult Cancer Risk.

Very little is known about the influence of early life exposures on adult cancer risk. The purpose of this narrative review was to summarize the epidemiologic evidence relating early life tobacco use, obesity, diet, and physical activity to adult cancer risk; describe relevant theoretical frameworks and methodological strategies for studying early life exposures; and discuss policies and research initiatives focused on early life. Our findings suggest that in utero exposures may indirectly influence cancer risk by modifying biological pathways associated with carcinogenesis; however, more research is needed to firmly establish these associations. Initiation of exposures during childhood and adolescence may impact cancer risk by increasing duration and lifetime exposure to carcinogens and/or by acting during critical developmental periods. To expand the evidence base, we encourage the use of life course frameworks, causal inference methods such as Mendelian randomization, and statistical approaches such as group-based trajectory modeling in future studies. Further, we emphasize the need for objective exposure biomarkers and valid surrogate endpoints to reduce misclassification. With the exception of tobacco use, there is insufficient evidence to support the development of new cancer prevention policies; however, we highlight existing policies that may reduce the burden of these modifiable risk factors in early life.

Sex differences in the association of obesity and colorectal cancer risk.

Epidemiological research has convincingly shown that obesity increases colorectal cancer (CRC) risk, with generally stronger associations observed in men than in women. Evidence from the past several years has demonstrated a divergent pattern between men and women regarding the weight changes throughout life or timing of obesity for CRC risk. For men, weight gain later in life appears to be an important risk factor for CRC that mostly accounts for their generally strong association between adult body mass index and CRC risk. For women, however, early life obesity seems to be more important than adult weight gain in determining CRC risk. A knowledge of these sex patterns may have implications on better understanding colorectal carcinogenesis and may further improve prevention efforts for CRC.

Epigenética y obesidad

Current evidence supports the notion that exposure to various environmental conditions in early life may induce permanent changes in the epigenome that persist throughout the life-course. This article focuses on early changes associated with obesity in adult life. A review is presented on the factors that induce changes in whole genome (DNA) methylation in early life that are associated with adult onset obesity and related disorders. In contrast, reversal of epigenetic changes associated with weight loss in obese subjects has not been demonstrated. This contrasts with well-established associations found between obesity related DNA methylation patterns at birth and adult onset obesity and diabetes. Epigenetic markers may serve to screen indivuals at risk for obesity and assess the effects of interventions in early life that may delay or prevent obesity in early life. This might contribute to lower the obesity-related burden of death and disability at the population level. The available evidence indicates that epigenetic marks are in fact modifiable, based on modifications in the intrauterine environment and changes in food intake, physical activity and dietary patterns patterns during pregnancy and early years of adult life. This offers the opportunity to intervene before conception, during pregnancy, infancy, childhood, and also in later life. There must be documentation on the best preventive actions in terms of diet and physical activity that will modify or revert the adverse epigenetic markers, thus preventing obesity and diabetes in suceptible individuals and populations.

Early life Phthalate Exposure and Obesity and Cardiometabolic Traits in Childhood.

Introduction: Phthalates are industrial chemicals with endocrine disrupting properties. Human evidence on the effects of early life phthalate exposure on obesity and cardiovascular risks is limited to a few cross-sectional studies. We evaluated the associations between early life phthalate exposure with offspring obesity and cardiometabolic risk factors in 500 mother-child pairs from the RHEA pregnancy cohort in Crete, Greece. Methods: Seven phthalate metabolites were measured in spot urine samples collected from mothers (1st trimester) and their children at 4 years of age. We calculated the sum of DEHP metabolites (MEHP, MEHHP, and MEOHP) and combined high and low molecular-weight phthalate metabolites as ΣHMWPm (ΣDEHPm and MBzP) and ΣLMWPm (MEP, MiBP, and MnBP) respectively. We measured child weight, height, waist circumference, skinfold thicknesses, blood pressure (BP) and blood levels of lipids and C-reactive protein (CRP) at 4 and 6 years. Adjusted associations were obtained via multivariable regression analyses. Results: DEHP exposure during pregnancy was associated with higher CRP (β=0.41 mg/dL; 95% CI: 0.21, 0.61) at 4 years of age but was not associated with child adiposity measures at 4 and 6 years of age. Higher levels of ΣHMWPm at 4 years corresponded with 2.46 mm greater waist circumference and 8.07 mm greater sum of skinfolds gain during follow up only in girls (p for interaction &lt;0.05). Similarly, ΣHMWPm at 4 years was associated with lower BMI z-scores in boys (β= -0.37; 95% CI: -0.70, -0.03) and with higher BMI z-scores in girls at 6 years (β= 0.56; 95% CI: 0.06, 1.07; p for sex interaction = 0.001). Phthalate exposure in pregnancy or childhood was not associated with child blood levels of lipids or blood pressure. Conclusions: Our findings suggest that early life phthalate exposure may affect child growth and adiposity in a sex-specific manner.

Weighing Evidence from Mendelian Randomization-Early-Life Obesity as a Causal Factor in Multiple Sclerosis?

In this Perspective, Alberto Ascherio and Kassandra Munger discuss the implications of Richards and colleagues' study exploring the role of early-life obesity in risk of multiple sclerosis.

Adiposity in Children and CVD Risk: ApoB48 Has a Stronger Association With Central Fat Than Classic Lipid Markers.

Atherosclerotic vascular disease begins in childhood and while progression is multifactorial, obesity in early life is an important risk factor for its development. To determine whether fasting apoB48 remnant lipoproteins (relative to classic lipid markers), is elevated with increasing central adiposity over time in a cohort of Canadian children with a family history of obesity. Data were drawn from the ongoing prospective cohort of 630 Caucasian families in Québec, Canada, recruited to assess determinants and effects of childhood obesity (Québec Adiposity and Lifestyle Investigation in Youth [QUALITY]cohort). Children who attended baseline and first followup clinic visits (n =570; age 9.6 y). Trunk fat mass was determined by dual energy x-ray absorptiometry. Central fat mass index was calculated as CFMI = trunk fat mass/height(2) (kg/m(2)) and groups created (CFMI <1.5; 1.5-3.0; ≥3.0 kg/m(2)) to suggest lower, moderate, or higher central adiposity. Changes over time in outcomes (apoB48, triglyceride and total, low-, and high-density lipoprotein cholesterol) were compared using paired t test and multiple regression that adjusted for age, sex, and Tanner stage. Classic lipid markers (total and low-density lipoprotein cholesterol) improved at followup, whereas apoB48 became worse (increased). ApoB48 increased with increasing central adiposity, highest (37%) in children who transitioned from lower- to moderate-CFMI groups (ΔapoB48 = 1.5 μg/mL). For every 1 kg/m(2) increase in central adiposity over the 2-y period, an increase in apoB48 was 14-fold greater among children with lower baseline CFMI, compared with higher CFMI. Increased fasting concentrations of apoB48 may be representative of changes in adiposity at lower levels of central fat (early periods of risk).

Epidemiology of Multiple Sclerosis: From Risk Factors to Prevention-An Update.

Although genetic susceptibility explains the clustering of multiple sclerosis (MS) within families and the sharp decline in risk with increasing genetic distance, it cannot fully explain the geographical variations in MS frequency and the changes in risk that occur with migration, which support the action of strong environmental factors. Among these, vitamin D status, obesity in early life, infection with the Epstein-Barr virus, and cigarette smoking are the most consistent environmental predictors of MS risk. The authors review the epidemiological data, critically discuss the evidence for causality of these and other associations, and briefly review the possibility of interventions to reduce MS risk.

Preventing Obesity Across Generations: Evidence for Early Life Intervention.

To prevent the intergenerational transfer of obesity and end the current epidemic, interventions are needed across the early life stages, from preconception to prenatal to infancy through the age of 2 years. The foundation for obesity is laid in early life by actions and interactions passed from parent to child that have long-lasting biologic and behavioral consequences. The purpose of this paper is to examine the best evidence about (a) factors in parents and offspring that promote obesity during the early life stages, (b) the social determinants and dimensions of obesity in early life, (c) promising and effective interventions for preventing obesity in early life, and (d) opportunities for future research into strategies to disrupt the intergenerational cycle of obesity that begins early in life. The pathway for halting the intergenerational obesity epidemic requires the discovery and development of evidence-based interventions that can act across multiple dimensions of influence on early life.